Phẫu Thuật Da Liễu: Khía Cạnh Ngoại Khoa (Surgery of the Skin)

83
Chapter 5  Patient Evaluation, Informed Consent, Preoperative Assessment, and Care
27. Dietrich W, Dilthey G, Spannagl M, et al. Warfarin pretreatment does
not lead to increased bleeding tendency during cardiac surgery. J Cardi-
othorac Vasc Anesth 1995;9:250–254.
28. Alam M, Goldberg LH. Serious adverse vascular events associated with
perioperative interruption of antiplatelet and anticoagulant therapy. Der-
matol Surg 2002;28:992–998; discussion 8.
29. Kovich O, Otley CC. Thrombotic complications related to discontinua-
tion of warfarin and aspirin therapy perioperatively for cutaneous opera-
tion. J Am Acad Dermatol 2003;48:233–237.
30. Foster CA, Aston SJ. Propranolol–epinephrine interaction: a potential
disaster. Plast Reconstr Surg 1983;72:74–78.
31. McGillis ST, Stanton-Hicks U. The preoperative patient evaluation: pre-
paring for surgery. Dermatol Clin 1998;16:1–15.
32. Dzubow LM. The interaction between propranolol and epinephrine as
observed in patients undergoing Mohs’ surgery. J Am Acad Dermatol
1986;15:71–75.
33. Glinert RJ, Zachary CB. Local anesthetic allergy. Its recognition and
avoidance. J Dermatol Surg Oncol 1991;17:491–496.
34. Campbell JR, Maestrello CL, Campbell RL. Allergic response to
metabisulfite in lidocaine anesthetic solution. Anesth Prog 2001;48
21–26.
35. Goodman EJ, Morgan MJ, Johnson PA, et al. Cephalosporins can be given
to penicillin-allergic patients who do not exhibit an anaphylactic response.
J Clin Anesth 2001;13:561–564.
36. Anne S, Reisman RE. Risk of administering cephalosporin antibiotics to
patients with histories of penicillin allergy. Ann Allergy Asthma Immunol
1995;74:167–170.
37. Katz BE, Fisher AA. Bacitracin: a unique topical antibiotic sensitizer.
J Am Acad Dermatol 1987;17:1016–1024.
38. Liss GM, Sussman GL, Deal K, et al. Latex allergy: epidemiological study
of 1351 hospital workers. Occup Environ Med 1997;54:335–342.
39. Woods JA, Lambert S, Platts-Mills TA, et al. Natural rubber latex allergy:
spectrum, diagnostic approach, and therapy. J Emerg Med 1997;15:
71–85.
40. Sorensen LT, Jorgensen S, Petersen LJ, et al. Acute effects of nicotine
and smoking on blood flow, tissue oxygen, and aerobe metabolism of the
skin and subcutis. J Surg Res 2009;152:224–230.
41. Sorensen LT, Karlsmark T, Gottrup F. Abstinence from smoking reduces
incisional wound infection: a randomized controlled trial. Ann Surg
2003;238:1–5.
42. Lind J, Kramhoft M, Bodtker S. The influence of smoking on complica-
tions after primary amputations of the lower extremity. Clin Orthop
Relat Res 1991:211–217.
43. Yaffe B, Cushin BJ, Strauch B. Effect of cigarette smoking on experimen-
tal microvascular anastomoses. Microsurgery 1984;5:70–72.
12. Wilson W, Taubert KA, Gewitz M, et al. Prevention of infective endo-
carditis: guidelines from the American Heart Association: a guideline
from the American Heart Association Rheumatic Fever, Endocarditis and
Kawasaki Disease Committee, Council on Cardiovascular Disease in the
Young, and the Council on Clinical Cardiology, Council on Cardiovascu-
lar Surgery and Anesthesia, and the Quality of Care and Outcomes
Research Interdisciplinary Working Group. J Am Dent Assoc
2008;139(Suppl):3S–24S.
13. Roberts HW, Redding SW. Coronary artery stents: review and patient-
management recommendations. J Am Dent Assoc 2000;131:797–801.
14. Wright TI, Baddour LM, Berbari EF, et al. Antibiotic prophylaxis in
dermatologic surgery: advisory statement 2008. J Am Acad Dermatol
2008;59:464–473.
15. LeVasseur JG, Kennard CD, Finley EM, et al. Dermatologic electrosur-
gery in patients with implantable cardioverter-defibrillators and pacemak-
ers. Dermatol Surg 1998;24:233–240.
16. El-Gamal HM, Dufresne RG, Saddler K. Electrosurgery, pacemakers and
ICDs: a survey of precautions and complications experienced by cutane-
ous surgeons. Dermatol Surg 2001;27:385–390.
17. Rozner MA. Corrections to electrosurgery in patients with cardiac pace-
makers or implanted cardioverter defibrillators. Ann Plast Surg 2007;58:
226–227.
18. Dawes JC, Mahabir RC, Hillier K, et al. Electrosurgery in patients with
pacemakers/implanted cardioverter defibrillators. Ann Plast Surg
2006;57:33–36.
19. Peterson SR, Joseph AK. Inherited bleeding disorders in dermatologic
surgery. Dermatol Surg 2001;27:885–889.
20. Santos-Dias A. CO2 laser surgery in hemophilia treatment. J Clin Laser
Med Surg 1992;10:297–301.
21. Starr PA, Vitek JL, Bakay RA. Deep brain stimulation for movement
disorders. Neurosurg Clin N Am 1998;9:381–402.
22. Weaver J, Kim SJ, Lee MH, et al. Cutaneous electrosurgery in a patient
with a deep brain stimulator. Dermatol Surg 1999;25:415–417.
23. Dinehart SM, Henry L. Dietary supplements: altered coagulation and
effects on bruising. Dermatol Surg 2005;31:819–826; discussion 26.
24. Rand ML, Packham MA, Kinlough-Rathbone RL, et al. Effects of ethanol
on pathways of platelet aggregation in vitro. Thromb Haemost
1988;59:383–387.
25. Kovich O, Otley CC. Perioperative management of anticoagulants and
platelet inhibitors for cutaneous surgery: a survey of current practice.
Dermatol Surg 2002;28:513–517.
26. Billingsley EM, Maloney ME. Intraoperative and postoperative bleeding
problems in patients taking warfarin, aspirin, and nonsteroidal antiinflam-
matory agents. A prospective study. Dermatol Surg 1997;23:381–383;
discussion 4–5.

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85
6
Antibiotics
Ann F Haas MD
Summary box
 Routine use of antibiotics to prevent wound infection and
endocarditis is discouraged because antibiotic-resistant
organisms are becoming more common.
 Patient factors, local wound factors, preparation of
surgical personnel, and surgical technique are all potential
contributory factors to the development of surgical wound
infections.
 Antibiotics to prevent wound infection should only be
considered in situations where the consequences of infection
would be especially serious.
 The choice of antibiotic is based on the most likely infecting
organism.
 If used prophylactically, antibiotics need to be in the tissue
before the time of wounding and contamination (i.e. there
must be a preoperative dose).
 The routine use of antibiotic prophylaxis in dermatologic
surgery is neither cost-effective nor indicated, as the
incidence of wound infection is extremely low.
 INTRODUCTION
With increasing attention to antisepsis and aseptic technique,
dermatologic surgeons, like our general surgical colleagues,
have emphasized both the prevention of surgical site infec-
tions (SSIs) and appropriate treatment when they occur. The
routine use of prophylactic antibiotics to prevent wound
infection or endocarditis has fallen into disfavor across all
specialties, especially because of the recent prevalence of
antibiotic-resistant organisms. In addition, many studies have
now conclusively proven that the incidence of wound infec-
tion in dermatologic surgery is extremely low. This chapter
examines factors involved in the development of SSIs, as well
as the recently updated endocarditis prophylaxis recommen-
dations, and proposes reasonable guidelines for the use of
antibiotics in dermatologic surgery.
Antibiotic resistance
Most antibiotic resistance develops inside hospitals, but the
major development outside hospitals has been an increase in
the prevalence of β-lactamase-producing bacteria, rendering
penicillins less effective. The most important resistance prob-
lems facing dermatologists involve Staphylococcus aureus,
coagulase-negative staphylococci, streptococci, and Propioni-
bacterium acnes (with resistance of Enterobacteriaceae and
Pseudomonas aeruginosa primarily involving in-hospital
immunocompromised patients).1 Recently, the major resist-
ance problem has been caused by methicillin-resistant S.
aureus (MRSA), with the frequency in hospital-acquired
infections often upwards of 50%. The coagulase-negative sta-
phylococci, which often cause infections in immunocompro-
mised patients, are also showing resistance to methicillin and
other antibiotics.
We have also recently seen hospital infections with vanco-
mycin-resistant enterococci, which, although normally not
particularly pathogenic, might be able to transfer their van-
comycin resistance genes to S. aureus (vancomycin resistance
in S. aureus is already being reported). Resistance of S. aureus
to erythromycin, tetracycline, fusidic acid, and quinolones is
now being reported. Coagulase-negative staphylococci can
apparently become resistant for some drugs (penicillin and
methicillin) based on the same genes as for S. aureus. Clearly,
physicians have contributed to the emergence of resistant
organisms by their extensive use of antibiotics.
As the best established infection control practice has been
thought to be hand washing, and antimicrobial use is the
major determinant in the development of resistance, it is
conceivable that paying more attention to aseptic technique
and less to overprescribing antibiotics can help reduce the risk
of resistant organisms developing (see Chapter 2).
Factors involved in the potential
development of wound infection
Contamination of surgical wounds by microorganisms sets the
stage for the potential development of SSIs. Essentially, the
dose of the bacterial contamination combined with the viru-
lence of the microorganism exceeds the resistance of the host
patient and so increases the risk of SSI.
According to the National Nosocomial Infections Surveil-
lance (NNIS) published by the Centers for Disease Control
and Prevention (CDC), the profile of pathogens seen in SSIs
seemingly has been stable.2
The most frequently isolated pathogens were S. aureus,
coagulase-negative staphylococci, Enterococcus spp., and
Escherichia coli. The increase in SSIs caused by MRSA,
Candida albicans, and fungal infections over the time period
was also noted and attributed to both the increasing numbers

86
Part 1  Basic Surgical Concepts
remove the tumors, noted that the only statistically signifi-
cant infection rates were discovered for patients with carti-
lage fenestration with secondary healing, and for those
patients with diagnosis of malignant melanoma.10
Anatomic site is certainly a controversial risk factor and,
unfortunately, published antibiotic guidelines for dermato-
logic surgery reflect this variability.3,7,11 Obviously there are
many risk factors for surgical site infections with many of
them probably acting in concert, and it is therefore difficult
to attribute SSI development to any one specific factor in
isolation.
Distant focus of infection
Usually a distant focus of infection is a respiratory, urinary,
or skin infection that seeds the operative site.2,12 Remote skin
infection may be a consideration in those with severe acne,
actively inflamed epidermal inclusion cysts, or significant
atopic dermatitis, and can be a significant problem for those
undergoing implantation of a prosthetic device.
Diabetes mellitus
Diabetes mellitus has been associated with defects in leuko-
cyte mobilization and other immune system abnormalities,
many of which can be corrected by normalizing blood glucose.
Although some studies have associated both increasing levels
of HbA1c and elevated glucose levels in the immediate post-
operative period with increasing SSI rates, this phenomenon
has not been studied in a strictly controlled fashion, in the
absence of other potentially contributing factors.2 The inci-
dence of SSI development in people with diabetes mellitus
is variable, depending on the study quoted. It has been shown
that people with well-controlled diabetes mellitus do not
seem to have an increased infection rate compared with
people who do not have diabetes mellitus, so it may be well
worth the effort to achieve good control of diabetes mellitus
preoperatively.12,13
Smoking
Nicotine use delays primary wound healing and has been
noted in studies as an important SSI risk factor. However,
the contribution of smoking as an independent variable has
not been strictly analyzed in the absence of other potential
contributing variables.2
Malnutrition
It would seem reasonable that a low serum albumin would
be a causal factor in wound healing problems, but it has not
been explicitly implicated as a single predictive variable in
SSIs. Although nutritional support is routinely given to
patients undergoing general surgery and to those undergoing
prolonged intubation after trauma, there are many reasons for
this and it is not specifically aimed at preventing SSIs.
Age
Advanced age is a variable that is probably additive in con-
tributing to the potential risk of SSI. Older patients have a
higher tendency to have multiple medical problems, which
can cause malnutrition and hypoxia for example. Addition-
ally, elderly patients may be on a significant number of med-
ications, which can adversely affect wound healing and so
potentially increase the risk of development of SSI.
of very ill and immunocompromised patients as well as the
frequent use of broad-spectrum antibiotics.
The CDC has estimated that approximately 75% of all
operations performed in the US are carried out in an ‘ambu-
latory, or outpatient setting.’2 Many of the early studies
evaluating the development of SSIs came from hospital oper-
ating rooms, so may not therefore be directly applicable to
outpatient dermatologic surgery. Additionally, many of the
specific factors evaluated (even in the recent dermatologic
surgery literature) have not been examined ‘in isolation’ apart
from other potential confounding factors. However, examina-
tion of some of these issues is still of benefit to the derma-
tologic surgeon and they may at least partially be applicable
to the outpatient or office ambulatory surgery setting.
Patient factors
Many pre-existing and sometimes coexisting patient factors
have been identified in the literature as risk factors for SSIs.
These can include bacterial colonization, malnutrition,
obesity, advancing age, diabetes mellitus, chronic renal insuf-
ficiency, peripheral vascular disease, immunosuppression,
corticosteroid use, concurrent remote infection, periopera-
tive transfusion of blood products, and tobacco and alcohol
use. For dermatologic surgery, location of the wound, nature
of the lesion being removed, and type of procedure have also
been considered as potential contributing factors.
Location of the wound
There are several studies in dermatologic surgery that give
antibiotic prophylaxis recommendations based on the ana-
tomic site of the surgery.3–7 A recent study in Australia looked
at 5091 lesions removed on 2424 patients over 3 years (none
of whom received prophylactic antibiotics).5 Although most
of the rates of SSIs were low, there were a few scenarios
which resulted in SSI rates over 5%. These included all pro-
cedures below the knee, wedge excisions of the lip or ear,
skin grafts, and lesions in the groin. It was interesting to note
that diabetic patients, those on warfarin and/or aspirin, and
smokers showed no difference in infection incidence.
Another large study of SSIs after dermatologic surgery
documented that infections were more common in flap/graft
reconstruction, with use of non-sterile gloves, with hematoma
formation, and in patients with immunosuppression.8 A study
of 464 facial surgeries revealed a higher infection rate for
surgical sites on the nose and ear, and an elevated risk of
infection with skin flaps and grafts, and for surgery involving
tumors rather than benign diseases.9 However, in a large
prospective trial of 1115 tumors undergoing Mohs surgery or
modified Mohs surgery, of the eight reported SSIs, five
occurred on the nose and had been repaired with flaps, one
occurred on the back of the hand with a high-tension closure,
one occurred on the chin with a flap closure, and one occurred
on the scalp with a high-tension flap closure. Of the patients
involved, four were over age 75, one was a two pack a day
smoker, one had chronic lymphocytic leukemia and was
taking prednisone, and one patient admitted to applying
make-up to the surgical site daily after the procedure.7
In a study of 1037 Mohs patients, the mean area of the
defects which became infected was twice that of the non-
infected group, and the ear had a higher rate of wound infec-
tions.4 A study actually designed to measure infection rates
for Mohs surgery, where non-sterile gloves were used to

87
Chapter 6  Antibiotics
SSI is markedly increased (but the dose of microorganisms
to induce infection may actually be less if foreign material is
present in the wound).2 For most SSIs, the source of patho-
gens is the endogenous flora of the patient’s skin or mucous
membranes. The organisms are usually aerobic Gram-positive
cocci (staphylococci), but can include anaerobic bacterial and
Gram-negative aerobes if the surgical site is close to the
perineum or groin. For dermatologists, patients in this cate-
gory might include those with extensive atopic dermatitis,
psoriasis, or other dermatitis. Although preoperative showers
can reduce the skin’s microbial count, they have not been
directly correlated with a reduction in SSI development.
 PREOPERATIVE PREPARATION
Many aspects of preoperative site preparation are addressed
in the chapter on Aseptic Technique (Chapter 2). There are
some specific topics that should be re-emphasized.
Hair
It has been shown that shaving a preoperative site the night
before surgery is associated with much higher SSI rates than
with using a depilatory or not removing the hair at all.2 The
higher rates of SSI with shaving are thought to be due to the
resultant microscopic nicks in the skin, which can serve as
nidus for the development of subsequent skin infection. It
has been shown that, if it can be managed, not removing hair
at the surgical site is preferable in reducing the potential for
SSI. If hair must be removed, clipping the hair immediately
before the procedure is associated with a lower risk of SSI
than having the patient shave or clip the hair the night before
the procedure.2,13
Hand washing
In a study specific to physician practice, it was noted that
hand washing adherence was only 57%.18 In addition, hand
washing was noted to be one of the five critical areas identi-
fied to consider in reducing sternal wound infections.19 In
recent studies involving hand hygiene, it was shown that
bacterial reduction on the hands is best accomplished by
alcohol-based hand rubs rather than washing with soap and
water, unless hand are visibly soiled or washing is performed
for 15 seconds.19 The wearing of artificial nails is increasingly
being banned in standard operating rooms because of their
risk of carrying Gram-negative organisms.2 The literature is
less clear about the risks of nail polish and the transmission
of potentially pathogenic organisms (see Chapter 2).
Warming
In a study of patients undergoing clean, non-implant proce-
dures, preoperative warming was provided to the patients
using a local warming device 30–60 minutes prior to surgery.
There was a significant decrease in the SSI rate among those
patients who had received preoperative warming.20
 PRACTICAL APPLICATIONS
Wound classification
Surgical wound classification has long been used in general
surgery to attempt to define potential intraoperative microbial
contamination, and therefore provides guidelines for the deci-
Intranasal colonization with Staphylococcus aureus
The CDC reports a large study indicating that treating nasal
carriage of S. aureus effectively reduced SSI development in
cardiac surgery.2 The use of prophylactic mupirocin for those
with intranasal colonization is discussed later in this chapter.
If a patient repeatedly seems to develop superficial staphylo-
coccal infections without any obvious underlying immunode-
ficiency, consideration might be given to intranasal cultures.
Altered immune response
Many studies have equated immunosuppressant medications
and immunosuppressant states (leukemia, Chediak–Higashi
syndrome, Job’s syndrome) with difficulties in wound healing.
Whether this extrapolates to the development of SSIs spe-
cifically is clearly controversial. For example, corticosteroid
use suppresses wound healing by a number of mechanisms,
but the relationship between corticosteroid use and SSI risk
has not been definitively proven. It has been suggested that
stopping corticosteroids a couple of days preoperatively
might positively influence wound healing. Whether this is
possible for most patients and whether this would affect the
rate of SSIs remains uncertain.12
The use of prophylactic antibiotics in patients receiving
cytotoxic drugs is also controversial. The Medical Letter con-
sultants have recommended prophylactic oral antimicrobial
agents in those receiving cytotoxic drugs when their granulo-
cyte counts are below 1000/mm3; or when the insult of the
surgical procedure will result in significant bacterial contam-
ination; or when the patient’s host defenses are inadequate
to resist a bacterial insult of any size.14 However, it is also
possible that this may increase colonization of the patient
with organisms resistant to these antimicrobial agents.15
A study of patients receiving anti-tumor necrosis factor
(TNF) treatment indicated that continuation or interruption
of anti-TNF therapy didn’t have a major influence on the risk
of development of SSIs, but wound dehiscence and bleeding
did occur more frequently with those who continued their
anti-TNF therapy.16 If the dermatologic surgeon is planning
a surgical procedure on a patient on immunosuppressant
medication, it would be prudent to contact the hematologic
specialist to discuss the low potential risk of bacteremia in
light of the patient’s overall immune status, before making a
decision about prophylactic antibiotics.
HIV infection and AIDS
Because of the variable clinical features of HIV infection and
AIDS, it is difficult to make global assessments of the risk of
SSI development for this group of patients. According to
studies of patients with HIV infection undergoing emergency
surgery, morbidity and mortality rates appeared to be not
directly related to HIV infection.17 Instead, most of the SSIs
in patients with HIV infection undergoing exploratory
laparotomy were related to the presence of intra-abdominal
malignancy, and perioperative CD4+ counts did not predict
postoperative outcomes. Although these outcomes may vary
with the type of surgical procedure, it appears that, as an
isolated variable, HIV infection does not in itself predispose
to SSI.
Heavy microbial colonization
It has been shown that if a surgical site is contaminated with
more than 105 microorganisms per gram of tissue, the risk of

88
Part 1  Basic Surgical Concepts
In surgery of the skin, the incidence of wound infection is
very low. The reported incidence of bacteremia following
dermatologic surgical procedures is also low, and although
surgical implantation of prosthetic material is becoming more
common in dermatology, it is still relatively infrequent.3,13
The Medical Letter consultants have concluded:14
The small number of wound infections that would be
prevented by antimicrobial prophylaxis make it unwar-
ranted for … varicose vein surgery, most dermatologic
and plastic surgery … repair of simple lacerations, out-
patient treatment of burns …
In dermatology, there are those who advocate the use of
antibiotics for treatment of infections only, and never advo-
cate that antibiotics be given prophylactically for prevention
of potential wound infections.11
For further information on antibiotic guidelines in the pre-
vention of SSIs, see Table 6.2.
Timing and dosing of antibiotics
The timing of prophylactic antibiotic administration has been
well documented, and needs to reach adequate tissue concen­
trations before the time of wounding and contamination. This
allows the drug to be incorporated into the wound coagulum,
which normally develops within the first couple of hours after
wounding, and can protect trapped bacteria from systemic
antibiotics if they are given after the coagulum develops.2,12
If it is necessary to give antibiotic prophylaxis, only a single,
preoperative dose is recommended. Most dermatologic
sion to give antibiotic prophylaxis based on a surgical wound
class for a given operation. This has been extrapolated to der-
matologic surgery (Table 6.1), where most of the wounds
encountered are either class I or class II wounds, with rela-
tively low infection rates.12 There have been a large number of
articles published suggesting that the incidence of SSI follow-
ing dermatologic surgery, including Mohs surgery, is very
low.3,6,7,11,12 Even the Australian study, which had an overall
low infection rate but a much higher infection rate of certain
regions (skin grafts 8.7%, below knee location 6.92%), still had
infection incidences which were less than the approximately
10% infection rate one would expect in the clean-contami-
nated class.1 Antibiotic prophylaxis is not indicated for class IV
wounds; rather, antibiotics are given therapeutically for estab-
lished infections. Clearly, all skin infections in patients with
prosthetic joints or valves should be vigorously treated.
Antibiotics to prevent wound infection
Generally, antibiotic prophylaxis is considered to prevent
potential wound infection, endocarditis, and infection of
implanted prosthetic devices. The risk–benefit ratio for pro-
viding prophylactic antibiotics must be weighed against the
risk of toxic or allergic reactions, bacterial resistance, drug
interactions, and superinfection. The medical literature con-
tinues to suggest giving prophylactic antibiotics only for pro-
cedures with high infection rates, for those involving the
implantation of prosthetic material, and for procedures in
which the consequences of infection are especially serious.2,3,12,21
Table 6.1  Classification of surgical wounds and antibiotic prophylaxis
CLASS
INFECTION RATE (%)
CONSIDER ANTIBIOTIC PROPHYLAXIS
FOR DERMATOLOGIC SURGERY
I. Clean – non-contaminated skin, sterile technique
5
No
II. Clean-contaminated – wounds in: oral cavity, respiratory
tract, axilla/perineum
10
Rarely; case-by-case basis
III. Contaminated – trauma, acute, non-purulent
inflammation, major breaks in aseptic technique
20–30
Yes
IV. Infected – foreign body contamination, devitalized tissue
30–40
Antibiotics therapeutic, not prophylactic
Table 6.2  SSI prevention: antibiotic guidelines
AREA
POTENTIAL PATHOGEN
ANTIBIOTIC CHOICES
1-HOUR-PREOPERATIVE DOSE*
Skin
S. aureus
First-generation cephalosporin
1–2 g orally
Dicloxacillin
1–2 g orally
Clindamycin
300–600 mg orally
Azithromycin/clarithromycin
500 mg orally
Oral
S. viridians
Amoxicillin
1–2 g orally
Clindamycin
300–600 mg orally
Azithromycin/clarithromycin
500 mg orally
Gastrointestinal/genitourinary
E. coli
First-generation cephalosporin
1 g orally
TMP–SMX – double strength†
1 tablet orally
Levofloxacin/ciprofloxacin
500 mg orally
*Single preoperative dose in virtually all cases; if second dose is necessary, reduce the dose by half at 6 hours; 12-hour dosing interval with TMP–SMX and levofloxacin/
ciprofloxacin; implantation of prosthetic materials (e.g. expanded polytetrafluoroethylene [ePTFE]).
†TMP–SMX, trimethoprim–sulfamethoxazole.

89
Chapter 6  Antibiotics
and topical mupirocin have significantly decreased episodes
of infections in those with recurrent staphylococcal skin
infections.25 Because there is now some staphylococcal resist-
ance with mupirocin, it has been recommended that nasal
mupirocin should not be used in patients with culture-proven
staphylococcal skin infections unless these patients also dem-
onstrate nasal culture-positive S. aureus.25,26
The use of intraincisional antibiotics has also been described
in dermatologic surgery, both by direct administration into
the wound, or mixed with lidocaine, and injected at the time
of local anesthetic administration.27,28 Side effects have been
demonstrated, and although the antibiotic–lidocaine mix did
reduce the (low) infection rate in the study further, it is
unclear whether this is necessary, given the known low inci-
dence of wound infection for dermatologic surgery.
Special situations in dermatology
Laser resurfacing
There has been controversy regarding the routine use of
prophylactic antibiotics to prevent SSIs following full-face
ablative laser resurfacing (non-fractionated). The use of pro-
phylactic antiviral medication for those with a history of oral
cold sores (used until the wound is re-epithelialized) is prob-
ably more routine. The antibiotic studies were complicated
by small size, comparison of infection rates with and without
antibiotics, and with and without use of a variety of occlusive
dressings. One study that looked at comparisons among many
of the published reports noted that the overall reported infec-
tion rate was less than 10%, and recommended that these
wounds be considered as the ‘clean-contaminated’ type II
wound which would not require prophylactic antibiotics.13
This is consistent with the CDC’s recommendation not to use
prophylactic antibiotics for laser resurfacing. Since the newer
fractionated lasers do injury to a smaller surface area (so re-
epithelialization occurs more rapidly), there would certainly
be no need for antibiotic prophylaxis for these procedures
either. What may be more important for resurfacing patients
is close follow up after laser resurfacing for an extended
period of time, with meticulous patient guidance about post-
procedure wound care and culture as necessary, followed by
appropriate treatment of any subsequent infections.
Tumescent liposuction
Tumescent liposuction appears to be associated with a low
risk of postoperative infection. One expert attributes this to
a variety of factors, including in-vivo bacteriostatic and bac-
tericidal effects of buffered lidocaine with epinephrine, the
low incidence of hematomas and seromas, less surgical trauma
when carried out as a single surgical procedure, and the
careful selection of healthy patients.29
Although there are some surgeons who do use prophylactic
antibiotics for liposuction, the incidence of infectious com-
plications following this procedure, especially in the outpa-
tient setting, appears to be low.13 For that reason, it would
seem that routine preoperative administration of antibiotics
for tumescent liposuction would not be necessary.
The most common pathologic organism causing infection is
S. aureus, but rapidly growing atypical mycobacteria and fatal
necrotizing fasciitis (caused by Streptococcus pyogenes) fol-
lowing liposuction have been reported.30–32 Technique-related
factors that may minimize the potential for infection after
surgery cases are of short duration, and the single preopera-
tive dose should be adequate. Once the wound is closed,
there is generally no further contamination. Even wounds
that are created by electrodesiccation and curettage (ED and
C), a surgical technique unique to dermatology, tend not to
become infected. It has been noted that wound colonization
with normal skin flora does not influence wound healing, light
colonization with pathogenic bacteria may not interfere, but
infection will inhibit wound healing.22 Wound infection of
wounds healing by second intention is ‘rare’ if the wounds
are properly cared for.23 Finally, it would be rare that a pro-
longed dermatologic procedure would require a second dose
of antibiotics. If deemed necessary, the second dose is usually
given 6 hours postoperatively to maintain tissue levels of
antibiotic.
Role of topical and incisional antibiotics
Topical antibiotics are traditionally used in dermatologic
surgery to cover wounds left to heal by second intention.
However, sutured wounds would not be expected to become
contaminated after closure, so the postoperative application
of topical antimicrobials would not seem to decrease the risk
of SSI. A study comparing applications of bacitracin and
white petrolatum after dermatologic procedures demon-
strated no significant difference in overall infection rate
between the two groups.24 The dermatologic procedures
included in the study were shave and punch biopsy, curettage
and electrodesiccation, excision, Mohs micrographic surgery
with simple and complicated repairs (flaps and grafts), and
dermabrasion. The infections that occurred in the bacitracin
group (also the group with the higher incidence of contact
dermatitis) were caused by Gram-negative bacilli, requiring
systemic antibiotic coverage that was more costly than the
antibiotics needed to treat the S. aureus infections occurring
in those in the petrolatum group.24
In addition there have been reports of not only contact
dermatitis (the North American Contact Dermatitis Group
moved bacitracin into their top 10 allergy list in 1998) but
also anaphylaxis and Stevens–Johnson syndrome with use of
topical antibiotics.13 Given the fact that most dermatologic
surgery procedures are either clean or clean-contaminated
(with low infection rates), the high incidence of contact
dermatitis, and the high cost of topical antibiotics when com-
pared to petrolatum, it has been recommended that the use
of topical antibiotics in dermatologic surgery be reserved for
only class III and class IV wounds.13
A compelling case has been made with respect to the use
of silver sulfadiazine, which is routinely used in burn units.13
Silver sulfadiazine has good antimicrobial activity against both
Gram-positive and Gram-negative bacteria, as well as yeast.
It appears that silver sulfadiazine has less contact sensitivity,
anaphylaxis, and other adverse events when compared to the
topical antibiotics which are routinely used in dermatology.
There are very few cases of argyria in the medical literature,
and the risk of leukopenia seems to be related to the total
body surface area upon which the product is applied.
Mupirocin is the most effective narrow-spectrum anti-
staphylococcal topical antibiotic, and has been used both for
the treatment of infected wounds and to eliminate nasal car-
riage of S. aureus (for prophylaxis against incisional wound
infections in patients with recurrent staphylococcal skin
infections). Additionally, regimens of both oral clindamycin

90
Part 1  Basic Surgical Concepts
through the bloodstream to the non-bacterial thrombus and
proliferate there.
Bacteremia in dermatology
It has clearly been demonstrated that bacteremias occur fre-
quently after normal activities of daily living such as brushing
teeth or eating hard candy. Endocarditis prophylaxis ideally
would be used against significant bacteremias caused by
organisms associated with endocarditis, and attributable to
identifiable procedures. Manipulation of clinically infected
skin is associated with a high incidence (>35%) of bacteremia
with organisms known to cause endocarditis.3 Although few
studies have investigated bacteremia associated with derma-
tologic surgery procedures, those that do exist seem to indi-
cate that the incidence of bacteremia following dermatologic
surgery is low, and the bacteremia, generally occurring within
the first 15 minutes of the procedure, is short-lived.12 In one
small study where blood cultures were obtained from patients
30 minutes after undergoing excision or ED and C of eroded,
non-infected or intact skin lesions, all blood cultures were
negative.34 In another study of a small number of patients
undergoing a variety of dermatologic surgery procedures,
blood cultures obtained from three patients were positive at
15 minutes, but grew organisms not commonly causing endo-
carditis.35 The fact that transient bacteremia from other sur-
gical and dental procedures involving mucosal surfaces or
contaminated tissue also rarely persists for more than 15
minutes has also been recognized by the American Heart
Association (AHA).
New guidelines from the American Heart
Association
In 2007, the AHA did a substantive revision of their guide-
lines for prophylaxis of endocarditis.36 They noted that cases
of IE that were either temporarily or remotely associated
with an invasive procedure (particularly a dental procedure)
were often the basis of a malpractice claim against the pro-
vider. They noted that the prevention of IE is not a precise
science and that the prior recommendations published by the
AHA were often ambiguous and inconsistent and were based
on ‘minimal published data or expert opinion’ and so were
subject to conflicting interpretations among patients, health-
care providers, and the legal system. There were four specific
revisions for IE given by the AHA in the 2007 revision state-
ment. The first was that IE is much more likely to result from
frequent exposure to random bacteremias associated with
daily activities than from bacteremia caused by a dental,
gastrointestinal or genitourinary tract procedure. Second,
prophylaxis might prevent only an ‘exceedingly small number’
of cases of IE, if any, in individuals who undergo a dental,
gastrointestinal or genitourinary tract procedure. Third, the
risk of antibiotic-associated adverse events exceeds the
benefit, if any, from prophylactic antibiotic therapy; and
finally, the AHA felt that maintenance of optimal oral health
and hygiene may reduce the incidence of bacteremia from
daily activities and is more important than prophylactic anti-
biotics for a dental procedure to reduce the risk of IE.36 The
AHA also noted a very large number of patients in a placebo-
controlled, multicenter, randomized, double-blinded study to
evaluate the efficacy of IE prophylaxis in patients who
undergo dental, GI, or GU tract procedures. This study has
yet to be (and logistically, may never be) completed.
liposuction include extensive tumescent infiltration, open
drainage (elimination of sutures that can predispose to foreign
body reaction, wound inflammation, and incision site infec-
tions), adequate compression (to eliminate the possibility of
seromas and hematomas that could predispose to infection),
awake patients (which permits early diagnosis of inadvertent
visceral penetration by the cannula), cleaning the patient’s
skin after the procedure, and removing surgical drains as soon
as possible.33
Management of postoperative surgical
site infection
Patients who develop a postoperative SSI usually present
between postoperative days 4 and 10 with swollen, tender,
erythematous wounds that may be draining malodorous,
purulent material. In a sterile setting under local anesthesia,
some or all sutures are removed and, after a wound culture
is sent, the wound is lavaged to remove debris. The wound
can then either be packed with sterile gauze or allowed to
remain open to heal by second intention. In cases of purulent
drainage, the latter is indicated. Empirical antibiotics are
commenced, based on the presumed causal pathogen, and can
be adjusted based on the culture susceptibility profile. The
most common organism seen in SSIs of the skin is S. aureus
and therapy should be directed at that organism. If a Gram-
negative infection or Pseudomonas is a consideration, oral
ciprofloxacin should be considered.
Careful wound care instructions and close follow up are
mandatory (especially of those patients with higher risk
factors, as has been discussed) to guard against the progres-
sion of the infection or unusual complications, such as necro-
tizing fasciitis. Scars can always be revised at a later date, but
generally these wounds will demonstrate acceptable wound
healing, depending on location.
Antibiotics for prophylaxis of endocarditis
The two types of endocarditis are infective endocarditis (IE)
and prosthetic valve endocarditis (PVE). IE refers to infection
of the endocardial surface of the heart, usually the heart
valves (most often the mitral valve), but may also involve
septal defects, mural endocardium, arteriovenous and arte-
rioatrial shunts, and coarctation of the aorta. Certain strains
of bacteria appear to adhere more selectively to platelets or
fibrin. The most common microorganisms implicated in IE
are streptococci and staphylococci.
PVE is associated with valve replacement surgery and can
be a cause of significant morbidity and death. The ‘early’ form
of PVE is usually the result of a hospital-acquired microorgan-
ism and occurs within the first 60 days of valve placement.
The most common cause of early PVE is S. epidermidis,
although aerobic Gram-negative bacilli and fungi can also be
causal. The ‘late’ form of PVE occurs after the first 60 days
of valve placement and most often involves the aortic valve.
The most common cause of late PVE is non-group D strep-
tococci. As the microbial cause of late PVE closely resembles
native valve endocarditis, the potential pathogenesis has been
postulated to be similar.
The events which need to occur in order for endocarditis
to develop start with the formation of non-bacterial throm-
botic endocarditis on the surface of a cardiac valve or at some
other location where endothelial damage occurs. Bacteremia
needs to be present and the bacteria need to then travel

91
Chapter 6  Antibiotics
Prophylaxis for indwelling devices
Prosthetic joints
In 2008, the American Dental Association and the American
Academy of Orthopedic Surgeons released an advisory state-
ment on the use of antimicrobial prophylaxis for dental pro-
cedures.37 The advisory statement does not recommend the
routine use of dental prophylaxis for most patients with total
joint arthroplasty. Prophylaxis ‘is considered’ only for certain
categories of patients (Box 6.2). The ‘higher incidence’ dental
procedures did not specifically involve the lip, but rather
were intraoral procedures. Since skin is an origin for hema-
togenous transmission, particularly to a newly placed total
joint, zealous treatment of any skin infection in these patients
is mandatory. Although there is no consensus in the derma-
tologic surgery literature, there are some who would give
prophylactic antibiotics to high-risk orthopedic patients who
undergo ‘perforating dermatologic surgical procedures on the
oral mucosa.’3 In those rare instances where the dermatologic
surgeon feels it is necessary to provide prophylactic antibiot-
ics for infective endocarditis or to prevent hematogenous total
joint infection, antibiotic suggestions are given in Table 6.3.
Other implanted devices
The 1997 AHA guidelines dealt with cardiac pacemakers and
internal defibrillators by placing them in the ‘negligible risk’
category and not recommending antibiotic prophylaxis for
Where does that leave dermatologic procedures and the
risk of IE? As IE and hematogenous total joint infection have
been known to occur after skin infection, it is certainly
prudent to treat any cutaneous infection in patients with
either joint or valve replacements. The new AHA guidelines
recommend IE prophylaxis for surgical procedures that
involve infected skin, skin structure, or musculoskeletal tissue
only if they are patients who are in the ‘high-risk’ category
(Box 6.1). The AHA noted that these infections tend to be
polymicrobial, but as only staphylococci and β-hemolytic
streptococci are likely to cause IE, selection of an antibiotic
active against these organisms is reasonable. The AHA also
recommends against body piercing for patients who are con-
sidered ‘high risk’ for developing IE (although they acknowl-
edge that there isn’t much data available regarding the risk
of either bacteremia or endocarditis associated with body
piercing).
According to the new AHA guidelines,36 patients defined
as being at high risk for IE should receive antibiotic prophy-
laxis for any of the following procedures; manipulation of the
gingival tissue, the periapical region of teeth or perforation of
the oral mucosa.’ This is further qualified by noting that
‘routine anesthetic injections through noninfected tissue …
and bleeding from trauma to the lips or oral mucosa in this
same patient population does not require endocarditis
prophylaxis.’
Box 6.2  ‘High-risk’ patients for
hematogenous total joint infection
 Within first 2 years of joint replacement therapy.37
 With prior history of prosthetic joint infection.
 Having specific conditions:
n Hemophilia
n Type I diabetes
n HIV infection
n Malignancy
n Malnourished.
 Immunocompromised/immunosuppressed patients:
n Rheumatoid arthritis
n Systemic lupus erythematosus
n Drug-/radiation-induced immunosuppression.
Table 6.3  Endocarditis/hematogenous total joint infection prophylaxis for ‘high-risk’ patients (see Boxes 6.1 and 6.2)
AREA
POTENTIAL PATHOGEN
ANTIBIOTIC CHOICES
1-HOUR PREOPERATIVE DOSE*
Contaminated skin
S. aureus
First-generation cephalosporin
2 g orally
Dicloxacillin
2 g orally
Clindamycin
600 mg orally
Vancomycin†
1 g intravenously
Oral
S. viridans
Amoxicillin
2 g orally
Clindamycin
600 mg orally
Azithromycin
500 mg orally
Clarithromycin
500 mg orally
*As most dermatologic surgery procedures are short duration (15 minutes of bacteremia), the 6-hour postoperative dose is rarely necessary. If given, the 6-hour postoperative
dose is generally half the preoperative dose.
†For pathogenic S. epidermidis, MRSA, or patients with newly implanted prosthetic cardiac valves.
Box 6.1  ‘High-risk’ cardiac patients
requiring endocarditis prophylaxis
(AHA 2007 guidelines)
 Prior history of infective endocarditis.
 Has a prosthetic cardiac valve.
 Has had cardiac valve repair done with prosthetic material.
 Cardiac transplant patient who develops cardiac valvulopathy.
 Unrepaired congenital heart disease (including palliative
shunts/conduits).
 Repaired congenital heart defect (either prosthetic material or
device) within first 6 months after the procedure.*
 Repaired congenital heart defect with residual defects at or
adjacent to site of prosthetic patch or device.**
Based on Wilson et al. 2007.36
*Endothelialization occurs within 6 months of procedure.
**Inhibits endothelialization.

92
Part 1  Basic Surgical Concepts
Mansfield, MA) and tape or the self-adhesive bandage wraps
(with or without pressure to encourage hemostasis) are
important in preventing wound infection.
With the advent of the cyanoacrylate ‘tissue glue,’ wound
care may be modified from the class of occlusive dressing,
depending on the surgeon’s preference. An interesting in-
vitro study demonstrated that 2-octyl-cyanoacrylate is effec-
tive as an antimicrobial barrier for the first 72 hours after
application. A plastic surgery study demonstrated that, for
certain plastic surgery procedures, there were fewer postop-
erative complications with treated wounds than with those
which didn’t receive the tissue glue.30 Patient education for
appropriate wound management that is carefully detailed
verbally and in writing is a valuable component of good surgi-
cal technique.
 PITFALLS AND THEIR MANAGEMENT
Surgical technique
Good surgical technique is critical in the prevention of SSIs.2
Hematomas have long been associated with the development
of postoperative wound infection. Maintaining good hemo­
stasis and eliminating ‘dead space’ with the appropriate use
of sutures are significant surgical considerations in minimizing
postoperative morbidity. The use of pressure dressings
designed to cover areas where there has been extensive
undermining or ‘bolster’ dressings over grafts to minimize
shearing forces and prevent fluid loculation also help negate
the risk of hematoma. Gentle handling of tissues, including
the use of hooks or delicate teethed forceps on the wound
margins, helps to prevent ischemia. Well-designed flaps and
grafts will maximize blood supply and minimize ischemia,
which can lead to the development of devitalized tissue and
the potential for wound infection. Removal of devitalized
tissue while at the same time maintaining good blood supply
is essential, and should be the end point of careful and metic-
ulous electrocautery. Minimizing foreign bodies during wound
closure can minimize inflammation at the surgical site and
decrease the possibility of SSI. Suture material is a commonly
used foreign body, with monofilament sutures seeming to
have the lowest potential for the development of infection.2
An interesting study showed that in the pediatric population,
there was a significant decrease in wound infections when a
coated polyglactin 910 suture with triclosan was used. Tri-
closan is a broad-spectrum antiseptic agent which has been
used for many years and is effective against many organisms
which commonly cause SSIs, including MRSA. When the
suture with triclosan was used, there were no adverse effects
either in wound appearance or discomfort level (patients
had less postoperative discomfort with the triclosan-coated
suture).38 Finally, wound dressings that include an occlusive
contact layer (petrolatum) followed by sterile Telfa (Kendall,
Optimizing outcomes
 Good surgical technique, including meticulous hemostasis,
reduces the risk of SSI.
 Minimize the entry of foreign bodies during wound closure
and use sutures that have minimal potential for infection
development (monofilament sutures).
 Treat ‘remote site’ skin infections.
 Application of appropriate postoperative dressing.
 Educate patients about postoperative wound care.
them. It appears that the incidence of infection of vascular
grafts and shunts, as well as ventriculoperitoneal shunts and
neurostimulators, is highest at the time of implantation. Since
studies have shown that less than 1% of late shunt infections
are attributed to bacteremia (and the incidence of bacteremia
following dermatologic surgery is very low), it seems reason-
able to conclude that it would not be cost-effective to provide
prophylaxis for these items for dermatologic surgery. Elective
dermatologic surgery in those with vascular graft or shunt
placement should be delayed to allow time for the formation
of a pseudointima. If it is necessary to do a procedure rela-
tively soon after implantation of such a device, further discus-
sion with the other specialty would be prudent.
 OPTIMIZING OUTCOMES AND
POSTOPERATIVE CARE
Pitfalls and their management
 Selecting an inappropriate antibiotic: consider the location of
the planned surgery; make the antibiotic selection based on
the possible causal organism.
 Increasing risk of drug-resistant organisms: do not give
prophylactic antibiotics unless absolutely necessary. After
deciding prophylactic antibiotics are needed, give them only
as a preoperative dose.
 Increased cost to patient and increased possible adverse
side effects of antibiotic, which may significantly influence
mortality and morbidity: do not give preoperative prophylactic
antibiotics unless absolutely necessary.
 Increased risk of contact dermatitis: use vaseline petroleum
jelly postoperatively rather than topical antibiotics.
 SUMMARY
Many factors can contribute to the development of SSIs, and
rarely is any one factor the single cause. Reducing infectious
complications involves knowing the patient and understand-
ing the significance of patient risk factors, preparation of the
surgical site, and maintaining good surgical and aseptic tech-
nique. As the incidence of SSIs in dermatologic surgery is
low, it is not necessary to provide antibiotic prophylaxis to
prevent wound infections or endocarditis in the vast majority
of dermatologic surgery cases. When the dermatologic surgeon
feels they are necessary, antibiotics are selected to cover the
probable pathogenic organism and are best given as a single
preoperative dose. When in doubt, it is advisable for the
dermatologic surgeon to consult with the patient’s particular
specialist to discuss the potential risks and benefits of prophy­
laxis. Hopefully dermatologic surgery can be a specialty that
can eliminate the use of ‘routine’ antibiotics, and so help to
minimize the development of bacterial resistance.
 REFERENCES
1. Shapiro DB. Postoperative infection in hand surgery. Hand Clin
1998;14:669–681.
2. Mangram AJ, Horan TC, Pearson M, et al. Guideline for prevention of
surgical site infection. Am J Infect Control 1999;27:97–134.
3. Wright TI, Baddour LM, Berbari EF, et al. Antibiotic prophylaxis in
dermatologic surgery: advisory statement 2008. J Am Acad Dermatol
2008;59:464–473.

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Chapter 6  Antibiotics
23. Zitelli JA. Secondary intention healing. Clin Dermatol 1984;2:92–
106.
24. Smack DP, Harrington AC, Dunn C, et al. Infection and allergy incidence
in ambulatory surgery patients using white petrolatum vs bacitracin oint-
ment. A randomized controlled trial. JAMA 1996;276:972–977.
25. Hirschmann JV. Antimicrobial prophylaxis in dermatology. Semin Cut
Med Surg 2000;19:2–9.
26. Kluytmans J, vanBelkum A, Verbrugh H. Nasal carriage of Staphylococcus
aureus: epidemiology, underlying mechanisms and associated risks. Clin
Microbiol Rev 1997;10:505–520.
27. Bencini PL, Galimberti M, Signorini M, et al. Antibiotic prophylaxis
of wound infections in skin surgery. Arch Dermatol 1991;127:1357–
1360.
28. Griego RD, Zitelli JA. Intraincisional prophylactic antibiotics for derma-
tologic surgery. Arch Dermatol 1998;134:688–692.
29. Klein JA. Tumescent technique; tumescent anesthesia and microcannular
liposuction. St Louis: Mosby 2000;129.
30. Murillo J, Torres J, Bofill L, et al. Skin and wound infection by rapidly
growing mycobacteria; an unexpected complication of liposuction and
liposculpture. Arch Dermatol 2000;136:1347–1352.
31. Behroozan DS, Christian MM, Moy RL. Mycobacterium fortuitum
infection following neck liposuction: a case report. Dermatol Surg
2000;26:588–590.
32. Heitmann C, Czermak C, Germann G. Rapidly fatal necrotizing fasciitis
after aesthetic liposuction. Aesth Plast Surg 2000;24:344–347.
33. Klein JA. Tumescent technique; tumescent anesthesia and microcannular
liposuction. St Louis: Mosby 2000;88–89.
34. Zack L, Remlinger K, Thompson K, et al. The incidence of bacteremia
after skin surgery. J Infect Dis 1989;159:148–150.
35. Halpern AC, Leyden JJ, Dzubow LM, et al. The incidence of bacteremia
in skin surgery of the head and neck. J Am Acad Dermatol
1988;19:112–116.
36. Wilson W, Taubert KA, Gewitz M, et al. Prevention of infective endo-
carditis. Guidelines from the American Heart Association. A guideline
from the American Heart Association Rheumatic Fever, Endocarditis and
Kawasaki Disease Committee, Council on Cardiovascular Disease in the
Young and the Council on Clinical Cardiology, Council on Cardiovascular
Surgery and Anesthesia, and the Quality of Care and Outcomes Research
Interdisciplinary Working Group. Circulation 2007;116:1736–1757.
37. Wright TI, Baddour LM, Berbari EF, et al. Antibiotic prophylaxis in
dermatologic surgery: advisory statement 2008. J Am Acad Dermatol
2008;59:464–473.
38. Ford HR, Jones P, Gaines B, et al. Intraoperative handling and wound
healing: controlled clinical trial comparing coated VICRYL plus antibac-
terial suture (coated polyglactin 910 suture with triclosan) with coated
VICRYL suture (coated polyglactin 910 suture). Surg Infect 2005:6:
313–321.
4. Cook JL, Perone JB. A prospective evaluation of the incidence of com-
plications associated with Mohs micrographic surgery. Arch Dermatol
2003;139:143–152.
5. Dixon AJ, Dixon MP, Askew DA, et al. Prospective study of wound
infections in dermatologic surgery in the absence of prophylactic antibiot-
ics. Dermatol Surg 2006;32:819–827.
6. Maragh SL, Otley CC, Roenigk RK, et al. Antibiotic prophylaxis in der-
matologic surgery: updated guidelines. Dermatol Surg 2005;31:83–93.
7. Maragh SL, Brown MD. Prospective evaluation of surgical site infection
rate among patients with Mohs micrographic surgery without the use of
prophylactic antibiotics. J Am Acad Dermatol 2008;59:275–278.
8. Rogues AM, Lasheras A, Amici JM, et al. Infection control practices and
infectious complications in dermatological surgery. J Hospital Infect
2007;65:258–263.
9. Wahie S, Lawrence CM. Wound complications following diagnostic
skin biopsies in dermatology inpatients. Arch Dermatol 2007;143:
1267–1271.
10. Rinehart BM, Murphy ME, Farley MF, et al. Sterile versus nonsterile
gloves during Mohs micrographic surgery; infection rate is not affected.
Dermatol Surg 2006;32:170–176.
11. Babcock MD, Grekin RC. Antibiotic use in dermatologic surgery.
Dermatol Clin 2003;21:337–348.
12. Haas AF, Grekin RC. Antibiotic prophylaxis in dermatologic surgery.
J Am Acad Dermatol 1995:32:155–179.
13. Messingham MJ, Arpey CJ. Update on the use of antibiotics in cutaneous
surgery. Dermatol Surg 2005;31:1068–1078.
14. The Medical Letter. Antimicrobial prophylaxis and treatment in patients
with granulocytopenia. Med Lett Drugs Ther 1981;23:55–56.
15. Peterson LJ. Antibiotic prophylaxis against wound infections in oral and
maxillofacial surgery. J Oral Maxillofac Surg 1990;48:617–620.
16. den Broeder AA, Creemers MC, Fransen J, et al. Risk factors for surgical
site infections and other complications in elective surgery in patients with
rheumatoid arthritis with special attention for anti-tumor necrosis factor:
a large retrospective study. J Rheumatol 2007;34:689–695.
17. Burns J, Pieper B. HIV/AIDS: impact on healing. Ostomy Wound
Manage 2000:46:30–40.
18. Pittet D, Simon A, Hugonnet S, et al. Hand hygiene among physicians:
performance, beliefs, and perceptions. Ann Int Med. 2004:131:1–8.
19. Haycock C, Laser C, Keuth J, et al. Implementing evidence-based prac-
tice findings to decrease postoperative sternal wound infections following
open heart surgery. J Cardiovasc Nurs 2005;20:299–305.
20. Leaper DJ, Mellig AG. Antibiotic prophylaxis in clean surgery: clean
non-implant wounds. J Chemother 2001;13:96–101.
21. The Medical Letter. Antimicrobial prophylaxis in surgery. Med Lett
Drugs Ther 1999;41:75–80.
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95
7
Wound Healing
Jie Li MD PhD, Zuleika L Bonilla-Martinez MD, and Robert S Kirsner MD PhD
Summary box
 Wound healing occurs in overlapping phases: the
inflammatory, the proliferative, and the remodeling phases.
 The depth of the wound determines the degree of contraction
and the source of keratinocytes used for re-epithelialization.
 Sharp wounds created by scalpels heal faster than wounds
created by destructive or ablative methods.
 Platelets are the first cell to appear in the healing process,
and macrophages are the most important cell in the healing
process; they both mediate their actions through cytokines or
growth factors.
 Wound healing is a complex event that is highly regulated by
signals from both serum and the surrounding extracellular
matrix environment.
 Physicians can speed wound healing by a variety of
mechanisms; by avoiding placing toxic substances on the
wound, by keeping the wound free of necrotic tissue, and by
using occlusive dressings appropriately.
 INTRODUCTION
Dermatologists and dermatologic surgeons create and care for
more wounds than all other specialties combined. Wound
healing is a dynamic process involving the complex interac-
tion of many cell types, their cytokines or chemical media-
tors, and the extracellular matrix. Vascular responses, cellular
and chemotactic activity, and the effects of chemical media-
tors within wounded tissues form the interrelated compo-
nents of healing. Understanding the processes involved in
wound repair is exquisitely important to a specialty that
devotes a significant amount of time to create wounds with
either diagnostic or therapeutic procedures.
Wound repair is an orderly, continuous process that can be
divided into three phases – the inflammatory, the prolifera-
tive, and the remodeling phases (Fig. 7.1). However, the
process is not a simple linear one because the phases overlap.
Therefore, the conceptual distinction between phases serves
only as an outline to facilitate the discussions about events
occurring during wound repair. The beginning of wound
healing and its end often have been based on macroscopic
clinical visual examination. Though not seen clinically, injury
and repair of the skin occurring at a microscopic or a molec-
ular level likely occur with even greater frequency. Although
not yet quite clear, our understanding of events that occur
during wound repair may be invaluable for enhancing our
knowledge of wound repair, and for improving healing,
leading to the restoration of both anatomic and functional
integrity of the wounded tissue.
 TYPES OF WOUNDS
Acute versus chronic wounds
Wounds can conveniently be classified as acute or chronic,
whereby the healing process proceeds in a timely or an
untimely (slow) fashion, respectively. Determining the exact
time taken to heal and whether a wound is designated acute
or chronic remains arbitrary; such decisions are based on
several factors that include location, shape, and cause of the
wound, as well as the age and physical condition of the
patient. For example, an elliptical wound on the face of a
healthy child will heal faster than a circular burn wound on
an elderly infirm person, even though both might heal in a
timely fashion given the circumstances. The age of the patient
when a wound is created plays an important role in wound
healing. For example, fetal cutaneous wounds are known to
heal without scarring and inflammation as opposed to wounds
in adults or the elderly. Additionally, older patients tend to
heal slower and their wounds tend to have less tensile strength
which correlates with reduced amounts of collagen and a
better cosmetic outcome.
Partial-thickness versus
full-thickness wounds
Injury to only the epidermis differs from injury involving the
underlying dermis. If an injury is limited to the epidermis,
the epidermis restores itself to a structure similar to the pre-
injury state. In contrast, if the injury is deeper and extends
into the dermis, regeneration does not normally occur, but
rather repair occurs and the wound heals with scarring. In
certain situations regeneration occurs after dermal injury.
This occurs in early fetal skin wounds, where higher concen-
trations of type III collagen and glycosaminoglycans and
decreased amounts of transforming growth factor-β1 (TGF-
β1) as well as a reduced inflammatory response are likely to
be important in mediating regeneration as opposed to repair.1

96
Part 1  Basic Surgical Concepts
Skin wounds can be categorized depending on their depth
as erosion, partial-thickness, or full-thickness wounds. If only
the epidermis is lost, this is called erosion. When the wound
involves structures deep to the dermis, it is termed an ulcer.
Ulcers that involve the epidermis and varying parts of the
dermis are termed partial-thickness wounds, while those that
involve all of the dermis and deeper structures are called
full-thickness wounds (Fig. 7.2). Chronic wounds are also
categorized by the thickness of the wound, for example
staging of pressure ulcers depends upon wound depth
(Fig. 7.3).2
For acute wounds there is the added importance of dif-
ferentiating partial-thickness wounds from full-thickness
wounds in that they epithelialize by different mechanisms
(Table 7.1). Since the deep dermis has not been lost or
destroyed in partial-thickness wounds, skin appendages
remain and serve as a reservoir of epithelial cells to repopulate
the epidermis. Keratinocytes from these structures, as well
as from the wound edge, migrate across the wound surface,
forming new epidermis that covers the wound (Fig. 7.4). In
full-thickness wounds, adnexal structures have been destroyed
and keratinocytes can only migrate from the wound edge. In
addition, wound repair will not regenerate these appendageal
structures but replaces them with scar.
The wound depth influences the healing outcome. Full-
thickness wounds heal to some extent by contraction, while
there is minimal contraction in partial-thickness wounds (Fig.
7.5).3 During contraction, the wound area is decreased and
pre-existing tissue moves centripetally. Clinically, contrac-
tion of the wound may result in cosmetically disfiguring dis-
placement of free margins such as the eyelid.
Primary versus second intention healing
When an acute wound heals on its own, it is termed second
intention healing. Although the mechanism is still unknown,
second intention healing is primarily by contraction of myofi-
broblasts.4 Primary intention healing occurs when a surgeon
directs closure of the wound by approximating the wound
edges. A surgeon chooses among the three methods to repair
a defect: direct closure, flap, or graft repair, depending on the
size, shape, and location of the wound. Direct closure is a
direct side-to-side closure, where the two sides of the wound
are sutured or stapled together. The flap repair involves
moving adjacent tissue into the wound defect to close the
wound, where the blood supply is moved with the tissue. The
graft method utilizes tissue from a distant location. By defini-
Remodeling
Proliferative
Inflammatory
Minutes
Hours
Days
Weeks
Months
Three overlapping phases of wound healing
Figure 7.1  Three overlapping phases of wound healing.
A
B
C
Blood vessels
Epidermis
Dermis
Subcutaneous fat
Muscle
Hair follicle
Comparison of erosion, partial-thickness,
and full-thickness wounds
Figure 7.2  Comparison of erosion, partial-thickness, and
full-thickness wounds. (A) Erosion: only the epidermis is lost.
(B) Partial-thickness wound: the epidermis and part of the
dermis are missing but some adnexal structures remain.
(C) Full-thickness wound: all of the epidermis and dermis along
with adnexal structures are missing. The full-thickness skin loss
involves the subcutaneous fat tissue and may extend down to,
but not through, the underlying fascia.

97
Chapter 7  Wound Healing
inoculated into the wound, causing prolongation of the
inflammatory phase.
 PHASES OF WOUND HEALING
Inflammatory phase
The initial reaction to wounding can be subdivided into a
vascular and cellular response, and in total is manifest as the
inflammatory response (Fig. 7.6). Early in the wounding
process local vasodilatation, blood and fluid leakage into the
extravascular space, and blocking of lymphatic drainage can
produce the five cardinal signs of inflammation: rubor
(redness), tumor (swelling), calor (heat), dolor (pain), and
functio laesa (loss of function). This acute inflammatory
response usually lasts 24–48 hours and may be misinterpreted
as an infectious process. Although usually lasting 1–2 days, it
may persist for up to 2 weeks in some cases and proceed into
chronic inflammation.
Tissue injury causes blood vessel disruption and bleeding
which activates keratinocytes to release interleukin-1 (IL-1).
Platelets, the first cells to appear after wounding, not only
aid in homeostasis but also initiate the healing cascade via
release of important mediators including chemoattractants
and growth factors such as platelet-derived growth factor
(PDGF), epidermal growth factor (EGF), and TGF-β1.5,6
Some authors have defined healing as occurring in four stages:
hemostasis, inflammatory, proliferative, and remodeling,
which highlights the importance of platelets in the healing
process. In response to chemoattractants and cytokines, leu-
kocytes (including neutrophils and macrophages) infiltrate
the wounded area and clear damaged tissue debris and foreign
particles. Other infiltrating cells such as mast cells, basophils,
and eosinophils participate in the inflammation by releasing
chemicals or proteases. In the tissue, monocytes become
tion, a graft has been separated from its own blood supply
and therefore its blood supply is provided by the wound bed
on which it is placed. Even if the wound edges are approxi-
mated using a primary intention method, the wound still
proceeds through the three phases of healing.
Methods of creating acute wounds
The method by which wounds are created may also influence
their healing. Acute wounds may be created in a variety of
ways. For example, a surgeon may utilize a scalpel (steel),
laser (heat), liquid nitrogen (cold), or chemicals (acid) to
create a wound. Alternatively, a patient may accidentally
sustain an acute wound through thermal or chemical burns
or traumatic accidents. Depending upon how the wound was
created, wounds heal differently and at different rates. In
general, wounds created by sharp steel, such as surgical inci-
sions, heal faster than other methods of wounding. Healing
of traumatic wounds may be slowed due to foreign substances
Figure 7.3  Sacral pressure ulcer in nursing home patient.
Table 7.1  Wound depth and repair types
WOUND TYPE
DERMIS INVOLVEMENT
RE-EPITHELIALIZATION
MAIN REPAIR TYPE
Erosion
None
From wound edge and appendages
Regeneration
Partial thickness
Partial
From wound edge and appendages
Repair with scar
Full thickness
All
From wound edge
Scar and contraction
A
B
Figure 7.4  Re-epithelialization of a partial-thickness wound in a pig. After partial-thickness wounding, microscopic adnexal
structures remain as a source of keratinocytes. (A) Two days after wounding, keratinocytes migrate from both the wound edges and
hair follicles (arrows). Magnification ×50. (B) Higher magnification of (A) (×100) showing that keratinocytes migrate from a hair follicle
(arrow).

98
Part 1  Basic Surgical Concepts
activated and transform into macrophages. In addition to the
phagocytosis, macrophages produce several growth factors
and cytokines important for the initiation of formation of
granulation tissue (Fig. 7.7).
Vascular response
Initially, vasoconstriction causes injured small vessels to be
pressed together. This induces stickiness within the endothelial
lining that is capable of occluding vessels. Shortly thereafter,
histamine is released into the area from mast cells, basophils,
and platelets, which causes vasodilatation and blood leakage
and an increase in permeability of the endothelial wall.
A
B
Figure 7.5  Leg ulcers secondary to
sickle cell anemia. (A) Wound prior to
split-thickness skin graft. (B) Several
days after placement of split-thickness
skin grafts.
Figure 7.6  Acute inflammatory response. A 2-day-old partial-
thickness wound in a pig shows leukocyte infiltration in the
wound area and emigration from surrounding blood vessels
(×200). Insert: infiltration with neutrophils predominant (×600).
Figure 7.7  Formation of granulation tissue. A 5-day-old
partial-thickness wound in a pig shows that underneath the
newly formed epidermis, the granulation tissue characterizes
the proliferative phase with angiogenesis and fibroplasia (×320).
Using the surgical incisional wound as a conceptual model,
one can easily envision that there is bleeding due to the disrup-
tion of blood vessels and extravasation of blood components.
Therefore, the first immediate step of wound healing is
hemostasis.7 Hemostasis can be divided into two parts – devel-
opment of a fibrin clot, and coagulation (Table 7.2). Platelets

99
Chapter 7  Wound Healing
growth factors. In addition, platelets influence leukocyte infil-
tration by releasing chemotactic factors. Platelets also promote
new tissue regeneration by releasing some growth factors
implicated in wound repair. These include TGF-α, TGF-β,
PDGF, and EGF. They have strong effects on promoting cell
migration and proliferation and formation of granulation
tissue. These functions mean that platelets are not only
im­portant in hemostasis but also significantly contribute to
re-epithelialization, fibroplasia, and angiogenesis.9 PDGF was
recently reported to differentially effect the wound healing
phases. In the inflammatory phase, at day 4 after wounding,
PDGF works by initiating migration of keratinocytes and
fibroblasts, and promoting granulation tissue formation and
angiogenesis. However, prolonged inflammatory response and
cell proliferation prevent epithelial cell migration, ultimately
delaying the re-epithelialization process.9
The second part of hemostasis is coagulation, which can be
divided into intrinsic and extrinsic pathways, both of which
converge at the point where factor X is activated. Damaged
tissue releases a lipoprotein known as tissue factor, which acti-
vates the extrinsic coagulation pathway. The activated mono-
cytes and endothelial cells also express this tissue factor on
their surface and participate in the coagulation. Platelet aggre-
gation triggers a specific enzyme in blood known as Hageman
factor XII to initiate the cascade of intrinsic coagulation with
a series of converting proenzymes to activate enzymes, culmi-
nating in the transformation of prothrombin into thrombin.
This in turn converts soluble fibrinogen to insoluble fibrous
fibrin. In addition to coagulation, thrombin has multiple effects
on platelets, macrophages, fibroblasts, and endothelial cells.
Cellular response
Leukocytes
The inflammatory phase of wound healing derives its name
from the influx of white blood cells into the area of injury.
Almost immediately after injury, leukocytes (polymorphonu-
clear leukocytes) begin to adhere to the sticky endothelium
of venules. Within 1 hour of the onset of inflammation, the
entire endothelial margin of the venules may be covered with
neutrophils (this is termed margination). Soon after, poly-
morphonuclear leukocytes begin amoeboid activity by insert-
ing narrow projections into the junctions between endothelial
cells, and they release chemotactic factors. In the early
inflammatory state, neutrophils and monocytes are the pre-
dominant cells at the site of injury (see Fig. 7.6). Later in
inflammation, the number of neutrophils declines and mac-
rophages (tissue-derived monocytes) predominate.
Neutrophils, the first white blood cells to arrive, and mono-
cytes are recruited to the wound by chemotactic factors
released from mast cells (Table 7.3) or produced by the
coagulation cascade. Substances released by mast cells, such
as tumor necrosis factor (TNF), histamine, proteases, and
some other substances such as leukotrienes and cytokines
(interleukins), represent chemotactic signals for the recruit-
ment of leukocytes. Growth factors of PDGF and TGF-β are
also potent chemotactic factors for leukocytes. The chemo-
tactic factors from the coagulation process (kallikrein, fibri-
nopeptides released from fibrinogen, and fibrin degradation
products) also serve to upregulate the expression of impor-
tant intercellular adhesion molecules. Upregulated adhesion
molecules allow cell–cell interactions, which facilitate dia-
pedesis of neutrophils. Vascular endothelial cells that were
are the first cells to appear after injury. With injury to endothe-
lial cells and blood vessels, collagens and other extracellular
matrix proteins are exposed. Platelets, which are activated by
locally generated thrombin at the site of blood vessel injury,
promote adhesion and aggregation of the exposed extracellu-
lar matrix, especially fibrillar collagen. Upon activation, plate-
lets release many mediators from their granules including
serotonin, adenosine diphosphate (ADP), thromboxane A2,
fibrinogen, fibronectin, thrombospondin, and von Willebrand
factor VIII. Induced by these chemicals, other passing plate-
lets adhere to the exposed extracellular matrix of the endothe-
lial wall, resulting in a relatively unstable platelet plug that
may temporarily occlude injured small vessels. Concomi-
tantly, endothelial cells produce prostacyclin, which inhibits
platelet aggregation and thus limits the extent of platelet
aggregation. Platelet-derived fibrinogens are converted by
thrombin to fibrins, which are deposited into and about the
platelet plug and form a more stable fibrin clot that slows or
stops bleeding. This fibrin clot also acts as a scaffold matrix8
(called provisional matrix) for the migration of leukocytes,
fibroblasts, and endothelial cells, and serves as a reservoir of
Table 7.2  Hemostasis in wound healing
ACTIVITIES/
SUBSTANCES
MAJOR EFFECTS
Development of platelet fibrin clot
Substances of platelet granule
ADP
Platelet aggregation
Fibrinogen
Platelet aggregation
Fibronectin
Platelet aggregation
Thrombospondin
Platelet aggregation
von Willebrand factor VIII
Platelet activation and adhesion to
fibrillar collagen
PDGF, TGF
Leukocyte recruitment, extracellular
matrix synthesis
Serotonin
Vasoconstriction, fibroblast
proliferation, collagen cross-linking
Chemoattractants
Leukocyte recruitment
Products during fibrin clot development
Thrombin
Platelet activation, conversion of
fibrinogen to fibrin
Platelet aggregation
Core of fibrin clot
Fibrin
Core of fibrin clot
Fibrin clot
Hemostatic plug, provisional matrix
for cell migration, reservoir of
growth factor
Coagulation
Hageman factor fragments
Initiate intrinsic coagulation,
increased vasopermeability
Bradykinin
Vasodilatation, increased
vasopermeability
Complement activation
Leukocyte recruitment, increased
vasopermeability
Thrombin
Leukocyte recruitment, conversion
of fibrinogen to fibrin, fibroblast
proliferation
ADP, adenosine diphosphate; PDGF, platelet-derived growth factor; TGF, transform-
ing growth factor.

100
Part 1  Basic Surgical Concepts
matrix proteins within the wound bed. The neutrophil infil-
tration normally lasts only a few days. The presence of wound
contamination prolongs the neutrophilic presence within the
wound. The eosinophil also has low capacity for phagocytosis,
but the basophil does not. Basophils contain histamine, which
is released locally following injury, to contribute to the early
increased vascular permeability (see Table 7.3).
Monocytes migrate from the capillary into the tissue spaces;
once in the tissue they are activated and transformed into
larger phagocytic cells – the macrophages. Monocytes and
their tissue counterparts, macrophages, soon become the
dominant figures in inflammation. Monocytes are initially
attracted to the wound site by some of the same chemoat-
tractants that attract neutrophils, and their recruitment
continues through signals released by monocyte-specific che-
moattractants, such as monocyte chemoattractant protein-1
(MCP-1)10 and macrophage inflammatory protein-1 (MIP).11
Extracellular matrix degradation products – collagen frag-
ments, fibronectin fragments, and thrombin – are also chem-
oattractants specific for monocytes.12 Macrophages are critical
to repair and are considered the most important regulatory
cells in the inflammatory reaction during wound healing
(Table 7.4). Macrophages phagocytize, digest, and kill patho-
genic organisms, scavenge tissue debris, and destroy any
remaining neutrophils. After binding to the extracellular
membrane, bacterial, cellular, and tissue phagocytosis and
subsequent destruction are accomplished through release of
biologically active oxygen intermediates and enzymatic pro-
teins. These all-important processes performed by the mono-
cyte/macrophage allow for induction of angiogenesis and
formation of granulation tissue.
Macrophages tolerate severe hypoxia well. This may explain
why they are usually present in chronic inflammation.
In addition, macrophages release chemotactic factors (for
example, fibronectin) which attract fibroblasts to the wound
and play a role in localizing inflammation and in adhesion of
fibroblasts to fibrin during the transition between the inflam-
matory and proliferative phases of wound repair. In this
regard, macrophages may enhance collagen deposition because
their depletion markedly decreases deposition of collagen
in the wound.13 In the absence of macrophages, fibroblasts
Table 7.3  Inflammatory cells and their major
proteases/chemicals
CELL TYPE
PROTEASE/
CHEMICALS
MAJOR EFFECTS OR
SUBSTRATES
Mast cell
Histamine
Vasopermeability,
vasodilatation, EC
proliferation
Heparin
Anticoagulation,
fibrinolysis
Serotonin
Vasoconstriction
Fibroblast proliferation,
collagen cross-linking
tPA
Plasminogen
PAF
Platelet activating and
aggregation
Protease-3
Trypsin-like effect
MMP-9
Gelatin, collagen IV and V
Tryptase
ProMMP-3, uPA
Chymase
ProMMP-1, -3
Leukotrienes
Chemotactic for
granulocytes
Neutrophil
Elastase
Elastin, proteoglycans,
collagen III, V
MMP-8
Collagens I, III, VII, and X
MMP-9
As above
MT1-MMP
ProMMP-2, -13, collagen I,
III, fibronectin
Heparanase
Heparan sulfate,
proteoglycans
Eosinophil
MMP-1
Collagens I, III, VII, and X
MMP-9
As above
β-Glucuronidase
Proteoglycans
Basophil
Histamine
As above
Monocyte/
macrophage
MMP-9
As above
MMP-12
Elastin, collagen IV,
laminin, fibronectin
MT1-MMP
As above
tPA
As above
PDGF, IGF-1, FGF,
TGF-β, VEGF
See Table 7.5
T lymphocyte
MMP-2
Gelatin, collagen VI, V
and I, laminin, fibronectin,
proMMP-9, -13
MMP-9
As above
EC, endothelial cell; FGF, fibroblast growth factor; IGF, insulin-like growth factor;
MMP, matrix metalloproteinase; MT1, membrane type 1; PAF, platelet-activating
factor; PDGF, platelet-derived growth factor; TGF, transforming growth factor; tPA,
tissue plasminogen activator; uPA, urokinase-like plasminogen activator; VEGF, vas-
cular endothelial growth factor.
Table 7.4  Macrophages in wound repair
ACTIVITIES
MAJOR EFFECTS
Recruitment and maturation
Transformation from monocyte
to tissue macrophages
Chemoattractant release
Leukocyte recruitment
Phagocytosis of bacteria
Wound decontamination
Phagocytosis of tissue debris
Wound debridement
Phagocytosis of extravasated
granulocytes
Resolution of inflammation
MMP release
Matrix degradation (collagen,
elastin), granulation tissue
formation and remodeling
Growth factor release (FGF,
IGF-1, PDGF, TGF-α, TGF-β,
VEGF)
Regulation of fibroplasias,
angiogenesis, tissue remodeling
FGF, fibroblast growth factor; IGF, insulin-like growth factor; MMP, matrix metallo-
proteinase; PDGF, platelet-derived growth factor; TGF, transforming growth factor;
VEGF, vascular endothelial growth factor.
previously thought to be bystanders in inflammatory proc-
esses are now believed to play an active role in facilitating
leukocyte migration. Neutrophils release elastase and colla-
genase, which likely enhance their passage through the blood
vessel basement membrane. Once in the wound site, integrin
receptors found on the surface of neutrophils enhance cell–
matrix interactions. This allows neutrophils to perform their
functions of killing and phagocytosing bacteria and damaged

101
Chapter 7  Wound Healing
lived increase in permeability of venules. Heparin, an antico-
agulant, serves to prevent coagulation of the excess tissue
fluid and blood components during the early phase of the
inflammatory response.
Serotonin
Serotonin, or 5-hydroxytryptamine (5-HT), is released from
platelets and mast cells and is a potent vasoconstrictor,
though it is unlikely that it has a significant effect on vascular
permeability in humans. However, serotonin appears to be
involved in other activities related to the later phases of
wound healing, such as fibroblast proliferation and the cross-
linking of collagen molecules. Cross-linking of collagen mol-
ecules not only affects the tensile strength of newly formed
desirable scar tissue but also accounts for certain negative
effects of scarring such as toughness, and the lack of resilience
of unwanted fibrous adhesions.
Kinins
The kinins are biologically active and nearly indistinguishable
peptides that are found in areas of tissue destruction. The
most familiar kinin, bradykinin, is a potent inflammatory
substance released from plasma proteins in injured tissue by
the plasma enzyme, kallikrein. The action of the kinins on the
microvasculature is similar to that of histamine: that is, potent
vasodilatation. Kinins are rapidly destroyed by tissue pro-
teases, suggesting their importance is limited to the early
inflammatory stage of wound healing.
Prostaglandins
Prostaglandins (PGs) are extremely potent biologic sub-
stances and are produced by nearly all cells of the body in
response to cell membrane injury. When cellular membranes
are altered, their phospholipid content is degraded by the
enzyme phospholipases that result in the formation of arachi-
donic acid. Oxidation of arachidonic acid by the enzyme
lipoxygenase forms a series of potent compounds, the leuko-
trienes. Several types of leukotrienes combine to form slow-
reacting substance of anaphylaxis (SRS-A) which alters
capillary permeability during the inflammatory reaction.
Subsequently a cascade effect occurs, as arachidonic acid
is converted by cyclo-oxygenases to thromboxanes and several
prostaglandins. Specific classes of prostaglandins appear to
control or perpetuate the local inflammatory response. Pros-
taglandin E2 (PGE2) may increase vascular permeability by
antagonizing vasoconstriction, and its chemotactic activity
may attract leukocytes to the locally inflamed area. Some
prostaglandins are proinflammatory (for example, PGE2) and
synergize with other inflammatory substances such as brady-
kinin. Proinflammatory prostaglandins are thought to be
responsible for sensitizing pain receptors, causing a state of
hyperalgesia associated with the inflammatory reaction, while
other classes of prostaglandin act as inhibitors. Together,
these opposing effects of various prostaglandins lead to a
tightly controlled response. Prostaglandins may also regulate
the repair processes during the early phases of healing by
contributing to the synthesis of mucopolysaccharides.
One action of corticosteroids such as prednisone and non-
steroidal anti-inflammatory drugs (NSAIDs) such as aspirin
is inhibition of prostaglandin synthesis via inhibition of cyclo-
oxygenase activity. Suppressing the inflammatory response
and its associated pain may be appropriate treatment for
migrate to the site of injury in considerably reduced numbers,
and when found they are somewhat immature. The ang-
iogenic potential of macrophages has also been demonstrated
by inducing neovascularization in the cornea using a rat model
with macrophage-derived growth factor. New blood vessel
growth follows a gradient of angiogenic factor produced by
hypoxic macrophages, as macrophages do not produce this
angiogenic factor when either fully oxygenated or anoxic.
Macrophages can be considered factories for production of
growth factors, for synthesizing and secreting PDGF, fibro­
blast growth factor (FGF), vascular endothelial growth factor
(VEGF), TGF-β, and TGF-α.14 These cytokines are impor-
tant in inducing cell migration and proliferation, as well as in
matrix production. Thus, macrophages appear to play a
pivotal role in the transition between inflammation and repair.
Mast cells
Mast cells have acquired increasing attention in the wound
healing field. Studies have found that skin mast cells, which
are usually located near vessels and nerves in the dermis, are
activated directly by immunological signals and stimuli of
nerve origin, as well as by numerous stimuli of physical,
chemical, or mechanical nature. Once stimulated by direct
tissue injury, mast cells are immediately activated by degran-
ulation and release mediators (see Table 7.3), such as hista-
mine and TNF, which are essential for triggering the
inflammatory response and influencing the local endothelial
cells, causing vasodilatation and increased vascular permeabil-
ity. Mast cells actively participate in the regulation of hemo­
stasis by release of substances such as platelet-activating
factor (PAF), heparin, tryptase, chymase, and t-plasminogen
activator (tPA). In addition, TNF, histamine, proteases, and
other substances such as leukotrienes and cytokines (inter-
leukins) serve as chemotactic signals for the recruitment of
leukocytes. Further, the histamine, heparin, cytokines, and
growth factors released from mast cells (such as PDGF,
VEGF, TGF, and FGF) also mediate the processes of angio-
genesis, extracellular matrix deposition, and remodeling.
Chemical mediators of inflammation
A number of chemical substances are involved in the initia-
tion and control of inflammation. These chemicals work in
concert; some are protagonists and others are antagonists of
inflammation. The actions of some of these substances may
be synergistic, while for many their precise role has not
clearly been elucidated.
Histamine
One of many substances released from mast cell granules is
histamine. Mast cells are the major source of histamine pro-
duction, which is also found in blood platelets and basophils.
Histamine acts on the type 1 histamine receptor (H1) and
causes dilatation of arterioles and increased permeability of
venules. When mast cells are depleted of histamine, or H1
receptors are blocked, the early increase in vascular perme-
ability is prevented. Histamine’s accelerated wound healing
activity has been reported to be mediated by the activity of
basic FGF (bFGF) which ultimately leads to angiogenesis.15
In addition to histamine, mast cell granules, released at the
time of injury, contain a number of active materials including
serotonin and heparin, which lead in part to the initial short-

102
Part 1  Basic Surgical Concepts
chronic inflammation but is usually not indicated for the
normal acute inflammatory response.
Complement system
The complement system collectively describes a system of
about 11 principal proteins, many of them enzyme precur-
sors. All of these proteins may be present among the plasma
proteins that leak from capillaries into the tissue spaces.
When antibody binds antigen, the same antibody also binds
with a specific protein molecule of the complement system.
This triggers a cascade of sequential reactions that produce
multiple end products which help prevent damage by the
invading organism or toxin. With regard to wound healing,
some of the end products activate phagocytosis by both neu-
trophils and macrophages, whereas others enhance lysis and
agglutination of invading organisms. Still others activate mast
cells and basophils to release histamine.
Growth factors
Numerous terms are used to designate growth factors, includ-
ing cytokines, interleukins, and colony-stimulating factors.14
This fact, coupled with the fact that the name of a growth
factor does not in reality identify its only or its primary bio-
logic role, has made the nomenclature for growth factors
quite confusing. For instance, PDGF is found in platelets but
is also found in keratinocytes and other cells.5 Growth factors
work through cell surface receptors and may bind to single
or multiple receptors. Growth factors can have an effect on
the cells of origin (autocrine mode), on neighboring cells
(paracrine mode), or on distant cells (exocrine mode).
Growth factors have been shown to play multiple and critical
roles in wound repair processes (Table 7.5). Many growth
factors secreted by macrophages are pleiotropic and influence
cell proliferation, angiogenesis, and extracellular matrix syn-
thesis. For example, TGF-α plays an important role in wound
re-epithelialization, TGF-β1, -β2, and -β3 strongly promote
the migration of fibroblasts and endothelial cells, and deposi-
tion of extracellular matrix by fibroblasts during formation of
granulation tissue. While increased TGF-β1 promotes scar
formation, TGF-β3 exhibits an antiscarring effect.1 PDGF is
chemotactic and mitogenic for fibroblasts and smooth muscle
cells in vitro.5 PDGF is also chemotactic for monocytes,
macrophages,16 and neutrophils17 and thrombin-activated
platelets possess angiogenic activity.18
Chronic inflammation
Most of the symptoms associated with the acute inflamma-
tory response last approximately 2 weeks. However, if inflam-
mation persists for months or years, it is called chronic
inflammation. Chronic inflammation associated with wounds
often occurs when a wound is habitually sealed by necrotic
tissue, is contaminated with pathogens, or contains foreign
material that cannot be phagocytized or solubilized during the
acute inflammatory phase. Granulocytes disappear through
lysis and migration with the resolution of the acute inflam-
matory phase, while mononuclear cells – specifically lym-
phocytes, monocytes, and macrophages – persist at the site
of inflammation. The chronic inflammatory response may not
be characterized by the cardinal signs of inflammation. At
times, the body responds to the presence of persistent foreign
material and/or infection by local proliferation of mononu-
clear cells. In particular, macrophages that have ingested
Table 7.5  Growth factors in cutaneous wound healing
GROWTH FACTORS
MAJOR EFFECTS
EGF
Epidermal keratinocyte migration,
proliferation, differentiation, re-
epithelialization
FGF-1, -2
Fibroblast and keratinocyte
proliferation, endothelial cell
proliferation, migration, survival,
angiogenesis
IGF
Cell proliferation
KGF
Keratinocyte proliferation
PDGF
Fibroblast chemotaxis, proliferation,
contraction
TGF-α
Similar to EGF
TGF-β1, -β2, -β3
Fibroblast chemotaxis, promotion of
extracellular matrix deposition, inhibition
of cell proliferation, inhibition of
protease inhibitor secretion, endothelial
cell migration, survival, angiogenesis
VEGF
Endothelial cell proliferation, migration,
survival, increases vasopermeability,
angiogenesis
EGF, epidermal growth factor; FGF, fibroblast growth factor; IGF, insulin-like growth
factor; KGF, keratinocyte growth factor; PDGF, platelet-derived growth factor; TGF,
transforming growth factor; VEGF, vascular endothelial growth factor.
foreign particulate material will remain in the tissue if they
are unable to solubilize the material. Macrophages attract
fibroblasts, and over time may produce increased quantities
of collagen, leading to a slowly forming encapsulated mass of
fibrous tissue – a granuloma – and this is considered to be the
body’s last defense against a foreign material that cannot be
phagocytized or solubilized.
Keratinocyte migration in chronic wounds may be directly
inhibited by bacterial lipopolysaccharide,19 suggesting that
bacterial products in the wound directly affect the healing
process.
Proliferative phase
The initial inflammatory responses to injury provide the nec-
essary framework for the production of a new functional
barrier. In this phase of healing, cellular activity predomi-
nates. Proliferation requires the creation of a permeability
barrier (re-epithelialization) accompanied with the establish-
ment of an appropriate blood supply (angiogenesis) and rein-
forcement of the injured tissue (fibroplasia).
Re-epithelialization
Re-epithelialization is the process responsible for restoring an
intact epidermis following cutaneous injury. In general, re-
epithelialization involves several processes: the migration of
epidermal keratinocytes from wound edges; the proliferation
of keratinocytes that are used to supplement the advancing
and migrating epithelial tongue; differentiation of the neoep-
ithelium into stratified epidermis; restoration of an intact
basement membrane zone that connects the epidermis and
underlying dermis; and the repopulation of specialized cells
that direct sensory function (Merkel’s cells), pigmentation
(melanocytes), and immune functions (Langerhans cells).

103
Chapter 7  Wound Healing
sibly due to contact inhibition, keratinocytes reattach them-
selves to the underlying substratum, reconstitute the
basement membrane, and then resume the process of termi-
nal differentiation to generate a new, stratified epidermis.
One can observe that towards the wound center there are
single-layered keratinocytes, while near the wound edges
there are multiple-layered or stratified keratinocytes. Near
the wound margin, the differentiation of the neoepidermis
(keratins 1/10, filaggrin, and loricrin) and regeneration of the
dermoepidermal junction (laminins and collagen IV) are more
advanced than toward the wound center, where the prolif-
erative index is found to be significantly increased.20
Epidermal differentiation is an ongoing process which bal-
ances keratinocyte proliferation in the non-differentiating
layers and continues until the wound is covered by the epi-
dermis. This suggestes that the initiation of wound healing
primarily depends on keratinocyte migration.21
Restoration of the basement membrane zone
The formation of intact basement membrane zone (BMZ),
which is normally located between the epidermis and dermis,
is essential for re-establishing the integrity and function of
the skin. Within 7–9 days of the reformation of the epider-
mis, the BMZ returns to normal. The BMZ forms an adhesion
structure, the upper part of which serves as an attachment
site for basal keratinocytes through the formation of a
hemidesmosome-anchoring filament complex; the lower
portion stabilizes the attachment to the underlying dermis by
anchoring fibrils (Fig. 7.8). The importance of individual
BMZ proteins is evidenced by a group of inherited blistering
diseases known as epidermolysis bullosa (EB). These include
the mutations of hemidesmosomal component collagen XVII
in atrophic EB, the defects of laminin-332 (or laminin-5) of
major anchoring filaments in junctional EB, and the deficiency
of collagen VII anchoring fibrils in dystrophic EB.23
Collagens
The BMZ of the skin consists of many extracellular matrix
proteins, with collagens and laminins as the major compo-
nents. Collagen IV, collagen VII, and collagen XVII are the
major collagens in the BMZ, while collagen IV is the most
abundant. Collagen IV forms a three-dimensional lattice
network within the lamina densa of skin BMZ. In addition,
collagen IV is also the predominant collagen in the BMZ of
dermal blood vessels. Collagen VII proteins, also called
anchoring fibrils, span from the lamina densa to the upper
papillary dermis where they form a structure known as
anchoring plaque that also contains collagen IV. Anchoring
fibril loops are also associated with interstitial collagens of
primarily types I and III. Collagen XVII, also known as bullous
pemphigoid antigen (BPAG-2 or BP180), is a 180-kDa trans-
membrane protein located on the hemidesmosome complex
of basal keratinocytes. Collagen XVII has a short N-terminus
inside the cell and a long triple helix collagenous extracellular
domain at its C-terminus that associates with anchoring fila-
ments at the lamina lucida of the cutaneous BMZ.23
Laminins
Laminins are the major non-collagenous extracellular matrix
components in a wide range of BMZ within human tissues.
All laminins are large heterotrimeric glycoproteins, each com-
posed of an α, β, and γ chain, forming an asymmetric cross-
Keratinocyte migration
Keratinocyte migration is an early event in wound re-epithe-
lialization. Epidermal keratinocytes initially respond to an
epidermal defect by migrating from the free edges of the
wound within 24 hours. The keratinocyte migration in partial-
thickness wounds also occurs from the remaining skin append-
ages, including the hair follicle (see Fig. 7.4). A change in the
activity of keratinocytes is required for re-epithelialization to
occur. In the unwounded stable state, cuboid-shaped basal
keratinocytes interact with each other by a desmosomal inter-
cellular bridge, and are connected to their own basement
membrane zone by hemidesmosomes. Approximately 12 hours
after wounding, epidermal cells become somewhat flattened
and elongated, develop pseudopod-like projections named
lamellipodia, lose their cell–cell and cell–matrix attachments,
retract their intracellular tonofilaments, and form actin fila-
ments at the edge of the cell cytoplasm. While epidermal cells
are migrating, their proliferative potential is inhibited.
The mechanisms of wound re-epithelialization have been
debated for a long time but remain unclear. The migration of
keratinocytes over the wound surface may occur in several
ways. Currently, a ‘leap frog’ theory is the more commonly
accepted model20 whereby epidermal cells migrate two or
three cell lengths from their initial position and slide or roll
over epidermal cells previously implanted in the wound. The
migrating cells become fixed, and other epidermal cells suc-
cessively migrate over these cells. The epidermal layer pro-
gressively advances and closes the epithelial defect.
Keratinocytes use their surface integrin receptors to inter-
act with fibronectin from fibronectin-rich provisional matrix
for their migration. The direction of migration is also regu-
lated by the binding of keratinocytes through integrin to the
newly formed collagen molecules in the wound bed. Subse-
quent dissociation of the bindings allows the keratinocytes to
move forward. A recent report states that keratinocytes can
migrate over any wound-related matrix, such as clot-related
debris, and are therefore not restricted to migration over the
newly formed matrix.21 Fibronectin produced from plasma
initially, and from plasma and fibroblasts later, may also be
derived from the migrating keratinocytes themselves. This
suggests that the migrating tongue of epithelial cells may
provide its own lattice for continued migration. Among the
stimuli for re-epithelialization thought to be important are
TGF-β, keratinocyte growth factor (KGF), and EGF.
Migrating keratinocytes produce matrix metalloproteinases
(MMPs) to degrade damaged matrix. An example of the
active role of basal keratinocytes in cell migration is their
secretion of MMP-1 (collagenase-1) when in contact with
fibrillar collagens, but not while on intact basement mem-
brane.22 MMP-1 disrupts any attachment to fibrillar collagen
and allows for continued migration of keratinocytes. Once the
wound is epithelialized, keratinocytes bind to α2β1 integrin,
and production of MMP-1 stops. The specificity described
above with regard to MMP-1 impacts not solely on the
outcome of epithelial migration but also on the maintenance
of the directionality of the migrating tongue of epithelium.
Keratinocyte proliferation and differentiation
Re-epithelialization also involves increased proliferation of
the keratinocytes located behind the migrating cells at front
of the tongue, thus ensuring an adequate supply of cells to
migrate and cover the wound. When migration ceases, pos-

104
Part 1  Basic Surgical Concepts
shaped structure (Fig. 7.9). Several laminins have been
reported to be present in the BMZ of the dermal–epidermal
junction.24 Laminin-111 (α1β1γ1; previously called laminin-
1) was the first laminin identified in the lamina densa. Three
α3-chain-containing laminins, laminin-332 (α3β3γ2; laminin-
5, kalinin, epiligrin, nicein, BM600), laminin-311 (α3β1γ1;
laminin-6, k-laminin) and laminin-321 (α3β2γ1, laminin-7)
are the integral components of the anchoring filaments, tra-
versing from the hemidesmosome across the lamina lucida to
Intermediate filaments
Keratins 5, 14
Collagens I, III, V, VI
Collagen IV
Laminins -111, 511
Perlecan, Nidogen
BP230
Hemidesmosome
HD1/plectin
Stratum basal
of epidermis
Basement
membrane
Lamina lucida
Lamina densa
Dermis
Anchoring fibrils
Collagen VII
Anchoring filaments
α6β4 Integrin
Anchoring plaque
Collagen IV, VII
BP180/collagen XVII
Laminins -332, 311, 321
Dermal–epidermal basement membrane zone
Figure 7.8  Schematic structure of dermal–epidermal basement membrane zone.
α5
γ1
β1
Laminin-511of the lamina densa
Figure 7.9  Schematic structure of laminin-511.
the lamina densa.25 Deficiency in any chain of laminin-332 is
associated with clinical blistering disease, junctional epider-
molysis bullosa. There is evidence that laminins are also
actively involved in wound repair. In response to wounding,
the leading keratinocytes in the migrating front edge deposit
laminin-332 which serves as a track that migrating keratino-
cytes can follow to spread across the surface.26 More recently,
a new laminin member, laminin-511 (α5β1γ1, or laminin-10),
has been located within the lamina densa.27 Laminin-511
showed strong promoting effects on human keratinocyte
attachment. Mice lacking laminin α5 chain showed develop-
mental defects in multiple systems. The skin of laminin-511
knockout mice exhibited discontinuity in the lamina densa of
BMZ and there was a defect in hair development.28 In addi-
tion, laminin-511 and laminin-411 (α4β1γ1, or laminin-8)
have recently been found to be major laminins of dermal
microvascular blood vessels. Laminin-α4-deficient mice dis-
played hemorrhages at birth, reflecting impaired microvessel
maturation. Laminin-411 was found to promote endothelial
cell attachment, migration, and capillary tubule formation.29
Reconstitution of the dermis
Granulation tissue, a sign of progression of healing, begins to
form within 3–4 days of injury. The provisional extracellular
matrix, fibrin clot, which is rich in fibronectin, promotes
formation of granulation tissue by providing scaffolding and
contact guidance for cells to migrate into the wound space,
and for angiogenesis and fibroplasia to occur to replace the
wounded dermal tissue.
Fibroplasia
Granulation tissue consists of new vessels that migrate into
the wound as well as the accumulation of fibroblasts and
ground substances (see Fig. 7.7). Fibroplasia is used to
describe a process of fibroblast proliferation, migration into
the wound’s fibrin clot, and production of new collagens and

105
Chapter 7  Wound Healing
fibrin, fibronectin, and thrombospondin, for stable clot for-
mation. During later phases of wound healing, migration of
cells including leukocytes, keratinocytes, fibroblasts, and
endothelial cells into the wound requires rapid binding and
dissociation with extracellular molecules to permit cell move-
ment. After fibroblasts cease migration and begin wound
contraction, they need to bind tightly to collagens and
fibronectin and organize a contractile cytoskeleton. Integrins
may play central roles in these processes. Cells might express
and use different integrins for their migration and attach-
ment. For example, in normal epidermis, α3β1 integrins
mediate the interactions between keratinocytes, α6β4
integrins connect basal keratinocytes to the BMZ laminins,
α2β1 and α5β1 integrins mediate keratinocyte migration on
collagen and fibronectin,38,39 and α9β1 integrins mediate
effective keratinocyte proliferation during re-epithelialization
of cutaneous wound repair.40
Mechanism of wound contraction
The degree of wound contraction varies with the depth of
the wound. For full-thickness wounds, contraction begins
soon after wounding and peaks at 2 weeks. In these wounds,
contraction is an important part of wound healing, accounting
for up to a 40% decrease in the size of the wound. In partial-
thickness wounds, parts of the adnexa remain and allow epi-
thelialization to occur from within the wound. Therefore,
partial-thickness wounds contract less than full-thickness
wounds and in direct proportion to their depth. Myofibro­
blasts are the predominant mediator of this contractile
process because of their ability to extend and retract.
During formation of granulation tissue, fibroblasts are grad-
ually modulated into myofibroblasts after expressing α-smooth
muscle actin (α-SMA) de novo, which increases their ability
to contract.41 By day 7, abundant extracellular matrix has
accumulated in the granulation tissue and fibroblasts begin to
change into myofibroblast phenotype, which is characterized
by actin microfilaments bundles, similar to those seen in
smooth muscle cells, along their plasma membrane. The
normal skin fibroblasts generally contain β and γ cytoplasmic
actins that are organized in a network (not in bundles). A
study of electron microscopy and immunohistochemical
other matrix proteins, as well as cytokine regulation; this
process contributes to the formation of granulation tissue
during wound repair. As an early response to injury, fibro­
blasts in the wound edges begin to proliferate, and at about
day 4 they start to migrate into the provisional matrix of the
wound clot where they lay down collagen-rich matrix.30 First,
fibroblasts migrate and later produce large amounts of matrix
materials, including collagen, proteoglycans, and elastin.31
Once the fibroblasts have migrated into the wound, they
gradually switch their major function to protein synthesis and
change to profibrotic phenotype, which is characterized by
abundant rough endoplasmic reticulum and Golgi apparatus
filled with new matrix proteins. As was the case for fibroblast
proliferation, optimal conditions for fibroblasts to produce
matrix proteins consist of an acidic, low-oxygen environment.
Fibroblasts are also modulated into the phenotype of myofi-
broblasts and participate in wound contraction.3
Fibroblastic chemotactic factors are complex but are, in
part, derived from macrophages already present in the wound.
Both PDGF and TGF-β can stimulate fibroblast migration
and upregulate the expression of integrin receptors.32 EGF
and FGF, among others, modulate fibroblast proliferation and
migration.33,34 Fibroblast proliferation is also stimulated by
low oxygen conditions found in the center of the wound. As
angiogenesis proceeds with the formation of new vessels and
increased oxygen-carrying capacity, this stimulus diminishes.
Structural molecules of the early extracellular matrix, such
as fibronectin and collagen, also contribute to the formation
of granulation tissue by providing a scaffold for contact guid-
ance and a reservoir for cytokines and growth factors.
Fibronectin, a glycoprotein, is a major component of the gel-
like cellular substance initially secreted and provides for
enhanced fibroblast activity. Thrombin and EGF stimulate
fibronectin synthesis and secretion. Fibronectin allows fibro­
blasts to bind to the extracellular matrix and provides an
adherent base for cell migrations, allowing fibroblasts to
attach to collagen, fibrin, and hyaluronic acid.35 The fibronec-
tin matrix provides a scaffold for collagen fibrils and mediates
wound contraction. The vectors of fibroblast migration into
the wound are directed by the molecular and gross fibrillar
structure of fibronectin and, therefore, play a critical role in
the speed and direction of dermal repair. Fibroblasts migrate
by pulling themselves along a fibronectin matrix, which
occurs by contraction of intracellular microfilaments.
Integrin receptors in wound healing
Extracellular matrix binds cells through specific cell surface
receptors, of which integrins are the major receptors for
extracellular matrix. The sequence Arg-Gly-Asp (RGD) has
been found frequently to be the major recognition sequence
for integrin receptors. Integrins are a family of heterodimeric
transmembrane proteins, each consisting of one α chain and
one β chain. Integrins mediate the cell–cell and cell–matrix
interactions, and transduce the signals between them (Fig.
7.10). Many signaling pathways activated by integrin activa-
tion are also activated following growth factor stimulation,
suggesting that cellular responses mediated by integrins and
growth factors may act synergistically or coordinate cellular
biochemical changes.36,37
Integrin receptors are involved in all phases of wound
repair. Immediately after injury, integrin αIIbβ3 conducts the
interaction of platelet with extracellular matrix, including
Cell membrane
Integrin
Extracellular matrix
Linkers
Cytoskeleton
α
β
Integrin signal pathway
Figure 7.10  Schematic model of integrin signal pathway.

106
Part 1  Basic Surgical Concepts
tion of granulation tissue and provide nutrition and oxygen
to growing tissues. In addition, inflammatory cells require
interaction with and transmigration through the blood vessel
to enter the site of injury. During angiogenesis, endothelial
cells also produce and secrete biologically active substances
or cytokines. Neovascularization involves a phenotypic alter-
ation of endothelial cells, directed migration, and various
mitogenic stimuli. Cytokines released by cells such as mac-
rophages stimulate angiogenesis during wound healing, as do
low oxygen tension and lactic acid, and biogenic amines can
potentiate angiogenesis.46
As in most normal adult tissues, the dermal blood vascula-
ture remains quiescent. In response to injury, the microvas-
cular endothelial cells initiate an angiogenic process consisting
of activation of endothelial cells, local degradation of their
basement membrane, sprouting into the wound clot, cell
proliferation, formation of a tubule structure, reconstruction
of basement membrane and stabilization, and eventually
regression and involution of the newly formed vasculature as
tissue remodeling (Fig. 7.11).47 Similar to the migrating
tongue of epithelium, endothelial cells at the tips of capillar-
ies migrate into the wound, but do not undergo active pro-
liferation. Cytoplasmic pseudopodia extend from endothelial
cells on the second wound day, collagenase is secreted, and
there is migration into the perivascular space.48 On the other
hand, proliferation of endothelial cells has been postulated to
be a secondary effect to cell migration. Therefore fibronectin,
heparin, and platelet factors that are known to stimulate
endothelial cell migration into the wound also directly or
indirectly stimulate endothelial cell proliferation.
Angiogenic growth factors
Growth factors playing critical roles in wound angiogenesis
are VEGF, angiopoietin (Ang), FGF, PDGF, and TGF-β.
Among them, VEGF and Ang are endothelial cell specific,
while FGF, TGF-β, and PDGF have a broad range of target
staining identified a gradual increase of the expression of α-
SMA, smooth muscle myosin, and desmin, which are markers
for smooth muscle differentiation, in wound granulation
tissue. This started on day 6 and reached a maximum at day
15, when 70% of fibroblasts showed positivity for these
markers. Then there was progressive regression.42
Myofibroblasts probably contain higher concentrations of
actinomyosin than any other cell. Unlike other cells, myofi-
broblasts within the wound align themselves along the lines
of contraction. This muscle-like contraction of the myofi-
broblasts is mediated by prostaglandin F1, 5-HT, angiotensin,
vasopressin, bradykinins, epinephrine, and noraepinephrine.
This contraction is unified and requires cell–cell and cell–
matrix communication.43 Myofibroblast pseudopodia extend
with its cytoplasmic actin binding to extracellular fibronectin,
attach to collagen fibers and retract, drawing the collagen
fibers to the cell, thereby producing wound contraction.
Mechanical adherens junctions and electrochemical gap junc-
tions play an important role in myofibroblast differentiation.
A recent study proposed a model of mechanical communica-
tion between contacting myofibroblasts showing that adher-
ens (cell–cell) junctions rather than gap junctions are
responsible for synchronization of myofibroblasts contraction
through Ca2+ influx.44
Contraction of the wound occurs in predictable directions,
via so-called ‘skin tension lines.’ Surgeons often place inci-
sions in the direction of the skin tension lines to direct the
contracture. A full-thickness graft or an acellular dermal
equivalent may be placed into a full-thickness wound to
inhibit wound contraction and subsequent contracture.45
Wound angiogenesis
Angiogenesis refers to new vessel growth or neovasculariza-
tion by sprouting of pre-existing vessels. New capillary buds
extend to the wound from blood vessels adjacent to the
wound. Newly formed blood vessels participate in the forma-
Activation with
growth factors
1
2
3
4
5
6
Protease secretion
BMZ break down
Capillary sprout
Cell migration
Cell proliferation
Lumen formation
BMZ reformation
Schematic processes of wound angiogenesis
Figure 7.11  Schematic
processes of wound
angiogenesis. Angiogenesis
is initiated when blood vessel
endothelial cells in the wound
edge are activated by growth
factors (activation) to produce
and release proteases that
degrade the basement
membrane zone (BMZ).

107
Chapter 7  Wound Healing
is critical for blood vessel growth and maintenance, by acting
as both scaffold support, through which endothelial cells may
migrate, and reservoir and modulator for growth factors, such
as FGF-2 and TGF-β, to mediate intercellular signals.53
As a good example, when grown in two-dimensional col-
lagen matrix gel, endothelial cells migrate, proliferate, and
express PDGF receptors, a situation that mimics the cell
population of an active, migrating, and proliferating tip of an
angiogenic sprout. In this case, deposition of basement mem-
brane proteins of laminin and collagen IV is irregular and
discontinuous. When grown in a three-dimensional system,
cell proliferation is inhibited and cells form a capillary-like
tubule structure, and lose expression of PDGF receptors.
This pattern simulates the quiescent, differentiating cell pop-
ulation away from the angiogenic sprout tip and close to the
parental vessel, where laminin and collagen IV are deposited
in a continuous pattern.47 Once again, depending on the
model system, differential effects may be observed. One
measure of the significance of the extracellular matrix is that
pharmacological agents aimed at affecting angiogenesis by
interfering with the structure and function of the extracel-
lular matrix have been studied.54
Remodeling phase
Remodeling, the third phase of wound repair, consists of the
deposition of matrix materials and their subsequent change
over time (Fig. 7.12). In fact, the remodeling occurs through
the whole process of wound repair, from the provisional
matrix of the fibrin clot that contains much fibronectin, to
the granulation tissue that is rich in type III collagen and
blood vessels, and to the mature scar that is collagen I pre-
dominant with less blood supply.
Long after the skin’s epidermal barrier is restored, events
continue to occur that are related to wound injury and repair.
The total amount of collagen increases early in repair, reach-
ing a maximum between 2 and 3 weeks after injury. Tensile
strength, a functional assessment of collagen, increases to
40% of strength prior to injury at 1 month, and may continue
to increase for up to a year. Even at its greatest, the tensile
strength of the healed wound is never greater than 80% of its
pre-injury strength.55
cells, such as fibroblasts, keratinocytes, macrophages, and
pericytes. The cooperative expression of these angiogenic
growth factors is essential in wound angiogenesis (Table 7.6).
VEGF, in particular VEGF-A, exerts its biological activity
predominantly on endothelial cells. Many different cell types,
such as keratinocytes, fibroblasts, endothelial cells, neu-
trophils, macrophages, and platelets, are able to produce
VEGF-A. It is a key mediator of angiogenesis, which per-
forms multiple functions on endothelial cells through two
specific receptors, VEGFR-1 or Flt-1 and VEGFR-2 or Flk-1/
KDR. VEGF is known also as vascular permeability factor
(VPF), due to its potent vasopermeability actions. VEGF
is a potent mitogen for endothelial cells and induces endothe-
lial cell migration and sprouting by upregulation of several
integrin receptors including αvβ3, α1β1, and α2β1.49 VEGF
acts as a survival factor for endothelial cells through induction
of the expression of the antiapoptotic protein Bcl-2.50 VEGF
is expressed at low levels in normal human skin, but its
expression is highly upregulated during wound healing. Low
oxygen tension, as occurs in tissue hypoxia during tissue
injury, is a major inducer of VEGF-A release by endothelial
cells.51
Different from VEGF, PDGF promotes the formation of
mature and non-leaking blood vessels due to its direct effect
on recruiting vascular mural cells, pericytes, and vascular
smooth muscle cells. PDGFs exist as heterodimers (PDGF-
AB) or homodimers (PDGF-AA or -BB). Knockout of the
PDGF-B chain or PDGF receptor (PDGFR)-β in mice leads
to severe vascular defects owing to lacking pericytes. PDGF
has been found to promote endothelial cell proliferation and
migration. The impact of PDGF on angiogenesis is also related
to its role in stimulating the release of and interaction with
other growth factors.52
Extracellular matrix in wound angiogenesis
Migration of endothelial cells and development of new capil-
lary tubule structure is dependent upon not only the cells and
cytokines present but also the production and organization of
extracellular matrix components, including fibronectin, col-
lagen, vitronectin, and laminin, both in granulation tissue and
in endothelial basement membrane. The extracellular matrix
Table 7.6  Growth factor regulation of endothelial cells in
wound angiogenesis
VEGF
Ang-1
FGF-1, -2
TGF-β
Proliferation
+
±
+
−
Migration
+
+
+
+
Tubule formation
+
+
+
+
Survival
+
+
±
±
EC-specific receptors
Yes
Yes
No
No
Upregulation of
integrin, ECM
+
±
+
+
Vasopermeability
+
−
±
−
Vessel wall integrity
−
+
±
+
Ang-1, angiopoietin-1; EC, endothelial cell; ECM, extracellular matrix; FGF, fibroblast
growth factor; TGF, transforming growth factor; VEGF, vascular endothelial growth
factor.
+, positive effect; −, negative effect; ±, no established effect.
Figure 7.12  The remodeling phase of wound healing. A
3-week-old partial-thickness wound in a pig shows some
fibroblasts among abundant collagen fibers in the dermis with a
new blood vessel supply (×200).

108
Part 1  Basic Surgical Concepts
providing structure, strength, and stiffness to dermal tissue.57
In normal adults, type I collagen accounts for approximately
80% of collagen, and type III collagen constitutes 10% of
collagen in the dermis. In addition to their structural scaffold
roles, collagens promote cell attachment and migration. Col-
lagen varies genetically and structurally. All collagens possess
triple helix structures but differ in the primary structure of
their polypeptide chains (α-1 and α-2). Biochemically, col-
lagen is composed of three polypeptide alpha chains. Type I
collagen is formed by two α-1 (type I) and one α-2 (type I)
chains, whereas type III collagen consists of three α-1 (type
III) chains. The three alpha chains are arranged in a triple
helix. Several helices are cross-linked to form collagen fibrils
that are subsequently entwined to form collagen fibers. The
fibers align in directions that accommodate applied stress,
thereby allowing the skin to stretch.57
Type III collagen presents in large quantities in fetal dermis
and is a minority component of normal adult collagen, but
during early wound healing it is the predominant collagen
synthesized. Type III collagen first appears after 48–72 hours
and is maximally secreted after 5–7 days. With wound
closure, a gradual turnover of collagen occurs, as type III col-
lagen undergoes degradation and type I collagen synthesis
increases. Stimulus for this conversion may be the biome-
chanical stress and strain placed across a closed wound. As in
wound repair, type III collagen is gradually replaced by type
I collagen with aging. Stress and strain also may direct realign-
ment of connective tissue fibers. Collagen fibers under tension
appear to be resistant to the action of collagenase. Random
fibers not under tension are susceptible to lysis by colla-
genase. The amount of stress on the wound is responsible for
how much scar tissue forms. For example, more scar tissue
is necessary in wounds that are on mobile extremities than
over a less mobile area such as the abdomen.
Biosynthesis of collagen
Collagen synthesis begins with transcription from DNA to
messenger RNA within the fibroblast nucleus (Fig. 7.13).
Protein translation occurs in endoplasmic reticulum. Both
magnesium and zinc trace minerals are needed for translation
to occur. Following the synthesis, polypeptide chains undergo
several enzymatic modifications, including hydroxylation of
proline and lysine which requires oxygen, ferrous iron, and
ascorbic acid (vitamin C). Following hydroxylation, the
polypeptide chains aggregate into a triple helix molecule,
procollagen, which is released from the fibroblast. Once
extracellular, the terminal propeptides are removed by pepti-
dases, and tropocollagen is formed. Tropocollagen then aligns
in a quarter-staggered array reflected as a helix. The tropocol-
lagen molecules are initially united by hydrogen bonding,
then stable covalent cross-links, both intramolecularly and
intermolecularly, are formed. This creates collagenous fibrils.
The intermolecular cross-links are likely to be responsible for
tensile strength.
The regulation of collagen synthesis is controlled at several
levels. A number of growth factors including TGF-β and FGF
have strong effects on collagen gene expression. TGF-β stim-
ulates the deposition of both type I and III collagens. Excess
TGF-β1 has been found in the dermis of chronic venous
ulcers and may play a role in fibrosis.58 Oxygen and trace
minerals also play critical roles in collagen synthesis. Collagen
deposition and remodeling are also controlled by various pro-
teinases that degrade collagens (see Fig. 7.13).
Type III collagen, as mentioned above, is the major collagen
synthesized by fibroblasts in granulation tissue. Over the
period of a year or more, the dermis returns to the stable
pre-injury phenotype, consisting largely of type I collagen. In
addition, the composition of other extracellular materials
within the wound changes as the water content and gly-
cosaminoglycan level decrease. The process of this conversion
of the dermis is accomplished through tightly controlled syn-
thesis of new collagen and lysis of old collagen through the
action of collagenases. This leads to a change in the orienta-
tion of scar tissue.
Extracellular matrix
Connective tissues are composed of three elements: cells,
fibers, and amorphous ground substance. Fibers and ground
substances collectively are referred to as extracellular matrix,
in part made up by glycosaminoglycans and proteoglycans.
Ground substance is an amorphous viscous gel secreted by
fibroblasts, which occupies the spaces between the cells and
fibers of connective tissue. It helps determine compliance, flex-
ibility, and integrity of the dermis and also provides strength,
support, and density to tissue; reduces friction between con-
nective tissue fibers during tissue stress or strain; and protects
tissue from invasion by microorganisms. Ground substance
allows tissue fluid, which contains nutrients for the cells as well
as waste products, to diffuse among cells and capillaries. It also
transports many soluble substances and stores electrolytes and
water. Substrates of ground substance are water, salts, and
glycosaminoglycans. Most glycosaminoglycans are linked cova-
lently to protein and, thus, are termed proteoglycans.
Hyaluronic acid is non-sulfated glycosaminoglycan, and is
found in the highest amounts in the first 4–5 days of wound
healing.56 Hyaluronic acid serves as a stimulus for fibroblast
proliferation and migration56 and can absorb large amounts of
water, producing tissue edema. This swelling provides addi-
tional space for migration of fibroblasts into the wound.
Hyaluronidase enzymatically degrades hyaluronic acid.
Sulfated glycosaminoglycans are proteoglycans. They
provide a stable and resilient matrix that inhibits cell migra-
tion and proliferation. The sulfated glycosaminoglycans chon-
droitin-4-sulfate and dermatan sulfate eventually replace
hyaluronic acid as the major glycosaminoglycan on days 5–7.
Saccharide chains in the chondroitin sulfate–protein complex
cross-link with collagenous fibers. There are proportional dif-
ferences in the glycosaminoglycan content of human skin,
with a progressive decrease from fetal development to matu-
rity in non-weight-bearing skin. In contrast, weight-bearing
skin, such as the plantar aspect of the foot, demonstrates
minimal change in glycosaminoglycan composition with aging.
Constituents of glycosaminoglycans, particularly chondroitin
sulfate, increase proportionally in pathologic states of altered
skin, such as Dupuytren’s contracture or hypertrophic scar-
ring. Proteoglycans regulate collagen fibrillogenesis and accel-
erate polymerization of collagen monomers. Heparan sulfate,
a proteoglycan which is absent initially after wounding, con-
trols cell division and inhibits the growth of smooth muscle
cells. The synthesis of these matrix proteins occurs con-
comitantly with the production of new collagen.
Collagen
Collagen fibers constitute approximately 80% of dry weight
of the dermis in human skin and are the principal proteins

109
Chapter 7  Wound Healing
Elastic fibers
Elastic fibers are long, thin, and highly retractile. Elastin, as
its name implies, provides elasticity and extensibility to the
dermis and assists in recovery from deformation.59 Elastin
is a highly hydrophobic structural protein making up only
2% of the total protein in the dermis.59 Elastin, lipids, and
glycoproteins bind to form microfibrils that serve as the
scaffolding or as a foundation for fiber orientation. The micro-
fibrils are infiltrated and surrounded by elastin and fuse to
form solid elastic fibers. The characteristically wavy elastic
fibers are entwined among collagenous fibers. The orienta-
tion of elastin varies from a horizontal arrangement in the
deep dermis to a more vertical arrangement closer to the
epidermis. With aging, the number of microfibrils declines;
however, the amount of the amorphous component, elastin,
increases.
Proteinases and tissue remodeling
Tissue remodeling is characterized by high levels of extracel-
lular proteolytic activities. The degradation of collagens and
Cytokines,
growth factors
Transcription
Mg2+, Zn2+
Translation
Collagen genomic DNA
Messenger RNA
O2, vitamin C
Hydroxylation,
glycosylation
Polypeptide chains
Terminal peptide
cleavage
Triple helix procollagen
O2
Cross-linking
Tropocollagen
Matrix metalloproteinases
Degradation
Collagen fibrils
Collagen fragments
Collagen synthesis and regulation in wound healing
Figure 7.13  Collagen synthesis, degradation, and regulation in
wound repair.
Table 7.7  Major human matrix metalloproteinases (MMPs)
GROUPS
MMP
TYPE
MAJOR SUBSTRATES
Collagenases
Collagenase-1
(interstitial
collagenase)
MMP-1
Fibrillar collagens (types I, II, III VII,
X), proMMP-2, -9
Collagenase-2
(neutrophil
collagenase)
MMP-8
Fibrillar collagens
Collagenase-3
MMP-13
Fibrillar collagens
Gelatinases
Gelatinase-A
MMP-2
Gelatin, collagen types IV, V,
laminin, fibronectin, proMMP-9,
-13
Gelatinase-B
MMP-9
Gelatin, collagen types IV, V
Stromelysins
Stromelysin-1
MMP-3
Non-fibrillar collagen, gelatin,
laminin, fibronectin, proMMP-1,
-9, -13
Stromelysin-2
MMP-10
Non-fibrillar collagen, gelatin,
laminin, fibronectin
Stromelysin-3
MMP-11
Weak activity with non-fibrillar
collagen, gelatin, laminin,
fibronectin
Matrilysins
Matrilysin-1
MMP-7
Non-fibrillar collagen, gelatin,
laminin, fibronectin,
proMMP-1, -9
Matrilysin-2
(endometase)
MMP-26
ProMMP-9, fibronectin, vitronectin
Membrane-type MMPs
MT1-MMP
MMP-14
ProMMP-2, -13, fibrillar collagens,
gelatin, fibrin, laminin, fibronectin
MT2-MMP
MMP-15
ProMMP-2, gelatin, laminin,
fibronectin
MT3-MMP
MMP-16
ProMMP-2, collagen III, gelatin,
laminin, fibronectin
MT4-MMP
MMP-17
Gelatin, fibronectin, fibrinogen
MT5-MMP
MMP-24
ProMMP-2, gelatin, fibronectin
MT6-MMP
MMP-25
ProMMP-2, collagen IV, gelatin,
fibrin, fibrinogin, fibronectin
Other
Macrophage MMP
(metalloelastase)
MMP-12
Elastin
other extracellular components is controlled by a group of
proteinase enzymes released from inflammatory cells, kerati-
nocytes, and fibroblasts under appropriate stimulation. The
most important proteinases are MMPs.60 MMPs can be
divided into several groups, including the collagenases, the
stromelysins, and the gelatinases (Table 7.7). The best char-
acterized subgroup of MMPs are tissue collagenases, which
cleave the triple helix of native fibrillar collagens (types I, II,
and III) in a site-specific fashion.22 Thus the actions of these
enzymes are the rate-limiting step in the turnover of the
major extracellular matrix in the dermis, type I, and type III

110
Part 1  Basic Surgical Concepts
collagens. After this cleavage, at body temperature, collagen
will be denatured (turn into gelatin) and become susceptible
to further degradation by the gelatinases.
With a few exceptions (matrilysin produced in eccrine
glands; gelatinase A stored but not produced), MMPs are not
detectable or are at very low levels in healthy resting tissue,
but are induced in physiologic (repair, remodeling, prolifera-
tion) or pathologic states (inflammation, tumor growth) in
response to cytokines, growth factors, and cell contact with
extracellular matrix. The catalytic activity of MMPs is also
controlled, in part, by a family of tissue inhibitors of metal-
loproteinases (TIMP-1, TIMP-2, TIMP-3, TIMP-4), which
specifically bind MMPs and are natural inhibitors of MMPs.
The balance between the activities of MMPs and TIMPs is
critical to the wound repair process and remodeling.60
 FACTORS AFFECTING
WOUND HEALING
Wound healing can be delayed by various systemic and local
factors. Systemic factors that may be detrimental to wound
healing include malnutrition, protein deprivation, and defi-
ciencies of vitamin A and vitamin C. Medications such as
corticosteroids, penicillamine, nicotine, NSAIDs, and antineo­
plastic agents may interfere with the wound healing at various
stages. Chronic debilitating illness, endocrine disorders, sys-
temic vascular disorders, and connective tissue disease often
have adverse effects on wound healing. In addition, advancing
age contributes to poor wound healing, possibly through
impaired expression of metalloproteinases.61
Local factors that adversely affect wound healing include
poor surgical techniques (excessive tension or excess devital-
ized tissue); vascular disorders (arteriosclerosis or venous
insufficiency); tissue ischemia; infectious processes; certain
topically applied medications; extravasation of antineoplastic
drugs; hemostatic agents such as aluminum chloride or ferric
subsulfate; foreign body reactions; or an adverse wound
microenvironment (such as the use of dry versus occlusive
dressings). Pressure, neuropathy, and chronic radiation injury
all adversely affect wound healing.
Lack of cellular oxygen impedes wound healing. Hypoxia
that occurs without neovascularization reduces energy pro-
duction. In addition, tissue oxygen tension is important in
collagen synthesis and for the tensile strength of wounds.62
Wound environments that are anoxic inhibit collagen cross-
linking as oxygen is a necessary cofactor. Some elements that
may hinder wound healing include medications such as anti-
neoplastic agents and antibiotics. Penicillin, for example,
decreases cross-linking of collagen and, therefore, impairs the
strength of the wound. Ascorbic acid (vitamin C) is also a
cofactor for the collagen cross-linking.63 Lack of available
ascorbic acid (e.g. vitamin C deficiency or scurvy) impedes
the hydroxylation and, consequently, the collagen fails to
aggregate into fibers. Vitamin A also potentiates epithelial
repair and collagen synthesis by enhancing inflammatory reac-
tions, particularly macrophage availability.64 Minerals also
may affect healing; zinc deficiency reduces the rate of epi­
thelialization and retards cellular proliferation and collagen
synthesis.65
A direct relationship exists between available macrophages
and fibroblast production. In fact, if the initial inflammatory
process is blocked by the use of systemic steroids during the
first 3 days after wounding, healing time is retarded with a
resultant loss of skin turgor. Furthermore, the mitotic activity
of fibroblasts is suppressed by steroids. The suppression of
wound healing caused by corticosteroids has been shown to
be ameliorated with administration of local and systemic
vitamin A,64 and a single injection of TGF-β.66
 OPTIMIZING OUTCOMES
In acute wounds, wound edges may be brought together by
direct closure. The apposition of the edges of the wound
decreases the distance that cells need to migrate and the size
of granulation tissue that must be produced. Aseptic surgical
technique minimizes the risk of bacterial contamination
which can prolong healing. Prevention of hematoma forma-
tion through proper hemostasis and elimination of necrotic
tissue also decreases the chance for infection. Therefore,
surgical techniques involving steel instruments – as opposed
to electrosurgery or cryosurgery – limit the risk for infection,
because less necrotic tissue is produced, and hasten healing.
Elimination of dead space through the appropriate use of
buried deep sutures also lessens the risk for hematoma and
subsequent infection. However, wounds closed too tightly
with sutures may become ischemic and subsequently necrotic
at the edges, and healing may be delayed.
The intelligent use of occlusive dressings can be most effec-
tive in speeding wound healing (Fig. 7.14). Stemming from
observations in which blisters that remained roofed healed
faster than those that had their roof removed, it was found
that wounds covered with an occlusive dressing healed up to
40% faster than those left exposed to air. There are many
ways in which occlusive dressings might function, including
enhancement of keratinocyte migration by maintaining a
moist environment, prevention of infection, establishment of
an electromagnetic current, or containment of wound fluid
and the growth factors present within it.67
The choice of occlusive dressings in acute wounds is gen­
erally dictated by the clinical setting. Film dressings are
commonly used on the face and other cosmetically impor-
tant areas. Hydrocolloid dressings are recommended in unu-
sually exudative wounds, as they absorb wound fluid as well
as provide protection in areas susceptible to trauma. Foam
dressings are also absorbent and are extremely effective in
reducing the pain associated with some wounds. It is recom-
mended that these dressings be left on the wound until the
build up of exudate causes the fluid to leak from the sides.
Because early removal of adherent occlusive dressings can
strip away newly formed epithelium, the misuse of occlusive
dressings can lead to the prolongation of healing.
Several growth factors including PDGF, EGF, and FGF
have been shown to speed the healing of acute wounds in
various settings. The use of autologous and allogeneic grafts
speeds healing of acute wounds as well. Cultured keratino­
cyte grafts, autologous bone marrow cell grafts, and gene
therapy using viral vectors are among the promising therapies
for treating cutaneous wounds.
Despite its long history, honey has also been proposed as a
novel therapy for wound healing. Although used since ancient
times for rotten and hollow ulcers, recent reports about the
properties of honey for wound healing have helped it gained
worldwide attention. The variability of its medicinal effects
may be directly affected by its source. Honey has many favo-
rable characteristics that may be helpful in treating wounds.
Secondary to its high sugar level, honey exerts an osmotic

111
Chapter 7  Wound Healing
A
B
Figure 7.14  Use of occlusive dressings on acute wounds speeds healing and improves cosmesis even when used over primarily
closed wounds. (A) Hydrocolloid dressing on the right cheek. (B) Polyurethane film dressing covering a sutured wound.
effect on the wound, attracting wound fluid. It also produces
hydrogen peroxide which functions as a barrier to bacterial
growth. In burn wounds, honey exerts anti-inflammatory
properties by decreasing oxidative stress.68 Honey also causes
an increased release of proinflammatory cytokines from mono-
cytes, such as TNF-α, IL-1β as well the anti-inflammatory
mediator IL-6.69 Allergies to honey, although rare, may be
secondary to the bee pollen.70
Clinical trials and case reports support the use of honey as
a wound therapy. Although some randomized trials have been
conducted, none have been double blinded. The Cochrane
group recently reviewed 19 randomized trials and concluded
that honey, as adjuvant therapy to compression, may reduce
healing time in mild to moderate burns (superficial and partial
thickness) but it does not significantly decrease healing of
chronic leg ulcers at 12 weeks.71 Animal studies have reported
that inflicted wounds heal faster after honey treatment com-
pared to control wounds.71 Due to its valuable properties, it
is evident that honey may be used in the clinical setting to
treat wounds with some success. However, further research
(double-blind randomized trials) is needed to assess the
effect of honey as adjuvant therapy to compression in the
treatment of cutaneous wounds.
 PITFALLS AND THEIR MANAGEMENT
Pitfalls and their management
 Failure to heal in an orderly and timely fashion leads to chronic
wounds, which can happen in any stage during the wound
healing process.
 Impaired cell migration, delayed re-epithelialization, reduced
granulation tissue formation (collagen production and
angiogenesis), abnormal extracellular matrix deposition,
and deregulated activities of growth factors/cytokines and
proteinases are among the hallmarks of chronic or non-healing
wounds. Understanding the pathogenesis and mechanisms
will guide our practice and improve the outcomes for patients.
 Chronic wounds are associated with wound location, depth
and shape, cause of the wound, as well as age and physical
condition of the patient. Improving the systemic and local
condition of the patient will stimulate cell function and
accelerate wound healing. The apposition of the edges of the
wound decreases the distance that cells need to migrate and
the size of granulation tissue that must be produced.
 Persistent infection prolongs the wound healing process.
Aseptic surgical technique and elimination of necrotic tissue
by using steel instruments and appropriate debridement of
non-viable tissue minimize the risk of infection. Prevention
of hematoma formation through proper hemostasis also
decreases the chance of infection.
 Lack of cellular oxygen reduces energy production and
impairs collagen synthesis and tensile strength of wounds.
Appropriate debridement to eliminate necrotic tissue,
reduction of local pressure, and correction of underlying
vascular disorders to improve tissue ischemia and hypoxia
and increase wound perfusion will stimulate wound healing.
 Imbalanced regulation of growth factors, prolonged
inflammation, and abnormal activities of proteinases that
impede cellular function and delay wound healing are
common in chronic wounds. Treatments with growth factor
application, anti-inflammatory agents and proteinase inhibitors
are showing promise. Gene and stem cell therapy have the
potential to benefit patients with chronic wounds in the near
future.
 SUMMARY
Wound healing is a complex process, and an understanding
of its underlying mechanisms is vital for practitioners of a
discipline in which wound creation and repair are fundamen-
tal. Advances in immunology and molecular biology have
greatly increased our knowledge of the events that take place
in the overlapping inflammation, proliferation, and remode-
ling phases of healing.
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115
8
Wound Healing and its Impact on
Dressings and Postoperative Care
Katherine L Brown MD MPH, May Leveriza-Oh MD, and Tania J Phillips MD FRCP FRCPC
Summary box
 Dressings cover the wound, absorb drainage, apply pressure,
and provide a moist environment.
 Dressings should be selected to keep the wound moist, but
not too wet nor too dry.
 Moist wound healing enhances epithelial migration, stimulates
angiogenesis, helps in retention of growth factors, facilitates
autolytic debridement and fibrinolysis, protects against
exogenous organisms, and maintains voltage gradients.
 Healing of acute wounds is accelerated in a moist
environment. In chronic wounds, moist dressings can relieve
pain, promote autolytic debridement, and decrease the
frequency of dressing changes.
 Various types of occlusive dressings, as well as skin grafts and
skin substitutes, are currently available as dressing options.
 INTRODUCTION
Dressings
A dressing is defined as a covering applied to a wound. This
simple definition belies the importance of dressings in wound
healing and the complexities of choosing the correct dressing
for a particular indication. At present, there is a myriad of
categories, subcategories, and types of dressings with different
functions, structural compositions, and physical and chemical
characteristics, some common and some very unique.
Historical perspective
Even the ancient Egyptians had a keen interest in wound
healing. They formulated home-made concoctions of lint,
grease, and honey as topical therapy for wounds, or soaked
strips of bandage material in oils and resins to use as dressings.
They even used raw, fresh meat to cover wounds during the
first day of healing.1
In 1867, the first antiseptic dressings were introduced by
Lister who soaked lint and gauze in phenol and then applied
them to wounds. In general, before the 20th century, it was
believed that wounds healed best when left open (to allow
them to breathe) and dry (to keep them ‘germ free’) as
advocated by Pasteur.2 This view began to change in 1958
when Odland observed that a blister healed faster when left
unbroken.3 Winter’s landmark study on swine in 1962 showed
that superficial wounds kept moist by covering them with a
film healed twice as fast as those exposed to the air.4 Hinman
and Maibach repeated Winter’s study in humans and found
a similar increase in epithelialization rate for occluded wounds.5
These studies revolutionized the approach to wound care by
demonstrating the importance of moist wound healing. A
multitude of sophisticated occlusive dressings have been for-
mulated, studied, and become commercially available.
 FUNCTIONS OF DRESSINGS
Dressings serve several basic functions (Table 8.1).
Acute wounds vs chronic wounds
Acute wounds
Acute wounds are wounds with no underlying healing defect
that heal in an orderly and timely fashion, passing through
well-defined phases of an inflammatory response, granulation
tissue formation, and remodeling.6 In acute wounds, the func-
tion of dressings in maintaining a moist environment is criti-
cal in facilitating healing. In fact, acute wounds have been
shown to heal 40% faster in a moist environment than when
air exposed.7 The specific effects of a moist environment and
occlusion on wound healing are well-established in this wound
type.
Enhancement of epithelial migration
Rovee established that in moist wound healing of acute
wounds, wound resurfacing occurs more rapidly because
keratinocytes begin to migrate sooner, and not because of a
higher rate of mitosis.8
Stimulation of angiogenesis
Moist wound healing promotes a greater rate of vasculariza-
tion. The accumulation of angiogenesis-stimulating factors,
such as tumor necrosis factor and heparin, under the dressing
partly accounts for this.3 In addition, because hypoxia often
stimulates angiogenesis, the dressing establishes a steep
oxygen gradient, which stimulates capillary growth toward
the more hypoxic center.9
Retention of growth factors
Acute wound fluid beneath occlusive dressings stimulates
proliferation of fibroblasts, keratinocytes, and endothelial

116
Part 1  Basic Surgical Concepts
degradation products of vitronectin and fibronectin, which
inhibit keratinocyte migration.16 Further, when chronic
wound fluid is added to cultures of keratinocytes, fibroblasts,
or endothelial cells, it fails to stimulate DNA synthesis
directly, contrasting the DNA-synthesizing ability of acute
wound fluid.17,18 Another important biochemical difference
in chronic wounds is that they exhibit considerably higher
protease activity than acute wounds.19
A study on occluded versus non-occluded venous ulcers
showed that the difference in the number of wounds healed
at the end of 12 weeks was not statistically significant;
however, the rate of healing was more rapid in the occlusive
dressing group.20 For patients with chronic wounds, moisture-
retentive dressings do offer the advantages of pain relief,
painless wound debridement, containment of wound exu-
dates, reduction in the incidence of complications, and
improved quality of life.3
 TYPES OF DRESSINGS
Dressings may be classified based on their clinical functions as
well as their physical appearance and composition (Box 8.1).
Non-adherent fabrics
Non-adherent fabrics are derived from a combination of
fine mesh gauze and tulle gras, commonly impregnated
with chemicals to potentiate the dressing’s occlusive or non-
adherent characteristics, its ability to facilitate healing, or its
antimicrobial properties.21 They may be subdivided into
hydrophobic and hydrophilic types. Hydrophobic fabrics
cells.10 The growth factors involved in this are platelet-derived
growth factor (PDGF), basic fibroblast growth factor (bFGF),
transforming growth factor (TGF)-β, epidermal growth
factor (EGF), and interleukin (IL)-1.3 PDGF is a powerful
mitogenic, chemotactic, and angiogenic factor. EGF is impor-
tant in epidermal cell growth, survival, and differentiation.
TGF-β induces angiogenesis, fibrosis, differentiation, and
proliferation.11
Facilitation of autolytic debridement
Retained water and proteolytic enzymes interact and achieve
painless wound debridement of necrotic tissue.
Protection against exogenous organisms
Although the bacterial count is higher in occlusive dressings
than non-occlusive dressings, this does not predispose to
infection.12 Overall infection rate is 2.6% for occlusive dress-
ings versus 7.1% for non-occlusive dressings.13 As well as
acting as a physical barrier, occlusive dressings allow neu-
trophils to infiltrate and function more actively. Occlusion is
also associated with the presence of higher levels of lysozymes
and globulins.3 Lastly, occlusion maintains a mildly acidic pH,
which is inhibitory to the growth of some bacteria, especially
Pseudomonas and Staphylococcus spp.14
Maintenance of voltage gradients
Moist wound healing helps in the maintenance of an electric
field, which is essential in keratinocyte migration. Also, an
increase in the synthesis of growth factors by human fibro­
blasts has been demonstrated during in-vitro electrical
stimulation.7
Chronic wounds
In chronic wounds, the normal process of healing has been
disrupted at one or more points in the phases of hemostasis,
inflammation, proliferation, and remodeling.6 In this wound
type, there is usually an underlying pathology, which pro-
duces a delay in the healing process.15 The effect of occlusion
in these wound types is not as well established because there
is a dearth of randomized controlled trials for chronic wounds.
In contrast to acute wound fluid, chronic wound fluid was
found to be inhibitory to epithelialization, and to contain
Table 8.1  Basic functions of wound dressings
FUNCTION
BENEFIT
Cover wound
Protection from trauma and
contamination from bacteria and
foreign materials
Minimize fluid and heat loss
Absorb wound drainage
Keep wound moist, but not wet
Minimize maceration
Compression
Increase hemostasis
Minimize edema and hematoma
formation
Prevent dehiscence
Provide moist environment
Facilitate healing of acute wounds
Reduce pain in chronic wounds
Box 8.1  Types of dressings
Non-adherent fabrics
Absorptive
Gauze
Foams
Alginates
Occlusive/moisture-retentive dressings
Non-biologic – traditional
Foams
Films
Hydrocolloids
Hydrogels
Alginates
Non-biologic – new
Hydrofiber dressings
Collagen dressings
Hyaluronic acid dressings
Biologic – grafts
Split-thickness skin grafts (STSGs)
Full-thickness skin grafts (FTSGs)
Composite grafts
Biologic/biosynthetic – skin substitutes
Cultured epidermal grafts
Dermal replacements
Composite skin substitutes
Antimicrobial dressings

117
Chapter 8  Wound Healing and its Impact on Dressings and Postoperative Care
is desired.21 Foam dressings and alginates are classified as both
absorptive and occlusive/moisture-retentive dressings.
Occlusive/moisture retentive
A moist wound environment is provided by a dressing that
transmits moisture vapor at a rate lower than that at which
a wound loses moisture. This is measured as moisture vapor
transmission rate (MVTR) through the dressing when it is
left in place for 24 hours. MVTR of intact normal skin is
about 200 g/m2/day, while that of wounded skin is 40 times
higher. Dressings with an MVTR of less than 35 g/m2/hour
are defined as occlusive or moisture retentive.22
Non-biologic occlusive dressings
Traditional occlusive dressings are classified into five basic
categories (Table 8.2).
Foam dressings
Foam dressings are composed of hydrophobic, polyurethane
foam sheets and are characteristically soft, highly absorbent,
and opaque (Fig. 8.1). They may be adhesive or non-adhesive,
have greater occlusive capability, but hinder fluid drainage
through them. These include Vaseline gauze (The Kendall
Co, Mansfield, MA), Xeroform (The Kendall Co), and Telfa
(The Kendall Co). In contrast, the hydrophilic dressings are
less occlusive, but have the ability to readily facilitate the
drainage of fluids and exudates into overlying dressings.
Examples are Xeroflo (The Kendall Co), Mepitel (Molnlycke
Health Care, Gotenberg, Sweden), Adaptic (Johnson &
Johnson Medical, Arlington, TX), and N-Terface (Winfield
Laboratories, Dallas, TX).
Absorptive dressings
Gauze is one of the most commonly used absorptive dress-
ings. It is excellent at drawing fluids and exudates away from
the wound surface, but loses its efficacy when saturated. It
is usually used to cover non-occlusive, non-adhering fabric
dressing materials and absorb discharge, which drains through
them. It may also be used over occlusive dressings as a sec-
ondary dressing to fix them in place. Wide mesh gauze is
usually not placed in direct contact with wounds because it
adheres to the surface of the wound, resulting in pain on
removal. The only exception is when mechanical debridement
Table 8.2  Types and characteristics of occlusive/moisture-retentive wound dressings
TYPE
ADVANTAGES
DISADVANTAGES
INDICATIONS
EXAMPLES
Foams
Absorbent, conform to
body contours
Opaque, require
secondary dressing
Partial-thickness wounds,
moderately to heavily exudative
wounds, pressure relief
Allevyn
Flexzan
Hydrasorb
Lyofoam
Vigifoam
Films
Transparent, create
bacterial barrier, adhesive
without secondary
dressing
May adhere to wounds,
can cause fluid
collection
Donor sites, superficial burns and
ulcers, partial-thickness wounds
with minimal exudates
Tegaderm
Bioclusive
Blisterfilm
Omniderm
Transeal
Hydrocolloids
(+) autolytic debridement,
enhance angiogenesis,
absorbent, create
bacterial and physical
barrier
Opaque, gel has
unpleasant smell,
expensive
Partial- or full-thickness wounds,
mildly to moderately exudative
wounds, pressure ulcers, venous
ulcers, donor sites, acute
surgical wounds
Duoderm
NuDerm
Comfeel
Cutinova
Replicare
Hydrogels
Semitransparent,
soothing, do not adhere
to wounds, hydrating
Require secondary
dressing, frequent
dressing changes
Painful wounds, partial-thickness
wounds, wounds after laser,
dermabrasion or chemical peel,
donor sites
Vigilon
Tegagel
Curagel
Clearsite
Curafil
Elasto-Gel
Solosite wound gel
2nd Skin
Alginates
Highly absorbent,
hemostatic, do not adhere
to wounds, fewer dressing
changes
Require secondary
dressing, gel has
unpleasant smell
Highly exudative wounds, partial-
or full-thickness wounds, after
surgery
Algiderm
Algisite
Algisorb
Kaltostat
Curasorb
Polymen
SeaSorb
Sorbsan

118
Part 1  Basic Surgical Concepts
Figure 8.1  A foam dressing on a lesion on the medial aspect of
the lower leg.
Figure 8.2  A film dressing covering an ulcer on the medial
malleolus.
and thick or thin. They have the unique ability of being able
to expand to conform to the size and shape of the wound.
The primary advantages of foam dressings are that they can
be used on wounds with unusual configurations and are highly
absorptive. Other advantages are that they do not stick to the
wound surface and can thus be easily removed for cleaning,
and that they may be utilized for pressure relief, such as in
cushioning bony prominences.23 Foam dressings are used on
moderately to heavily exudative wounds as well as infected
wounds and may be used as secondary dressings when addi-
tional absorption is needed. Because of their dehydrating
capabilities, they are not used on dry wounds.
Because they are opaque, foam dressings allow limited
inspection. Their high absorptive properties may also be a
disadvantage in that they may dry the wound bed. Foam
dressings often require a secondary dressing. Some commer-
cially available foam dressings are Allevyn (Smith & Nephew
United, Largo, FL), Biopatch (Johnson & Johnson Medical),
Curafoam (The Kendall Co), Flexzan (Dow B Hickam, Inc,
Sugarland, TX), Hydrasorb (Tyco Health Care/The Kendall
Co, Mansfield, MA), Lyofoam (ConvaTec, Princeton, NJ),
Mepilex (Molnlycke Health Care), Polymen (Ferris Corp,
Burr Ridge, IL), and Vigifoam (Bard, Murray Hill, NJ).
Technique:  During application, a 2-cm margin is left
around the wound edges. The non-adhesive foam dressing is
kept in place with tape or gauze rolled around it. Foam dress-
ings are relatively easy to remove. If the dressing dries up, it
is soaked with saline solution before removal to prevent
damage to the epithelium.23
Film dressings
Films are generally made of clear polyurethane membranes
with acrylic adhesive on one side for adherence. They are
thin, transparent sheets that are permeable to oxygen, carbon
dioxide, and water, and impermeable to fluids and bacteria.
The degree of permeability is determined by the product,
such as Tegaderm (3M Healthcare, St Paul, MN), Bioclusive
(Johnson & Johnson Medical), Blisterfilm (The Kendall Co),
Omniderm (Omikron Scientific Ltd, Renovot, Israel),
Polyskin II (Kendall Healthcare, Mansfield, MA), Proclude
(ConvaTec), Mefilm (Molnlycke Health Care), Carrafilm
(Carrington Lab, Irving, TX), and Transeal (DeRoyal, Powell,
TN).
Because this dressing is relatively transparent, it has the
distinct advantage of permitting easy visualization of the
underlying wound for observation and monitoring purposes
(Fig. 8.2). In addition, because they are thin and self-adhe-
sive, they generally do not require a secondary dressing,
minimizing their interference with the patient’s normal func-
tion. This type of dressing can also stay in place for several
days and decreases pain.
The biggest disadvantage of film dressings is that because
they are non-absorptive, there is a tendency for fluid to
collect under them. When the fluid eventually leaks, this
breaks the antibacterial seal created by the dressing’s adhesive
and necessitates frequent dressing changes.21 It also requires
intact periwound skin for dressing adherence because there
is the possibility that it could adhere to the wound itself, and
thereby strip away newly formed epidermis on removal.
Minor disadvantages of films are their tendency to wrinkle
easily, making them hard to handle, and occasional contact
dermatitis from adhesives.
Film dressings are ideally used for mildly exuding wounds,
including lacerations, superficial surgical and burn wounds,
donor sites, superficial ulcers, and arterial and venous cath-
eter sites. They may also be used as secondary dressings over
alginates, foams, and hydrogels. They are not to be used as
primary dressings of moderately to heavily exuding or infected
wounds, sinus tracts, or cavities. They are also not recom-
mended for patients with fragile skin, such as the elderly.
Technique:  The area surrounding the wound should be
clean and dry. The recommended margin is 3–4 cm around
the wound.23 The best way to apply the film is to gradually
peel off the backing while simultaneously pressing the dress-
ing onto the skin. The uninitiated should be forewarned that
the film sticks to latex gloves and to itself very easily.

119
Chapter 8  Wound Healing and its Impact on Dressings and Postoperative Care
Indications for the use of hydrocolloids are abrasions, post-
operative wounds, pressure and venous ulcers, burn wounds,
and donor sites. They are not to be used in third-degree burns
or actively infected ulcers.
Technique:  The periwound area is cleansed and dried for
maximum adherence. Ideally, the dressing extends 2  cm
beyond the wound margins. Using scissors to round the
corners will minimize rolling up of the hydrocolloid dressing.
The backing is peeled off carefully while pressing the pad
gently on the skin. The warmth of the hand can be used to
help seal the dressing. At the start of treatment, the dressing
usually needs to be changed frequently, sometimes daily.
However, as the amount of material draining from the wound
decreases, the frequency of changing the dressing is likewise
decreased, eventually becoming every 3–7 days. Zinc oxide
applied to the wound margins can minimize the maceration,
irritation, or inflammatory responses of the periwound area.23
For removal, hydrocolloids are peeled off the skin with
minimal trauma. Remnants of the hydrocolloid left sticking
on the intact skin are removed easily using mineral oil. The
wound bed is subsequently cleaned with saline to make sure
there is no hydrocolloid left on the bed. Patients and caregiv-
ers should be advised that removing the dressing prematurely
can injure newly formed epidermis.
Hydrogels
Hydrogel dressings consist of a hydrophilic polymer, usually
a starch polymer such as polyethylene oxide, and up to 80%
water.21 They are available as gels, sheets, or impregnated
gauze, which are absorbent, non-adherent, semitransparent,
and semipermeable to water vapor and gases. Their high
water content gives them the ability to rehydrate dry wounds,
giving them a soothing and cooling effect.25 Hydrogels also
act on necrotic tissue by autolytic debridement, thereby
facilitating granulation tissue formation.23
Trade names are Vigilon (CR Bard, Murray Hill, NJ),
Nu-gel (Johnson & Johnson Medical), Tegagel (3M), Flex-
iGel (Smith & Nephew), Curagel (The Kendall Co), Flex-
derm (Dow B Hickam, Inc), Clearsite (Conmed Corp, Utica,
NY), Curafil (The Kendall Co), Curasol (The Kendall Co),
Carrasyn (Carrington Laboratories), Elasto-Gel (SW Tech-
nologies, North Kansas City, MO), Hypergel (Scott Health
Care, Philadelphia, PA), Normgel (SCA Hygiene Products,
Eddy Stone, PA), Solosite wound gel (Smith & Nephew),
2nd Skin (Spenco Medical, Ltd, Waco, TX), and Transigel
(Smith & Nephew).
Because they are semitransparent, hydrogels allow some
degree of wound inspection. Refrigeration augments their
cooling and soothing effects on the wound. As hydrogels are
non-adherent, they require a secondary dressing or tape to
hold them in place. They also have very little absorptive ability.
Wounds that respond best to hydrogels are dry and mildly
exuding wounds, after-procedure wounds such as dermabra-
sion and chemical peeling wounds, superficial burns, and blis-
ters and ulcers with a necrotic bed. Heavily exuding wounds
should not be dressed with hydrogels.
Technique:  The hydrogel sheet must be cut to the appro-
priate size in relation to the size and configuration of the
wound. These sheets are manufactured with a protective
covering on both sides. The covering on one side of the sheet
is removed to expose the hydrogel (Fig. 8.4), and the exposed
During removal, film dressings should be peeled off with
care. Stretching the film with light pressure disrupts the
continuity of the adhesive and makes it easier to remove. The
accumulation of a pocket of fluid within the dressing signals
that it is time for a dressing change.23
Hydrocolloids
Hydrocolloid dressings are a family of dressings containing a
hydrocolloid matrix consisting of materials such as gelatin,
pectin, and carboxymethylcellulose (Fig. 8.3). They are
opaque, absorbent, adhesive, waterproof wafers that contain
hydrophilic colloidal particles in a hydrophobic polymer.
Upon contact with wound exudates, the hydrophilic particles
absorb water, swell, and liquefy to form a gel, which enhances
autolytic debridement. Hydrocolloids are impermeable to
water vapor, oxygen, and carbon dioxide. They come in prep-
arations of varying thickness and are even available as powders
and pastes.
Examples of hydrocolloid dressings are Duoderm (Con-
vaTec), NuDerm (Johnson & Johnson Medical, Arlington,
TX), Comfeel (Coloplast Sween, Inc, Marietta, GA), Hydro-
col (Dow B Hickam, Inc), Cutinova (Smith & Nephew),
Tegasorb (3M, New York, NY), Replicare (Smith & Nephew
United), and Restore (Hollister, Libertyville, IL).
The advantage of using hydrocolloids is that autolytic de­
bridement enhances angiogenesis, granulation tissue forma-
tion, and healing.23 Hydrocolloid dressings are slightly bulkier
than other dressings such as films, providing more physical
protection for the wound. In practical terms, their imperme-
ability to water allows patients to bathe and swim freely.
One of the disadvantages of hydrocolloids is that due to
their debriding abilities, they may initially cause the size of
the wound to increase. Occasionally the skin surrounding the
wound macerates.24 Hydrocolloids are also associated with
the formation of a yellow gel, which has a characteristic
unpleasant odor and can be easily confused with infection of
the wound.
Figure 8.3  A hydrocolloid dressing covering a lesion on the
anterior aspect of the ankle.

120
Part 1  Basic Surgical Concepts
rounding skin is dried. The alginate is applied in a dry condi-
tion to the wound surface extending at least 2 mm beyond
the wound edges.23 When ribbons or ropes are used, they are
placed in a loose spiral fashion into the wound, doubling back
on themselves until the entire wound is covered. A secondary
dressing is placed over the dressing.
For removal, the gel formed by the alginate is simply lifted
carefully from the wound surface. Irrigation with saline solu-
tion and the use of forceps after moistening may remove any
components of the dressing left behind after removal.
side is then placed on the wound. Tape is then used to secure
it. The gel form of this type of dressing can be squeezed into
the wound cavity. A secondary dressing such as film, foam,
or hydrocolloid is used as a protective cover.
To prevent the hydrogel from adhering to the wound bed,
the sheets should not be allowed to dry out. They are usually
changed every 3 days for necrotic wounds, and every 7 days
for granulating wounds.23 They must be removed very gently
to avoid damage to the granulation tissue. The gel form is
irrigated with saline to facilitate removal.
Alginates
Alginate dressings consist of the soft non-woven fibers of a
cellulose-like polysaccharide derived from the calcium salts
of seaweed.26 They are biodegradable, hydro­philic, non-
adherent, and highly absorbent. When the insoluble calcium
alginate of this type of dressing comes into contact with
wound exudate, a soluble sodium salt is produced, and a
hydrophilic gel is formed as a byproduct in the process. Algi-
nates are commercially available as pads (Fig. 8.5), ropes, or
ribbons.
Examples are Algiderm (Bard), Algisite (Smith & Nephew),
Algisorb (Calgon-Vestal, St Louis, MS), Algosteril (Johnson
& Johnson Medical), Kaltostat (ConvaTec), Curasorb (The
Kendall Co), Carasorb (Carrington Lab), Dermacea (Sher-
wood Medical Co, St Louis, MO), Melgisorb (Molnlycke
Health Care), SeaSorb (Coloplast, Holtedam, Denmark),
Kalginate (DeRoyal), and Sorbsan (Dow B Hickam, Inc).
Because of their exceptional absorptive qualities, alginates
are primarily used for heavily exuding wounds.21 They can
also be utilized for deep wounds, sinuses, and cavities. The
rope and ribbon forms can be used for packing narrow wounds
and sinuses. They are to be avoided in dry or mildly exuding
wounds because they may excessively dry these wounds.
Their use in deep, narrow sinuses is also contraindicated
because removal may be difficult.27
As well as their absorptive ability, alginates have hemostatic
properties. This sometimes lessens the number of dressing
changes needed. Their disadvantages are that the gel formed
may be foul smelling or misleadingly appear purulent, and
because they are non-adherent, a secondary dressing is needed.
Technique:  Before the application of an alginate dressing,
the wound is cleaned with saline and left wet while the sur-
Figure 8.5  An alginate dressing on a lesion on the medial
malleolus.
Figure 8.6  A hydrofiber dressing on a moderately exudative
lesion on the lateral malleolus.
Figure 8.4  A hydrogel dressing being peeled carefully from its
backing.

121
Chapter 8  Wound Healing and its Impact on Dressings and Postoperative Care
Hyaluronic acid dressings
Hyaluronic acid dressings are biodegradable, absorbent
biopolymers that form a hydrophilic gel with the serum or
wound exudates. Topical application accelerates granulation
tissue formation and re-epithelialization. An example is
Hyalofil (ConvaTec).
Biologic dressings: grafts
Grafts are pieces of skin that have been separated completely
from their local blood supply and transferred to other loca-
tions so that they are wholly dependent on the development
of a new blood supply from the recipient bed.28 They may be
classified according to the source of donor tissue. A xenograft
is a graft transplanted between different species. In humans,
the most commonly used xenografts are derived from pig
skin.21 They are temporary dressings that are eventually
rejected and replaced by host epithelium.29
Autografts are grafts taken from the patient; meaning skin
in one area of a patient is harvested and transplanted to
another area.
Allografts are taken from donors of the same species. This
could mean cadaveric skin or skin from other living humans.
Technological advances have resulted in cultured dermal and
epidermal components in vitro, which have been used indi-
vidually or combined as biologic wound dressings, commonly
referred to as skin substitutes.
Skin grafts can be categorized based on their thickness or
composition. Partial- or split-thickness skin grafts (STSGs)
contain epidermis and a portion of the dermis while full-
thickness skin grafts (FTSGs) contain the entire thickness of
the epidermis, dermis, and may include various amounts of
subcutaneous tissue.30 Table 8.3 compares STSGs and
FTSGs.
Hydrofibers
Hydrofiber dressings are composed of soft, absorbent car-
boxymethyl cellulose fibers that interact with wound exu-
dates to form a soft gel. They are available as non-woven pads
or ribbons under the trade name Aquacel.
They are especially useful for moderately to heavily exuding
wounds (Fig. 8.6) and wounds that are prone to bleeding
because they are almost three times more absorbent than
alginates.23 They are indicated for abrasions, lacerations, exci-
sional wounds, pressure or leg ulcers, burns, and graft donor
sites. Hydrofiber ribbons may also be used for packing wound
cavities.
Technique:  Hydrofibers are applied to the wound site and
reinforced with a secondary dressing. In removing the dress-
ing, it may be necessary to irrigate the wound with saline
solution to remove the gel and prevent stripping of the gran-
ulating tissue.
Collagen dressings
Collagen dressings are derived from cow hide and consist of
type 1 bovine collagen. They are available as particles, sheets,
or gels, and are used for moderately exudative wounds and
recalcitrant ulcers.23 They act by providing a collagen matrix
for cellular migration. Examples are Fibracol (Johnson &
Johnson, Skillman, NJ), Medifil (Biocore Medical Technolo-
gies, Inc, Silver Spring, MD), and Nugel collagen wound gel
(Johnson & Johnson Medical). They have been known to
occasionally cause irritation or initially increase drainage.
Technique:  First clean the wound, then apply the collagen
dressing directly, followed by a secondary dressing. Carefully
remove the secondary dressing, then moisten with saline
solution.
Table 8.3  Split-thickness versus full-thickness skin grafts
SPLIT-THICKNESS SKIN GRAFTS
FULL-THICKNESS SKIN GRAFTS
Composition
Epidermis plus part of the dermis
Epidermis plus dermis plus various amounts of fat
Survival
Greater, because requires less revascularization
Less chance of survival
Resistance to trauma
Less resistant
More resistant
Cosmetic appearance
Poor cosmetic appearance owing to poor color and texture
match; partially prevents contraction
Superior cosmetic appearance; it is thicker,
preventing wound contraction or distortion
Indications
Placed initially to monitor for recurrence of skin cancer. May
be placed permanently in some locations with a high
chance of recurrence
When a flap is not feasible due to limited vascular supply,
then a STSG may be viable in areas with limited vascular
supply
When aesthetic outcome is essential (e.g. facial
defects)
Common uses
Chronic lower leg ulcers (e.g. venous, irradiated tissues;
exposed periosteum, cartilage, or tendon)
Surgically induced large defects (e.g. for birthmarks, nevi)
Facial defects – nasal tip, dorsum, ala or sidewall,
lower eyelid, ear
Donor site tissue
Anteromedial thigh
Others – buttock, abdomen, inner or outer aspect of arm,
inner forearm
Nearby site, with similar color or texture to skin
surrounding the defect (e.g. preauricular and
postauricular, supraclavicular, clavicular, neck,
nasolabial folds, inner arms)
Disadvantages
Poor cosmetic appearance (e.g. color and texture mismatch,
greater chance of distortion or contraction)
Greater risk of failure
If not closed primarily, the donor wound site has
a prolonged healing time and a greater risk of
distortion and hypertrophic scar formation
Adapted from Valencia IC, Falabella AF, Eaglestein WH. Skin grafting. Dermatol Clin 2000;18:521–532.28

122
Part 1  Basic Surgical Concepts
was designed in 1975 by Rheinwald and Green. By serial
subculture of human keratinocytes, they grew large epider-
mal sheets from a small sample in vitro.32
Epidermal cultured autografts are sutured or stapled onto
the recipient’s tissues to prevent separation from the wound
bed. At least two other layers of dressings are needed to
protect the autograft. A secondary dressing, usually mesh
gauze, is used to cover the graft and is left in place for 7–10
days. Another more outer dressing is then placed over the
secondary dressing.33 This functions to absorb wound exu-
dates, and is changed every day or every other day depending
on the amount of drainage from the wound. Cultured kerat-
inocyte autografts were initially used in the 1980s to treat
severely burned patients.34 At present, they are utilized for
burns, chronic leg ulcers, epidermolysis bullosa wounds, scar
revision, wounds resulting from excision of giant congenital
nevi, and vitiligo.35
One of the major disadvantages of cultured autografts is
that they require a 2–3-week period for growth of an ade-
quate amount of epithelial sheets. Other disadvantages
include the difficulty of handling fragile keratinocyte sheets,
the lack of a dermal component, and the short-term stability
of the graft.
Composite grafts are composed of at least two different
types of tissues, most frequently skin and cartilage. They are
very useful for the repair of full-thickness nasal alar rim
defects (see also Chapter 19).
Biologic/biosynthetic dressings: skin substitutes
The quest for developing a widely available product with
structural and functional properties as close as possible to
those of natural skin continues. Skin substitutes act as a scaf-
fold for tissue regeneration in vivo, or as tissue replacement,
providing matrix material and cells when grown in vitro. They
can be temporary or permanent; synthetic, biosynthetic, or
biologic.
Based on their components, skin substitutes can be classi-
fied into three categories – epidermal grafts, dermal replace-
ments, or composite grafts consisting of both epidermal and
dermal components (Table 8.4).
Cultured epidermal grafts
Cultured epidermal autografts:  Cultured epidermal
autografts are grown from the patient’s own skin. The tech-
nique currently in use for the culturing of epidermal grafts
Table 8.4  Advantages, disadvantages, and indications for skin substitutes
TYPE
ADVANTAGES
DISADVANTAGES
INDICATIONS
Epidermal
Cultured keratinocyte autograft
Coverage of large area from
small skin biopsy
Permanent wound coverage
Acceptable cosmetic results
3 weeks for graft cultivation
Graft fragility, blistering
Susceptibility to infection
Unstable without dermal
substitute
Expensive
Burns
Leg ulcers
Cultured keratinocyte allografts
(Epicel; Genzyme Tissue Repair
Co, Cambridge, MA)
No biopsy necessary
Immediate availability
Cryopreservation and banking
Possibility of disease
transmission
Expensive
Not commercially available
Acute and chronic wounds
Dermal
Human cryopreserved allograft
skin
Immediate availability
Good base for cultured
keratinocytes (when
de-epidermized)
Temporary coverage
Possible disease transmission
Burns
Human allograft skin treated
by decellularization, matrix
stabilization, and freeze drying
(Alloderm)
Immediate availability
Immunologically inert
Allows ultrathin STSG
Allograft procurement
Virus screening
Surgical wounds
Bovine collagen and chondroitin
sulfate over silastic (Integra)
Immediate availability
Allows ultrathin STSG
Less scarring than STSG alone
Susceptibility to infection
Complete wound excision before
application
Excised burn wounds
Fibroblasts in bioabsorbable
mesh (Dermagraft)
Immediate availability
Expensive
Multiple applications
Burns (Transcyte)
Diabetic foot ulcers (Dermagraft)
Composite
Bilayered skin equivalent:
bovine collagen, fibroblasts, and
keratinocytes (Apligraf)
Immediate availability
Easy handling
Does not require subsequent
skin grafting
Limited viability
Expensive
Venous ulcers
Diabetic ulcers
Adapted from Bello YM, Phillips TJ. Recent advances in wound healing. JAMA 2000;283:716–718.31 Copyright © (2002) American Medical Association. All rights reserved.

123
Chapter 8  Wound Healing and its Impact on Dressings and Postoperative Care
fabric containing porcine collagen peptides as the biological
component.35 When used on donor sites, Biobrane proved
superior to Scarlet Red (The Kendall Co) in pain relief,
healing time, and absorption of exudates.44
Another biosynthetic porcine-derived dermal substitute is
EZ Derm in which the porcine collagen is chemically cross-
linked using an aldehyde. There are perforated and non-
perforated types and it comes attached to a gauze liner, which
is detached before grafting. It is used for temporary coverage
of partial-thickness skin loss injuries, including burns and
ulcers. It has the advantages of immediate availability, a long
shelf life, and the absence of human communicable disease.34
Limited clinical studies have been carried out.
Oasis is a biologic dressing derived from porcine small intes-
tinal submucosa that has been processed to exclude the serosa,
smooth muscle, and mucosa layers, producing a collagenous,
acellular matrix rich in cytokines and cell adhesion molecules.
Because it is packaged dry and then rehydrated, Oasis has the
advantage of a longer shelf life than other porcine hetero-
grafts. It is also relatively easy to apply and reapply.35 One of
its primary disadvantages is that because it is very thin, it is
easily traumatized, so requiring a secondary dressing for addi-
tional protection and to prevent it from drying up.
Integra (Integra LifeSciences Corp, Plainsboro, NJ) is a
biosynthetic, temporary, bilaminated skin substitute consist-
ing of a matrix of bovine collagen and chondroitin-6-sulfate
covered by a synthetic silicone elastomer (Silastic). It is
approved by the Food and Drug Administration (FDA) for
the treatment of burns. In a 2-year study, Integra was suc-
cessfully used in the reconstruction of burn scars of the upper
extremities, and was shown to be a good alternative for
patients with severe burns in whom there is insufficient skin
available to use as a donor for a FTSG.45 The dermal compo-
nent is designed to be slowly biodegradable when the silicone
layer is removed and covered with an autograft. This allows
for harvesting of thinner epidermal autografts compared to
conventional autografts. Thinner autografts enable donor sites
to heal faster, allowing earlier reharvesting and less hyper-
trophic scarring of the donor site.35 The FDA requires clini-
cians to complete a company-sponsored training program
before using Integra. Its application procedure is complex,
and there is an increased susceptibility to infection in com-
parison to autografts.35
Refinements of the matrix concept led to the development
of Transcyte (formerly known as Dermagraft-TC). This is a
live, metabolically dynamic, immunologically inert human
dermis made up of a matrix synthesized by the proliferation
of allogeneic human neonatal fibroblasts on a nylon bioabsorb-
able mesh and an outer silicone polymer layer. The fibroblasts
are capable of undergoing cell division and secreting growth
factors. Transcyte provides a temporary covering that helps
protect the wound from desiccation and contamination. It
has been successfully used for temporary wound coverage of
partial-thickness burns. It was shown to be superior to silver
sulfadiazine in achieving faster re-epithelialization in partial-
thickness burns.46
Dermagraft evolved as a modified version of Transcyte. It
consists of neonatal fibroblasts seeded on a three-dimensional
polyglactin bioabsorbable mesh with no outer silicone mem-
brane, so allowing for a single-step procedure (Figs 8.7 and
8.8). This skin substitute stimulates the formation of granula-
tion tissue, re-epithelialization, and angiogenesis.35 The
fibroblasts produce fibronectin, glycosaminoglycans, colla-
Cultured epidermal allografts:  While cadaver skin was
initially used as the source of cultured allografts, the potential
for transmitting disease, limited supply, and variable quality,
have reduced its use.36–38 Neonatal skin is now the tissue
source of choice for cultured epidermal allografts owing to
its increased sensitivity and responsiveness to incorporated
mitogens, and its own release of growth-stimulating factors
and mediators, such as epidermal-derived thymocyte activat-
ing factor, interleukins, fibronectin, and TGF-β.39
Cultured allografts were originally thought to act directly
as a skin replacement. However, recent studies have shown
that allografts are progressively replaced by the patient’s own
skin. Some investigators suggest that cultured epidermal allo-
grafts function by stimulating migration and multiplication of
the recipient’s keratinocytes,40 probably by way of growth
factors rather than by permanent take of the allograft itself.41
Others theorize that allografts provide a potent stimulus for
wound healing simply by the production of a biologic dressing
that prevents dehydration.42 Although they do not survive
permanently on the wound bed, cultured allografts provide
efficient pain relief within hours after grafting in addition to
their protective functions.
Cultured epidermal allografts have been used to treat donor
sites, partial-thickness burns, chronic leg ulcers, epidermolysis
bullosa, and wounds resulting from tattoo removal.28 Many
investigators have reported the acceleration of healing of
STSG donor sites and partial-thickness burns, resulting in re-
epithelialization in 4–7 days.43 Cultured epidermal allografts
have the significant advantage of avoiding the creation of a
donor wound site. In addition, they are readily available, and
do not require the 2–3-week growth interval of cultured epi-
dermal autografts. Cultured epidermal allografts are not com-
mercially available in the US. They are available in only some
centers, are expensive, and require a tissue culture facility.
Dermal replacements
Synthetic, biosynthetic, or biological materials with func-
tional or structural similarities to the dermis are available as
dermal replacements. The dermis is composed of cellular
(fibroblasts) and extracellular (collagen, matrix proteins)
components and plays a vital role in the healing of skin by
influencing epithelial migration and differentiation, dermoepi­
dermal junction formation, wound contraction, and scar for-
mation. Skin substitutes functioning as dermal replacements
include cadaveric allograft skin, Biobrane (Dow B Hickam,
Inc), EZ Derm (Brennen Medical Inc, St Paul, MN), Oasis
(Cook Inc, Bloomington, IN), Transcyte (Smith and Nephew),
and Dermagraft (Advanced Tissue Sciences Inc, La Joya, CA).
In cadaveric dermal replacements, human cadaver skin is
chemically treated to remove its antigenic components, which
are usually found as cellular elements. This results in an
immunologically inert complex made up of an acellular col-
lagen dermal matrix and an intact basement membrane. This
can be used alone or in combination with other grafts or skin
substitutes. AlloDerm (Life Cell Co, Woodlands, TX), a
human cryopreserved, acellular cadaveric de-epidermalized
dermis has been successfully used in combination with STSGs
to treat burn wounds and dermal defects, and for periodontal,
and plastic and reconstructive surgery.35
Biosynthetic dressings were initially introduced for the cov-
erage of burns and donor sites. Biobrane consists of a bilami-
nate biosynthetic material made up of silicone film and nylon

124
Part 1  Basic Surgical Concepts
gens, and growth factors. Dermagraft was designed as a skin
substitute for full-thickness wounds. It has the advantages of
avoiding the use of non-human tissue, ready availability, less
chance of wound contracture and scarring, and mesh absorp-
tion in 60–90 days.
In the treatment of chronic diabetic ulcers, Dermagraft was
shown to be of significant clinical benefit in achieving wound
closure within 12 weeks compared to conventional therapy
alone (30% vs 18.3%, P = 0.023).47 It has also been shown
to be cost-effective,48 and currently has FDA approval for this
indication. For venous leg ulcers, the total ulcer rate of healing
(0.82 cm2/week vs 0.15 cm2/week, P = 0.001) and the linear
rate of healing (0.14 cm/week vs 0.033 cm/week, P = 0.006)
were significantly improved in patients treated with Derma-
graft and compression as compared with those treated with
compression alone.49
Composite skin substitutes
Composite skin substitutes contain both epidermal and
dermal components. The first true composite skin equivalent
consisting of both epidermal and dermal elements, each with
living cells, approved for use by the FDA is Apligraf (Orga-
nogenesis, Canton, MA; also known as Graftskin). This is a
biosynthetic, bilayered living construct made up of cultured
human neonatal foreskin keratinocytes overlying fibroblasts
cultured on a dermal matrix of bovine type I collagen (Figs
Figure 8.9  The meshed-type Apligraf before application.
Figure 8.10  A close up of the meshed-type Apligraf overlying
an ulcer.
Figure 8.8  Dermagraft being applied to an ulcer.
8.9 and 8.10). It is metabolically, morphologically, and bio-
chemically similar to human skin,28 but lacks appendages,
nerves, and blood vessels, and is immunologically inert.
Because it lacks macrophages, lymphocytes, and Langerhans’
cells,21 there appears to be no host antibody or cell-mediated
response or clinical rejection.
Apligraf is a useful adjuvant to standard ulcer therapy for
patients with venous leg ulcers or neuropathic diabetic foot
ulcers that do not respond to conventional ulcer therapy,50,51
and is FDA approved for these indications. In a multicenter
study of 293 patients with non-healing venous ulcers, treat-
ment with Apligraf in conjunction with standard compression
was shown to be more effective than compression therapy
alone in achieving wound closure within 6 months (63% vs
49%, P = 0.02), and to be superior in healing larger
(>1000 mm2, P = 0.02) and deeper ulcers (P = 0.003), and
ulcers of more than 6 months’ duration (P = 0.001). Median
time to complete wound closure was also significantly short-
ened in the Apligraf-treated group (61 vs 181 days, P =
0.003).52 In a multicenter study of 208 patients with diabetic
foot ulcers comparing Apligraf treatment with saline-mois-
tened gauze (both with standard adjunctive therapy including
debridement and foot off-loading), Apligraf resulted in com-
plete wound closure in 56% of patients versus 38% in the
control group (P = 0.0042) at the end of 12 weeks. Median
closure time was also shorter (65 vs 90 days, P = 0.0026).53
When applied over meshed autografts Apligraf was a suit-
able and clinically effective treatment for debrided burn
Figure 8.7  Preparation for applying Dermagraft. The
configuration of the ulcer is traced on the transparent protective
covering of the Dermagraft.

125
Chapter 8  Wound Healing and its Impact on Dressings and Postoperative Care
and easy for the patient, the wound should be monitored for
infection (particularly with anaerobes).
Mechanical debridement
Mechanical debridement typically is accomplished by wet-to-
dry dressings, by which a moist dressing is applied to a wound
and then removed after drying. This approach is a non-selec-
tive process, which can be painful to the patient and may
traumatize healthy tissue. Hydrotherapy is another form of
mechanical debridement with potential side effects of infec-
tion with waterborne pathogens and tissue maceration.
Surgical debridement
Surgical debridement, which is typically performed under
anesthesia, is a rapid and selective form of debridement used
for wounds with a significant amount of necrotic tissue.
Enzymatic debridement
Debridement of wounds with proteolytic enzymes is thought
to enhance granulation tissue formation and epithelialization.
Unfortunately, there are no large, high-quality, published
randomized controlled trials comparing the efficacy of this
form of debridement with others.62
Maggot therapy (biosurgery)
The beneficial effects of maggots on wounds dates back cen-
turies, when Baron Larrey, physician-in-chief to Napoleon’s
armies, and Dr Joseph Jones, a medical officer during the
American Civil War, noticed that maggots destroyed necrotic
wound tissue in traumatic wounds.63 William Baer reported
successful treatment of chronic osteomyelitis in children
after 6 weeks of maggot therapy in 1931, and also developed
a means of sterilizing maggots prior to application.64 Maggot
therapy was abandoned after the introduction of antibiotics,65
but has resurged in the treatment of chronic wounds refrac-
tory to conventional treatment. Today, Lucilia sericata (green
bottle fly) are the most commonly used maggots for biosurgery.
Maggots may facilitate healing by multiple mechanisms,
including secretion of proteolytic enzymes that liquefy
necrotic tissue, maggot digestion of necrotic tissue and bac-
teria, increase in wound pH secondary to larval excretion of
ammonia and calcium carbonate, and secretion of allantoin
and urea.66 Maggots appear to be most efficacious in wounds
infected with Gram-positive bacteria,67 including MRSA.68
 POSTOPERATIVE CARE AND
WOUND CARE
Acute wounds
Postoperative wound management involves caring for patients
from the conclusion of their surgical procedure through
the early remodeling phase of the surgical site (which may
take weeks to months).56 The importance of postoperative
management in obtaining satisfactory results cannot be
overemphasized.
The desired end result is the most cosmetically acceptable
healed wound in the least amount of time.54 This involves the
absence of scarring, infection, and contact dermatitis from
topical medications; and can be achieved by good postopera-
tive care techniques including the proper choice of dressings.
wounds. Furthermore, cosmetic and functional advantages
were demonstrated over standard therapy.54
Bilayered cellular matrix (BCM) or OrCel (Forticell Bio-
science Inc, New York, NY) consists of a porous collagen
sponge containing cultured keratinocytes and fibroblasts
derived from allogeneic cells harvested from neonatal fore-
skins. This has been FDA approved for use in treatment of
split-thickness donor sites of burn patients and patients with
recessive dystrophic epidermolysis bullosa. OrCel is thought
to work by providing extracellular matrix components and
growth factors for host cell migration. It does not serve as a
permanent skin substitute, as it is reabsorbed within 2 weeks
of application. There are no published, peer-reviewed studies
using Orcel for venous leg ulcers. Combined data from a prior
study by Forticell Bioscience along with data from a recent
FDA-requested confirmatory trial showed that 50% of OrCel-
treated patients had complete wound closure by 12 weeks as
compared to 31% with standard care. With regard to diabetic
ulcers, the company’s pilot study reported 47% complete
wound closure in 12 weeks with a cryopreserved version of
OrCel as compared to 23% with standard care.55
Antimicrobial dressings
Silver-impregnated dressings, popular antimicrobial dress-
ings, are bactericidal without antibiotics and maintain a moist
environment to facilitate wound healing.56 Silver has broad-
spectrum action on bacteria, including against vancomycin-
resistant enterococci and methicillin-resistant Staphylococcus
aureus (MRSA).57 It acts on bacterial cell wall synthesis,
ribosome activity, and transcription. It also exhibits activity
against fungi and yeast. Commercially available examples of
silver-containing dressings include Aquacel Ag (ConvaTec),
Contreet (Coloplast Sween, Inc), Arglaes (Medline Indus-
tries, Mundeline, IL), Acticoat (Smith & Nephew, London,
UK), Silveron (Silveron Consumer Products, Mundeline, IL),
and AcryDerm Silver (AcryMed, Inc, Portland, OR). These
dressings can release antibacterial levels of silver for 3–7 days,
and so far, despite extensive testing, there is no evidence of
resistance.58 In a matched-pair, randomized study on burns,
silver-coated Acticoat dressings resulted in less pain and
decreased sepsis compared to the application of silver nitrate.59
Cadexomer iodine, a slow-release formulation of iodine, is
composed of starch microspheres cross-linked with ether
bridges and iodine. It slowly absorbs moisture while releasing
iodine in low concentrations, which are antibacterial yet not
cytotoxic.3 Cadexomer iodine provides broad-spectrum anti-
biotic coverage, and can significantly decrease the bacterial
load on the wound surface. It resulted in a significant reduc-
tion in S. aureus (P < 0.001), β-hemolytic streptococci,
Proteus, and Klebsiella in a randomized controlled trial on
venous ulcers.60 Iodosorb, a cadexomer iodine ointment, is
antibacterial and an effective debriding agent in pressure,
venous, and diabetic ulcers.61
 DEBRIDEMENT
Autolytic debridement
Autolysis is a selective process by which the body’s own
enzymes and moisture liquefy necrotic tissue. Autolytic de­
bridement is enhanced with dressings that maintain fluid
contact with necrotic tissue – such as with films, hydrogels,
and hydrocolloid dressings. While this is relatively painless

126
Part 1  Basic Surgical Concepts
spray to treat combat wounds. The gel is applied with a dual
syringe and only sticks to intact skin (not the wound itself),
results in rapid hemostasis, and is hard enough to resist abra-
sions. The prospect of civilian applications and the creation
of medicated versions to treat infections and severe bleeding
are in discussion.77–79
Postexcision wounds healing by
second intention
‘Shave’ or tangential removal of skin is usually performed by
dermatologists for biopsy, or transverse excision of lesions
such as moles.56 (See also Chapter 44.) It results in an open
wound, which is left to heal by second intention and will
generally take longer to heal than a sutured wound.
The traditional approach to this type of wound is to apply
an ointment followed by two or more layers of dressing. Many
dermatologists prefer Polysporin (Pfizer, Inc, New York, NY)
or bacitracin (Fougera and Co, Melville, NY) ointments, and
avoid neomycin-containing ointments because of their well-
established increased potential for causing contact dermati-
tis.80 However, randomized controlled trials have shown that
white petrolatum is as safe and effective as bacitracin with
less risk for inducing allergy.81
After the ointment layer, the contact layer, which directly
touches the wound, is applied. It is usually composed of non-
adherent pads such as Telfa and Adaptic, which do not
disturb forming granulation tissue. An absorptive layer con-
sisting of gauze pads can be used for draining wounds.
The last layer is the binding or securing layer, which keeps
the dressing in place and may also function in compression
and immobilization, if needed. Adhesive tape is most com-
monly used; however, tubular gauze, elastic bandages, and
gauze rolls may be added. To increase the holding property
of tape, especially when working on a mobile or sebaceous
region, the area can be degreased with acetone or alcohol and
prepped with liquid adhesive (Mastisol-Ferndale Labs, Fern-
dale, MI).82 Hairy areas on which tape is to be applied should
be shaved, except for the eyebrows.
The dressing is to be left undisturbed for 48–72 hours after
surgery, mainly to reduce the risk of incidental trauma and
contamination to the fresh wound.69 This also allows the
patient physical and psychological relief at the time the
wounds are most likely to cause pain and discomfort.
However, if the dressing becomes soaked with blood or
wound exudate before then, a change of dressing is necessary.
At home, gentle cleansing is carried out once or twice a day
using soap and water, saline solution, or half-strength hydro-
gen peroxide. There is some controversy about the use of
hydrogen peroxide because it has been shown to have an
inhibitory effect on fibroblasts and the microcirculation,83 and
might therefore actually retard healing. However, its effer-
vescence is excellent in removing dried-up debris and crusts
on wounds, and the few minutes of contact with it have been
deemed more helpful than harmful.69 Saline is the most com-
monly used irrigation solution for the removal of inflamma-
tory contents from the wound surface.61
In removing the initial dressing, the patient is instructed to
wash or wet the dressing first to reduce pain and prevent
damage to the granulating wound bed. Cleansing the wounds
with normal saline delivered at 8 lb/in2 (35-ml syringe and
19-gauge angiocatheter) is usually enough to dislodge debris
from the wound bed.23 A sterile cotton-tipped applicator may
Excisional surgery is one of the most common procedures
carried out by dermatologists. After excision, wounds may
heal by primary or second intention. In primary intention
closure, there is direct apposition of wound edges by suturing.
In contrast, in second intention healing, the wound is left open
after the surgery and allowed to epithelialize from its edges.28
Postexcision wounds healing by
primary intention
Wounds sutured closed after excisional surgery, in most
instances, do not require special dressings because normal
immunity from phagocytes ingesting and killing bacteria is
often sufficient to prevent infection.69 A simple low- or non-
adherent gauze dressing secured with tape or a semiper-
meable film will usually suffice. For postexcision sites that
are still actively bleeding, a thicker, more absorbent dressing
is needed. Despite the low infection rate, some clinicians still
opt to include an antibiotic or aquaphor ointment in the
contact layer, if only to make the patient more comfortable.
Wounds healing by primary intention rarely require cleans-
ing.70 In fact, disturbance of the dressing should be minimized
to prevent bacterial contamination as well as removal of
reforming epithelium. When needed, cleansing is usually
done with care using saline. Changes of dressing are likewise
carried out as needed.
It takes approximately 1 week for sutured wounds to re-
epithelialize. The correct time for suture removal depends on
several factors, and therefore the practitioner can only follow
general guidelines: 4–6 days for the head and neck, 7 days for
the upper limbs, 10 days for the trunk and abdomen, and 14
days for the lower limbs.70 Some problems that may be
encountered in sutured wounds are dehiscence, hematoma
formation, and suture reactions.71
Liquid adhesive bandages
Liquid adhesive bandages are chemical mixtures – typically
containing polymer dissolved in water, alcohol, or another
solvent – that create a polymeric layer that binds to skin once
the solvent evaporates. Some types are based on cyanoac­
rylates, which are better for actively bleeding wounds.72
Liquid adhesive bandages have been used in the treatment of
minor lacerations and abrasions, partial-thickness wounds,
shave biopsies, and postsurgical procedures, including repairs
after Mohs micrographic surgery.73,74
Liquid adhesive bandages are convenient and cost-effective,
requiring fewer dressing changes and costing less than routine
postsurgical wound care materials for facial excisional
surgery.75 According to a study comparing a cyanoacrylate
liquid bandage to traditional bandages, the liquid bandage
enhanced the rate of epithelialization, provided complete
hemostasis, and reduced scab formation.76
Liquid adhesive bandages are good for difficult-to-reach
areas, highly mobile areas, and in certain patient populations
(elderly, disabled, pediatric, and those who live alone).73
They facilitate healing by protecting wounds from outside
contaminants and decreasing loss of moisture, and some
studies have shown liquid bandages to have antibacterial and
antimycotic activities on superficial fungi.74
Commercially available examples of liquid bandages include
Nexcare (3M, New York, NY), Band-Aid brand (Johnson &
Johnson Medical, Arlington, TX), and New-Skin (Medtech,
Inc, Irvington, NY). Recently, the FDA approved a gel-based

127
Chapter 8  Wound Healing and its Impact on Dressings and Postoperative Care
tion, or cool water are performed to reduce the oozing and
crusting. Ointment such as petrolatum or aquaphor is used
over the wounded area to protect it and prevent it from
drying up. Topical antibiotics are avoided because of their
potential for sensitization.84
In the closed technique, an occlusive or semiocclusive
dressing, such as Flexan (Dow B Hickam, Inc), 2nd Skin,
N-Terface, and Omniderm, is used after initially cleansing
the resurfaced area. These are generally changed once or
twice a day because of the copious exudate.
The disadvantages of the closed technique are difficult
visualization and inspection, an increased potential for infec-
tion, and patient discomfort. Patients generally do not toler-
ate having the face covered for more than 48 hours.25
However, in studies comparing the open and closed tech-
nique, the closed technique showed more rapid epithelializa-
tion85 and was associated with less pain. Some authors
recommend a combination of the two approaches with the
closed technique being used for the first 48 hours, then fol-
lowed by the open technique.86
Uncomplicated partial-thickness and
full-thickness wounds
An approach applicable for both partial- and full-thickness
wounds is the use of the moisture-retentive occlusive dress-
ings. The moist environment provides the optimal conditions
to facilitate healing and relieve pain. The choice of dressing
depends on the type of wound and its characteristics.
Options for the treatment of partial- and full-thickness
burns are biologic and biosynthetic skin grafts and skin sub-
stitutes such as STSGs, FTSGs, cultured epidermal autografts,34
Alloderm,35 Integra,45 Transcyte,46 and Apligraf.54
Chronic wounds
For chronic wounds, it is essential to define and treat the
underlying cause. The most common causes such as venous
also be used to carefully remove debris from more superficial
wounds. For deeper wounds, the cleansing solution can be
poured over the surface, then blotted with sterile gauze. The
layered dressing is then reapplied. This is continued until
complete re-epithelialization has occurred (several weeks or
more for open wounds). Usually, if no complications occur,
changes of dressing become less frequent as the wound site
gradually re-epithelializes and exudes less fluid.
Another alternative for postexcision wounds is the use of
occlusive dressings with or without a secondary dressing. This
gives adequate protection from trauma, desiccation, contam-
inants, and bacteria while providing a moist environment,
which facilitates wound re-epithelialization.21 For the more
superficial wounds with minimal exudation, films may be
used. For the deeper wounds, hydrogels or hydrocolloids may
be used. If the wound is highly exudative, foams and alginates
are preferred. There are no hard-and-fast rules about how long
this type of dressing should stay on the wound, but it is rec-
ommended that the dressing is changed before leakage occurs.
For superficial wounds on the face, one of the more practical
options is to simply apply an antibacterial ointment. Its main
advantage is that it is a one-step procedure, and interferes
minimally with function and appearance.21 Its main disadvan-
tage is that the ointment can be easily wiped off unintention-
ally, so providing limited protection and absorption.
Postoperative care in laser resurfacing
After laser resurfacing, there is swelling, pain, burning, and
stinging for the first few days. During the first 1–2 days, there
is oozing of exudate, with some sloughing of thermally dena-
tured collagen, crusting, and erythema. Bleeding rarely occurs
because of the hemostatic action of the laser.25 During this
period, the application of ice packs is recommended to reduce
pain, swelling, and discomfort.
Two techniques commonly employed postoperatively are
the open and closed techniques (Table 8.5). In the open
technique, frequent soaks with dilute acetic acid, saline solu-
Table 8.5  Postoperative care in laser resurfacing
TECHNIQUE
ADVANTAGES
DISADVANTAGES
Closed
Decreased pain
Decreased pruritus
Less erythema
Less crust formation
Comfortable
Promotes moist healing environment
Decreased exudative phase of wound healing
Faster re-epithelialization
Decreased scarring
Difficult to keep in place on motile areas (perioral)
Not tolerated for long period of time (>2 days)
Risk of infection if left in place >72 hours
Expensive
Time-consuming
Cosmetically unattractive
Patient discomfort, claustrophobia
Open
Inexpensive
Easy to use
Less time-consuming for doctors
Hypersensitivity reactions
Crusting, desiccation
Prolonged erythema
Trauma when sleeping (sticking to the pillows)
Wound care relies on patient compliance
Frequent application of the ointment (every 2 hours)
More intense erythema
Milia and acne from overuse
Adapted from Lopez AP, Phillips TJ. Wound healing. In: Fitzpatrick RE, Goldman MP, eds. Cosmetic laser surgery. St Louis: Mosby; 2000.25

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Part 1  Basic Surgical Concepts
which allow them to slide onto the leg more easily, while
others have a zipper to make them easier to put on and remove.
Compression bandages
Elastic bandages:  Various types of elastic bandages are
available. One of the more familiar ones is the ACE type,
which has the advantage of being reusable. Its primary disad-
vantage is that because it is not self-adherent, it often unrav-
els. If improperly applied, the bandage does not achieve the
correct level of compression.
Compression bandages:  Compression bandages should
be applied evenly from right above the toes to just below the
knee. A useful guide for instructing caregivers about how to
apply the appropriate tension to elastic compression bandages
is to use a bandage with a rectangle drawn on it – Setopress
(ConvaTec) or Surepress (ConvaTec). This rectangle turns
into a square when the bandage is stretched to the correct
tension. It should be applied in a spiral with 50% overlap
between turns to produce a double-layer bandaging effect and
provide sustained pressures.87
Unna boot:  The Unna boot is a semirigid paste bandage
that is applied by a physician or nurse with the foot at a 90°
angle (Fig. 8.11). It should be replaced weekly, or more fre-
quently if heavy drainage is present. Some physicians theorize
that rigid compression is beneficial in that it makes the calf
muscles press against the rigid bandage when the patient
walks, ensuring the pumping effect of the calf muscles. Other
physicians feel that the rigidity is disadvantageous in that the
bandage fails to accommodate changing leg volume during
fluctuations in edema. The Unna boot can also cause an
unpleasant odor, which develops from the wound exudates
and has the potential for causing contact dermatitis.
insufficiency, arterial insufficiency, diabetic neuropathy, and
pressure necrosis are considered first.56 When these are ruled
out or unlikely, less common causes such as vasculitis, pyo-
derma gangrenosum, malignancy, and infection are to be
taken into account. Determining the etiology of the wound
is a key component in deciding how to approach treatment
of the wound as well as the underlying condition. Treatment
of the most common types of chronic wounds is briefly dis-
cussed below.
Venous ulcers
Venous ulcers are the most common form of leg ulcers.70 The
cornerstone of treatment is compression, edema reduction,
and improvement of venous return. This can be achieved by
bed rest, leg elevation, and the use of compression devices,
such as elastic support stockings, elastic bandages, non-elastic
bandages such as Unna’s boots, and pneumatic compression
pumps.
To improve abnormal venous return, patients are advised
to elevate the affected leg 18 cm above the level of the heart
or ‘toes higher than the nose’ for 2–4 hours during the day
as well as the night.87 Before compression is applied to the
limb, occlusive arterial disease should be ruled out, and the
ulcer base should be clean and uninfected. Compression
should be applied on arising from bed and removed at bed
time. The recommended ankle pressure in patients with
venous ulcers of the leg is 30–40 mm Hg.87 The most effec-
tive way of delivering compression remains controversial. The
advantages and disadvantages of different compression
systems are shown in Table 8.6.
Compression stockings
Patients who are elderly and have arthritis find it difficult to
put on compression stockings. Some stockings have silk liners,
Table 8.6  Types of compression therapy
TYPE
ADVANTAGES
DISADVANTAGES
Elastic wrap
Inexpensive, can be reused
Often applied incorrectly by the patient, tends
to unravel, does not maintain sustained
compression, loses elasticity after washing
Self-adherent wraps
Self-adherent, maintain compression
Expensive, cannot be reused
Unna boot
Comfortable, protects against trauma, full maintenance of
ambulatory outpatient status, minimal interference with regular
activities, substitute for a failing pump
Pressure changes over time, needs to be
applied by trained physician or nurse, does
not accommodate highly exudative wounds
Four-layer bandage
Comfortable, can be left in place for 7 days, protects against
trauma, maintains a constant pressure for 7 days due to the
overlap and elasticity of the bandages, used for highly exudative
wounds
Needs to be applied by well-trained physician
or nurse
Graduated
compression stocking
Reduces the ambulatory venous pressure, increases the venous
refilling time, improves calf pump function, different types
of stocking accommodate different types of leg, dressings
underneath can be changed frequently
Often cannot monitor patient compliance,
difficult to put on
Orthotic device
Adjustable compression, sustained pressure, easily put on and
removed, comfortable
Expensive, bulky appearance
Compression pump
Augments venous return, improves hemodynamics and
microvascular functions, enhances fibrinolytic activity, prevents
postoperative thromboembolic complications in high-risk
patients
Expensive, requires immobility for a few
hours/day
Adapted with permission from Blackwell Publishing Ltd from Phillips TJ. Current approaches to venous ulcers and compression. Dermatol Surg 2001;27:611–621.85

129
Chapter 8  Wound Healing and its Impact on Dressings and Postoperative Care
episodes of inflammatory phlebitis, or when increased venous
or lymphatic return is undesirable.
Wound dressings
Moisture-retentive dressings combined with compression
therapy may produce more rapid healing rates initially, but
long-term follow up has failed to demonstrate any statistically
significant advantage over compression therapy alone.20
However, these dressings are beneficial in that they relieve
pain, reduce the infection rate, and enhance autolytic debride­
ment and granulation tissue formation.88
Larger venous ulcers may require the use of skin grafts or
skin substitutes. Meshing of STSGs is helpful for venous
ulcers because it allows drainage of wound fluid without
disturbing the adherence of the graft to the wound bed.
Another treatment option for persistent venous ulcers is
shave therapy. This involves the excision of ulcers with the
surrounding lipodermatosclerotic tissue and covering the
wounds with meshed STSGs. Healing rates of 79% of 59
patients after 3 months, and 88% of 18 patients after an
average of 2 years after shave therapy were observed.89
Apligraf is FDA approved for the treatment of venous
ulcers, and in combination with compression therapy has
been shown to be significantly better at healing ulcers second-
ary to venous insufficiency compared to compression alone.
It is especially helpful in treating venous ulcers of greater than
6 months’ duration.51
Arterial ulcers
Management of arterial ulcers requires surgical re-establish-
ment of an adequate vascular supply whenever possible. Dia-
betes mellitus, cigarette smoking, hypertension, and
hyperlipidemia should be controlled. Moderate exercise may
promote development of collateral circulation, and elevation
of the head of the bed 10–15  cm (4–6  inches) improves
gravity-dependent arterial flow.90 Limbs should be kept
warm. Patients should observe good foot care. General prin-
ciples for proper wound care as well as choice of dressings
are observed for arterial ulcers.
Diabetic foot ulcers
Good diabetic foot ulcer care starts with a thorough assess-
ment of the ulcer, including determining whether neuropathy
or peripheral vascular disease is present. The principles of
good wound care include use of proper footwear and the
correct antibiotics when needed, avoidance of weight bearing,
pressure-relieving aids, debridement as necessary, aggressive
revascularization, and control of the serum glucose levels.91
There is a remarkable lack of consensus over dressing
choice for the diabetic foot ulcer.92 The principle of moist
healing does still apply, but it has been questioned whether
this philosophy applies to all diabetic wounds.93 The ideal
dressing should protect the wound from secondary contami-
nation, maintain a moist environment, remove exudates, be
able to be removed without trauma to the wound, and resist
the stresses of standing and walking.
Topical antibiotics keep the surface bacterial colony count
low while providing a moist environment in which healing
may occur. Saline-moistened gauze also provides a moist
wound environment. Occlusive dressings such as hydrogels,
hydrocolloids, and polymers play a big role in the treatment
of diabetic ulcers.91 In addition to the traditional occlusive
Four-layer bandage:  The four-layer compression bandage
has been proposed as the optimal device for achieving com-
pression. It is more flexible and absorbent than the Unna
boot, and is capable of maintaining evenly distributed pres-
sure throughout the affected limb for long periods of time.
From innermost to outermost, its four layers consist of an
orthopedic wool layer, a crepe layer, an elastic layer applied
in a figure-of-eight pattern, and an elastic layer applied in a
spiral pattern.
Orthotic device:  A legging orthosis with Velcro tape is an
adjustable device that can be loosened and tightened as
needed to adjust to changes in leg circumference (Fig. 8.12).
It is useful in patients who cannot tolerate other compression
modalities or who require frequent dressing changes.
Pneumatic compression:  For patients who are unre-
sponsive to conventional compression bandages or stockings,
home compression pumps may be used. They were devel-
oped for the prophylaxis of deep venous thrombosis, and
should be considered when a venous ulcer does not respond
to standard compression therapy. They can be rented or
purchased for outpatient use. They are contraindicated in
patients with uncontrolled congestive heart failure, during
Figure 8.11  Unna boot application. The boot is applied with
the foot at a 90° angle, starting just above the toes, in a
figure-of-eight manner around the ankle, and up to the knee in
a spiral fashion with 50% overlap. A layer of self-adherent
elastic bandage is frequently wrapped around it.
Figure 8.12  A legging orthosis using Velcro tape.

130
Part 1  Basic Surgical Concepts
dressings, the latest state-of-the-art biosynthetic dressings
Dermagraft47 and Apligraf51 have likewise been shown to be
effective in the treatment of these ulcers, and have been
approved for this use by the FDA. Bilayered Cellular Matrix
(BCM; Ortec International Inc, New York, NY) has also
shown promise in the treatment of diabetic ulcers, but is not
yet FDA approved for this indication.94
The total contact cast is commonly used in the US, but
requires skilled application and close follow up.92
Pressure ulcers
The most important aspect of treatment of pressure ulcers
is tissue load management.95 This refers to specific interven-
tions designed to decrease the magnitude of pressure, friction,
and shear on the tissue. The goal is to create an environment
that enhances soft tissue viability and promotes healing of
the pressure ulcers, and can be met through vigilant use of
proper positioning techniques and support surfaces, whether
the individual is in bed or sitting on a chair.95
Management also involves addressing factors such as nutri-
tion, immobility, and co-morbid disease, and protection from
fecal or urine soiling.96 Nutrition is very important in prevent-
ing and healing pressure ulcers, especially adequate protein
content in the diet. Incontinence contributes significantly to
the development of pressure sores because constant exposure
of skin to urine and stool leads to maceration, weakening of
the tissue, and eventual breakdown. Containment devices
and skin-protective barriers are useful in counteracting mois-
ture from incontinence.
Wound care of the pressure ulcer involves debridement of
devitalized tissue, wound cleansing, application of dressings,
and possible adjunctive therapy with electrical stimulation for
stage III and IV unresponsive ulcers. These are full-thickness
ulcers that may extend to the subcutaneous tissue (stage III)
or to muscle and bone (stage IV).95 Normal saline is the
preferred cleansing agent. In the selection of dressings, the
cardinal rule is to choose a dressing that will keep the ulcer
tissue moist and the surrounding intact skin dry.95 Studies
comparing different types of moist wound dressings showed
no differences in pressure ulcer healing outcomes;95 however,
sequential dressing therapy using alginates followed by hydro-
colloids showed significantly faster healing (P < 0.001) in
stage III and IV ulcers compared to hydrocolloid alone.97
Foam dressings or wound fillers may be adjunctively used to
eliminate dead space in deep ulcers.96 Dressings applied near
the anus should be given special attention because they are
difficult to keep intact. Picture framing or taping the edges
of the dressing may reduce this problem.95
 OPTIMIZING OUTCOMES
Figure 8.13  Leakage through a foam dressing applied on the
ankle occurs because of an inadequate inferior margin.
Optimizing outcomes
 Avoid leakage – provide adequate margins of dressing
around wound edges (Fig. 8.13), vary frequency of dressing
changes as needed, increase thickness of absorptive layer,
select proper dressing (e.g. alginates and foams for heavily
exuding wounds).
 Control pain – avoid trauma to site, use moisture-retentive
dressings (especially hydrogels), oral analgesics (e.g.
acetaminophen), apply EMLA (Astra-Zeneca Pharmaceuticals,
Wilmington, DE) for 30–45 minutes before debridement.
 Prevent maceration – apply zinc oxide paste on the
periwound area (Fig. 8.14); do not leave on dressings for
prolonged periods of time.
 Minimize odor – apply Metrogel (Galderma Laboratories, Inc,
Fort Worth, TX), use odor-absorbing dressings, for example
Actisorb Plus (Johnson & Johnson Medical), Lyofoam C
(ConvaTec), Carboflex (ConvaTec).
 Remove necrotic tissue – perform debridement: mechanical
(Fig. 8.15), autolytic, enzymatic, or biologic; irrigate under
pressure during cleansing.
 Ensure patient compliance – instruct the patient and
caregiver thoroughly, regular follow-up visits.
 Check intrinsic factors – address any underlying systemic
conditions (e.g. venous or arterial disease, hypertension,
psychological stress, debility, immunocompromised state),
ensure proper nutrition (especially protein).
 Keep wound moist, but not wet – use dressings of
appropriate absorbency (e.g. alginates for highly exudative
wounds).

131
Chapter 8  Wound Healing and its Impact on Dressings and Postoperative Care
Figure 8.14  Zinc oxide paste is applied on the periwound area
to function as a protectant and minimize maceration.
Figure 8.15  Surgical debridement using a curette to remove
necrotic tissue and debris from the ulcer bed.
Figure 8.16  Necrotic tissue such as eschar is an optimal
substrate for microbial growth which may lead to local and
systemic infection.
Figure 8.17  Typical appearance of contact dermatitis on the
periwound area. Note the erythema.
 PRACTICAL APPLICATIONS
In general, once the underlying cause of a wound has been
addressed along with any conditions that may impair healing,
wounds have relatively straightforward requirements. Spe-
cific needs may be determined by the physical characteristics
of the wound including its size, shape, location, depth, phase
of healing, tissue type and quantity, condition of the skin
surrounding it, and bacterial and exudate levels. Dressing
functions to be considered are absorptive capacity, hydrating
capacity, adhesive quality, debriding capabilities, conforma-
bility, and odor control ability (Table 8.7).98
No single dressing can provide all things to all wounds,
especially because most wounds have a variety of needs. This
leaves clinicians to weigh the pros and cons of possible dress-
ing choices, and to make the decision about which they think
is the most appropriate. As the patient’s wound progresses,
several different categories of dressing may be necessary
during the wound healing process to address the changing
wound parameters.
 PITFALLS AND THEIR MANAGEMENT
It is always easier to avoid complications than to treat them.
Pitfalls and their management
 Infection – use topical and systemic antibiotics as needed, practice
clean or aseptic techniques for dressing wounds, irrigate under
pressure or debride to remove necrotic tissue (Fig. 8.16).
 Contact dermatitis (Fig. 8.17) – switch to another type of
dressing, adhesive, or topical ointment or antibiotic, apply zinc
oxide or other lubricating protectants to periwound area, apply
low-potency topical corticosteroids.
 Seroma formation – aspirate with a large-bore needle, puncture
with a lancet.
 Excessive pressure from dressing – loosen dressing.
 Excessive granulation tissue – apply pressure, change dressing
type, pare with curette, cauterize with silver nitrate.
 Pigmentary alteration – improves with time.
 Milia or suture granuloma – usually resolve spontaneously;
however, if it does not resolve, puncture with a needle and
extract the foreign materials.