Phẫu Thuật Tạo Hình Grabb & Smith’s (Bản Cập Nhật – Kevin C. Chung)

Arterial Ulcers
Arterial ulcers occur because of arterial insufficiency where there is narrowing of the arterial lumen most
commonly secondary to atherosclerosis. They are classically located over bony prominences including the
toes, heels, and ankles. Apart from atherosclerosis, other conditions that cause arterial obstruction include
embolism, diabetes mellitus, vasculitis, pyoderma gangrenosum, and hematological disorders of sickle
cell disease and thalassemia.
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Diabetic Foot Ulcers
The prevalence of diabetic foot ulcers in individuals with diabetes mellitus is common and occurs in
approximately 15% of patients over their lifetime. 23 There are several pathophysiological factors that
contribute to aberrant healing in diabetic individuals. These include abnormal and chronic inflammatory
response, hyperglycemia, microvascular abnormalities, hypoxia, and changes of the ECM scaffold.
Peripheral neuropathy, peripheral arterial disease, and trauma also contribute to diabetic ulceration.
Chronic inflammation and an impaired inflammatory response is also the hallmark of diabetic wounds.
Studies have demonstrated persistent and raised levels of proinflammatory cytokines, such as IL-1, IL-6,
and tumor necrosis factor α. 24 Wounds also typically have imbalances in protease production and their
inhibitors, which stop normal matrix synthesis and remodeling. 25
Hyperglycemia leads to nonenzymatic binding of sugar residues to proteins through free amino acid
groups, and further alterations lead to advanced glycation end-products. Advanced glycation end-
products are known to decrease the solubility of the ECM and exacerbate the inflammatory changes. 26
Glycation of the ECM is linked to cell apoptosis and disruption of normal wound healing processes such
as angiogenesis, cell migration, and proliferation. 27 High levels of glucose induce expression of MMP by
fibroblasts, endothelial cells, and macrophages to break down the matrix.
Oxygen supply to a wound is also essential for healing, and hypoxic environments adversely affect
wound healing. Chronic hyperglycemia prolongs inflammation and delays wound healing by increasing
the levels of free radicals. 26
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Pressure Injuries
The pathophysiology underlying pressure injury is a combination of pressure, friction, shearing forces
between tissue planes, and moisture. Pressure exceeding arteriolar pressure results in tissue hypoxia, the
creation of free radicals, an ischemic reperfusion injury, and consequent tissue necrosis. 28 Factors
contributing to the development of pressure ulcers include prolonged immobility, patient position,
neuropathy, and existing arterial or venous insufficiency. 28 The National Pressure Ulcer Advisory Panel
(NPUAP) staging system defines four stages of severity to pressure injuries: stage 1 pressure injury is
nonblanchable erythema of intact skin (Figure 2.5A), stage 2 pressure injury is a partial-thickness skin loss
with exposed dermis (Figure 2.5B), stage 3 pressure injury involves full-thickness skin loss (Figure 2.5C),
and stage 4 pressure injury involves full-thickness skin and tissue loss (Figure 2.5D). 29
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FIGURE 2.5 Pressure injury staging. A. Stage 1 is the least severe according to NPUAP staging system. It is defined as
nonblanchable erythema of intact skin. B. Stage 2 is defined as a partial-thickness skin loss with exposed dermis. C. Stage 3
involves full-thickness skin loss. D. Stage 4 is the most severe stage of pressure injury. It involves full-thickness skin and tissue
loss.
Reproduced with permission from National Pressure Ulcer Advisory Panel, European Pressure Ulcer Advisory Panel, Pan Pacific Pressure Injury Alliance.
Prevention and treatment of pressure ulcers: quick reference guide. In: Haesler, E, ed. Cambridge Media: Osborne Park, Western Australia; 2014.
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Factors That Adversely Affect Wound Healing
Radiation Therapy
Radiation therapy such as those used as part of oncologic therapies disrupts the complex pathways of
wound healing. Ionizing radiation produces both acute and late effects on tissues. Acutely, basement
membrane is damaged, and increased vascular permeability introduces edema to reduce
neovascularization of wounds. 30 During the inflammatory phase, there is excess expression of several
growth factors, leading to tissue fibrosis. Fibroblasts are also injured and contribute to the late effects of
radiation injury such as fibrosis and contraction. 30
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Nutrition
Nutrition has long been known to affect wound healing and chronic wounds. This includes a general
malnutrition state, inadequate caloric intake, and deficiencies in vitamins, micronutrients, and
macronutrients. Malnutrition is known to prolong the inflammatory phase of wound healing through
reducing the proliferation of fibroblasts and the formation of collagen. 31 It can also increase the risk of
infection of wounds by altering the function of immune cells, such as reducing phagocytosis and
decreasing complement levels. 31 Micronutrients such as copper, zinc, and magnesium are elements and
minerals that are essential to bodily chemical processes and, in particular, in wound healing. Deficiencies
in these micronutrients can adversely affect wound healing, for example, in copper deficiency.
Macronutrients include protein, amino acids, carbohydrates, fiber, water, and fats. These are required at
sufficient levels to promote optimal wound healing. Significantly reduced protein intake is associated
with increased rates of wound infection and wound strength. 31 Similarly, lipid deficiencies are associated
with altered wound healing. 31
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Microorganisms
Microorganisms have long been known to influence the healing of chronic wounds, and all open wounds
contain microbes. Bacteria predominantly exist in biofilms in clinical and natural settings, as opposed to
planktonic states (single organisms/free-floating). Biofilms describe adherent populations of microbes
that form three-dimensional populations and are organized on extracellular polymers. Over time, chronic
wounds are known to develop biofilms, as complex interactions between the host wound
microenvironment and heterogeneous bacterial populations mean they are able to proliferate unchecked.
Biofilm bacterial populations delay and inhibit wound healing by not only producing toxins and
damaging enzymes, but also promoting the complex chronic inflammatory pathways. 32 Proteases
released from bacteria impede growth factors and wound healing proteins. Large levels of microbial
exudate have also been shown to affect cell proliferation and wound healing. 32
Biofilm-infected chronic wounds are clinically challenging to manage and are resistant to elimination by
antimicrobials and by the immune system. The current mainstay management of dealing with
microorganism-related complications in chronic wounds includes pressure off-loading, appropriate
dressings, systemic antibiotics, tissue debridement, and the instillation of NPWTs such as vacuum-
assisted closure devices.
Similarly, antiseptic dressings such as those containing chlorhexidine, silver, or iodine and topical
antimicrobials (e.g., fusidic acid creams) have been developed over the years to a limited degree of
success. Topical antimicrobials have promoted bacterial resistance, and several studies concluded that
antiseptic dressings are not significantly better than saline gauze alone. 33 However, there are special
situations when topical antimicrobials are proven beneficial. They are particularly useful in burn injuries
(especially second-degree burn injuries) to treat infection and therefore prevent sepsis. 34
Systemic antibiotics are beneficial in infected chronic wounds but are not indicated for most chronic
wounds that are merely colonized with bacteria. Antibiotics should have high tissue bioavailability and
should be targeted to the specific organisms from deep wound cultures. Studies demonstrate that
superficial cultures do not represent the diverse populations of bacteria of the biofilm. 33
Debridement involves the removal of necrotic tissue and debris at the wound edges and is often surgical,
although other mechanical modes and enzymatic and autolytic methods are also utilized. The current
theory is that debridement reduces biofilm. It is thought to promote wound healing and decrease the
biofilm load. Recolonization of the wound after debridement is common, and often sequential
debridements are required for successful healing.
NPWTs, such as vacuum-assisted closure devices, are known to aid wound healing. Several studies have
investigated their effect on the microorganisms within chronic wounds, and observational data of NPWT
with adjunctive topical dressings have demonstrated decreased biofilm load. 33 A recent small
randomized trial (n = 20) of NPWT with instillation and adjunctive sodium hypochlorite solution was
effective at reducing both planktonic and nonplanktonic (biofilm) microorganisms. 35
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Obesity and Metabolic Syndromes
Obesity is correlated with increased rates of wound complications such as wound infection, impaired
wound healing, pressure injuries, venous ulcers, hematoma, and seroma formation. Hypovascularity,
difficulty in repositioning, and friction between skin-to-skin contact points in skin folds are all known to
contribute to the formation of pressure injuries in obese individuals.
On a molecular level, obesity is related to lower levels of lymphocyte proliferate, altered cytokine levels
and peripheral immune function which improves upon weight loss. 23
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Advanced Wound Healing Strategies
Nonsurgical, advanced would healing strategies can briefly be categorized into those that employ
biological therapeutics, use or enhance the matrix, and exploit biophysical forces (see Figure 2.1).
Although these modalities are important, basic and simple strategies still form the foundation of wound
care. These measures are manifold and include optimizing the management of primary pathological
conditions that lead to wound formation, such as optimal lifestyle measures (e.g., nutrition), medication,
and patient education. Other measures include debridement of necrotic tissue, local ulcer care,
mechanical off-loading, mechanical compression (for venous ulcers), and infection control.
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Biological Therapies
Biological therapies have been of great interest in wound healing therapies, and we specifically discuss
the use of cadaveric skin and xenografts, placental constructs, growth factors, hyperbaric oxygen therapy
(HBOT), biological skin equivalents, and stem cells (see Figure 2.1).
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Growth Factors
Growth factor–related wound repair has been of immense interest in wound healing science.
Commercially marketed growth factors currently available include recombinant human fibroblast growth
factor, recombinant human platelet-derived growth factor, and recombinant human epidermal growth
factor. Several other growth factors are also being developed.
Recombinant human epidermal growth factor is a well-known growth factor that can be applied topically
or injected and has been shown to improve wound healing in small clinical trials worldwide. 36 Fibroblast
growth factor has also shown promising results, in particular an isoform known as recombinant human
keratinocyte growth factor-2 to be applied as a topical spray. The trial showed significantly increased
wound healing compared with placebo. 37
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Platelet-Derived Growth Factors and Platelet-Rich Plasma
Several studies shown the efficacy of platelet-rich plasma (PRP) and PDGFs obtained from centrifugation
of blood. 38
PDGF has been demonstrated to be effective when compared with placebo, with 7 studies totaling 685
patients that showed a statistically significant percentage of ulcers healed compared with sham therapy. 39
The first commercially available topical PDGF in the United States is becaplermin gel (Regranex®), which
was studied in chronic diabetic foot ulcers. It is important to note that becaplermin gel contains the US
Food and Drug Administration (FDA) black box warning, whereby consumers are cautioned to the
increased risk of rate of mortality secondary to malignancy if several tubes are used. 40
Conversely, the evidence for PRP has been scant, with randomized controlled trial (RCT) data showing
no significant difference in the percentage of ulcers healed when compared with placebo or platelet-poor
plasma therapy. 39
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Stem Cells
There has been significant interest in the use of stem cells to address the defective pathways in aberrant
wound healing. Stem cells are undifferentiated cells that possess the ability to mature into differentiated
cells of either one embryonic germ layer (multipotent) or all three embryonic germ layers (pluripotent). 41
Perhaps one of the most widely studied multipotent adult stem cells in wound healing research has been
mesenchymal stem cells (MSCs). In several animal-based studies, MSCs have demonstrated the ability to
migrate to areas of cutaneous injury, secrete angiogenic and immune-mediating factors, and differentiate
into skin cells. 41 There are now several ongoing and published clinical trials using MSCs in wound
healing as well as a few commercial products. 41 Multiple clinical trials have shown promising outcomes
with regard to wound closure rates; however, they have been limited by small sample sizes and lack of
controls. 41 At the time of writing, several clinical trials in the United States are recruiting patients to
study the use of MSCs in healing cutaneous wounds. 41
However, challenges remain with stem cell technologies. Firstly, there are numerous ethical concerns
surrounding its use, in particular, pluripotent stem cells; hence, much of the research has focused on
multipotent stem cells. 41 Secondly, there are still many questions that need to be answered in the field.
Two important questions posited by Sorice et al are which population of stem cells are the most effective
in healing wounds and what is the best method to deliver stem cells into a wound? 41 These are important
considerations if stem cells are to move into clinical translation.
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Hyperbaric Oxygen Therapy
HBOT utilizes compression chambers to deliver high levels of oxygen concentration at raised
atmospheric pressures. HBOT aims to promote oxygen-dependent wound healing pathways and has
particularly been a treatment strategy when revascularization in vascular insufficiency has been
unsuccessful. 42 Systematic review evidence of four long-term studies totaling 233 patients concluded that
there was a significant difference in percentage of healed ulcers compared with sham therapy when
HBOT was used adjunctively, with one short-term study finding no significant difference. However,
strength of evidence was deemed low for all studies. One study of poor quality found HBOT less effective
compared with ESWT (n = 84). 39
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Cell Cultured Products
Cell cultured products, also known as tissue-engineered constructs, include Apligraf, Epicel, and
Dermagraft. Apligraf (Organogenesis, Canton, MA) utilizes a bovine collagen matrix incorporated with
human neonatal fibroblasts and neonatal keratinocytes to act as a scaffold as well as providing cells that
produce growth factors and ECM components. Similarly, Dermagraft (Organogenesis, Canton, MA)
comprises a polyglactin scaffold with dermal neonatal fibroblasts. A large Apligraf RCT (n = 309) found a
significant increase in the number of healed ulcers and a reduced length of time to complete healing
compared with standard therapy with compression. 39 Furthermore, cultured epithelial autografts using
patients’ own keratinocytes, such as Epicel, have been utilized to treat large burns and take 2 to 3 weeks
in culture to grow. 43 Genetic manipulation of keratinocytes has recently been reported to regenerate an
entire fully functional epidermal layer in junctional epidermolysis bullosa. 44
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Scaffolds
Scaffolds act as a platform for cell migration and angiogenesis and are a key therapeutic modality.
Scaffolds can be of human origin (donated tissue or cadaveric) and nonhuman origin (porcine or
synthesized through extraction and cross-linking). Several such scaffolds are commercially available.
Integra™ (Integra LifeSciences) is a bilayer matrix of bovine collagen and glycosaminoglycan derived
from shark skin that is lyophilized to form a highly porous scaffold. Integra™ has been used with
considerable success in burns, and clinical trial data have attested its use in the healing of chronic
wounds, specifically decreasing time to wound closure in diabetic foot ulcers. 45 Allopatch®, which is a
decellularized scaffold derived from human cadaveric tissue, has demonstrated efficacy in closure of
nonhealing diabetic foot ulcers. 46 Placental constructs, such as Grafix, which is a cryopreserved placental
membrane, have shown to significantly improve diabetic foot ulcer healing and reduce related
complications. 47
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Biophysical Forces
Negative-Pressure Wound Therapy
NPWT effectively ensures wound drainage, aids granulation tissue development, and expedites wound
contraction. 48 RCT data have shown improved healing of ulcers as well as reduced second amputations.
39
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Extracorporeal Shock Wave Therapy
ESWT delivers high-energy acoustic pulses to tissues and is the standard of care in treating
nephrolithiasis and various musculoskeletal conditions. It has been reported to improve cutaneous
wound healing through increasing cell proliferation and stimulating angiogenesis. 49
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Electromagnetic Therapies
Electromagnetic therapies, such as pulsed electromagnetic field therapy, have effectively been used in
orthopedic practice, and numerous in vitro and animal studies have demonstrated improved cutaneous
wound healing. These therapies are thought to interact with endogenous electric fields in the skin to
increase expression of growth factors and nitric oxide and also promote angiogenesis 50 (see Figure 2.4).
However, RCT data showed mixed results, with one showing no difference between placebo and
electromagnetic therapy and another reporting a significant increase in the percentage of healed ulcers
between the two groups. 39
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Knowledge Gaps
There has been an explosion in therapeutic options for wound healing in the last 30 years, as the number
of wounds has increased because of our aging population, increases in the incidence of type 2 diabetes,
and increases in obesity. Currently, there is a lack of clinical data in well-controlled prospective studies to
document the clinical efficacy of several of the modalities now used clinically including HBOT, PRP,
antimicrobial dressings, topical oxygen therapy, and pulsed electromagnetic stimulation. There is also
almost a complete lack of comparative studies on advanced wound healing modalities. Prospective RCTs
are challenging in wound healing because of the difficulty in binding both the patient and practitioner as
well as the desire by both to achieve a healed wound. Registry studies may provide a powerful method to
look at comparative advanced healing modalities and also allow us to better assess the cost-effectiveness
of these therapies.
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Acknowledgment
We would kindly like to acknowledge Mr. Ilya Shiltsin for the artwork in this chapter.
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Questions
1. A 65-year-old woman with diabetes mellitus presents with a heel ulceration not involving the
calcaneus. She has palpable pulses. Which therapy has the best published efficacy for healing?
a. HBOT
b. Silver alginate dressings
c. NPWT
d. Pulsed electromagnetic therapy
2. A 25-year-old man with paraplegia presents with a large ulcer over his right ischium that probes to
bone. What stage of pressure injury would this be considered?
a. Stage 1
b. Stage 2
c. Stage 3
d. Stage 4
e. Unstageable
3. A patient presents with a heavy scar 3 weeks following a stab wound to the back. What phase of
wound healing would this be considered?
a. Hemostasis
b. Inflammatory
c. Proliferation
d. Remodeling
4. Which of the following wound care modalities would mechanical forces be considered a major
factor in the mechanism of action?
a. Platelet-derived growth factor
b. Placental-derived constructs
c. Negative-pressure wound therapy
d. Saline wash
5. Which of the following would be considered a chronic wound?
a. A 67-year-old man with a 2-cm heel ulceration for 1 month who just completed external iliac
angioplasty
b. A 75-year-old woman with a prosthetic heart valve on Coumadin who presents with severe
bruising of her anterior tibial area 3 weeks after injury
c. A 30-year-old man with Crohn disease on steroids presents with a dehisced laparotomy
wound 1 month following surgery
d. A 45-year-old woman with breast cancer who has severe desquamation of her skin at the end
of her radiation therapy
e. A 24-year-old man paraplegic with an ischial stage 4 pressure injury for 3 months
1. Answer: c. Although all of these modalities have been proposed for use in this patient population,
NPWT has the most published high-level studies in wounds.
2. Answer: d. Pressure injuries that go to bone are considered stage 4.
3. Answer: d. Although there are components of inflammation and proliferation that are still
occurring, 3 weeks after an injury, the wound is being actively remodeled and would generally be
considered to be in the remodeling phase.
4. Answer: c. Negative-pressure wound therapy. This therapy is commonly used by placing an open-
pore polyurethane sponge directly over the wound and connecting this to suction. This induces
deformations to the wound surface and draws the wound together.
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5. Answer: e. Wounds should be present for 6 weeks to be considered chronic. Although the severe
bruising and the radiation injury cases could turn into chronic wounds, at this point these patients do
not have an actual wound.
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References
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Ingber, DE. Tensegrity, II. How structural networks influence cellular information processing networks. J Cell Sci. 2003;116(Pt 8):1397-1408.
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importance of extracellular matrix and cytoskeletal tension in cell signalling and cell growth.
Hunckler, J, de Mel, A. A current affair: electrotherapy in wound healing. J Multidiscip Healthc. 2017;10:179-194.
Wong, VW, Rustad, KC, Akaishi, S, et al. Focal adhesion kinase links mechanical force to skin fibrosis via inflammatory signaling. Nat Med.
2012;18(1):148-152.Key research paper that concluded the importance of mechnical forces in inflammatory pathways, particularly through focal
adhesion kinase signalling.
Wynn, TA. Common and unique mechanisms regulate fibrosis in various fibroproliferative diseases. J Clin Invest. 2007;117(3):524-529.
Prosdocimi, M, Bevilacqua, C. Exogenous hyaluronic acid and wound healing: an updated vision. Panminerva Med. 2012;54(2):129-135.
Lautenschlager, S, Eichmann, A. Differential diagnosis of leg ulcers. Curr Probl Dermatol. 1999;27:259-270.
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response to fibrinopeptide B. J Cell Physiol. 1995;162(1):9-14.
Schmid-Schonbein, GW, Takase, S, Bergan, JJ. New advances in the understanding of the pathophysiology of chronic venous insufficiency.
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Ochoa, O, Torres, FM, Shireman, PK. Chemokines and diabetic wound healing. Vascular. 2007;15(6):350-355.
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Blakytny, R, Jude, E. The molecular biology of chronic wounds and delayed healing in diabetes. Diabet Med. 2006;23(6):594-608.
Kuo, PC, Kao, CH, Chen, JK. Glycated type 1 collagen induces endothelial dysfunction in culture. In Vitro Cell Dev Biol Anim. 2007;43(10):338-
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Fernandez-Montequin, JI, Valenzuela-Silva, CM, Diaz, OG, et al. Intra-lesional injections of recombinant human epidermal growth factor
promote granulation and healing in advanced diabetic foot ulcers: multicenter, randomised, placebo-controlled, double-blind study. Int
Wound J. 2009;6(6):432-443.
Robson, MC, Phillips, TJ, Falanga, V, et al. Randomized trial of topically applied repifermin (recombinant human keratinocyte growth factor-
2) to accelerate wound healing in venous ulcers. Wound Repair Regen. 2001;9(5):347-352.
Driver, VR, Hanft, J, Fylling, CP, Beriou, JM. A prospective, randomized, controlled trial of autologous platelet-rich plasma gel for the
treatment of diabetic foot ulcers. Ostomy Wound Manage. 2006;52(6):68-70.
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Sorice, S, Rustad, KC, Li, AY, Gurtner, GC. The role of stem cell therapeutics in wound healing: current understanding and future directions.
Plast Reconstr Surg. 2016;138(3 suppl):31s-41s.
Kranke, P, Bennett, M, Roeckl-Wiedmann, I, Debus, S. Hyperbaric oxygen therapy for chronic wounds. Cochrane Database Syst Rev.
2004(2):Cd004123.
Carsin, H, Ainaud, P, Le Bever, H, et al. Cultured epithelial autografts in extensive burn coverage of severely traumatized patients: a five
year single-center experience with 30 patients. Burns. 2000;26(4):379-387.
Hirsch, T, Rothoeft, T, Teig, N, et al. Regeneration of the entire human epidermis using transgenic stem cells. Nature. 2017;551(7680):327-
332.Recent seminal research paper demonstrating that genetic manipulation of keratinocytes can regenerate an entire fully functional epidermal layer
in junctional epidermolysis bullosa.
Driver, VR, Lavery, LA, Reyzelman, AM, et al. A clinical trial of Integra Template for diabetic foot ulcer treatment. Wound Repair Regen.
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cost to closure of an acellular reticular allogenic human dermis versus standard of care in the treatment of chronic diabetic foot ulcers. Int
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Lavery, LA, Fulmer, J, Shebetka, KA, et al. The efficacy and safety of Grafix((R)) for the treatment of chronic diabetic foot ulcers: results of a
multi-centre, controlled, randomised, blinded, clinical trial. Int Wound J. 2014;11(5):554-560.
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C H A P T E R 3
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Management of Scars
Wyatt G. Payne and David J. Smith
Key Points
Keloids: Heaped scars that extend beyond the margins of the original wound; rarely spontaneously
regress; frequently result from minor trauma; familial predisposition common.
Hypertrophic scar: Raised; erythematous; pruritic; remains confined to the limits of the original
wound.
Fibroproliferative scars/healing describe a state of excessive healing with collagen formation
imbalance.
TGF-beta excess contributes to fibroproliferative scar formation (keloids and hypertrophic scar).
A combination of treatment modalities may be required for scar improvement management.
With the exception of fetal healing, 1,2 the end result of wound healing is a scar. In terms of evolution, this
process developed as a necessity to traumatic injury and as a response to the alternative—failure to
survive.
Scars can pose numerous problems and complications: seizures (brain scar), intestinal obstruction (bowel
scar), loss of range of motion (soft tissue, skin, muscle, joint scar), etc. Although normal scarring is
beneficial, as it achieves a healed wound, the site and extent of scar, as related to plastic surgery, may
pose both aesthetic and/or functional problems.
Normal wound healing is a complex series of dynamic interactive processes that begin at the moment of
wounding and involves soluble mediators, many cell types, and extracellular matrices. The process
follows a specific time sequence and includes coagulation, inflammation, deposition and differentiation
of extracellular matrix, fibroplasia, epithelialization, contraction, and remodeling with the end result—
formation of a healed wound, by scar. 3,4 The end result of normal scar is an equilibrium between collagen
synthesis/deposition and collagen lysis/degradation; the mature scar, which has approximately 80% of the
tensile strength of normal unwounded skin, occurs between 6 and 18 months after wounding. 5
Proliferative healing has been described by Dvorak as a spectrum with normal healing on one end and
tumor cell proliferation at the other. 6 Proliferative scar formation describes a series of events resulting in
overhealing as if an equilibrium point between collagen deposition and collagen lysis has never been
reached. 3,7
Types of proliferative scar formation include the following:
Keloids 3,5,8 (Figure 3.1)
Familial predisposition
Enlarged heaped-up scar that extends beyond the margins of the original wound
Rarely regress
Frequently result from relatively minor injury or insult
Elevated TGF-beta
Hypertrophic scars 3,5,8-10 (Figure 3.2)
Raised
Erythematous
Pruritic
Remain at the site or confines of the original wound
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Partial or total resolution or regression can spontaneously occur
Result from trauma, incision, burns
Result from prolonged wound healing
Increased epidermal/dermal thickness
Lack of epithelial ridges
Random orientation of collagen fibrils
Decreased collagen content
Elevated TGF-beta
Increased number of mast cells
Decreased collagen production
FIGURE 3.1 A. Keloid scarring of the ear after ear piercing. B. Massive keloid scarring of the ear. C. Extreme keloid formation
on the back and neck.
(Photos courtesy of Matthew Hiro, MD.)
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FIGURE 3.2 A,B. Hypertrophic burn scar of the hand with thumb web space contracture. C to E. Hypertrophic burn scar of the
axilla with axillary contracture.
(Photos courtesy of Matthew Hiro, MD.)
Related fibroproliferative disorders, all of which demonstrate similarities to proliferative scar 3,11-13 :
Periprosthetic capsules—capsular contracture
Dupuytren contracture—palmar fascia contractures
Rhinophyma—tissue fibrosis
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The Problem
Aesthetic Problems
Scarring may create a variably noticeable abnormality because of the direction, quality, position, size, or
orientation of the scar. Beauty is in the eye of the beholder. Assessing scars can be problematic, and
subjective measures sometimes determine the aesthetic problem for the patient, significant others,
professionals, or casual observers. Validated scar measures are described and used; however, what one
may declare acceptable, another may deem unsightly and unacceptable. 14-20 The displeasing scar is no
less problematic for some patients as functionally impairing scars.
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Functional Problems
Scarring can limit functional capability, and the mere presence of scar can be symptomatic, in and of
itself. Pain and pruritus are common symptomatic complaints. Scar contractures leading to diminished
range of motion at joints, or other structures dependent upon mobility for their function, can cause
variable disability. Scar bulk can also lead to pain, decreased function, and aesthetic concerns (as with
keloids).
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Prevention
As with most problems, an ounce of prevention is worth a pound of cure. The use of sound, meticulous
surgical wound closure technique to optimize operative incisional and traumatic wound closures to
minimize tension, adequately debride nonviable tissue, remove foreign bodies, approximate layers, fill
dead space, prevent hematoma and seroma, and prevent infection, and removing sutures at appropriate
time intervals, can contribute to minimizing scarring. 21-23 Adequate undermining with deep dermal
suturing creating wound edge eversion can aid to reduce wound tension and diminish/minimize scar
width. 21,24-26
Reducing chronic inflammation by alleviating foreign bodies, infection, and/or prolonged time to healing
can improve eventual wound/scar outcomes. 27 Adequate debridement, minimization of foreign materials
(including sutures), and wound closure timing (especially as with burn wound grafting) are all
advantageous to improve scarring outcomes. 28
Incision placement and orientation are of prime concern to eventual scar formation/noticeability and also
to relieve incisional tension. The noticeable scar is a function of light reflection that catches attention.
Placing scars in natural creases, in junctions between contours, and at the edges of hair-bearing skin can
camouflage to produce more inconspicuous scar lines. Working within the relaxed skin tension lines, as
described by Borges, Kraissl, and Langer, allows scars to lie in planes and directions of less obvious
orientation, and reduces the tension on incisions to produce less widened scars. 29-31
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Scar Management
Medical Management
Massage
Frequently advised for postoperative scarring, this noninvasive, inexpensive method of scar
manipulation/reduction does have evidence of effectiveness. 27,28 Although its usefulness is generally
limited, massage can aid in the flattening and softening of scars and limiting some scar contractures (e.g.,
after lower eyelid procedures). Reported to be of benefit in the scenario of burn scarring, improvements
in scar appearance, pruritic pain, and psychologic effects have been shown. 32 Professional massage
therapists appear to be of benefit in scarring related to burn. 32
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Silicone Gel
Application of silicone gel has been shown to benefit the appearance of hypertrophic scar, keloids, and
surgical incisions. 33-38 The mechanism of action appears to be the occlusive nature of silicone dressing and
epithelial hydration, not that of temperature increase, nor by any chemical effects of absorbed silicone.
36,39,40 Likely the effect is an influence in the collagen remodeling phase of wound healing. There is
differing evidence as to the efficacy of silicone gel as a preventative treatment measure as compared with
good evidence to indicate effective management after scarring. 21,23,33,41 Recommendation for treatment is
to wear the silicone gel dressing for 12 to 24 hours per day for 2 to 3 months at the onset of visible scar
abnormality.
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Compression, Pressure, and Mechanomodulation
Pressure garments are commonly utilized after burn injury/treatment to aid in hypertrophic scar control.
28,42 Compression garments are recommended prophylactically in burn injury after extensive skin grafting
and/or if spontaneous wound healing requires longer than 10 to 14 days. 27,28,43 The exact mechanism that
pressure garments influence hypertrophic scarring is not completely understood; however, influence on
collagen synthesis and remodeling is a likely effect. 43 Pressure requirements for effectiveness have not
been established, although 15 to 25 mm Hg is the target pressure reported by many authors. 9,43,44 The
appearance, discomfort, texture, and heat reflection/generation (especially in warm climates) of pressure
garments limit patient compliance and therefore their effectiveness.
Pressure therapy is also effective for keloid treatment/therapy, generally as a postoperative adjunctive
measure. 9,45 Compression earrings (for ear lobe keloids) are commercially available for postoperative
application but require patient compliance. Effectiveness may be up to 80% following complete surgical
excision. 9,21,22,45,46
Significant wound tension leads to widened scarring. 24-26,45 Mechanomodulation to relieve scar tension at
the time of incision closure can positively affect incisional scar formation and improve scar appearance.
23,25,26 Available as a commercial device and placed to redistribute and relieve tension across an incision
line, the device is well tolerated by patients, is effective, and has a minimal complication rate. 23,25 This
device is recommended for truncal incisions such as abdominoplasty.
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Corticosteroids
Injection of steroids (triamcinolone) is widely used as an initial treatment for keloids and hypertrophic
scars and is commonly applied in conjunction with other modalities including surgical excision to
decrease scar recurrence rates. 5,9,21,23,33,45 Dosage may range from 2.5 to 40 mg either as primary solo
treatment or prior to surgical excision and can be injected with a mixture of xylocaine + epinephrine to
diminish local pain and to decrease steroid dispersion, to maximize its effect. 22,46 Solo steroid therapy for
hypertrophic scars can be repeated at 4-week to 6-week intervals until the desired effect is observed, side
effects are observed, or if surgical excision is expected. Steroid pretreatment for keloids followed by
surgical excision and follow-up postoperative injections produce reported cure rates of up to 80%. 45,47-51
Complications and side effects arising from the use of injectable corticosteroids include skin atrophy,
hypopigmentation, and pain with injection. 45,47
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Radiation Therapy
Radiation therapy can be utilized as an adjunct therapeutic with surgical excision in the treatment of
keloids. Keloid excision followed by radiation therapy within 24 to 48 hours either as a single dose or as
multiple doses can reduce recurrence and lead to cure rates between 67% and 98%, depending on the
anatomic area. Although there is no overwhelming prospective evidence to indicate definitive
effectiveness of radiation therapy after surgical excision in keloid treatment, retrospective data from
relatively large clinical patient series indicate it as a worthwhile treatment. 52-55 Radiation damages keloid
fibroblasts, affecting collagen production and structure. 45,53,56 Radiation monotherapy is not effective.
Concern for generation of malignancy due to radiation therapy is advisable, especially in the pediatric
age patient or in areas prone to radiation-induced carcinomas, such as thyroid and breast. 57 The reported
rates for carcinogenesis are low, with few cases associating radiation therapy for treatment of keloids
with malignant tumor generation. Recommendations are for adequate shielding of vulnerable areas from
radiation and careful patient selection. 58
Radiation therapy for refractory/intractable hypertrophic scarring has been reported as effective;
however, there are few data to support its use. 53
Side effects of hyperpigmentation, hypopigmentation, and transient erythema have been reported. Few
wound healing problems have been attributed to the low-dose radiation, and soft tissue fibrosis as
encountered with higher doses of radiation therapy is not likely. 53
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Cryotherapy
Topical cryotherapy may achieve initial positive results in hypertrophic scars and keloid treatment;
subsequent recurrence rates are high, making this therapy less than optimal, unless repetitive
treatments/sessions are utilized. 58 Intralesional cryotherapy requiring a specialized cryoprobe does show
effectiveness, but this method is not widely used. 58
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Molecular Therapies
There is experimental (and some clinical) evidence to indicate that treatment of hypertrophic scar and/or
keloids with agents such as 5-fluorouracil, bleomycin, mitomycin C, tamoxifen, paclitaxel, methotrexate,
TGF-beta 3, and interferon may be of benefit. Likely the mechanisms of antiscarring action are due to
their interaction with TGF-beta receptors and downregulation of fibroblast function. 59-63 The current
utility of these agents is limited because of a lack of adequate clinical evidence.
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Botulinum Toxin
Botulinum toxin has recently been reported to improve surgical incisional scars. 64 Although only
reported as a small case series, final scar outcome improved with intraoperative injection of botulinum
toxin type A, 10 U/cm in a split-scar randomized trial. The presumed mechanism of action of botulinum
toxin is inhibition of TGF-beta 1 and cell cycle interaction, diminishing fibroblast cell
functions/regulation. 64
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Other Modalities
Vitamin E and onion extract have little clinical evidence to recommend their use for treatment. 21,65
Reviews of over-the-counter products with claims to scar treatment and scar improvement provide little
evidence for these products’ effectiveness beyond the earlier discussions. 66,67
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Surgical Management
Scar revision surgery can vary from excision(re-excision) and closure to more complex modalities and
combinations of modalities. The type of scar, extent of scarring, size, orientation, location, etiology,
symptomatology, and patient preferences are all factors to consider when planning surgical scar
treatments. Surgical adjuvants (corticosteroid injection, laser therapy, radiation therapy) deserve
consideration in planning scar treatment/management for their possible benefits (versus risks and side
effects).
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Excision and Direct Closure
Considered in instances where local tissue conditions warrant, minimal/no tension and optimal
orientation would be prime considerations. The etiology of unsatisfactory scar in this instance should be
considered so that results similar to the initial scarring problem are not repeated.
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Excision and Z-Plasty or W-Plasty Closure
Redirecting the orientation and tension of the scar to a more favorable or more optimal direction can
produce less tension, more proper alignment, and improved appearance. Borges 29,30 described
extensively the relaxed skin tension lines and the utilization of Z-plasty and W-plasty for the revision of
scars to improve their appearance as well as to describe the placement of incisions in orientations for
improved primary outcomes.
Z-plasty can be considered to realign tissue in instances of scar creating functional deficits such as joint
contracture. Functional reorientation and scar lengthening may improve limitation of motion and
decrease scar tension. A standard Z-plasty with equivalent length sides and an angle of 60 degrees
provides lengthening along the central limb of approximately 75% of its original length. A longer central
limb provides (theoretical) linear increase, as does increasing the Z-plasty angle. 29 Multiple in-series Z-
plasties can be used for longitudinal gain and reorientation. Adequate skin laxity lateral to the original
scar is necessary for adequate Z-plasty flap closure. W-plasty serves to break up the scar outline and
camouflage the appearance, producing less light reflection and less noticeability.
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Excision and Skin Grafting
This is helpful in instances of hypertrophic/widened scars with poor appearance and/or scars causing
functional limitations, such as with cicatricial ectropion of the eyelid or minor axillary contracture with
minimal linear banding. Attention to recreating the original tissue deficiency with adequate scar release
to the point of allowing full range of motion and overgrafting the original area of scarring can help to
minimize tension on the newly created site. Once skin grafting is complete, compression garments, range
of motion therapy, and scar massage may contribute to eventual improved outcomes.
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Excision, Dermal Replacement, and Grafting
Recent reports of improved scar revision outcomes have described the use of dermal replacement after
scar excision as a basis for secondary skin grafting as an adjuvant to scar and keloid surgical revisions. 68-
72 Acellular dermal matrix products allow for vascular ingrowth from contact of matrix edges with
normal tissue. These matrices are used over nonvascularized and minimally vascularized structures such
as exposed bones and tendons. As opposed to the time-limited nature of skin autografts, which require
relatively immediate revascularization for survival, dermal matrices time line of wound bed preparation
are longer but provide immediate wound coverage until second-stage grafting can be successfully
accomplished.
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Excision/Flap Closure
Flap closure after scar excision is worthy of consideration. Flaps including cutaneous, myocutaneous, and
fasciocutaneous, whether local, random, pedicled, perforator, or a free tissue transfer, can serve to relieve
tension in the area of original scar, fill dead space, and improve aesthetics and/or function. The more
severe the scar contracture, especially across major joints such as the knee, elbow, and axilla, the more
likely flap closure is indicated and beneficial. Maximal scar release, dead space filling, and tension-free
closure are required for adequate results.
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Combination Surgical Revision With Adjuvants
Excision with radiation therapy, excision with corticosteroids, and excision with pressure garments have
been discussed earlier.
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Laser Treatment
Laser has been successfully utilized and shown to improve scar appearance, although further
investigations are warranted. 72-75 Much of the positive supporting data are reported for hypertrophic
burn scarring utilizing pulsed dye 585/595-nm wavelength as treatment for pruritus and erythema. 72,76,77
Treatments for scar prevention as well as established hypertrophic scar therapy indicated response rates
in the range of 70%. 72,74 Other hypertrophic scarring etiologies such as median sternotomy and
inframammary scars have been reported to respond to, with good results. 78,79 Results concerning the
timing of pulsed dye laser treatments on hypertrophic burn scars appear to indicate that earlier treatment
with pulsed dye laser may lead to improved outcomes. 75,80 Hypertrophic scars, treated when early, less
than 1-year while still erythematous, responded better than those of more mature age.
Pulsed dye laser therapy works by destruction of scar microvasculature via photothermolysis, and
possibly collagen modulation by reducing TGF-beta expression. 75,76 CO2 laser is ablative, causing tissue
vaporization due to selective absorption by water in the tissues. 76
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