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Review Skin Grafts Jo Jo Leung, H.B.Mus, Faculty of Medicine (1T0), University of Toronto Dr. Joel Fish, M.D., M.Sc, FRCSC, Chief Medical Officer, St. John's Rehab Hospital; Past Director, Ross Tilley Burn Unit, Sunnybrook Health Sciences Centre; Associate Professor, Department of Surgery, University of Toronto; Attending Staff Surgeon, Sunnybrook Health Sciences Centre Abstract Skin grafting is one of the most commonly used techniques of the plastic and reconstructive surgeon and has progressed over the last century to the varied methods and materials used today. Skin substitutes range from wound dressings such as Biobrane, Dermagraft, and cultured allogenic keratinocytes to wound closure materials (including Integra, Alloderm, and cultured autologous keratinocytes.) The gold standard, however, remains the autologous split thickness skin graft. In this paper, we review the history of the skin graft, the physiology of graft take, and current surgical indications, procedures, and complications, as well as graft types and materials. Introduction S kin grafting is one of the most commonly used techniques of the plastic and reconstructive surgeon. The skin is the body’s largest organ and serves many physiological functions. Damage to this organ can lead to high rates of morbidity and mortality from infections and the inflammatory response. In the last century, techniques of skin grafting have progressed from relatively simple trial and error methods of skin transfer to the varied surgical techniques, skin substitutes, and physiological understanding of wound healing used today. History The concept of skin transplantation through flaps and grafts has long been in existence. The earliest use of skin grafting reportedly took place 2500 years ago by the Hindus. In the 1500s, Gaspare Tagliacozzi wrote a treatise describing a skin flap1 and in 1823, Buenger, a German physician, documented the first successful human skin graft, transferring skin from the buttock to the nose.2 Around 1870, Reverdin, a surgical resident in Paris, and George David Pollack, a British surgeon, separately reported attempts at skin grafting.3 Pollock experimented with various donor sources, including an unspecified human donor and then himself. He went on to describe one of the earliest accounts of transplant rejection. In 1872, Ollier experimented with split-thickness skin grafting (STSG) and in 1875, Wolfe first described fullthickness skin grafting.2 Plastic and reconstructive surgery saw an accelerated growth in use at the beginning of the 20th century. Prior to WWI, only very thin or full-thickness grafts were used.3 Blair and Brown documented successful split skin grafts and Padgett and Hood invent- ed the dermatome, a device used even today to harvest large grafts. In World War II, the injuries suffered by many soldiers, especially those in the airforce, led to a boom in the range of plastic surgery techniques invented and refined; advances in burn injury treatment were especially prominent. Skin grafting is also notable as a model for describing the second set transplantation rejection phenomenon, where the first graft sensitizes the recipient’s body to reject the second graft. Graft Sources Materials from skin grafts come from a variety of sources. Biological grafts include: autografts, which are harvested from a donor site on the patient, isografts from a genetically identical donor (i.e. twins), allografts from another individual (e.g. cadaveric skin), and xenografts from an animal source. Prosthetic grafts are manmade skin substitutes.4 Split Thickness versus Full Thickness Skin grafts are either split thickness or full thickness. Split thickness skin grafts (STSG) contain the epidermis and varying thicknesses of dermis. Since blood and nutrients are initially supplied to the graft by osmosis, the thinner the graft, the easier it is to maintain (conversely, thicker skin grafts require a bigger blood supply.) An important benefit of STSG is that once the epidermis has regenerated (approximately 10 days), the donor site may be re-harvested, a critical characteristic if a patient has a shortage of healthy donor sites (e.g. post trauma.)2,3,4 STSG are indicated for large surface coverage, cavities, and mucosal defects. They are commonly used for muscle flap coverage as well as skin flaps. Techniques of harvesting a STSG include the knife or scalpel (e.g. Foulian, Weck or Blair) or dermatomes. Figure 1. Graft using a dermatome. UTMJ • Volume 86, Number 2, March 2009 61 Review Skin Grafts The knife is preferred for areas that are difficult to access or have irregular borders. Dermatomes are used for large areas of consistent contour and thickness (e.g. thigh or back) and may be driven by air or electricity.2,3,4 (See Figure 1) Physiology of Graft Take Graft take occurs in four stages (see Table 1 below). Table 1. Stages in Graft Take Stage Event Imbibition Day 0-3. The graft receives nutrients from the plasma through direct contact Revascularization Day 3-7. Exact mechanism is unknown. Graft and donor site regenerate or generate new blood vessels, which anastomose and allow blood flow to begin. Regeneration Dermal appendages and sweat glands regenerate. Reinnervation begins and the graft takes on recipient site sweating pattern. Reinnervation Graft takes on nerve pattern of recipient site. Although STSG are reinnervated faster, FTSG have a better final result. the graft is kept moist and sterile.2 A stiff plastic backing may be used to spread out the graft and to mesh if necessary. Once the grafts have been obtained, the recipient site is prepared as needed – for example, temporary skin dressings are removed and dead or unhealthy tissue debrided. Grafts are applied on the tissue bed and may be attached using staples or surgical glue. Grafts may be meshed (See Figures 2 and 3). This maximizes the area covered by a graft and minimizes the amount of donor site needed. It allows the graft to better achieve the contour of the recipient site, making for a better graft take and permitting fluid drainage, thereby decreasing the risk of a hematoma or seroma. However, the marks of meshing will remain, making it a technique to be avoided on areas like the face and arms, where a more desirable cosmetic effect can be achieved by sheet graft. Another characteristic of meshing is that the graft is more likely to contract; this effect may help shrink the wound, but is best avoided over joint areas.4 Applications/Indications Wounds that have skin loss close naturally by two main mechanisms: epithelial migration and wound contraction. Contraction is a consequence of granulation tissue formation and myofibroblasts, which allow the wound edges to tighten and shrink together. This creates an area of tight skin called a contracture, which may be undesirable in areas that are highly visible or require mobility, such as the skin over joints. Further, wounds closed through epithelial migration occur from the wound edges, but lack the anchors, called rete pegs, that secure epidermis and dermis so the tissue is easily avulsed.3 When these natural processes are insufficient, the surgeon has the option of a skin graft or flap. Basic Surgical Procedure Grafting takes place in several stages, often through multiple operations. The exact plan of action depends on the sites chosen, wound type, coverage needed, infection, patient’s medical condition, and other factors. Only when the plan is coordinated will the operations begin. The following is an example of skin graft harvest and placement, as performed by the authors while at the Ross Tilley Burn Centre at Sunnybrook Hospital in Toronto, Ontario. Many variations of this procedure exist. To prepare the donor site, the surgeon chooses an area based on availability of healthy skin, visibility of a scar, patient preference, etc. If the recipient site is above the clavicles, then the ideal donor site is also from the “blush zones” above the clavicles. This provides a closer colour and texture match for a better cosmetic result.3,4 Operative sites are marked, prepared, and draped. The donor site is injected with a tumescent solution containing saline to firm and even out the skin and epinephrine to locally vasoconstrict and decrease bleeding. If a dermatome is used, mineral oil is applied and the dermatome is used to harvest the skin. Once obtained, 62 Figure 2. Meshing device and graft. Figure 3. Meshed graft. UTMJ • Volume 86, Number 2, March 2009 Review Skin Grafts Complications and Failure Grafts are susceptible to a variety of complications leading to graft failure. Most commonly, these include hematoma, poor take due to shearing forces, infections, and rejection.2,3,4 Hematomas can be prevented through use of meshing, as well as proper and compressive dressings. Vacuum-assisted closure is one method of achieving proper drainage and contact with the wound bed. Elevation of the recipient site also aids in drainage.2,3,4 Infections are minimized through proper surgical and nursing techniques and antibiotic prophylaxis, as indicated. Allografts and other biological dressings are treated to maximize sterility and decrease infection rates.3,4 One less encountered, but still common and easily avoidable error is misplacing the graft dermis side up. Inspection will show that the dermal side is shinier2 and the authors have found that an easy way of distinguishing the correct side is to float the graft in saline and observe the direction of curl; the dermal side will be turned inwards. Skin Substitutes Figure 4. Hand with Biobrane. The current ideal is to use an autologous skin graft, however, depending on the patient’s condition, donor sites might not be available. The patient will also have large areas of scarring. There is a limited supply of allogenic grafts from cadavers and these will always be rejected within weeks to months.1 Thus, prosthetic skin substitutes are often used. There are two categories of skin substitutes – wound dressings and materials that are integrated as part of wound closure (See Table 2). Table 2. Skins Substitutes Purpose Wound Dressings Wound Closure Temporary cover; used Integrated into the wound bed; to protect the wound bed these materials also protect and prepare it to receive a permanent graft and prepare the wound bed, but some may function as the permanent graft Examples Cadaveric grafts Integra Amniotic membranes Alloderm Biobrane Autologous keratinocytes Figure 5. Hand with Jelonet and graft. Dermagraft Allogenic keratinocytes Wound Dressings Wound dressings are designed for temporary coverage and are used to protect and prepare the wound bed before the final skin graft is placed. There are many types currently in use. Allogenic cadaveric grafts are often used in Canada, but have limited availability and are subject to rejection.1 Amniotic membranes, taken from the innermost layer of the amniotic sac, have been used since 1910. Their effectiveness is similar to allografts, but they are more fragile, are not integrated into the skin, and are suitable mainly for shallow wounds.5 Biobrane is a bilaminate membrane of nylon mesh bonded to a thin layer of silicone. The mesh contains porcine collagen peptides to aid in adherence and revascularization. As the wound Figure 6. Hand healed. UTMJ • Volume 86, Number 2, March 2009 63 Review Skin Grafts heals, Biobrane separates and is easily peeled off. It can be used on the donor site to aid healing and is commonly used in Canada.6 (See Figures 4, 5 and 6) Dermagraft is a cryopreserved living dermal structure with neonatal allogenic fibroblasts on an absorbable matrix of polyglycolic acid or polyglactin-910 (marketed as Vicryl or Dexon). The fibroblasts secrete growth factors and dermal proteins, which stimulate ingrowth and epithelialisation.6 Dermagraft is not to be confused with Transcyte (formerly called Dermagraft TC, where TC refers to temporary cover), consisting of fibroblasts on a nylon mesh that is non-absorbable. Transcyte is not currently available in Canada.5,6,7 Cultured allogenic keratinocytes secrete growth factors and cytokines. After 7 days in culture, they no longer express MHC class II and HLA class I antigens so there is no acute rejection. However, these cells have a short life span, usually 1-6 weeks with greater life spans related to a healthy dermis.6,7 These are not yet available in Canada. and costs decrease, we may someday see a shift in the preferred materials for skin grafting. Acknowledgements The author wishes to thank the staff and patients of the Ross Tilley Burn Centre for their wonderful teaching. All photos courtesy of Dr. Joel Fish. References 1. 2. 3. 4. 5. 6. Wound Closure Integra is one of the most widely used products for wound closure and consists of two layers: a membrane of bovine collagen and glycosaminoglycan and a silicone membrane. The collagen is integrated to form a “neodermis”, which remains while the silicon layer is removed and a STSG applied over the neodermis.2,5,6,7 Integra is available in Canada. Alloderm is treated human cadaveric skin from which “cellular and dermal components are removed” so that there is no rejection. Its main function is to be a dermal regeneration template, similar to Dermagraft. Since it provides little barrier function, there is some debate over its classification as a skin substitute for closure or cover.6,7 It is used in Canada, albeit sparingly. Cultured autologous keratinocytes are grown from the patient’s own cells and grown in vitro to form sheets. Although there is no rejection and only a small donor site is needed, such a procedure is of limited use in trauma patients, since they take several weeks to produce. The sheets are also very fragile and may take weeks to months to develop firm anchors. Elastin production may take up to 4-5 years. These are available in Canada.6,7 7. Andreassi A, Bilenchi R, Biagioli, M, D’Aniello C. Classification and pathophysiology of skin grafts. Clinics in Dermatology. 2005 23:332-337. MacFarlane DF. Current Techniques in Skin Grafting. Advances in Dermatology. 2006; 125-138. Fisher JC, Dobke MK. Skin Grafting. In: Georgiade GS, Georgiade NG, Riefkohl R, Barwick WJ, editors. Textbook of Plastic, Maxillofacial and Reconstructive Surgery. 2nd ed. Williams and Wilkins; 1992. p. 19-28 Chang EY. Grafts. In: Brown DL, Borschel GH, editors. Michigan Manual of Plastic Surgery. Lippincott; 2004. p. 16-21. Atiyeh BS, Hayek SN, Gunn SW. New technologies for burn wound closure and healing - review of the literature. Burns 2005; 31:944-956. Jones I, Currie L, Martin R. A guide to biological skin substitutes. British Journal of Plastic Surgery 2002, 55:185-193. Bar-Meir E, Mendes D, Winkler E. Skin Substitutes. Israel Medical Association Journal. 2006; 8:188-191. Future Direction One of the main problems faced in biological skin substitutes is the rejection phenomenon. There is work towards the development of cultured allogenic keratocyte sheets that are not rejected and become fully incorporated in the tissue. Research is also ongoing in the area of molecular and genetic manipulation to selectively maximize patients’ own beneficial growth factors while suppressing unwanted inflammatory responses.5,6 Conclusion Skin grafting is a well-established and fundamental technique in the area of wound management and healing. Over the past century and a half, we have progressed from rudimentary trial and error methods to the range of surgical techniques and skin substitutes used today. The gold standard, however, remains the autologous split thickness skin graft. As technology progresses 64 UTMJ • Volume 86, Number 2, March 2009