NEW DIRECTIONS IN PLASTIC SURGERY, PART II 0094–1298/02 $15.00 .00

SKIN RESURFACING FOR THE BURNED PATIENT

Ryan A. Stanton, MD, and David A. Billmire, MD

The ultimate goal and eventual reward in factory quality of life and adapt a functional treating severely burned patients is the estab- postburn lifestyle. A rough indicator of indi- lishment of a protective barrier from the out- vidual psychologic rehabilitation is reflected side world. Skin resurfacing for the burned by employment status. Patients who return to patient has made large strides since the mid- work after burn injury have less behavioral twentieth century. Improvements in resuscita- avoidance, higher self esteem, and greater at- tion, management of inhalation injuries, and tention to goals. It has been shown that the other advances in critical care are responsible most significant predictors of return to work for survival rates in burned patients nearly are involvement of the hand, grafting, size of doubling since the 1950s, increasing by al- burn, and age. Patients younger than 45 have most 1% each year.49, 57 Several factors have a higher return to work rate.74 The care of a contributed extensively to the evolution of severely burned patient requires the infra- clinical burn care, including a better under- structure of a dedicated burn center with in- standing of the critical need for adequate terdisciplinary involvement of nursing, coun- fluid resuscitation immediately postburn, seling, group therapy, and occupational and prophylaxis against wound sepsis and its physical therapy. Interventions designed to complications, the importance of adequate aid adjustment, work hardening, and other nutritional support, burn pathophysiology rehabilitative services and marital and family and its inflammatory mediators, management therapy are also important. All these services of airway and pulmonary complications, and are crucial in maximizing a patient’s psy- early surgical intervention. As a result, chologic and functional outcome. burned patients commonly are surviving with greater than 90% total body surface area (TBSA) burns. As of the year 2000, with the MANAGEMENT OF THE ACUTE advances in tissue engineering, it was techni- BURN WOUND cally feasible to resurface a nearly 100% total body surface burn. The goal for managing an acute burn is Despite the long-term sequelae of burn in- coverage. The initial wound should be kept juries, many burned patients achieve a satis- moist and surrounding tissues protected from

From the Division of Plastic, Reconstructive, and Hand Surgery, University of Cincinnati College of Medicine (RAS); and Department of Plastic Surgery, The Children’s Hospital Medical Center and The Shriners Hospital for Children– Cincinnati Burn Unit (DAB), Cincinnati, Ohio

CLINICS IN PLASTIC SURGERY

VOLUME 29 • NUMBER 1 • JANUARY 2002 29 30 STANTON & BILLMIRE trauma. From the time the burn wound pre- thin walled, or across a joint. Another reason sents until the time it is resurfaced com- to remove blisters is that they can obscure pletely, it is subjected to a variety of modal- the view of tissue beneath and its ongoing ities, from the initial cleansing techniques to evaluation for healing or infection. application of topical agents and dressings, escharectomy, and grafting with temporary or permanent coverage by allograft, autograft, Topical Agents or various skin substitutes. A review of the steps from start to finish provides the clini- Topical agents were developed in the 1960s cian with an up-to-date, logical management to help prevent burn wound infection or sep- protocol for the burned patient. sis.47 When the eschar is still present, the clini- cian needs to use topical agents that have penetrating properties. All topical agents Cleansing Techniques should have the quality of being nontoxic locally and systemically. Location, depth of Most patients with a burn injury undergo the burn wound, and the type of micro-organ- some form of hydrotherapy.60 For obvious isms present will dictate the choice of topical full-thickness injury with frank eschar, pa- agent. Topical agents currently available in- tients simply are cleansed with a soapy solu- clude silver sulfadiazine, most commonly tion upon arrival to the burn unit. The pre- used as a topical preparation in the form of a ferred antimicrobial soap at the authors’ 1% soluble cream. It is effective against gram- institution is 4% chlorhexidine. The wounds positive and gram-negative bacteria, includ- then are cleansed daily and dressed with a ing some Pseudomonas. There is some eschar topical antimicrobial and gauze. Those pa- penetration, so it will kill some organisms tients whose burns have not yet declared below the surface. Unfortunately, it has been themselves as deep-partial thickness or full- shown to inhibit fibroblast growth and slow thickness injury are treated to some form of epithelial migration and hence may thwart nonsubmersion or immersion hydrotherapy. these processes in superficial partial-thickness In the nonsubmersion group, they usually are burns. Mafenide acetate is available in a treated daily with a shower or bed bath, de- cream or 5% solution. The cream is an ex- pending on their mobility. Showers must be tremely useful topical agent because of its combined with wiping or scrubbing to de- ability to penetrate eschar with relative ease. crease the bacterial load on the surface of the The solution is used for wet dressings. Both wound effectively. Immersion with or with- formulations are effective against essentially out agitation is used additionally in some all bacteria. It is not effective against yeast, facilities. This immersion is usually in the however, and therefore not recommended as form of a whirlpool and should be limited to prophylaxis or therapy for yeast infections. less than 30 minutes with water temperatures Because of its ability to inhibit carbonic anhy- of 90 to 100 Fahrenheit (32.3 to 37.8 Cel- drase, it can lead to metabolic acidosis, espe- sius). Slightly cooler temperatures are needed cially in large-percentage TBSA burns in the for the elderly and the young whose thinner pediatric population. Silver nitrate is avail- dermis is less tolerant to the warmer tempera- able as a 0.5% solution or a 95% stick. It can tures. be used to treat yeast colonization but does Although blisters may be thought of as bio- not penetrate eschar. If needed to target yeast logic dressings, there is controversy whether infection in the subeschar region, it is recom- blisters should be left intact or debrided. Re- mended to cross-hatch the eschar to allow its search has shown that the fluid in blisters can penetration into the subeschar plane. Al- inhibit white cell function and increase the though the ability to penetrate the eschar is a inflammatory response.55 For that reason, re- factor, it is of less concern in current therapy, moval of blisters is common in burn wound which is based on rapid excision and cover- management, particularly if they are large, age. Silver nitrate also is harmful to fibro- SKIN RESURFACING FOR THE BURNED PATIENT 31 blasts and should not be used on a clean, Deep Partial-Thickness Burns (Second De- healing partial-thickness wound. Topical anti- gree, Deep) biotic ointments include bacitracin (Poly- 17. Epidermis, papillary dermis, and par- sporin and Neosporin) and are used primar- tial reticular dermis ily for the antimicrobial activity against gram- 18. Mix of red and waxy white coloration positive organisms. They have not yet been 19. Large amounts of exudate shown to slow re-epithelialization, and they 20. Sluggish capillary refill can be used on clean, healing partial-thick- 21. Dull pain ness wounds if a topical agent is desired. It is 22. Massive edema, causing problems with important that they be used sparingly to range of motion over joints avoid maceration of the surrounding tissue. 23. Spontaneously heals within 21 days (re- As the wound begins to heal, antibiotic oint- epithelializes) ments are no longer necessary and should be 24. Hypertrophic scarring and scar con- halted to avoid a yeast infection. tractures evolve Other topical agents available include en- Full-Thickness Burns (Third Degree) zymatic debriding agents, arginine-glycine- 25. Epidermis and entire dermis involved aspartic acid-peptide matrix, and pheny- 26. Mosaic of colors possible including toin.39, 44 All have been shown in one study black, tan, red, and white or another to enhance the healing of partial- 27. No blanching; reddened areas stay red thickness burns and donor sites. The overall when pressure is applied because of use of these agents is probably rather modest. hemoglobin from trapped ruptured red Finally, the evolving understanding of basic blood cells wound healing and its growth factor milieu 28. Superficial veins may be thrombosed is being manipulated in the burn wound to 29. Dry, rigid, leathery tissue consistency accelerate healing of the skin graft donor site 30. Eschar appears depressed with signifi- and interstices of meshed skin grafts.27, 61, 62 cant edema distally BURN WOUND CLASSIFICATION 31. Escharotomy or fasciotomy may be re- quired Superficial Burns (First Degree) 32. Not painful or tender 1. Epidermis only 33. Hair is avulsed easily from burned 2. Red or pink coloration hair follicles 3. Dry and peels 34. No spontaneous healing 4. Occasional tiny blisters Subdermal Burns 5. Delayed pain 35. Involve subcutaneous tissue (fat, bone, 6. Modest edema, most pronounced in muscle, tendon), commonly from elec- eyelids trical burns 7. Spontaneously heals in 3–5 days 36. Slow demarcation (up to 5–7 days) with 8. No scar electrical burns Superficial Partial-Thickness Burns (Second 37. Mummified appearance Degree, Superficial) 38. Thrombosed blood vessels possible, su- 9. Epidermis and papillary dermis in- perficial and deep volved 39. Neuromuscular involvement/paralysis 10. Large, intact blisters possible 11. Weeps exudate 40. Insensate 12. Exquisite pain 41. No spontaneous healing 13. Blanches with brisk capillary refill 14. Variable, moderate edema 15. Spontaneously heals within 10–14 days BURNS REQUIRING RESURFACING (re-epithelializes) 16. Minimal scar (some dyschromia possi- Burns traditionally have been classified ac- ble) cording to depth of injury and hence, require- 32 STANTON & BILLMIRE ment for skin resurfacing. Generally speak- reducing the production of inflammatory me- ing, epidermal and superficial partial- diators that drive this process. thickness burns are those that will re-epithe- lialize in 10 to 14 days and do not need Escharectomy: Standard of Care resurfacing. Deep partial-thickness wounds usually heal with significant scarring and Concern about removal of unnecessary tis- wound contraction. These wounds should be sue during primary excision was addressed resurfaced for better results. Full-thickness by Janzekovic, who developed the technique wounds obviously require resurfacing. For of tangential excision.36 In this technique, se- most recorded history, burn wounds were at- rial layers of deep partial-thickness burns tended to in a conservative medical fashion. were shaved until pinpoint arteriolar bleed- They were essentially washed gently and ing was seen, indicating the level of viable then left open or lightly wrapped in dress- tissue had been reached. This approach ings. The eschar was left intact and allowed proved to have clear advantages compared to separate naturally during the next 2 to 3 with aggressive excisions down to fascia, in- weeks. This process allowed for the inevitable cluding more rapid healing, less surgical bacterial colonization of the intact eschar. Par- blood loss, shorter hospital stays, reduced tial-thickness burns would heal during this medical costs, less disfigurement, and de- process of natural separation, but full-thick- creased hypertrophic scarring. ness burns would granulate, providing a sub- By the 1990s staged primary excision of strate for autografting. The advantage that major burn wounds was instituted com- this process had in delaying surgical treat- monly during the acute phase of resuscita- ment until natural separation of the eschar tion, coinciding with approximately the third was the ability to delineate clearly the areas day postburn. Most burn surgeons today that would heal spontaneously from those would advocate undertaking early escharec- that would require grafting. In severe burn tomy from 1 to 3 days postburn.31, 32, 45, 46, 64 It injury, however, this advantage is outweighed should be noted that the process of incising by the protracted time of healing and the the burn eschar or escharotomy must be per- enormous likelihood that the bacterial coloni- formed emergently in cases of circumferen- zation of the burn wound will lead to wound tial burn wounds with compartment pres- infection, sepsis, and death. Further under- sures greater than 30 mm Hg to avoid standing of burn wound pathology was ad- compartment syndrome. Research (in lab an- vanced greatly by the work of Jackson,35 who imals) regarding early escharectomy has first described the three concentric zones of shown that immediate removal of dead and thermal injury, that is, zone of coagulation, severely damaged tissue interrupts and at- zone of stasis, and zone of hyperemia. Others tenuates systemic inflammatory response extended this work and showed that progres- syndrome and normalizes immune function sive microvascular compromise occurs in the after burn injury.11, 15, 17, 18, 19, 34 zone of stasis in unexcised burn wounds for The potential for significant blood loss up to 48 hours postburn. Progressive compro- should always be a serious concern of the mise of tissue perfusion, because of edema, burn surgeon. Recommendations to minimize release of vasoconstrictive inflammatory me- blood loss include doing staged excisions, es- diators, and arteriolar thrombosis, leads to pecially for large-percentage TBSA.16 A con- further tissue death in the zone of stasis and servative recommendation is to perform less effectively widens and deepens the nonviable than 25% TBSA escharectomy per session. It portion of the burn wound.8 Once these is possible to do up to 60% TBSA escharecto- mechanisms were understood sufficiently, the mies using the following recommendations, importance of removal of the burn eschar in however. a timely fashion was appreciated. Removal The subeschar tissue plain should be infil- of eschar not only eliminates a substrate for trated with a 1:1,000,000 epinephrine solution bacterial growth but also limits conversion (1 mL of 1:100,000 epinephrine per 1 L of of damaged tissue into devitalized tissue by lactated Ringers solution) and 10 minutes, SKIN RESURFACING FOR THE BURNED PATIENT 33 preferably 15 to 20 minutes are allowed for can be rather extensive when excising large the epinephrine to take effect before the burns and harvesting skin graft for their cov- escharectomy. When performing excisions on erage; therefore, staging these two procedures extremities, a pneumatic tourniquet can and fractionates the blood loss making blood/vol- should be used. Dilute epinephrine–soaked ume replacement safer. The extent, indetermi- laparotomy pads should be applied to the nate depth, and bleeding from the excision excised areas immediately after excision. Elec- often preclude acute definitive coverage. In trocautery is used to obtain hemostasis of these cases, the wound should be dressed the larger bleeding points as necessary. An in antibiotic gauze type dressing and efficient team of doctors and nurses helps this reinspected in 24 to 48 hours. At this time, process move along smoothly. the wound will be dry, and the physician Contraindications to early escharectomy can better assess whether the excision was are few and rare. Congenital or iatrogenic adequate. The coverage can be temporary or coagulopathies must be addressed before sur- permanent, depending on the availability of gery. In multitrauma cases, the patient some- donor sites. Factors involved in determining times requires diagnostic evaluation, stabili- coverage go beyond the percent TBSA in- zation, and treatment of other injuries that volved and the availability of donor sites. are more immediately life threatening than Burn wounds involving the face and hands the burn before primary burn excision is con- take priority. Although autogenous skin sidered. Finally, any patient who is in shock grafts are the coverage of choice, large burns on admission is not a candidate for early require some type of temporary coverage or escharectomy until obviously stabilized. dressing. Ideally the materials used for tem- In summary, escharectomy is an early treat- porary coverage have the following qualities ment modality of the burned patient that has and characteristics: they should adhere rap- evolved beyond the initial primary medical idly to the wound bed; once adherent, limit management of the burned patient and now bacterial colonization and proliferation; con- can be recognized as one of the most im- trol the permeability of water and oxygen; portant factors contributing to improved sur- limit fluid/electrolyte/heat loss; and alleviate vival after major burn injury. wound pain. They also should be elastic and durable, sterile, nonantigenic, and readily available for use. Ultimately they should pro- mote re-epithelialization of the wound. Fi- COVERAGE OF THE BURN WOUND nally, some of the coverage materials have the ability to provide wound healing growth After the debridement or tangential exci- factors to the burned wound bed. sion of the burn wound, the decision needs to be made on how the wound will be cov- ered. For those wounds not requiring graft- Temporary Coverage Materials ing, that is, superficial and superficial partial- thickness burns, the usual and necessary Temporary coverage materials generally wound cleansing and debridement of blisters fall into one of two categories: biologic or as needed are performed followed by a dress- bioengineered skin substitutes. Of the ing of the physician’s choice. For relatively biologic materials, fresh, irradiated or fro- small burns, a topical antimicrobial impreg- zen cadavaric skin (i.e., allograft), amniotic nated into a nonadherent gauze dressing fol- membrane, or porcine xenografts may be lowed by coarse cotton gauze may be em- used.41, 67, 70 These biologic dressings generally ployed. For larger-percentage TBSA, the maintain a clean wound environment until clinician may elect to do the same or place skin grafting can be achieved, or they may be one of the various biosynthetic dressings, al- the only dressing placed on a partial-thick- lograft, tissue-engineered skin substitutes, or ness wound until completely re-epithelial- dermal grafts. ized, at which time they slough off. Biologic Deep partial-thickness and full-thickness dressings provide a safe physiologic environ- burns require a different approach. Blood loss ment for healing. They reduce heat and fluid 34 STANTON & BILLMIRE loss from the wound and markedly reduce 1).41, 42, 43 In extensive full-thickness burns, the pain by protecting dermal nerve endings, allograft will maintain the wound bed integ- thus allowing early mobilization of the pa- rity until donor sites have healed and are tient. The body eventually rejects them as a ready for reharvesting. In partial-thickness foreign object, however. Enzymatic degrada- burns, the remaining dermal layers of the tion and digestion of the biologic dressings skin that are protected by this temporary bio- ensue relatively soon after their application. logic dressing produce permanent epidermal Additionally, biologic dressings are suscepti- wound coverage in an average of 8 days. At ble to infection and must be monitored 12 to 14 days postoperatively, the nonadher- closely for bacterial overgrowth. ent portions of the biologic dressings slough Fresh allograft is better than frozen.72 Fur- off spontaneously or occasionally require se- thermore, irradiation of allografts serves as a rial whirlpool debridements. If significant preservative and sterilizing agent, allowing nonhealing areas are seen after this treatment, storage at room temperature for up to a year elective autografting or other means of per- and a significant reduced risk for viral trans- manent coverage can be scheduled. Small mission. The graft will take but then is re- open areas that are likely to progress to heal- jected by cell-mediated immunity 10 to 14 ing without grafting can continue to be man- days later. Patients with massive burns are aged usually on an outpatient basis by daily essentially immunosuppressed, and the allo- cleansing and application of an antibacterial graft may remain intact for weeks (Fig. topical agent.

Figure 1. Patient with massive burn (80% total body surface area) status postescharectomy and temporary coverage of lower two thirds of back with fresh allograft. A, Two weeks postoperative showing Ͼ90% take and survival of allograft. B, Three weeks postoperative manifesting signs of rejection including cyanosis, loosening, and frank slough. (Courtesy of Glenn Warden, MD, Shriners Hospital for Children–Cincinnati Burn Unit, Cincinnati, OH.) (See also Color Plate 3, Fig. 5.) SKIN RESURFACING FOR THE BURNED PATIENT 35

Biobrane (Woodruff Labs, Santa Ana, CA) depending on these components, most, if not is a biosynthetic wound dressing constructed all, can be used as temporary coverage, and of a silicone film with a nylon fabric partially about half of them can be used for permanent embedded in the film. The fabric presents to closure of deep partial- and full-thickness the wound bed a complex, three-dimensional burns. structure of trifilamentous threads to which collagen has been bound chemically. Within 24 hours, blood and sera clot in the nylon Epidermal Substitutes matrix, thereby firmly adhering the dressing Epicel (Genzyme, Cambridge, MA) is pro- to the wound until epithelialization occurs. duced from culturing autologous human epi- While this is going on, the material is adher- dermal keratinocytes from a patient biopsy ent enough such that the patient can move and during a 3- or more week period can be freely. Because it is a semipermeable mem- grown up to 100-fold. The advantage of this brane, it establishes a homeostatic environ- product is that it is entirely autogenous and ment, decreasing fluid loss and pain, and therefore nonimmunogenic. It tends to be a does not have to be changed because it falls rather fragile permanent resurfacing material, off the wound bed as epithelialization occurs however. and is trimmed as needed.21 When it is placed on a full-thickness burn, it should be changed at any sign of bacterial colonization and infec- Dermal Substitutes tion or separation. Table 1 gives a fairly thorough explanation TransCyte (Smith and Nephew, Largo, FL) of the composition and use of many various is produced by culturing neonatal human biologic tissue–engineered materials avail- dermal fibroblasts on to a biosynthetic mate- able. Basically, these are made up of cellular rial consisting of an ultrathin, semipermeable or acellular materials and their combinations. membrane of silicone bonded to a scaffold of In essence, they provide an epidermal substi- nylon mesh and bovine collagen. The nylon tute or a dermal substitute. The agents that mesh forms a three-dimensional scaffold for are dermal substitutes also provide a sub- growth of dermal tissue and the membrane strate for eventual overgrafting with thin au- forms synthetic (nonimmunogenic) epider- togenous split thickness skin grafts (i.e., per- mis. As the fibroblasts proliferate in the nylon manent coverage). This approach allows mesh, they secrete structural proteins and earlier reharvest of donor sites. Of course, growth factors, thereby generating a three-

Table 1. TISSUE-ENGINEERED MATERIALS Material Structure Coverage

Oasis (Cook, Spencer, IN) Lyophilized, acellular porcine small Temporary for partial-thickness intestinal submucosa burns and skin donor sites TransCyte (Smith and Nephew, Silicone and bovine collagen polymer Temporary for partial-thickness and Largo, FL) membrane–containing cultured full-thickness burns neonatal human fibroblasts Alloderm (LifeCell, Woodland, TX) Freeze-dried (lyophilized) acellular Permanent for partial-/full- cadaveric dermis, which is thickness burns (when combined nonantigenic with epidermal graft) Integra Artificial Skin (Integra Life Acellular three-dimensional porous Permanent for deep partial- Sciences, Plainsboro, NJ) matrix of cross-linked bovine thickness and full-thickness burns collagen and chondroitin-6-sulfate (when combined with cultured with Silastic outer covering autologous keratinocytes or autologous thin epidermal grafts) Epicel (Genzyme, Cambridge, MA) Cultured human epidermal Permanent for full-thickness burns keratinocytes from patient biopsy Apligraf (Organogenesis, Canton, Bovine collagen matrix containing Temporary or permanent for small MA) neonatal human epidermal full-thickness burns keratinocytes and dermal fibroblasts 36 STANTON & BILLMIRE dimensional human dermal matrix. This reconstituting a functional dermis and epider- product is strictly for temporary coverage. mis. Advantages of this product are that it Integra Artificial Skin (Integra Life Sci- simultaneously provides temporary wound ences, Plainsboro, NJ) is a bioengineered der- coverage, improves the success of epidermal mal substitute (Fig. 2). It consists of a bilayer cell grafting (i.e., permanent coverage), and membrane system for skin replacement. The allows use of thinner autografts, which dermal replacement layer is made up of a speeds donor site healing. porous matrix of fibers of cross-linked bovine Alloderm (Lifecell, Woodland, TX) is made tendon collagen in a glycosaminoglycan of a lyophilized acellular cadaveric dermis, (chondroitin-6-sulfate) and is manufactured with all the immunogenic cells removed by with a controlled porosity and defined degra- special processing. Eliminating the immune dation rate. The epidermal substitute layer cells, which cause rejection of cadaver skin as is made of synthetic polysiloxane polymer a foreign object, essentially tricks the body (silicone) and functions to control moisture into believing its own dermis has been ap- loss from the wound. The collagen dermal plied. Again, like some of the other products, replacement layer serves as a matrix for the an extremely thin autogenous skin graft or infiltration of fibroblasts, macrophages, lym- cultured keratocytes can be used over the phocytes, and capillaries from the wound Alloderm to provide permanent coverage.73 bed. As healing progresses, an endogenous Oasis (Cook, Spencer, IN) is a biomaterial collagen matrix is deposited by fibroblasts derived from porcine small intestinal submu- and simultaneously the dermal layer of In- cosa and is recommended as a temporary tegra Artificial Skin is degraded. By about 2 coverage for partial-thickness burns. It has to 3 weeks of time, adequate vascularization been shown to provide excellent protective of the dermal layer has occurred and donor properties and to have an ability to act as a autograft tissue is available for reharvesting natural template for wound repair.53 Oasis is (Fig. 3). The temporary silicone layer is re- extracted from the porcine intestine using a moved, and a thin, meshed, nonexpanded process that retains the natural composition layer of epidermal autograft can be placed of matrix molecules such as collagen (Types over the ‘‘neodermis.’’ Cells from the epider- I, II, and V), and growth factors (TGF-␤ FGF- mal autograft grow and form a confluent stra- 2, VEGF). Glycosaminoglycans (hyaluronic tum corneum, thereby closing the wound and acid, chondroitin sulfate A and B, heparin,

Figure 2. Integra Artificial Skin (Integra Life Sciences, Plainsboro, NJ) applied to entire anterior trunk of patient in Figure 1. The widely meshed stretch netting used to help hold the Integra in place allows for good visibility and monitoring for signs of infection, fluid collection, and incision and drainage of these, if necessary. (Courtesy of Glenn Warden, MD, Shriners Hospital for Children– Cincinnati Burn Unit, Cincinnati, OH.) (See also Color Plate 3, Fig. 6.) SKIN RESURFACING FOR THE BURNED PATIENT 37

Figure 3. Histology (scale bar: 320 ␮m between inset notches) approximately 1 month after application of Integra Artificial Skin to excised full-thickness burn bed. The fibrovascular tissue ingrowth will support the application of an overlay epidermal autograft/substitute. (From Boyce ST, Kagan RJ, Warden GD: Cultured skin substitutes with Integra Artificial Skin used to replace native skin autograft and allograft for the closure of full-thickness burn injuries. J Burn Care Rehabil 20:453, 1999; with permission). and heparan sulfate), proteoglycans, and gly- All these engineered materials are contrain- coproteins (fibronectin) signal host cells to re- dicated for use on clinically infected wounds. populate the Oasis scaffold with host tissues. Also, patients with known allergies to any To date there have been no reports of serious of the xenogenic components should not be allergic responses to this material. treated with any of those materials. The as- tute burn clinician should always be familiar Dermal-Epidermal Substitutes with the individual bioengineered materials he or she may be using and the information Apligraf (Organogenesis, Canton, MA) is a in the product insert regarding product de- viable, bilayered skin construct; the epider- scription, indications, contraindications, mal layer is formed by human keratinocytes warnings, and directions for use, including and has a well-differentiated stratum cor- preoperative, intraoperative, and postopera- neum; the dermal layer is composed of hu- tive management. In summary, indications for man fibroblasts in a bovine Type I collagen using the various products available include lattice. Although matrix proteins and cyto- superficial and partial-thickness burns ex- kines found in human skin are present, Apli- pected to heal spontaneously, large wounds graf, like most other skin substitutes, does with permanent coverage unavailable, the not contain Langerhans cells, melanocytes, burned patients or burn wound beds too un- macrophages, lymphocytes, blood vessels, or stable to endure autografting, and as ‘‘overlay hair follicles. The source of skin cells for Apli- grafts’’ to cover widely meshed skin auto- graf comes from human neonatal male fore- grafts as a method to enhance epithelializa- skin tissue. The mechanism of permanent re- tion of the graft interstices.48, 63 surfacing is thought to occur by way of actual ‘‘take’’ of Apligraf with subsequent remodel- Permanent Coverage ing of the tissue to blend with the patient’s own. As noted in Table 1 and discussed later, Deep partial-thickness and full-thickness autologous cultured keratinocytes over a der- wounds require permanent coverage. Al- mal substitute constitutes a ‘‘skin substitute.’’ though full-thickness wounds usually can be 38 STANTON & BILLMIRE determined early, deep partial-thickness with the realization of the undesirable effects wounds may take 10 to 14 days to declare of meshed skin grafts and the availability of themselves. Nonhealing by this point in time skin substitutes, about the only absolute indi- signifies injury to the level of the reticular cation for the use of a meshed skin graft is dermis. Spontaneous healing at this level will on an elderly patient with a large burn. The produce significant hypertrophic scarring. increased metabolic demands of a large donor site and lack of concern about aesthetic out- come may make mesh grafting a better op- Split-Thickness Autografting tion. Autografts remain the preferred material When sufficient donor sites are available, sheet skin grafting should be the burn clini- for definitive wound closure after primary cian’s first, second, and third choice for auto- excision of deep partial-thickness and full- grafting. These grafts are by far more aestheti- thickness burns. Of course, availability of do- cally acceptable than meshed skin grafts. nor sites is the rate-limiting step. Several im- Because they have more dermis, they are also portant surgical decisions must be made more pliable, durable, and have significantly about the graft and donor site. The thickness less secondary contracture. Even in instances of the graft, whether it is expanded, and the of large-percentage TBSA, the ability to rehar- degree to which it is expanded affect the final vest donor sites makes the use of sheet graft- result. Generally, the thinner the graft, the ing a viable and preferred option. Indeed, higher rate of take, but the more the wound sheet skin grafts are technically more difficult undergoes secondary contracture and hyper- to use. They take more time because they trophic scarring. Meshed grafts have a better must be handled gingerly and the wound bed take rate and achieve closure effectively. A must be hemostatically prepared to prevent meshed skin graft can be expanded to pro- postoperative subgraft hematoma and seroma vide more coverage in burn wounds with less formation. available unburned skin. The interstices allow In large burns, harvesting autologous skin for drainage and thus diminish the risk for can be a problem because donor site availabil- seroma, hematoma, and infection. The higher ity sometimes is limited. Essentially, donor the ratio skin grafts are meshed or expanded, sites should be used from anywhere there however, the higher the rate of secondary is unburned skin (except the face). General contracture and ‘‘cobblestoning appearance’’ recommendations for donor graft thickness results.20 These two undesirable qualities according to age can be found in Table 2. Two present functional and aesthetic problems. As areas that frequently are overlooked and are alluded to earlier, the burn surgeon may excellent sites for donor skin are the back and choose to use a meshed skin graft as an scalp.14, 26, 40 The back frequently is unburned ‘‘overlay graft’’ with one of the previously and provides an area of skin with the thickest mentioned tissue-engineered materials.48 This dermis on the body and thus makes early technique may result in a smoother, more reharvesting possible (Fig. 4). The scalp, too, pliable end result. As would be expected, frequently is unburned, and because of its meshed skin grafts should not be used on vascularity, it re-epithelializes quickly and aesthetically sensitive areas such as the face, can be reharvested at intervals of as early as neck, and hands. In fact, in this day and age 7 to 10 days.

Table 2. SAFE THICKNESSES FOR HARVESTING SKIN GRAFTS RELATIVE TO AGE AND DONOR SITE

Thickness (inches) Age .008–.010 .010–.012 .012–.015 Infant Thigh, buttocks, scalp Trunk 3–12 years Thigh, buttocks, trunk, scalp Teenager/adult Thigh, buttocks, scalp, trunk Elderly Thigh, buttocks Scalp, trunk SKIN RESURFACING FOR THE BURNED PATIENT 39

Some unique features about harvesting skin and they possibly result in earlier re-epitheli- grafts from the scalp should be kept in mind. alization of the donor sites. Another long- Because of the increased vascularity of the term dressing that can be used is Xeroform.28 scalp, these tend to be bloody donor sites. This dressing can be placed at the end of the Because skin is being harvested from an area procedure and left on until re-epithelializa- with a dense population of hair follicles, there tion occurs. It naturally sloughs just trimming is a small but significant risk for hair transfer the edges as they lift up from the healing and donor site alopecia.9, 37, 38, 69, 75 Repeated wound bed. Alginates are also a convenient harvests from the same scalp donor site are donor site dressing material that consists of a more likely to produce hair transfer and do- calcium-sodium alginate composition derived nor site alopecia. Actual thickness of the graft from seaweed. Released calcium ions help has less propensity to produce these compli- with hemostasis. This type of dressing can be cations than repetitive harvesting. When us- left on for as long as 4 to 5 days. At day 5 or ing the scalp as donor skin, the skin from the 6 it can be soaked off and the wound dressed first pass should be used to resurface the face with a nonadherent gauze. and neck regions and subsequent passes used for less conspicuous areas (Fig. 5). Thinner Full-Thickness Autografts grafts should be harvested for each subse- quent pass to help prevent hair transfer.38 In Although full-thickness grafts are usually those instances with hair transplant from not a concern in the case of large-percentage scalp donor sites to head and neck burns or TBSA, they are mentioned here for complete- even from other donor sites to the face and ness and select use for burns to functionally palms, laser hair epilation is being trialed. As and aesthetically sensitive areas such as the would be expected, more darkly pigmented hands and eyelids.52, 59 As the name implies, hairs are eliminated more effectively. the entire thickness of skin is removed from Important techniques to keep in mind the donor site (usually the groin, supraclavic- when harvesting skin from the scalp: the hair ular area, preauricular or postauricular area) should be shaved; the subcutaneous plane and transplanted to the recipient site. These should be tumesced with 2:1,000,000 epineph- grafts have more primary contraction but less rine solution; the curvature of the skull makes secondary contraction compared with split- actual harvesting more technically de- thickness skin grafts and are more durable manding so the burn surgeon should enlist because the entire thickness of the dermis is an extra set of hands to help immobilize the included. Primary closure is used for the do- patient’s head; mineral oil then is applied and nor site. If the site is too large for primary the desired thickness skin graft harvested; im- closure, a split-thickness graft from another mediately thereafter, 1:100,000 epinephrine area may be used. solution–soaked laparotomy pads are applied and left on until the final donor site dressing can be placed. This technique also works well Skin Graft Fixation and Dressing when harvesting skin grafts from other parts of the body. Skin grafts can fail for five reasons: 1) sub- Dressing of the donor sites comes down to graft hematoma or seroma; 2) mobility and a matter of preference and experience with shearing of the graft on the recipient bed; 3) one modality or another. Any of the topical inadequate debridement of the burn wound; antimicrobials and nonadherent dressings 4) presence of infection; and 5) poor vascu- may be used and changed on a daily or twice larity of the bed. With these considerations in daily basis. Some studies have recommended mind, fixation techniques, including suture, one form or another of occlusive dressings. permanent versus absorbable staples, Opsite The occlusive dressings are low maintenance, spray, cyanoacrylates, and fibrin glue are changed as infrequently as every 5 to 7 days. used.24, 51, 65, 71 For full-thickness skin grafts They are thought to be less painful because over relatively small areas with convolutions they provide coverage for the nerve endings, and difficult topography, using some form of 40 STANTON & BILLMIRE

Figure 4. Resurfacing of full-thickness burns to the entire left hand using thick (0.015 in) split-thickness sheet autografts harvested from the patient’s back. A, Full-thickness burn to the volar surface. B, Full- thickness burn to the dorsum. The flexion contracture of the fingers (and wrist) and the necessary escharotomy are apparent. This burn was complex subdermal involving some of the extensor mechanisms. C, One month postoperative resurfacing with K-wires in digits 1, 3, 4, and 5 to hold interphalangeal joints in extension as extensor mecha- nisms granulate in and grafts mature. Illustration continued on opposite page SKIN RESURFACING FOR THE BURNED PATIENT 41

Figure 4 (Continued). D, Four months postoperative, volar surface. E, Eight months postoperative, dorsal surface. (Courtesy of Glenn Warden, MD, Shriners Hospital for Children–Cincinnati Burn Unit, Cincinnati, OH.) (See also Color Plates 3 and 4, Fig. 7.) 42 STANTON & BILLMIRE

Figure 5. Resurfacing of full-thickness burns to the entire left face using split- thickness sheet autografts harvested from the patient’s scalp. A, Full-thickness burn to face, shown from left lateral view. B, Post Operative Day 2 (POD), totally resurfaced face with completely adherent grafts. Facial aesthetic units were resurfaced individually with sheets of autograft.

a bolster dressing works well. Two methods red rubber irrigation catheters. The catheters that are convenient and efficient include Res- can be irrigated with antimicrobial solutions ton foam (3M, Forest City, IA) or moistened such as mafenide acetate (Sulfamylon) or GU burn cotton secured into place with staples or irrigant (neomycin/polymyxin). The irriga- tie over silk suture. The bolster usually can be tions continue until the first dressing change, left in place for approximately 7 days before at which time the skin grafts and wounds are removal. evaluated for potential colonization or infec- A nonadherent topical antimicrobial dress- tion. The decision can be made at that time ing should cover split-thickness skin grafts. to continue irrigations or to switch to a twice- In instances with increased risk for infection, a-day dressing change with a topical antimi- the authors recommend placing fine mesh crobial, nonadherent gauze dressing. Problem gauze immediately over the skin graft fol- areas can be addressed by stapling stretch- lowed by moistened coarse burn gauze and fabric over the dressing. For split-thickness SKIN RESURFACING FOR THE BURNED PATIENT 43

Figure 5 (Continued). C, Three months postoperative showing tailor-made continuous pressure face mask (and soft cervical collar for neck pressure/extension) being worn through the hypertrophic contractile phase of graft maturation. D, Fully matured resurfaced face with good symmetry, smooth- ness, pliability, and preserved facial animation. (Courtesy of Glenn Warden, MD, Shriners Hospital for Children–Cincinnati Burn Unit, Cincinnati, OH.) (See also Color Plate 4, Fig. 8.)

sheet grafts on postoperative day 1 (POD 2 hours, and, if all is well, again at 5 days for split-thickness meshed grafts), the span- postoperatively. dex can be incised down the middle and the For grafts over the extremities, irrigation rest of the burn dressing removed and the catheter and bulky burn gauze dressings skin graft inspected for any problems. Any work and can be held snugly into place with hematomas or seromas can be lanced and elastic wrap bandages. Grafts are inspected evacuated or rolled out. The irrigation cathe- on postoperative day 1 or 2 for adherence ter dressing is replaced until the second dress- and subgraft fluid collections, which are evac- ing change on day 5. uated as needed. For those grafts proximal to Skin grafts on the face and neck area usu- the knees and elbows, a second dressing ally are left open with a topical antimicrobial change is performed on day 5, and the patient ointment applied to keep them moistened is allowed to get out of bed at this time. For and minimally colonized. For the first 4 hours grafts distal to the knees and elbows, a second after grafting, these grafts should be rolled dressing change is awaited until day 7, and, every 15 minutes with a cotton swab to pre- if all looks well, the patients are allowed to vent any subgraft hematoma or seroma. get out of bed. For skin grafts over joints, Again, any fluid collections that get loculated splinting is an excellent method of immobili- should be lanced and drained. Perseverence zation to avoid shear forces. with this routine for the first 4 hours pays off, Hexcelite (X-lite, Runlite SA, Copenhagen, and the clinician can cut back to rolling the Denmark) is a light-weight, low-profile, user- grafts every 1 to 2 hours because they become friendly splinting material used for intraoper- more and more adherent during the first 24 ative application.25 Specific recommendations hours. Assuming a stable airway, patients for positions include the following: axilla 90 with skin grafts to the anterior neck should horizontal with bedside troughs or an air- be placed on a hyperextension mattress. plane splint; elbow: fully extended; wrist: For sheet skin grafts over the trunk region, slightly extended (10); metacarpal phalan- the irrigation catheter bulky burn gauze geal joints of the fingers: flexed 60 to 70; dressing with spandex fabric covering works interphalangeal joints: fully extended (K- well, and grafts can be inspected at 24 (or 48) wires may be necessary if the extensor mecha- 44 STANTON & BILLMIRE nism is involved); thumb: 40 to 50 of abduc- (with conventional autografting) may be tion with the interphalangeal joint in exten- treated more efficiently with cultured skin sion. Once again, the first dressing change is substitutes.7 The two general categories of on postoperative day 1 (or 2), when skin skin substitutes available are monolayer cul- grafts are evaluated and manipulated as tured kerotinocytes or bilayered composite needed. The patient is left at bed rest for a dermal-epidermal skin substitutes (see Table total of 5 days, at which time a second dress- 1). Cultured keratinocytes were the first op- ing change is performed and the patient then tion available. These are produced by harvest- allowed out of bed. ing a small biopsy of split-thickness skin from The timing of the first dressing change is the patient (less than 1% TBSA) then transfer- controversial. Hematomas and seromas will ring it to the laboratory for culturing of kera- not likely affect engraftment if drained within tinocytes. It is currently possible to expand the first 48 hours. Even dislodged or mis- these small skin biopsies to greater than 100- placed skin grafts can be repositioned suc- fold in approximately 3 to 4 weeks, at which cessfully in the first 2 days after placement. If time a significant-sized burn wound can be early graft infection is recognized at the first covered. These keratinocytes then can be en- dressing change, a more effective antimicro- grafted onto a stable burn wound bed. At bial agent such as mafenide acetate (Sulfamy- initial placement, these grafts must be cared lon) can be instituted. The above recommen- for delicately and diligently with an individu- dations for sheet autografting vary from alized protocol of nutrient and antimicrobial institution to institution. Suffice it to say that irrigations and dressing changes.4, 5 Obvi- for large burns with limited donor sites, there ously, lacking a dermis, these grafts provide is only one chance at engraftment, and, there- only epithelial coverage and, unfortunately, fore, the earlier a problem is recognized, the are fragile, subject to infection, and have a earlier it can be dealt with and the better the variable take rate. Long-term results have chance of graft survival and good outcome. been somewhat disappointing, with signifi- Mesh grafts, on the other hand, are a little cant graft contraction, hypertrophic scarring, more forgiving and, with the exception of a and hypopigmentation. The resulting epider- high suspicion for infection, rarely need a mis remains fragile and frequently blisters.54, 56 dressing change and evaluation until postop- This occurrence seems to be caused by the erative day 2. For completeness, Unna boot slow development of anchoring complexes. type management has been advocated by For these reasons, burn clinicians and re- some for skin grafts to areas such as the scalp, searchers now concentrate their efforts on the hand, and upper and lower extremities.10, 13, 58, 68 application and development of bilayered composite cultured skin substitutes, which SKIN SUBSTITUTES FOR provide not only autologous epidermis but PERMANENT COVERAGE also dermis made from fibroblasts, collagen, and glycosaminoglycans.1, 33 Tissue engineering has been used in burn Bilayered dermal-epidermal substitutes management since the early 1980s.22 The pri- come in various forms, from simply placing mary indication for using cultured skin is in a thin (less than or equal to .008Љ) autograft the management of extensive deep partial- over a chosen dermal substitute (i.e., Integra thickness and full-thickness burns. These or Alloderm) to a combination of cultured grafts provide permanent skin coverage in autologous keratinocytes over a dermal sub- circumstances in which adequate donor sites stitute versus cultured kerotinocytes and fi- for conventional skin grafting are not avail- broblasts placed over a dermal substitute able.6 The economics of cultured skin in burn (e.g., cultured skin substitute combined with wound management have not been eluci- Integra. S. Boyce, Shriners Hospital for Chil- dated fully; however, it seems as though dren–Cincinnati Burn Unit, Cincinnati, those burns with 50% or greater TBSA burn OH).28, 30, 76 The acute burn wound is managed in which the burn wounds cannot be excised in the typical fashion initially, and temporary and grafted within a 3- to 4-week period coverage is accomplished by placement of a SKIN RESURFACING FOR THE BURNED PATIENT 45 bioengineered material containing a dermal in a similar fashion as noted above for en- substitute. Autologous keratinocytes plus or graftment of monolayered cultured keratino- minus fibroblasts are cultured up to the de- cytes. With successful engraftment, these pa- sired volume (the timing of this coincides tients are allowed to get out of bed by with fibrovascular ingrowth into the artificial postoperative day 7, the grafted areas can be dermal substitute). At this time, the patient is put through a range of motion, and topical taken back to the operating room for en- antimicrobials can be discontinued and mois- graftment. Postoperatively, these are cared for turizing lotion commenced (Fig. 6).

Figure 6. Postoperative view of bilayered dermal-epidermal (staged Integra-Cultured Skin Substitute [CSS]) substitute resurfacing the entire back of patient in Figure 3. Tape measures in centimeters. A, POD 7, essentially 100% take, grafted wounds dry, keratinized, and clinically covered. B, POD 28; healed skin becoming smoother with a more confluent surface architecture and is tolerating physical therapy and pressure garments. (From Boyce ST, Kagan RT, Warden GD: Cultured skin substitutes with Integra Artificial Skin used to replace native skin autograft and allograft for closure of full-thickness burn injuries. J Burn Care Rehabil 20:453, 1999; with permission.) 46 STANTON & BILLMIRE

The microscopic anatomy of bilayered der- days after surgery), long-term planning and mal-epidermal substitutes resembles split- care must be instituted. The potential prob- thickness skin; it is made up of well-stratified lems of healing skin grafts must be antici- epidermal substitute and a dermal substitute, pated and measures instituted, if possible, be- and its total thickness is usually less than .5 fore their occurrence. Because skin grafts, mm (Fig. 7). Anatomic deficiencies of cul- especially for the first several months, lack tured skin include lack of vascularized glandular tissue, they have a tendency to dry plexus, glands, follicles, and nerve and im- out and therefore must be moisturized with a mune cells.3 During the ensuing first several thick moisturizing cream at least 3 times a months, the artificial dermal substitute mate- day. A set of goals for rehabilitative therapy rial gradually is replaced by ongoing fibro- should be used for every patient. vascular ingrowth and creation of a neoder- mis (Fig. 8).7 Because of the presence of a GOALS OF THERAPY neodermis, pliability and durability of this healed skin is excellent, and there are virtu- 1. Prevent, minimize, or correct deformity ally no problems with blistering or hypertro- 2. Protect weak muscles from overstretch- phic scarring, even between edges of adjacent ing grafts.2, 7, 76 The skin has pronounced hypopig- 3. Maintain range of motion mentation with an occasional few discrete foci 4. Provide positional function of pigmentation (Fig. 9), however. It is actu- 5. Protect any exposed joints or tendons ally now possible to impregnate the skin sub- 6. Provide immobilization across joints stitutes with cultured melanocytes and mini- after grafting mize or hopefully eliminate the problems of 7. Minimize scarring with pressure gar- hypopigmentation.66 ments or masks 8. Develop functional skills to facilitate in- POSTOPERATIVE CARE: LONG dependence in activities of daily living TERM and community/occupational reentry Once successful engraftment has been In general, active and passive range-of-mo- achieved and grafts are stable (usually 5 to 7 tion exercises are used to retain motion.

Figure 7. Histology of CSS as engineered 1 month past harvesting skin biopsy from patient in Figure 6 (scale bar: 320 ␮m between inset notches). CSS have well stratified epidermal substitute biologically attached to dermal substitute. (From Boyce ST, Kagan RJ, Warden GD: Cultured skin substitutes with Integra Artificial Skin used to replace native skin autograft or allograft for the closure of full-thickness burn injuries. J Burn Care Rehabil 20:453, 1999, with permission.) SKIN RESURFACING FOR THE BURNED PATIENT 47

Figure 8. Histology of wounds from patient in Figure 6; wounds are grafted with CSS over Integra Artificial Skin. A, POD 21, at which time stable epidermis attached to connective tissue and reticulations of Integra remain in wound (scale bar: 320 ␮m between inset notches). B, POD 63, at which time epidermis and dermis are stable and small fragments of Integra remain in connective tissue (scale bar: 256 ␮m between inset notches). (From Boyce ST, Kagan RT, Warden GD: Cultured skin substitutes with Integra Artificial Skin used to replace native skin autograft and allograft for closure of full-thickness burn injuries. J Burn Care Rehabil 20:453, 1999; with permission.) 48 STANTON & BILLMIRE

Figure 9. Postoperative view of patient in Figure 6 at 5 months demonstrating aesthetics of CSS/Integra resur- faced back. Surface architecture is smooth and soft, seams are fine and nearly imperceptible, overall pliability is excellent but pigmentation is mostly absent. (From Boyce ST, Kagan RT, Warden GD: Cultured skin substi- tutes with Integra Artificial Skin used to replace native skin autograft and allograft for closure of full-thickness burn injuries. J Burn Care Rehabil 20:453, 1999; with permission.)

Splinting is used to retain positioning when transforming growth factor in the scar.23 Hy- the patient is not moving. The guidelines for pertrophic scarring is more common and in- positioning are similar to those for immediate tense in children, darker-skinned races, and postoperative care. Because of the propensity in areas of stretch and motion. It is thought for intense wound contractures, early and ag- that the mechanism of action of pressure gar- gressive use of these modalities is essential to ments and masks is caused by a combination maintain function. When grafts are secure of pressure-induced collagen remodeling and and stable (usually by 2 to 3 weeks), most hypoxia-induced tissue atrophy. Silicone patients are measured for pressure garments, sheeting has been another commonly used which apply 25 mm Hg of pressure.12 modality to improve the appearance, soften, In general, scarring is most intense at about and reduce redness and itching of hypertro- 3 to 6 months and takes 12 to 15 months to phic scars. Frequently, these two modalities mature; however, hypertrophic scars can take are used in combination. Corticosteroid local much longer. The pathophysiology of hyper- injections also have been found to improve trophic scars is incompletely understood. It the appearance of hypertrophic scars and re- has been associated with elevated levels of duce itching. Injections usually are adminis- SKIN RESURFACING FOR THE BURNED PATIENT 49 tered on an every 5- to 6-week basis or as gressive, with the evolution of biologic tis- needed. Injections usually are rather painful sue–engineered skin substitutes and the re- and fraught with much apprehension by the search of growth factors in healing. Further burned pediatric patient. Finally, pulsed dye improvements in tissue engineering and tech- laser therapy is showing some success in the nology should result in even more effective management of subacute and chronic hyper- skin substitutes and hence better functional trophic scars. The mechanism of this is still and aesthetic outcomes with economic effi- under debate. It is possible that selective pho- ciency in large burns. tothermolysis of the scar vasculature leads to tissue ischemia, release of collagenases, al- ACKNOWLEDGMENTS tered collagen metabolism, and, ultimately, scar atrophy. Drs. Billmire and Stanton would like to extend their thanks and genuine appreciation to members of the Shriners Hospital for Children–Cincinnati Burn Unit who have helped us with this publication: to Dr. Glenn War- SUMMARY den for his input and use of photographs of his patients; Dr. Steve Boyce for his input and use of histology slides and clinical slides of his cultured skin substitute; Cathy It has been estimated that 2 million people McDannold of the Medical Records Department and her per year have burns requiring medical atten- staff; and the Visual Arts Department for their expedi- ency in reproduction of slides. tion in the United States.50 The available and expert clinicians in dedicated burn centers around the country have cared successfully References for these patients and given them a second chance at a functional life. It still behooves 1. 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David A. Billmire, MD Department of Plastic Surgery The Children’s Hospital Medical Center 3333 Burnet Avenue Cincinnati, OH 45229

e-mail: [email protected]