Application of split-thickness dermal grafts in deep partial- and full-thickness burns: a new source of auto-skin grafting

Early tangential excision of nonviable burn tissue, followed by immediate skin grafting with autograft or allograft, has resulted in the improvement of burn patient survival. The aim of this study was to add split-thickness dermal grafts (STDGs) as a new source of auto-skin grafting tool to our reconstructive armamentarium in deep partial- and full-thickness burns and soft tissue defects. The authors successfully applied STDGs along with split-thickness skin grafts as a new source of auto-skin grafting in 11 deep partial- and full-thickness burns over a period of 1 year without any significant donor site morbidity. Dermal graft take was complete in all but one patient. There was no donor site healing problem, and donor site epithelization was completed generally 1 week later than split-thickness skin graft by semi-open technique. Autologous split-thickness skin grafting still remains the standard therapy for burn wound closure but may be in limited availability in severe burns. The authors conclude that STDGs may be a new source of auto-skin grafting tool in extensive deep partial- and full-thickness burns.     

Reduced wound contraction after grafting of full-thickness burns with a collagen and chondroitin-6-sulfate (GAG) dermal skin substitute and coverage with biobrane

Full-thickness burns destroy both the epidermal and dermal tissues of the skin. This study evaluates a collagen and chondroitin-6-sulfate dermal skin substitute (graft) that was applied to excised full-thickness burns and covered with Biobrane. Experimental conditions included: (a) no burn, subcutaneous implantation of the graft; (b) burn, excision, graft, coverage with Biobrane and bandages; (c) burn, excision, no graft, coverage with Biobrane and bandages; (d) burn only. forty-one days post-surgery, subcutaneous implantation (N = 3) of the graft caused no detectable contraction or necrosis of the overlying skin, whereas all burn wounds contracted. Measurements of wounds (percentage of original wound size) showed statistically significant differences between the following treatments; (a) graft plus Biobrane (N = 10), 34%; (b) no graft plus Biobrane (N = 9), 25%; (c) untreated burns (N = 6), 16%. Semi-quantitative evaluation of time to healing indicated by spontaneous detachment of Biobrane from wounds showed that grafted, excised wounds healed in an average of 2.7 weeks, while ungrafted, excised wounds required an average of 4.3 weeks to heal. Histological appearance of healed wounds after grafting and coverage with Biobrane resembles undamaged skin without epidermal adnexal structures. Excision of full-thickness burn eschar, followed by grafting with a collagen and chondroitin-6-sulfate dermal skin substitute and coverage with Biobrane provides reduced wound contraction within a six-week period of observation compared to non-excised wounds. Both more rapid and more complete wound healing took place compared to excised wounds that were not grafted.     

Evaluation of cytotoxicity and antimicrobial activity of Acticoat Burn Dressing for management of microbial contamination in cultured skin substitutes grafted to athymic mice

Cultured skin substitutes (CSS) have become a useful adjunctive treatment for closure of burn wounds, but CSS are avascular and remain susceptible to microbial destruction longer than split-thickness skin grafts. Irrigation of CSS grafted to burn wounds with a topical antimicrobial solution (TAS) has been shown to promote engraftment of CSS, but TAS usage has potential limitations. Acticoat Burn Dressing (Acticoat; Westaim Biomedical, Exeter, NH) is a silver-coated barrier dressing reported to exhibit antimicrobial activity and to reduce infection in partial-thickness and full-thickness wounds. This study evaluated the cytotoxicity of Acticoat with CSS and the efficacy of Acticoat for the management of microbial contamination in CSS grafted to full-thickness wounds in athymic mice. The cytotoxicity of Acticoat was assessed in preliminary studies after 1 week of exposure to CSS during in vitro maturation or healing on wounds in athymic mice. Histologies were analyzed and cellular viability in the CSS was determined by MTT conversion on days 0, 1, and 7 of Acticoat exposure. At 1, 2, 3, and 4 weeks after grafting, wounds were traced, and areas of healing CSS were calculated by image analysis. At 4 weeks, wound biopsies were evaluated and scored for engraftment of human cells. In a subsequent study, wounds were inoculated with strain SBI-N of Pseudomonas aeruginosa at 1 x 10(5) cfu/wound before the application of CSS or inoculated onto the surface of Acticoat. At 4 weeks, swab cultures were collected from the surface of CSS and scored for the presence of SBI-N. Statistical significance was accepted at the 95% confidence level (P <.05). The data show that exposure in vitro of CSS to Acticoat was cytotoxic within 1 day, but 1 week of exposure in vivo did not injure CSS or inhibit wound healing. Contaminated wounds treated with Acticoat healed similarly to control treatments, with comparable rates of engraftment, and detection of SBI-N on the surface of only one graft. No SBI-N was detected on CSS after inoculation onto the surface of Acticoat. These results suggest that Acticoat may be suitable as a protective dressing to reduce environmental contamination of CSS, if used in conjunction with additional antimicrobials to control organisms present in the wound.     

Histologic study of artificial skin used in the treatment of full-thickness thermal injury

Integra artificial skin is an effective means of treatment for full-thickness burns. In extensive burn injury the use of such skin substitutes may become the treatment of choice. The artificial skin consists of a dermal substitute of bovine collagen and chondroitin-6-sulfate and an epidermal layer of synthetic polysiloxane polymer (Silastic). Serial biopsy specimens were obtained from 131 patients during a period of 7 days to 2 years after application. In this histologic study, six sequential phases of repair were discerned. In addition, there were occasional unusual histologic features, eosinophilic infiltration, and/or macrophage-derived giant cell formation in the wound area; however, such findings did not clinically correlate with a negative response to Integra artificial skin. Good repair was obtained, with rare exceptions. An intact dermis was achieved as well as definitive closure of a complete epidermal layer with a minimum of scarring.     

Xenogeneic acellular dermal matrix as a dermal substitute in rats.

Acellular dermal matrix (ADM) has been used as a dermal substitute for the treatment of deep burns, but the availability of cadaver skin for the production of ADM is limited. The usefulness of porcine ADM as a xenogeneic dermal substitute in rats was studied. With the use of Dispase II (Boehringer Mannheim, Indianapolis, Ind) and Triton X-100 (US Biochemicals, Cleveland, Ohio), xenogeneic ADM was prepared from commercially available, cryopreserved porcine skin, and allogeneic ADM from the rats was also prepared. Four full-thickness injuries 225 mm2 in size were created on the dorsum of each rat. One of these wounds was treated with xenogeneic ADM and 1 was treated with allogeneic ADM, and immediately a 0.005-in thick split-thickness skin graft was placed over the ADM. The other 2 wounds were covered with 0.005- or 0.017-in thick split-thickness skin grafts alone. The wounds were evaluated macro- and microscopically 10, 14, 20, and 30 days after grafting. At 30 days after grafting, contraction of the wounds that contained xenogeneic ADM was significantly greater than that of the wounds that contained allogeneic ADM. Graft take was poor in the wounds that contained xenogeneic ADM at 14 days after surgery and moderately good in those that contained allogeneic ADM. The use of thick autografts resulted in the best wound healing, whereas the use of thin autografts resulted in considerable wound contraction. Allogeneic ADM diminished this contraction, but wound healing was significantly worsened when xenogeneic ADM was used.     

Immunologic study of artificial skin used in the treatment of thermal injuries

Artificial skin (Integra) has been developed as an effective treatment of full-thickness burns. The material consists of a bovine collagen and chondroitin-6-sulfate dermal matrix with a silicone rubber "epidermal" layer. After burn wound excision, the artificial skin is implanted. Only the temporary silicone rubber epidermal membrane is removed. The dermal collagen matrix is incorporated by the host. Serial serum samples were obtained from patients who had grafts of Integra artificial skin for the determination of the humoral immune response to Integra. Integra artificial skin presents few if any humoral immunologic problems to patients. Increased antibody activity to bovine skin collagen, bovine skin collagen with chondroitin sulfate, and human skin collagen was not considered immunologically significant.     

Healing characteristics of expanded autografts on wounds covered with homograft and Biobrane temporary wound dressing

This study compared the healing characteristics of expanded autografts on wounds with interstices that were closed with cryopreserved cadaver homograft split-thickness skin and wounds with interstices that were closed with the synthetic skin substitute, Biobrane temporary wound dressing. Nine paired wounds in four patients with large burns were used in this study. When Biobrane temporary wound dressing adhered to a wound, epithelial migration did not proceed until it was removed. Although wounds covered with homograft immediately had the appearance of healed wounds, biopsy specimens showed evidence of a delay in epithelial migration. Although these results indicate impaired epithelial migration with the use of both materials, we concluded that homograft offered an advantage because the wounds that were covered with it remained closed during the entire reepithelialization process.     

Vascular endothelial growth factor overexpression increases vascularization by murine but not human endothelial cells in cultured skin substitutes grafted to athymic mice

Cultured skin substitutes (CSS) consisting of fibroblasts, keratinocytes, and biopolymers are an adjunctive treatment for large burns. Because CSS lack a vascular plexus, they vascularize more slowly than split-thickness autografts. Previously, CSS were prepared with dermal microvascular endothelial cells (ECs), which formed vascular analogs at a low frequency but did not contribute to increased vascularization after grafting. The present study addressed whether keratinocytes genetically modified to overexpress vascular endothelial growth factor (VEGF), an endothelial cell mitogen, could improve the persistence and organization of ECs in CSS. CSS were prepared with control or VEGF-modified keratinocytes, with (CSS + ECs) or without added ECs, and were grafted to full-thickness wounds in athymic mice. Elevated VEGF expression was detected in VEGF-modified CSS and CSS + ECs compared with controls, but no significant difference in EC density in vitro was observed. After grafting, VEGF-modified CSS and CSS + ECs showed enhanced vascularization, and organization of human ECs into multicellular structures in CSS + ECs was observed. However, VEGF overexpression did not significantly enhance the proliferation of human ECs, suggesting that other factors may be required. Improved persistence and organization of human ECs in vitro will likely be required for their participation in vascularization of CSS + ECs after grafting.     

Longitudinal assessment of Integra in primary burn management: a randomized pediatric clinical trial

BACKGROUND: Early excision with autograft-allograft closure is standard in severe burn management. Cadaver skin is associated with risks such as antigenicity, infection, and limited availability and shelf life. Previous studies have shown that Integra is safe to use in burns of <20% total body surface area. However, the suitability of its use in large burns (>50% total body surface area), its effects on postburn hypermetabolism, and the long-term cosmetic and functional results have not yet been evaluated. MATERIALS AND METHODS: Twenty children with an average burn size of 73 +/- 15% total body surface area (71 +/- 15% full-thickness burn) were randomized to be treated with either Integra or with autograft-allograft technique. Outcome measures such as length of hospital stay, mortality, incidence of infection and sepsis, acute phase protein levels, and muscle fractional synthetic rate were compared between and within groups during the acute stay (admission to discharge). Outcome measures such as resting energy expenditure, body composition data (measured by dual-energy radiograph absorptiometry), cardiac function indexes, and number of reconstructive procedures were compared during acute hospital stay and at long-term follow-up (up to 2 yrs postinjury). Scar evaluation was performed at long-term follow-up. RESULTS: There were no significant differences between Integra and controls in burn size (70 +/- 5% vs. 74 +/- 4% total body surface area), mortality (40% vs. 30%), and length of stay (41 +/- 4 vs. 39 +/- 4 days). In the short term, resting energy expenditure significantly decreased (p < .01), and serum levels of constitutive proteins significantly increased (p < .03) in the Integra group compared with controls. Long-term follow-up revealed a significant increase in bone mineral content and density (24 months postburn, p < .05), as well as improved scarring in terms of height, thickness, vascularity, and pigmentation (12 months and 18-24 months, p < .01) in the Integra group. CONCLUSION: Integra can be used for immediate wound coverage in children with severe burns without the associated risks of cadaver skin.     

Correction of hypercromic palmar graft with split-thickness instep plantar graft: case report.

The plantar skin is the best donor site for grafting third-degree burn wounds onto volar aspect of hands and digits. In children, however, it is difficult to harvest the instep for a split-thickness graft. Most of these cases are treated with full-thickness or split-thickness skin grafts and dyspigmentation of the grafted area becomes a reality. We present a case of full-thickness graft hyperpigmentation that was treated with instep plantar graft.     

Overexpression of vascular endothelial growth factor accelerates early vascularization and improves healing of genetically modified cultured skin substitutes.

Cultured skin substitutes (CSS) lack a vascular plexus, leading to slower vascularization after grafting than split-thickness skin autograft. CSS containing keratinocytes genetically modified to overexpress vascular endothelial growth factor (VEGF) were previously shown to exhibit enhanced vascularization up to 2 weeks after grafting to athymic mice. The present study examines whether enhanced vascularization compared with controls persists after stable engraftment is achieved and analyzes VEGF expression, wound contraction, and engraftment. Control and VEGF-modified (VEGF+) CSS were grafted onto full-thickness wounds in athymic mice. VEGF expression was detected in VEGF+ CSS 14 weeks after grafting. Graft contraction was significantly lower in VEGF+ CSS compared with controls, suggesting more stable engraftment and better tissue development. Positive HLA-ABC staining, indicating persistence of human cells, was seen in 86.7% (13/15) of grafted VEGF+ CSS, compared with 58.3% (7/12) of controls. Differences in dermal vascularization between control and VEGF+ grafts were significant 1 week after surgery, but not at later times. However, the distribution of vessels was different, with more vessels in the upper dermis of VEGF+ grafts. These results suggest that VEGF overexpression in genetically modified CSS acts to accelerate early graft vascularization and can contribute to improved healing of full-thickness skin wounds.     

Effect of sequential early burn wound excision and closure on postburn oxygen consumption

OBJECTIVE: To determine the effect of early excision and closure of burns on postburn hypermetabolism, measured as oxygen consumption (VO2). METHODS: Twelve patients with deep burns of 30% to 50% of total body surface underwent sequential excisions and wound coverage, beginning 1 to 3 days after burn. The majority of the deep burn was removed by day 7, but with the addition of a donor site area of 20% to 25% of total body surface. RESULTS: No decrease in VO2 was noted in relation to the percent removal of burn tissue. In addition, a transient further increase in VO2 was noted early after excision, especially with surgical procedures performed after 5 days. This response could not be attributed to wound manipulation-induced bacteremias. CONCLUSION: We conclude that early surgical excision and closure of burns in excess of 30% to 50% of total body surface do not decrease postburn hypermetabolism in proportion to the area closed. It is possible that remaining open wounds in the form of donor sites and nonexcised burn are sufficient to perpetuate the hypermetabolic process, once established.     

Burn therapy 1985: Acute management

Mortality occurs from a burn injury because of infections which result from the metabolic and bacterial consequences of a large open wound, depression of the host's resistance, and both protein and total caloric malnutrition. Systemic antibiotics, topical wound therapy, and gentle wound debridement constitute traditional burn therapy. The systemic antibiotics and topical wound therapy do not solve problems presented by large open wounds and the related protein and caloric deprivation. A more rational approach uses antibiotics and topical wound therapy only as adjuncts to a program of early operative removal or excision of the devitalized, burned tissue and immediate closure of the wound. The excised wound is normally closed with available autograft, but in massive burn injuries, donor skin is insufficient. In these massive injuries, artifical skin can provide that immediate wound closure. As long as devitalized, burned tissue remains present in the setting of depressed host resistance, cross infection tends to colonize those remaining devitalized burn wounds with more virulent organisms than those that were already present. Bacterial controlled nursing units (BCNU) provide strict protection against that cross infection. Though inevitably a catabolic response occurs with massive injury, intensive nutritional support provides the calories necessary for the response to injury to avoid a prolongation of that negative nitrogen balance.     

Salvage of ear cartilage in patients with acute full-thickness burns

Three cases in which the temporoparietal fascial flap was used to salvage denuded ear cartilage during the acute period after burn injury are reported. Patients' burns ranged from 30% to 75% total body surface area. The full-thickness burn was acutely excised, exposing the auricular cartilage. The temporoparietal facial flap was elevated and wrapped around the cartilage. The flap was then covered with a split-thickness skin graft. All flaps and skin grafts survived. Additional reconstructive procedures have been performed on two of the patients and are planned for the third.     

Cultured epidermal autograft and the treatment of the massive burn injury.

As a rule, adult and pediatric patients with thermal injuries that involve more than 90% total body surface area (TBSA) burn have poor prognoses. Even for patients who are 5 to 34 years old with a 70% TBSA burn, the mortality rate is 80%. Lack of autologous donor skin, which is essential for permanent wound closure, is the major problem. Recent advances in growth of cultured epidermal autograft (CEA) have allowed closure of full- and partial-thickness burns; in approximately 3 weeks, a 2 cm2 biopsy specimen will produce enough CEA to cover a pediatric patient. Since 1989, we have used this product on nine patients; the average age was 39, and the average TBSA burn was 70% (range, 44% to 93%). We report our approach to use of CEA in six of these patients, including topical applications of 1% silver sulfadiazine and excision of full- and deep partial-thickness wounds within 2 weeks of injury. Temporary closure was achieved with cadaver allograft. "Take" of the allograft forecasted take of CEA. The total operative time of CEA placement was decreased by a two-step technique that obviates repeating debridement: the technique consists of debriding and grafting with allograft, then removing it at the time of CEA placement. CEA take is best on early granulation tissue or freshly excised wounds. Early excision of burn eschar, temporary wound closure with cadaveric allograft and Biobrane (Winthrop Pharmaceuticals, Wound Care Div., Fountain Valley, Calif.), and permanent closure with CEA may improve survival rates among patients with massive burn wounds. CEA is a tremendous asset to the management of massive burn injuries.     

植皮供区的美学探讨

目的：探寻符合美学原则的植皮供区，方法：从患的腹股沟区切取全层皮肤，然后用皮鼓修至中厚皮片，供区直接拉扰缝合，皮片游离移植覆盖躯干及四肢部的创面，结果：从1998年11月－2001年12月，共26例患自腹股沟区取皮，供区伤口均Ⅰ期愈合，瘢痕隐蔽，不明显，疗效满意，结论：腹股沟区是瘢痕不明显的植皮供区，符合美学原则。     

A preliminary report on transplantation of microskin autografts overlaid with sheet allograft in the treatment of large burns

The technique of transplantation of autologous microskin grafts (MG) with overlays of split-thickness skin allografts was used in the treatment of nine extensively burned patients. Preparation of MG includes: 1) mincing small pieces of split-thickness skin autografts into skin particles (SPs); 2) dispersing the SPs evenly on a piece of silk cloth; 3) transferring SPs to the dermal surface of an allograft sheet (20/1000 in.); 4) transplanting the allograft with SPs to the excised wound. The mean burn area (total/3 degrees, mean +/- SEM) of this group was 74.9 +/- 16.6/62.1 +/- 18.1% TBSA (range 40 to 94/28 to 90%). The mean age was 27 years (range 19 to 38). Early staged excisions followed immediately by MG applications were performed on 35 large body sites, including extremities, chests plus abdomens and backs. The mean area excised and grafted with MG was 41.7 +/- 11.0% TBSA (range 26 to 62%). The average time for complete healing was about six to seven weeks postgrafting. Eight patients survived; one died of overwhelming pulmonary infection 22 days postburn. Advantages of this technique are: 1) the great potential of MG to provide a large expansion ratio of 8:1 to 15:1, average greater than 10:1 in this series; 2) good maintenance of the healed graft to withstand trauma except in areas of repeated flexion; 3) ease of preparation and application with less cost compared to cultured epidermal sheet grafts; 4) prevention of infection in extremely large burns by providing continuous epidermal coverage following sheet allograft application.     

Clinical trials of a living dermal tissue replacement placed beneath meshed, split-thickness skin grafts on excised burn wounds.

We evaluated the ability of Dermagraft (Advanced Tissue Sciences, La Jolla, Calif.), a living tissue analog that is composed of human neonatal fibroblasts, which are grown on a polyglactin acid Vicryl mesh (Ethicon Inc., Somerville, N.J.), to function as a dermal replacement when placed beneath meshed, expanded split-thickness skin grafts (MESTSGs). Full-thickness burn wounds in 17 patients with burns (mean age, 31 years; range, 6 to 69 years; mean burn size, 23.8% total body surface area) were excised to subcutaneous fat (nine patients), to fascia (three patients), or to a combination of deep dermis and fat (five patients). Dermagraft was placed over the experimental sites, which were then covered with MESTSGs. Paired control sites on each patient received MESTSGs only. The results showed that "take" of MESTSGs on control sites was slightly better than take on experimental sites that contained the Dermagraft; however, the differences were not statistically significant. Mesh interstices epithelialized over the surface of the full-thickness wound (control sites) or over the surface of Dermagraft (experimental sites). Wound biopsy specimens demonstrated no evidence of rejection of the cultured allogeneic fibroblasts and minimal inflammatory reaction to the Vicryl fibers. Evidence of continuous basement membrane formation at the epithelial-Dermagraft junction, which was identified by immunohistochemical staining for laminin and type IV collagen, was seen by day 14 beneath the healed epithelium in the skin graft interstices. The Vicryl fibers were hydrolyzed in the wound over a 2-to-4-week period, although some expulsion of fibers occurred as the healing epithelium advanced to close the MESTSG interstices. Elastic fibers were not seen in neodermal tissue in either control or experimental wounds at periods of up to 1 year after grafting. Further trials with this living tissue replacement are in progress.     

Primary excision and immediate wound closure

Surgical principles of early excision of devitalized tissue and prompt wound closure which govern the management of all traumatic injuries have been developed in the primary treatment of burns. Topical and systemic antibiotics which delay wound infection and control invasive sepsis provide an initial period of two to three weeks in which wound excision and closure is safe and effective. Full support of the central and peripheral circulation, respiratory function, nutrition, and musculoskeletal function are essential features of care until the burn wound is eliminated and closed.Following initial evaluation, wound excision is carried beyond the deepest level of injured tissue. Excision to the level of muscle fascia is used for fullthickness injury and sequential excision in or below the dermis for deep dermal injury. Techniques of skin grafting and subsequent care of the graft are described, including the use of human allografts.Primary excision has reduced mortality, morbidity and later reconstructive measures by a factor of 50% when compared to results obtained by awaiting spontaneous separation of eschar with later grafting.With massive burns the use of allografts from familial donors of close immunologic type and immunosuppression of the patient prolong the period before allograft rejection and permit repeated harvest of the patient's donor sites for permanent wound closure. Over 60% of young burn victims with greater than 70% full-thickness burn injury have survived with this method of treatment.     

Cultured epithelial autografts: three years of clinical experience with eighteen patients.

Eighteen patients with major burns (mean total body surface area burned was 49% and mean total body surface area with full-thickness burns was 38%) had cultured epithelial autografts applied to 2% to 35% of the body surface area. In six patients successful "take" of greater than 65% occurred, and in 12 patients less than 40% "take" occurred. Most wounds underwent early excision to subcutaneous fat or fascia, and the wounds of 16 patients had been treated previously with homograft. Cultured epithelial autografts were covered with either single or multilayered dressings. Perioperative wound cultures showed that all patients had microorganisms, and appropriate perioperative antibiotic coverage of Staphylococcus epidermidis and Pseudomonas aeruginosa was noted less frequently in the poor take group, which may have influenced subsequent cultured epithelial allograft take. Adherence and stability of cultured epithelial allografts lag behind adherence and stability of meshed split-thickness autograft. The anterior trunk and thighs are the best recipient sites. The number of autograft harvests that were required to close wounds and the length of hospital stay were not significantly decreased by the use of cultured epithelial allografts as compared with comparable full-thickness burns that were treated previously without cultured epithelial allografts. Presently, grafting with cultured epithelial allografts is an adjunct but not an alternative to conventional burn-wound coverage with split-thickness autograft, because engraftment is inconsistent.