ADVERTISEMENT
Clinical Experience Using Cadaveric Skin for Wound Closure in Taiwan
Abstract: Taiwan’s skin banking program was initially set up to provide a ready source of cadaveric skin for patients with severe burns. However, human cadaveric skin may offer a useful alternative to conventional dressings in other wounds as well. Methods. In this retrospective review, cadaveric skin transplantation was used as temporary coverage in 145 patients with chronic ulcers, diabetic foot ulcers (DFU), necrotizing fasciitis, and acute traumatic wounds. Sex, age, number of debridements, and number of cadaveric skin transplantations were analyzed using statistical methods. Results. After clinical determination of engraftment 1 week after cadaveric skin allograft, skin samples harvested for histology in 15 cases revealed migration of epithelia from patient’s skin to the surface of cadaver skin and the presence of granulation tissue in the base of the cadaver skin. All wounds exhibited good wound-bed preparation after cadaveric skin transplantation, and could eventually be resurfaced with a skin autograft. Conclusion. Human cadaveric skin, in addition to being the mainstay in burn therapy, is a good biological dressing for chronic ulcers, DFUs, necrotizing fasciitis, and acute traumatic wounds.
Introduction
Skin banking in Taiwan started in 2006 with the primary purpose of providing a ready source of skin allografts for severely burned patients to enable expedient wound coverage after early excisions of burn wounds. Many major burn centers use cadaveric skin as temporary biological dressings in cases of massive thermal injury. The relatively low cost and availability permit early, complete excision of the burn wound, which reduces mortality, length of hospital stay, and even blood loss.1–5 In addition, cadaveric skin mitigates pain and aids wound-bed preparation before the placement of autografts.6 Research demonstrates that many other applications in wound healing support the use of cadaveric skin as a true biological dressing.6 From the establishment of the skin bank at the Tri-Service General Hospital, Taiwan, in 2006 until 2011, human cadaveric skin was used as temporary coverage to treat 145 patients with chronic ulcers, diabetic foot ulcers (DFU), necrotizing fasciitis, and acute traumatic wounds. In this study, the authors describe their clinical experience using human cadaveric skin in the treatment of various wounds, and compare the number of debridements and cadaveric skin transplantations performed among them. The histological features of the interface between the patient’s skin and the cadaveric skin were also analyzed.
Methods
One hundred forty-five patients with chronic ulcers, DFU, necrotizing fasciitis, and acute traumatic wounds treated at the Tri-Service General Hospital between 2006 and 2011 were included in this study. Wounds with exposure of bone were excluded. All wounds underwent a series of debridements until no necrotic tissue or pus was found (Figure 1A-1B). Human cadaveric skin was obtained to cover the wounds. All cadaveric skin was harvested, processed, and frozen at the Tri-Service General Hospital skin bank in accordance with the guidelines of the American Association of Tissue Banks. All potential donors were screened for positive serology to hepatitis B surface antigen, hepatitis C, HIV, HTLV-1, and VDRL. Harvested skin samples were also sent for microbiological analysis and were released for use only if there was no evidence of infection with pathogenic organisms. Cadaveric skin-covered wounds were evaluated via clinical examination 1 week postoperatively. A skin sample (1 cm × 2 cm), including cadaveric skin and patient’s skin, was harvested for histological analysis in 15 patients (Figure 2). The wounds with good adherence of the cadaveric skin (Figure 1C) were definitively closed with a skin autograft (Figure 1D). Patients with cadaveric skin breakdown underwent another debridement and were covered with cadaveric skin, followed by re-evaluation of adherence 1 week later. The number of cadaveric skin allografts performed (229) and the number of skin allografts (184) were recorded. Retrospective statistical analyses were performed using the SPSS for Windows package, version 10.1. Patient profiles and number of cadaveric skin allografts were compared between the 5 groups using chi-squared and Kruskal–Wallis tests. The methodology chosen is reflected in Table 1, and the level of significance was set at P < 0.05 for all statistical analyses.
Results
Table 1 shows the patient profiles and the clinical results. Among the 145 patients included in the study, 51 had chronic ulcers, 26 had DFU, 16 had necrotizing fasciitis, and 52 had acute traumatic wounds. All wounds were resurfaced with a skin autograft after cadaveric skin allografting (Figure 1E). Patients with necrotizing fasciitis needed a significantly larger number (4.5 ± 0.6) of debridements (P < 0.05) than patients with chronic ulcers, DFU, and acute traumatic wounds. Patients with necrotizing fasciitis exhibited a significantly larger number (1.5 ± 0.1) of allografts than patients with chronic ulcers (1.0 ± 0.0), and acute traumatic wounds (1.2 ± 0.1; P < 0.05). In all chronic ulcers, only 1 skin allograft was required to achieve good wound-bed preparation for skin autografting. No breakdown of the skin grafts was found during the average 13-month followup. The average number of days for each wound type to be ready for allografting was 7 days for chronic ulcers; 9.8 days for DFU; 10.5 days for necrotizing fasciitis wounds; and 8.4 days for traumatic wounds. Skin samples (1 cm × 2 cm) harvested from 15 patients (5 with chronic ulcers, 3 with DFU, 2 with necrotizing fasciitis, and 5 with acute traumatic wounds) showed migration of epithelia from the patient’s skin to the surface of the cadaveric skin (Figure 3A) and the presence of granulation tissue at the base of the cadaveric skin, which is a hallmark of tissue repair (Figure 3B).
Discussion
Even though new materials (ie, Hyalomatrix®, Terudermis®, Integra®) were used over time at the Tri-Service General Hospital for wound bed preperation,7 cadaveric skin has long been the standard biomaterial for temporary skin replacement in patients with extensive burns.8 To date, there is no better alternative to the biological properties of cadaveric skin.9 Many studies have reported that cadaveric skin has dermal elements that modulate the nature of the wound bed to create a milieu that is ideal for keratinocyte growth and skin reconstitution.10–14 Although cadaveric skin traditionally offers temporary coverage for large wounds in burn patients, recent investigations suggest a host of additional applications.6 Snyder15 treated nonhealing ulcers with cadaveric skin, which appeared advantageous in preventing wound desiccation, controlling infection, and substantially reducing pain. Carucci et al16 suggested that cadaveric skin may be useful in stimulating granulation tissue after Mohs microscopic surgery for the treatment of skin cancers involving the nose. In the current study, human cadaveric skin was used as temporary biological coverage after adequate debridement in stable wounds of chronic ulceration, DFU, necrotizing fasciitis, and acute traumatic wounds. Foot ulcers continue to be one of the most serious complications of diabetes. A prospective comparison of DFU treated with either a cryopreserved skin allograft or a bioengineered skin substitute showed skin allografts resulted in a higher percentage of wounds closing.17 The authors used skin allografts for temporary coverage in DFU and achieved good wound bed preparation for skin autograft wound coverage. Snyder et al18 suggested that the severity of tissue damage, as indicated by undermining damage to fascia, may correlate with delayed wound healing. Necrotizing fasciitis is a rapidly progressive, devastating infectious disease of the soft tissue, clinically characterized by fulminant destruction of tissue, systemic signs of toxicity, and increased rate of mortality. Rapid progression and propensity for soft tissue destruction warrants early intervention to decrease mortality and morbidity.19 In the author’s experience, patients with necrotizing fasciitis need the largest number of debridements and more cadaveric skin allografts than patients with chronic ulcers and traumatic wounds. Histological studies postulate that cadaveric skin does not actually “take” in the traditional sense. It is hypothesized that granulation tissue actually replaces the cadaveric skin, which provides an appropriate matrix for epithelial relining. Studies performed by Oliver et al20 are in agreement with this hypothesis; their results indicate that, although cultured allografts do not survive, they may modulate the proliferation and differentiation of spontaneously regenerating epithelium. In this study, the authors found migration of epithelia from the patient’s skin to the surface of the cadaveric skin, and the presence of granulation tissue at the base of the cadaveric skin, in 15 patients with good histological adhesion of the cadaveric skin. All 145 wounds were eventually closed using a skin autograft because of the presence of adequate granulation in the wound bed. Dermal or bi-layered skin substitutes, hydrocolloids, and composite dressings are typically used by clinicians as temporary skin coverage;15 however, the author’s perspective of performance and clinical outcomes showed cadaveric skin can achieve the same purpose.
Conclusion
In conclusion, the authors described their experience using cadaveric skin allografts as temporary biological coverage in cases of chronic ulcers, DFU, necrotizing fasciitis, and acute traumatic wounds. The cadaveric skin yielded good wound-bed preparation and led to the closing of all wounds with a skin autograft. Patients with necrotizing fasciitis needed the largest number of debridements and more cadaveric skin allografts.
Acknowledgement
This study was supported by the Tri-Service General Hospital, National Defense Medical Center, Taiwan, Republic of China, under grant TSGH-C100-126.
References
1. Tompkins RG, Hilton JF, Burke JF, et al. Increased survival after massive thermal injuries in adults: preliminary report using artificial skin. Crit Care Med. 1989;17:734–740. 2. Tompkins RG, Burke JF, Schoenfeld DA, et al. Prompt eschar excision: a treatment system contributing to reduced burn mortality: a statistical evaluation of burn care at the Massachusetts General Hospital (1974-1984). Ann Surg. 1986;204:272–281. 3. Herndon DN, Barrow RE, Rutan RL, et al. A comparison of conservative versus early excision: therapies in severely burned patients. Ann Surg. 1989;209:547–553. 4. Herndon DN, Parks DH. Comparison of serial debridement and autografting and early massive excision with cadaver skin overlay in the treatment of large burns in children. J Trauma. 1986;26:149-152. 5. Desai MH, Herndon DN, Broemeling L, Barrow RE, Nichols Jr, RJ, Rutan, RL. Early burn wound excision significantly reduces blood loss. Ann Surg. 1990;211(6):753-762. 6. Spence RJ, Wong L. The enhancement of wound healing with human skin allograft. Surg Clin North Am. 1997;77(3):731-745. 7. Caravaggi C, Grigoletto F, Scuderi N. Wound bed preparation with a dermal substitute (Hyalomatrix® PA) Facilitates re-epithelialization and healing: results of a multicenter, prospective, observational study on complex chronic ulcers (The FAST study). WOUNDS. 2011;23(8):228-235. 8. Greenleaf G, Hansbrough JF. Current trends in the use of allograft skin for patients with burn and reflections on the future of skin banking in the United States. J Burn Care Rehabil. 1994;15(5):428-431. 9. Kreis RW, Hoekstra MJ, Mackie DP, Vloemans AF, Hermans RP. Historical appraisal of the use of skin allografts in the treatment of extensive full skin thickness burns at the Red Cross Hospital Burns Centre, Beverwijk, The Netherlands. Burns. 1992;18(suppl2):S19-S22. 10. Kangesu T, Navsaria A, Manek S, et al. Kerato-dermal grafts: the importance of dermis for the in vivo growth of cultured keratinocytes. Br J Plast Surg. 1993;46(5):401-409. 11. Hickerson WL, Compton CC, Fletchall S, Smith LR. Cultured epidermal autografts and allodermis combination for permanent wound coverage. Burns. 1994;20(suppl 1):S52-S56.. 12. Langdon RC, Cuono CB, Birchall N, et al. Reconstitution of structures and cell function in human skin grafts derived from cryopreserved allogeneic dermis and autologous cultured keratinocytes. J Invest Dermatol. 1988;91(5):478-485. 13. Compton CC, Hickerson WL, Nadire K, Press W. Acceleration of skin regeneration from cultured epithelial autografts by transplantation to homograft dermis. J Burn Care Rehabil. 1993;14(6):653-662. 14. Livesey SA, Herndon DN, Hollyoak MA, Atkinson YH, Nag A. Transplanted acellular allograft dermal matrix: potential as a template for the reconstruction of viable dermis. Transplantation. 1995;60(1):1-9. 15. Snyder RJ. Treatment of nonhealing ulcers with allografts. Clin Dermatol. 2005;23(4):388-395. 16. Carucci JA, Kolenik SA 3rd, Leffell DJ. Human cadaveric allograft for repair of nasal defects after extirpation of basal cell carcinoma by Mohs micrographic surgery. Dermatol Surg. 2002;28(4):340-343. 17. DiDomenico L, Emch K, Landsman AR, Landsman, A. A prospective comparison of diabetic foot ulcers treated with either a cryopreserved skin allgraft or bioengineered skin substitute. WOUNDS. 2011;23(7):184-189. 18. Snyder RJ, Doyle H, Delbridge T. Applying split-thickness skin grafts: a step-by-step clinical guide and nursing implications. Ostomy Wound Manage. 2001;47(11):20-26. 19. Nowar MA, Biswas AR, Sundaravadanam T. Limb salvage in necrotizing fasciitis. WOUNDS. 2011;23(9):E27-E33. 20. Oliver AM, Kaawach W, Mithoff EW, Watt A, Abramovich DR, Rayner CR. The differentiation and proliferation of newly formed epidermis on wounds treated with cultured epithelial allografts. Br J Dermatol. 1991;125(2):147-154. Yuan-sheng Tzeng, MD; Shyi-Gen Chen, MD; Niann-Tzyy Dai, MD, PhD; Ju-Peng Fu, MD; Shun-Cheng Chang, MD; Shou-Cheng Deng, MD; and Tim-Mo Chen, MD are from the Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, Republic of China. Fu-Huang Lin, PhD is from the School of Public Health, National Defense Medical Center, Taipei, Taiwan, Republic of China. Address correspondence to: Tim-Mo Chen, MD Division of Plastic Surgery Department of Surgery Tri-Service General Hospital No. 325, Sec. 2, Cheng Kung Road Nei-Hu 114 Taipei, Taiwan, Republic of China doc20383@mail.ndmctsgh.edu.tw