Design Principles and Clinical Trial of Autologous Engineered Skin Substitutes for Extensive Burns

Steven Boyce, PhD

Professor, Department of Surgery, University of Cincinnati

Stable closure of full-thickness burn wounds with autologous skin remains a limiting factor to recovery from burns of greater than 50% of the total body surface area (TBSA).  Hypothetically, engineered skin substitutes (ESS) consisting of autologous cultured keratinocytes and fibroblasts attached to collagen-based scaffolds may reduce requirements for donor skin, morbidity from autograft harvesting and widely-meshed skin grafts, and possibly mortality.

ESS were prepared from split-thickness skin biopsies collected after enrollment of 16 pediatric burn patients by Informed Consent into an investigative protocol approved by the local Institutional Review Board, and regulated by the US FDA.  Autologous keratinocytes and fibroblasts were cultured and cryopreserved as a cell bank for each subject.  Collagen-glycosaminoglycan scaffolds were fabricated in advance and stored sterile and lyophilized.  When sufficient cells were available, scaffolds were rehydrated, and inoculated sequentially with fibroblasts and keratinocytes followed by maturation of the construct for 10 days.  ESS and split-thickness skin autograft (AG) were applied in a matched-pair design to patients with full-thickness burns involving a mean of 76.9% of the total body surface area (TBSA).  Data collection consisted of photographs, area measurements of donor skin and healed wounds after grafting, biopsies of healed skin, comparison of mortality with the National Burn Repository, correlation of percentage closed wounds with percentage full-thickness burn, frequencies of regrafting within 28 days, and immunoreactivity to the biopolymer scaffold.

One subject expired before ESS were prepared.  Fifteen subjects received 2056 ESS grafts with a total area of 4.89 m2 which were applied in 59 operative procedures.  Mortality for these subjects was 6.25% (1/16), and 30.3% (305/1008) for a population with similar demographics in the National Burn Repository (p<0.05).  Engraftment at POD 14 was 83.5±2.0% for ESS and 96.5±0.9 for AG.  Percentage TBSA closed at POD 28 was 29.9±3.3% for ESS, and 47.0±2.0 for AG.  The ratio of closed to donor areas at POD 28 was 108.7±9.7 for ESS compared with a maximum of 4.0±0.0 for each harvest of AG.  Each of these values was significantly different between the graft types.  Correlation of % TBSA closed with ESS at POD 28 with % TBSA full-thickness burn generated an R2 value of 0.65 (p<0.001).  Healed areas of ESS were smooth, soft and strong, but hypopigmented and had no hair or glands.

These results indicate that autologous ESS reduce mortality and requirements for donor skin harvesting, for grafting of full-thickness burns of greater than 50% TBSA, and suggest that availability of autologous ESS for treatment of extensive, deep burns may reduce time to wound closure, long-term morbidity and mortality in this patient population.  Continuing research addresses restoration of skin pigmentation, and regeneration of hair, sebaceous glands and sweat glands.

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