350 Combinatorial Use of CEAs with Dermal Substitutes Containing Dermal Papilla-Like Structures

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Prompt closure of wounds is critical for recovery from massive burn injuries, but this can be challenging due to lack of available donor skin. Bioengineered therapies have been developed for treating these injuries including cultured epithelial autografts (CEAs). Although CEAs can facilitate wound closure, they are associated with disadvantages including graft fragility and blistering. To combat graft fragility and a weak epidermal-dermal junction, dermal substitutes with papillae-like structures (DS-PLS) were engineered and utilized in conjunction with CEAs. Human CEAs were fabricated by culturing primary epidermal keratinocytes for 19 days followed by release from plastic by brief exposure to dispase. Dermal substitutes were created by seeding electrospun collagen scaffolds with primary human fibroblasts at 500,000/cm2. Dermal substitutes were cultured for 5 days prior to creation of papillae-like structures. The surface of the engineered dermis was CO2 laser ablated to form a series of protrusions on the surface to mimic dermal papillae structure. On the day of surgery, CEAs were placed on the dermal substitutes containing papillae-like structures (DS-PLS) and immediately grafted to full-thickness surgical wounds in athymic mice; flat substitutes served as controls. Graft area, mechanical properties and structure were assessed 2 and 4 weeks post grafting. The DS-PLS promoted the interdigitation of the dermis and epidermis. Though the presence of the papillae-like structures did not significantly alter graft contraction, the epidermis was significantly thicker in this group versus flat controls. In addition, basement membrane deposition was increased in the DS-PLS versus controls and resulted in less delamination of the epidermis and dermis upon tensile testing. Dermal papillae play important roles in skin function; in particular, they enhance epidermal-dermal adhesive strength. The results of this study suggest that engineering dermal papillae-like structures into dermal substitutes can promote interdigitation of CEAs and the dermis and lead to improved epidermal-dermal adhesion. Methods to reduce blistering and enhance outcomes with CEA use may provide additional treatment options for patients with massive burn injuries.