Dermal
skin substitutes can be used to overcome the immediate problem of donor site shortage in the treatment of major skin loss conditions, such as
burn injury. In this study, the biocompatibility, safety, and potential of three variants of
NovoSorb (a family of novel biodegradable
polyurethanes) as dermal scaffolds were determined in a series of in vitro and in vivo systems. All three
polymers exhibited minimal cytotoxic effects on human skin cells, allowing keratinocytes, dermal fibroblasts, and microvascular endothelial cells to grow normally in coculture. Subcutaneous implantation of the
polymers in rats demonstrated no systemic toxic effects of the materials or their degradation products. The anticipated local
foreign body reaction compared favorably with commercially available medical
sutures. Assessment of a three-dimensional
polymer matrix followed. The success of sequential culturing of dermal fibroblasts and keratinocytes within the matrix indicated that the generation of a cultured
skin substitute is achievable. The polymeric matrix also provided a scaffold for the guided formation of a cultured microvasculature. When engrafted onto a surgically created full-thickness sheep
wound, the noncellular matrix integrated, healed with an epidermis supported by a basement membrane, and was capable of withstanding
wound contraction. The resistance to contraction compared favorably with a commercially available
collagen-based dermal matrix (Integra). These results suggest that the
NovoSorb matrix could form the basis of an elegant two-stage
burn treatment strategy, with an initial noncellular biodegradable temporizing matrix to stabilize the
wound bed followed by the application of cultured
skin substitute.