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.
From the *Burns Unit/Skin Engineering Laboratory, Royal Adelaide Hospital, South Australia, Australia; and †PolyNovo Biomaterials Ltd., Victoria, Australia.
NovoSkin is a joint venture established to investigate the role of NovoSorb™ in wound management applications between PolyNovo Ltd. (who own 80%) and Skin Pty Ltd. (20%). Dr John Greenwood is a 50% stakeholder of Skin Pty Ltd.
Address correspondence to John E. Greenwood, AM, Burns Unit, Royal Adelaide Hospital, North Terrace, Adelaide, South Australia 5000, Australia.