Physiological Cultured Skin Substitutes for Wound Healing

Abstract

Physiological dermal and dermal-epidermal skin analogs have been developed in our laboratory using a novel technology for three-dimensional tissue culture. Human neonatal dermal fibroblasts are seeded on a biodegradable mesh made of polyglycolic or polyglactic acid (PGA/PGL). As the fibroblasts proliferate, they stretch across the mesh openings and secrete growth factors and human dermal matrix proteins, including collagen types I & III and elastin. This process forms a metabolically active, three-dimensional dermal tissue around the mesh scaffolding. The mesh fibers are hydrolyzed over time and is completely resorbed in vivo within four to eight weeks. Multiple sheets of the PGA/PGL-dermal analog are grown simultaneously in a closed, continuous media-flow system, also developed in our laboratory. After attaining confluence, the dermal sheets may be seeded with keratinocytes, to create a living dermal-epidermal composite tissue.

Pre-clinical studies in mini-pigs and athymic mice have shown that the dermal analog “takes” and vascularizes rapidly in full-thickness wounds, and provides a viable dermal base for both meshed split-thickness skin grafts and cultured keratinocyte sheets. There has been no evidence of rejection. The dermal analog is now being studied clinically beneath thin meshed skin autografts in patients with severe bums. In vivo pre-clinical studies of the dermal-epidermal composite, as a complete skin replacement, are also in progress. This technology has potential for applications in severe burns and other full-thickness skin injuries.

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Halberstadt, C., Anderson, P., Bartel, R. et al. Physiological Cultured Skin Substitutes for Wound Healing. MRS Online Proceedings Library 252, 323–330 (1991). https://doi.org/10.1557/PROC-252-323

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