Promotion of acellular dermal matrix resolution in vitro by matrix metalloproteinase-2

Objective: To determine whether acellular human dermis is degraded by matrix metalloproteinases ( MMPs), a large class of matrix-degrading enzymes. Methods: The degradation of acellular human dermis specimens was evaluated in vitro. Wild-type murine fibroblasts with a broad-spectrum MMP inhibitor, GM6001, and MMP-2- deficient fibroblasts were placed on the basement membrane and dermal surfaces of acellular human dermis. Matrix degradation and fibroblast infiltration into the matrix were assessed after a 20-day incubation period. Results: The basement membrane thickness of the specimens cultured with wild-type fibroblasts was significantly less than that of specimens cultured with GM6001 ( P < . 001), and the infiltration of fibroblasts into the dermal surface was limited by the addition of GM6001 ( P=. 002). To determine whether MMP-2 was involved in this in vitro phenotype, MMP-2- deficient fibroblasts were assessed in comparison with wild-type fibroblasts. Wildtype fibroblasts degraded the basement membrane surface ( P < . 001) and infiltrated the dermal surface ( P=. 003) more efficiently than did MMP-2-deficient fibroblasts. Conclusions: The results from our in vitro experiments suggest that MMPs and specifically MMP-2 may play an important role in the resorption of acellular human dermis. Addition of MMP inhibitors to implanted dermal matrices may slow fibroblast infiltration and improve their longevity in vivo.