096 Contraction and Remodeling of Collagen Gels by Fetal and Adult Fibroblasts

Abstract

Scarless fetal wound healing in connective tissue is characterized by organized collagen deposition that leads to regeneration and apparently normal tissue structure and function. In contrast, adult wound healing is characterized by the deposition of unorganized collagen that leads to scar formation and a loss of functionally relevant structural organization. Fibroblasts are responsible for the synthesis and deposition of collagen and other extracellular matrix molecules, and the subsequent remodeling and contraction during the wound healing process. Therefore, fibroblasts play a key role in the different outcomes observed in fetal and adult wound healing. The hypothesis is that fetal fibroblasts, relative to adult fibroblasts, have an altered capacity to contract collagen gels and remodel collagen fibrils due to inherent differences in their contractile phenotype. In this study, an anchored collagen gel model was used to evaluate matrix contraction and remodeling by these different fibroblast phenotypes. Video microscopy was used to measure the changes in surface area of contracting collagen gels. Collagen gel reorganization was evaluated using a fitting algorithm to predict the distribution and orientation of collagen fibrils from scanning electron microscopy images. In addition, fibroblast morphology and proliferation on contracting collagen gels were examined. Understanding these phenotypic variations will elucidate key differences in the wound healing process that can be used for potential clinical applications involving cell therapy and tissue engineered constructs. Acknowledgments: Support was provided by the Children’s Hospital of Pittsburgh and the Pittsburgh Tissue Engineering Initiative.