Full-thickness dermal wounds in normal mice heal by a wound contraction process, involving closure of the defect by centripetal movement of the dermis and epidermis as a unit and a resulting in little scarring. The mutant tight-skin mouse heals with a delay of wound closure and formation of scar tissue with a hypertrophic scar-like appearance, based upon histological examination. The wound contraction process is carried out by fibroblastic cells in the granulation tissue exerting force on the surrounding collagen, compressing the granulation tissue and pulling the defect closed. The process bears many similarities to contracture of hypertrophic scars, and thus serves as an appropriate model for study o scar contracture mechanisms. Preliminary ultrastructural studies demonstrated an uncharacterized pericellular matrix material between the fibroblasts and collagen fibers which is present during the delay but is not apparent as wound contraction begins. The interposing location of the pericellular matrix suggests and interference with cell attachment to collagen and, thus, with exertion of force for wound closure. This proposal plans to characterize the pericellular matrix using specific histochemical and cytochemical techniques. Biochemical extractions designed to isolate identified pericellular matrix macromolecular components will aid in defining differences between tight-skin and normal mouse healing and will provide materials for testing in a fibroblast- populated collagen lattice culture model of wound contraction and scar contracture. Extracted pericellular matrix components will be tested for effects on lattice contraction in skin equivalents composed of epidermal cells and fibroblasts from normal or tight-skin mice gown in collagen lattices. The proposed research should aid in understanding the cell- matrix interactions which are critical to unimpeded wound healing and also those involved with scar contracture. Information gained could have a direct bearing on development of new techniques for treatment of burns and prevention of hypertrophic scar contracture.
