Wound Repair

Scope of this initiative within the CMB:

Wound healing requires the progressive activation of cell-matrix interactions during hemostasis, inflammation, proliferation and remodeling. These events are coordinated by paracrine, juxtacrine, and intercrine expression of cytokines and growth factors . Key biological processes include cell migration and proliferation, angiogenesis, and fibroplasia. As such, wound healing is a form of regenerative response that has been adapted to deal with environmental insults such as infection and contamination. Thus, the outcome of healing in the adult is repair – the restoration of tissue integrity – rather than perfect replacement of tissue architecture. Key targets of investigation in the wound healing arena are the acceleration of retarded wound healing and the suppression of an excessive (fibrotic) healing response. Current data support the concept that these processes can be modulated by altering the signaling within the wound environment or by directly modifying extracellular matrix metabolism.

Nearly the full spectrum of matrix molecules come into play during tissue repair, somewhat dependent on the site of injury. Collagens I, III, and V are the major matrix constituents to replace the provisional, blood-derived matrix of fibrin, fibronectin, and thrombospondin. Collagen architecture is then modified by proteoglycans such as decorin, and the new connective tissue will contain adhesive glycoproteins as well as space-filling proteoglycans. Cell migration, movement, and traction during these changes is largely dependent on the dynamic changes in patterns and levels of integrin expression in the various cell populations. Matrix architecture is constantly modified by the tightly-controlled expression of matrix metalloproteinases. Basement membrane constituents ( perlecan, laminin, and type IV collagen) are particularly critical for epithelial and endothelial cell behavior. The CMB will promote interdisciplinary studies in this area, particularly by providing expertise and, whenever possible, supporting the use of purified matrix macromolecules.