Wound healing both in surgical incisions in the compromised patient and in leg ulcers and pressure sores represents a major national health problem. The long term objective of this proposal is to develop quantifiable wound healing models with major similarities to clinical wound healing problems, to promote wound healing in these models by topically applied growth factors, and to elucidate their mechanism of action with the intent of providing a rationale and method to promote healing in clinical situations where it would be of benefit. A surgical linear incision model will be evaluated quantifiably by tensometry to measure wound healing strength, as well as histologically, immunohistochemically and by vascular perfusion studies. Our findings that growth factors PDGF and TGFB promote healing will be extended and the potential angiogenic and healing effects of FGF will be examined. Most models altered by systemic agents including steroids, irradiation, chemotherapeutic agents and macrophage toxins will be examined both for their clinical applicability and to elucidate the mechanism of action of the growth factors on healing. The interaction with systemic agents that promote healing will also be examined. A rabbit ear full thickness would model with similarities to clinical ulcer and pressure sores will be characterized and the epithelization and granulation tissue quantified on histological sections. The ability of growth factors PDGF, EGF, TGFB will be analyzed. Blood vessel formation will be analyzed by vascular perfusion studies. Further analysis of cell proliferation, collagen content and type, collagenase production and glycosaminoglycan production will be carried out in vitro. The altered healing states of ischemic, and irradiation will be analyzed in parallel fashion. An in vitro model of wound healing in the rat mesentery developed in my lab will be utilized to analyze the ability of respective growth factors to promote healing under controlled conditions and correlate to in vivo healing. Histological and immunohistochemical technique will be utilized as well as collagen analysis, and cell proliferation studies to elucidate the mechanism of action. Northern blot analysis of mRNA levels of growth factors and other protoncogenes will be carried out in collaboration.
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