we propose to determine the biocompatibility of ClotFoam and enhance its hemostastic and non-compressible sealing effects against a severe parenchymial hemorrhage caused by a wound grade V affecting major vessels, which represents a lethal case in combat injuries. The strategy is to develop a second-generation fibrin sealant that will be carried by the current scaffold to the lacerated site. SPECIFIC AIM 1: to determine the biocompatibility, toxicity, enzymatic degradation and cell viability properties of the conjugated/modified polymers used to produce the ClotFoam scaffold. SPECIFIC AIM 2: Develop a 2nd generation of fibrin sealant that enhances platelet plug formation and provides enhanced anchors and better affinity of the fibrin clot to endothelial tissue. SPECIFIC AIM 3. Develop a standardized ex vivo model to evaluate the adhesion and sealing properties of a second generation fibrin sealant to endothelial tissue. The strategy to develop such advanced sealant includes: a) a shorter polymerization time to produce a functional fibrin clot over lacerated bleeding tissue, b) stimulation of the platelet plug formation which is the primary hemostasis process that will help stop the bleeding, c) reduction of fibrynolitic activity through the use of thrombin mutants with no affinity to protein C, d) Identification of the role of fibronectin and vitronectin as bridge molecules between cells and fibrin through binding to the a5b1-or avb3-receptor. In addition, fibronectin also binds fibrin exclusively through the aC-domain. This binding site is not accessible in fibrinogen, but becomes exposed in fibrin. Vitronectin directly associates with fibrin, preferentially to the carboxy-terminal c¢-chain of the fibrin(ogen) cA/c¢-chain variant.
Keywords: Non-Compressible, Hemoststic Agents, Fibrin Sealants, Tissue Scaffolds, Gelatin
