Transglutaminase enzymes are ubiquitous Ca2+-dependent enzymes which catalyze the formation of crosslinks between glutamine and lysine residues of proteins. Extensive transglutaminase-mediated crosslinking of soluble proteins is believed to be responsible for rapid physical gelation of certain biological fluids. A common biological strategy for regulating the activity of transglutaminase enzymes is control of intracellular and extracellular Ca2+ concentration, mediated by lipid bilayer membranes. Stimuli-responsive synthetic lipid vesicles offer a unique opportunity to regulate transglutaminase-mediated gelation by sequestering and then releasing enzyme-activating ions such as Ca2+. The investigators hypothesize that Ca2+ release from temperature or light sensitive liposomes can be used to trigger TG-mediated crosslinking of proteins to form hydrogels suitable for the purposes of wound healing, drug delivery, and tissue engineering. In this study, natural proteins and synthetic polypeptides determined to be transglutaminase substrates will be used in combination with Factor XIII and tissue transglutaminase to formulate solutions which undergo rapid gelation upon activation of the enzyme by exposure to Ca2+. Gelation of these protein/enzyme solutions will be triggered by Ca2+ release from temperature and light sensitive liposomes, and the mechanical properties of the resulting hydrogels will be evaluated using dynamic mechanical analysis. The tissue adhesive potential of these hydrogels will be assessed by measuring the force required to separate skin surfaces bonded together by in-situ formed hydrogels, and drug release studies will be performed to evaluate the potential for release of drugs and growth factors from the hydrogels.
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