| The goal of the research presented in this dissertation was to examine the use of biomaterials approaches for the manipulation of wound healing. Specifically, cell non-adhesive barrier materials, formed by in situ photopolymerization of water-soluble precursors that consisted of a central polyethylene glycol chain with flanking oligomers of lactic acid that was further capped with reactive acrylate groups, were evaluated for the prevention of post-operative adhesion formation, a wound healing complication related to scar tissue formation on internal organs as a result of surgical trauma. Cell non-adhesive barriers were also evaluated for the prevention of thrombosis and long-term wound healing complications after arterial injury. Interfacial photopolymerization techniques were developed for the synthesis of very thin hydrogel barriers {dollar}(rm{lcub}<{rcub}50 mu m){dollar} on the luminal surface of an artery. These barriers, when formed from non-degradable polymers, also represent a novel tool for the study of wound healing responses in the arterial wall, as they can be utilized to mechanically separate the vessel wall from the blood and effectively prohibit thrombus formation, thus allowing the examination of the roles of vessel wall-derived factors independent of external influences.; In addition to serving as cell non-adhesive barriers, these photopolymerized hydrogel biomaterials may be utilized for localized drug delivery at the site of injury. This allows the combination of both biomaterial and pharmacological approaches for the manipulation of wound healing. Drug delivery from these hydrogel materials was characterized in vitro, and local delivery of fibrinolytic agents from hydrogel barriers was examined for the prevention of post-operative adhesion formation. Vascular delivery of platelet-derived growth factor and thrombin was utilized to investigate the role of these thrombus-derived factors in intimal thickening.; Additionally, a novel group of bioactive biomaterials were developed, termed "healing-responsive hydrogels". These materials are BAB block copolymers based on polyethylene glycol, similar to those described above. In these materials, however, the degradable segment is an oligopeptide rather than an {dollar}alpha{dollar}-hydroxy acid. The oligopeptides employed are targeted to be specificality degraded by proteases involved in wound healing. |
