Induction of endothelialization of tissue-engineeredcardiovascular constructs via in vivo angiogenesisduring post-implant remodeling

摘要

In vivo remodeling of implants is absolutely unavoidable. A major focus of tissue engineering should be the utilization of these remodeling processes to (1) induce capillarization to nourish three-dimensional tissue constructs, (2) recruit desired functional cells, (3) recruit supporting matrix components, (4) minimize fibrosis and apoptosis, (5) control cellular phenotype, (6) minimize immunologic reactions to allogeneic or xenogeneic cells, and (7) circumvent practical limitations and time requirements of in vitro utilization of autologous cells Selected biomolecules can either be induced endogenously by biomaterial characteristics or can be added exogenously as either proteins or as genes Induction of capillarization of implanted cardiovascular implants may be promoted using novel polymer chemistry, architecture or mechanics, or by application of either naturally occurring or engineered mutations of naturally occurring biologic agents As an example of the first approach, lactide/glycolide copolymeric vascular grafts induce an angiogenic network, which provides endothelium to the implant surface, phenomena not occurring in clinically used graft materials. This difference is mediated largely by generation of FGF-2 production and angiogenesis.