Angiogenesis and neovascularization in association with extracellular matrix protein modified biomaterials

Abstract

Synthetic biomedical implants are used to replace diseased tissues and organs. Unfortunately, these implants often fail due to a lack of biocompatibility and poor integration by the recipient. This implant failure is associated with the formation of an avascular fibrous capsule and chronic inflammatory response. Additionally, small diameter vascular grafts have complications associated with surface thrombogenenicity and intimal hyperplasia. Porous polymers are often incorporated in the construction of biomedical devices because they permit tissue integration and improved biocompatibility. While the inclusion of porosity has enhanced device performance, these devices still do not perform optimally. The incorporation of a vascular network in association with and within the pores of these materials is believed to improve tissue integration and long-term device function. Several approaches are actively being studied for their ability to stimulate new vessel growth, angiogenesis, as well as to improve the direct interaction of cells with material surfaces. The process of angiogenesis involves the coordinated involvement of both soluble and insoluble factors such as growth factors and cytokines, and extracellular matrix proteins respectively. Often, growth factors and cytokines are expressed by the inflammatory cells associated with the biomedical implants, but the microenvironment within the polymer remains unstable with respect to the presence of the appropriate extracellular matrix proteins. The overall hypothesis of this dissertation is that the reestablishment of an extracellular microenvironment on and within a porous polymer will provide the appropriate substrates for promoting angiogenesis and neovascularization of porous polymers. The results of the studies within this dissertation demonstrate that extracellular matrix modifications of commercially available expanded polytetrafluoroethylene (ePTFE) successfully promote new vessel growth in the tissue surrounding the implant, termed angiogenesis, and new vessel growth within the pores of the polymer, termed neovascularization. Furthermore, the extracellular matrix protein laminin 5 was determined to promote human microvessel endothelial cell adhesion to ePTFE as well as support angiogenesis and neovascularization when used as a surface modification of ePTFE. Based on these studies, the extracellular matrix protein, laminin 5, could be utilized in the tissue engineering of biomedical implant devices to promote increased new vessel integration and improve the long-term viability of these devices.