Macrophage response to polymeric vascular grafts

Abstract

The use of materials for replacement or repair of biological tissue and organs has been attempted for thousands of years. Regardless of material used or site of implantation all biomedical materials elicit a foreign body response by the host characterized by the presence of macrophages and foreign body giant cells with the polymer for the duration of the implant. This inflammatory response is believed to be responsible for the lack of biocompatibility of implanted materials. Furthermore, each type of biomedical device suffers from specific problems that may lead to the ultimate failure of the implant. Synthetic polymeric vascular grafts fail primarily due to the inherent thrombogenecity of the material and anastomotic neointimal thickening. In an attempt to create a non-thrombogenic lining on the blood contacting surface of vascular implants, the promotion of an endothelial lining on the luminal surface of vascular grafts has been investigated. This can be accomplished by both artificial and natural mechanisms. Regardless, it is believed that the inflammatory response elicited by the implant influences the angiogenic mechanisms and neointimal thickening associated with the implant. The relationship between inflammation and angiogenesis associated with biomedical implants remains to be delineated. Studies in this dissertation attempt to determine this relationship by examining the inflammatory response and inflammatory cytokines released by cells associated with polymeric implants and how these bioactive molecules influence the angiogenic response. Furthermore, an advancing technology in vascular repair, endovascular grafts, was tested in two vascular models to assess the general healing characteristics, inflammatory response and the formation of blood vessels associated with the device. The results from these studies suggest that the inflammatory response plays a fundamental role in the formation of blood vessels around polymeric implants and neointimal thickening on the luminal surface of vascular implants. From these experiments a greater understanding of the healing response associated with vascular grafts has resulted.