The goal of this research effort is to demonstrate that significant biomedical polymers can selectively affect the activation, function and Interleukin 1 production of tissue macrophages and this modulation of macrophage activity can be correlated to in vitro and in vivo cellular proliferation and synthesis. The macrophage is considered to be the major cellular component controlling the inflammatory response and the biocompatibility of the implanted biomedical polymer. Macrophage activation is known to lead to Interleukin 1, IL1, production; a species non-specific protein which induces fibroblast and endothelial cell proliferation and synthesis. Studies described in this application are directed toward understanding the biocompatibility of biomedical polymers and tissue/material interactions which lead to cellular proliferation and synthesis. Specifically, we will (1) evaluate the in vitro and in vivo effect of significant biomedical polymers, without and with preadsorbed proteins, on the activation and IL1 production of human and rat macrophages, and (2) evaluate the effect of in vitro and in vivo polymer-induced production of macrophage IL1 on human fibroblast proliferation and synthesis (collagen) and endothelial cell proliferation and synthesis (6-keto-PFT 1Alpha). Correlative data relating the in vitro and in vivo behavior of macrophages and IL1 production will be provided using cell culture bioassays. Results from the cell culture bioassays will be compared to results from in vivo subcutaneous implant studies to provide further in vitro-in vivo correlations. The clinically significant biomedical polymers to be studied are polyethylene (NHLBI-DTB reference), silica-free polydimethylsiloxane (NHLBI-DTB reference), silica-filled polydimethylsiloxane (Silicone Rubber), knitted Dacron velour, woven Dacron, expanded polytetrafluoroethylene (ePTFE) and Biomer. The proteins which will be preadsorbed onto the polymers prior to evaluation are albumin, fibrinogen, fibronectin, immunoglobulin G, and complement component C5a. These studies are important as they represent one of the first attempts to provide a quantitative understanding of biomedical polymer biocompatibility from a cell interaction and activation perspective. We expect that the results from the in vitro and in vivo studies proposed in this application will provide insight into cell-material, cell-protein and cell-cell interactions as they relate to the biocompatibility of polymers.
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