Implantation of medical devices that require transfer of mass across an interface includes such applications as indwelling sensors, controlled drug release, and cellular therapies. The latter includes primary cells, cell lines, or genetically engineered cells. Usually, the cells must be immunoisolated from the host by protection with a semipermeable to prevent immune rejection. Such materials often elicit a foreign body response characterized by a layer of avascular tissue. The resulting diffusion barrier to oxygen, nutrients, and wastes can adversely affect tissue viability or function. The overall goal of this research is to better understand the nature of the interactions between soft tissues and a recently discovered class of microporous membranes which, by virtue of their morphology and microarchitecture, induce neovascularization at the host tissue-material interface. Our objective is to understand on a fundamental cellular and molecular level how membrane architecture induces neovascularization. We hypothesize that the macrophage migrates into the membrane and that it secretes angiogenic factors in response to sensing hypoxic regions within the membrane. We will focus on obtaining a quantitative description of the materials and of the tissue neovascularization response, identifying the cells involved and characterizing their synthesized and secreted products, and developing insight into the mechanism(s) responsible for neovascularization.
Our specific aims are as follows: (1) To quantitatively characterize the size distribution of the interstices and of the solid elements of the microporous membranes which will be implanted; (2) To implant a variety of microporous membranes in Lewis rats to first replicate and later extend observations reported in the literature; (3) To investigate the three-dimensional spatial distribution of blood vessels in the vicinity of the implant; (4) To identify the cells that have migrated into the interior of the membrane as well as those on the external surface; (5) To investigate the production and secretion of angiogenic and other factors pertinent to the tissue response by cells located within and adjacent to the membrane; and (6) To use in vitro culture methods to examine the interaction of isolated macrophages with microporous membranes.
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