Impact of Electrospun Conduit Composition and Peritoneal Pre-conditioning on Patency and Remodeling of Tissue Engineered Vascular Grafts
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Overall goal of this project was to develop a tissue engineered vascular graft by implanting an electrospun tubular conduit into the peritoneal cavity to recruit autologous cells to it and provide the cells with the components of the hysiological environment prior to grafting the conduit into the artery. This was accomplished through three complimentary studies: finding the best ratio of poly(ε-caprolactone) (PCL) and collagen that improves inflammatory response within the peritoneal cavity; determining the effect of peritoneal pre-implantation and the amount of incorporated collagen on graft functionality; and reducing the potential side effect of peritoneal adhesion formation. In the first study, scaffold composition was systematically varied to determine the best collagen/PCL ratio that limits proinflammatory species production inside the peritoneal cavity, modulates cells phenotype, and maintains conduit mechanical integrity after 4 weeks of implantation inside the peritoneal cavity. It was found that adding collagen to the PCL conduits reduced the accumulation of oxidized lipid species. In addition, the ratio of collagen had a significant impact on the recruited cell phenotype and construct mechanics and it was shown that the conduit mechanical and biological response does not follow a linear trend with percent incorporated collagen. In the second study, conduits of different ratios of PCL and collagen with and without peritoneal pre-implantation were grafted into the abdominal artery of rats to determine graft remodeling and endothelialization in the arterial microenvironment. Peritoneal pre-implantation reduced overall lipid oxidation, intimal layer thickness, and expression of an M1 macrophage marker. Moreover, while increasing the collagen content reduced the expression of macrophage markers, it increased the thickness of intimal layer as well. In addition, interaction of these conduits with blood was studied in vitro in a preliminary study and it was found that none of the conditions caused hemolysis and peritoneal pre-implantation reduced the platelet adhesion to the conduits. In the third study, a new pouch composed of PEGDA hydrogel was designed to reduce formation of peritoneal adhesions and address the potential concern using this strategy. Overall, these results demonstrated the beneficial effects that blending natural and synthetic polymers and peritoneal pre-conditioning can provide for tissue engineered vascular grafts. This includes reducing the expression of inflammatory markers, accumulation of oxidized lipids, and thickness of intimal hyperplasia. Future work will involve rigorous characterization of PEGDA pouches and a detailed characterization of the biomaterial mechanism for response from the different blends of electrospun collagen/PCL.