A major objective of tissue engineering is the use of cultured cells to recreate tissues and organs as replacement parts that may be grafted into humans and animals. These efforts in vascular modeling have relied on synthetic materials to provide mechanical strength and served as scaffolds for endothelialization with respect to vascular grafts. Although this approach has been successful to some extent, problems due to incomplete healing (growth of neointima) and intimal hyperplasia (overgrowth) of smooth muscle cells persist. Intimal hyperplasia leads to vessel recluse and is suspected to be the result of incomplete endothelialization over the anastomosis which in turn is due to compliance mismatch between prosthesis and adjacent artery. The long-term objective of this proposal is the development of artificial vessel prostheses composed of cell-polymer composite membranes that will ultimately assemble biological functions in vivo. Initial studies will examine cell-biopolymer adhesion, growth and proliferation kinetics by culturing to seed endothelial (EC) smooth muscle cells (SMC) on polymeric membranes to mimic blood vessel. A double- chamber flow system will be constructed to supply nutrients to the proliferating cell layers as well as to investigate cell-cell and cell-polymer interactions. The extent of polymer degradation or disappearance and deposition of extracellular matrix will be assessed. The effects of polymer degradation products, if any, will be determined. The hypothesis is that sandwiching biodegradable membrane between SMC and EC in vitro may permit deposition of competent extracellular matrices (ECM) to bond as for adventita to produce layered hold, another method for controlling occlusion and hyperplastic breakthrough of EC monolayer by SMC would have been achieved. It is hoped that vascular constructs from bilayer seeding will respond better to diameter changes in response to local changes to blood flow than inert synthetic based vessels.
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