Tissue Engineering Plant-based Vascular Grafts II - Abstract Coronary heart disease patients do not always have a saphenous vein suitable for an arterial bypass graft. Despite advances in vascular replacement and repair, fabricating small-diameter vascular grafts with low immunogenicity that are capable of host tissue remodeling remains a challenge. These important clinical needs will be met by investigating heat treatment parameters for decellularized plant-based scaffolds. Recent advancements in plant decellularization have produced cost-efficient cellulose scaffolds providing promising alternatives for skeletal, cardiac and bone tissue engineering. We were the first to develop robust, endothelialized vascular grafts from decellularized leatherleaf viburnum that matched mechanical properties of native blood vessels. Our long-term goal is to tissue engineer and test a patent, non-thrombogenic vessel for engraftment that mimics mechanical and structural properties of native vessels. By evaluating a range of heat treatment techniques, we will improve biodegradation and reduce immunogenicity of our plant-based vascular grafts and offer new methodologies to expand its applications within this quickly growing plant decellularization field. We hypothesize that heat-treated plant-derived scaffolds will recapitulate the robust multi-layer structure of native vessels and enable host tissue remodeling, with greater patency and resistance to thrombosis in vivo. We have developed a highly innovative heat treatment disrupting lignin and hemicellulose in the cell wall, as well as intermolecular ester bonds. Our Specific Aims are: 1) optimize plant-based vascular grafts using heat treatment to degrade the scaffolds and inactivate harmful lectin proteins and 2) validate grafts in vivo to compare their patency, tissue integration and biodegradation to a field standard (PTFE). An immediate goal is to remove foreign DNA from the decellularized plant scaffold but maintain cellulose’s mechanical properties. After graft recellularization of the endothelial and smooth muscle cells, cyclic application of fluid shear stress will be applied to pre-condition the construct for implantation and validation in an animal model. Our preliminary tests providing heat treatment of plant leaves in alkaline solution, combined with decellularization, improved decellularization efficiency, degradation, and elastic modulus. Thus, we predict providing a key method for decellularizing plants and pre-conditioning cells in a natural scaffold capable of successful engraftment. Importantly, our proposed project will also enhance the research environment at Hofstra University by allowing undergraduate students to plan, execute and perform analysis of authentic hands-on research that serves a critical need in public health. The PI and his research team will provide a diverse group of undergraduate students with a closely mentored biomedical research experience and projects that they can work on independently. Students will prepare articles for journals and present at appropriate scientific conferences. This will allow students to acquire a broad range of skills in biomedical engineering that they would otherwise not have access to and is expected to have a significant impact on their future studies and career choices.
