Grant: Project Grant

Limited native vessels are available for arterial vascular grafts (AVGs) to address the needs of patients, some requiring many grafts and patient groups with varied vascular conditions, such as the growing adult population with diabetes which may have multiple other illnesses, complicating their condition. There are also many with more specific challenges related to critical vascular conditions, for example patients with complex congenital heart disease (CHD) due to genetic defects at birth or other events affecting heart development, leading to poor heart ejections, and subsequently vascular stenosis and clotting of the pulmonary arteries (PA). Small vessels (less than 10mm) tissue engineering has attracted research interest for generating living blood vessels given the inability to always have access to a patient's own vessels, and the inherent pro-clotting and poor mechanical match of synthetic implants. While the field has achieved some progress with natural tissue derived (e.g. collagen based) and polyester-based materials for AVG scaffolds, they still suffer from multiple factors including poor mechanical compliance, pro-inflammatory reactions resulting from the materials and their degradation by products, clotting nature, and reproducibility/cost issues. Our research is advancing the generation of a synthetic tissue engineered scaffold (made of patented degradable polar/hydrophobic/ionic (D-PHI) polyurethane), conceived to harness the body's own wound healing character with white blood cells. We will undertake the in vivo validation of AVGs generated from human cell sources and cultured on fibre-based DPHI scaffolds in dynamic bioreactors. Hypothesis: The hypothesis is that AVGs with diameters <10mm, generated using immuno-modulatory D-PHI scaffolds and combined with patient sourced cells (specifically fat and blood derived cells) can be conditioned into a living and functional AVG using biomechanical stimuli, and show integration and function in vivo.