Pre clinical evaluation of vascular grafts in an aging ovine model

ABSTRACT SUMMARY Cardiovascular disease is the leading cause of death in the United States Ref with high prevalence in age groups of years or older Coronary artery disease which is the most common form often requires autologous vessels which need to be used in a coronary artery bypass grafting CABG procedure However aged patients who often suffer from comorbidities do not have viable graftable options necessitating tissue engineered vessels that are available off the shelf A major inadequacy of current technologies is that these have not been assessed pre clinically in aged models where senescent phenotype of vascular cells plays a significant role in graft healing processes Here we propose to utilize acellular tissue engineered grafts that have been functionalized to be anti thrombotic and self endothelializing along with strategies for mobilization of circulating progenitor cells within the aged host We use base scaffold biomaterial small intestinal submucosa SIS FDA approved for other medical indications Cook Biotech functionalized sequentially with heparin and VEGF vascular endothelial growth factor Previously we have reported patency and development of biological function of these acellular graft in a young years old ovine carotid artery model In the current proposal we aim to evaluate the efficacy of our grafts in a more clinically relevant aged animal model years old sheep with GMCSF granulocyte macrophage colony stimulating factor pre treatment to increase migratory and proliferative properties of endothelial progenitor cells within the host Our objective is to establish long term applicability of our grafts with effective infusion of GMCSF for months in an ovine model which is a human equivalent of years In phase II following the formulation of final successful regimen storability sterility and GMP requirements will be outlined prior to an IDE application to the FDA NARRATIVE Assessment of a completely acellular vascular graft available on demand for surgical application in an aging animal model should have a major impact on current treatment of cardiovascular disease To achieve this goal we propose to develop off the shelf vascular grafts capable of resisting occlusion and developing endothelialized lumen in the elderly by mobilizing their own blood stem cells