ABSTRACT/SUMMARY Cardiovascular disease is the leading cause of death in the United States (Ref), with high (66%) prevalence in age groups of 75 years or older [1, 2]. 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 [3]. 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 (2-3 years old) ovine carotid artery model [4]. In the current proposal, we aim to evaluate the efficacy of our grafts in a more clinically relevant aged animal model (5-6 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 6 months in an ovine model, which is a human equivalent of 5 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.
NIH ExPorter
NIH ExPorter