Saphenous vein graft (SVG) failure following coronary artery bypass grafting (CABG) is a critical clinical problem,with recent studies revealing that as many as 25% of vein grafts develop stenosis within 12-18 months aftersurgery, and up to 50% of grafts occlude within 5-10 years. CABG surgery is the gold standard treatment forpatients with severe multi-vessel disease, with over 370,000 procedures performed annually in the U.S. andSVGs are used in 95% of cases. Identification of strategies and devices to prevent SVG failure represents apressing unmet clinical need. BioGraft will address this unmet need by developing an external biodegradablescaffold device to prevent SVG failure. It is well established that mechanical loading contributes to the cellularand structural changes leading to SVG failure. In current clinical practice, when the SVG is harvested andimplanted into the coronary circulation, it is subjected to an abrupt change in mechanical loading (20X changein pressure, 4X change in flow-induced shear), triggering SVG wall remodeling and, often, maladaptation andfailure. Our foundational R01-funded research, which laid the scientific foundation for the founding of BioGraft,showed that gradual increases in loading could mitigate or even eliminate graft failure. We demonstrated thisconcept in vivo, showing more favorable graft adaptation with a first-generation design in an ovine model. Here,to achieve a design that can be manufactured at scale, we propose a next-generation 3D printed biodegradablescaffold, which we will refine and test in this proposal. To achieve our goals, we propose three specific aims. InAim 1, we will screen 3D-printed design candidates with ex vivo testing and degradation studies. This will allowus to efficiently and inexpensively select designs matching desired targets. In Aim 2, we will perform pre-clinicaltesting of the scaffold device in an established ovine carotid-jugular interpositional vein graft model of CABGsurgery. This will establish preliminary safety and efficacy. In Aim 3, we will characterize device performanceusing mechanical testing and histopathology. These data will enable follow up fundraising, development of acommercialization plan and initiation of FDA discussions. BioGraft's founding team leverages a long-standingengineering and clinical collaboration and recent partnerships with renowned investigators at Stanford and Dukewho hold IP for unique bioabsorbable materials and bring expertise in rapid 3D printing manufacturing methods.We see a potential annual $1.6B total addressable market for the proposed device.
Public Health Relevance Statement: Coronary artery bypass graft (CABG) surgery is the gold standard treatment for patients with
multi-vessel coronary artery disease, however, saphenous vein grafts used in CABG fail at
alarmingly high rates, with 25% of SVGs failing within 12-18 months and 50% failing within 5-10
years. To overcome the current lack of clinical strategies for SVG failure prevention, BioGraft
aims to develop a novel 3D printed scaffold device, applied externally around the SVG at the
time of CABG, made from a unique elastomeric bioabsorbable material. We will perform
preclinical testing in a large animal model to prove preliminary safety and efficacy of the
proposed device in preserving SVG patency and inducing favorable remodeling.
Project Terms:
