Preclinical testing of a 3D printed external scaffold device to prevent vein graft failure after coronary bypass graft surgery

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 after
surgery, and up to 50% of grafts occlude within 5-10 years. CABG surgery is the gold standard treatment for
patients with severe multi-vessel disease, with over 370,000 procedures performed annually in the U.S. and
SVGs are used in 95% of cases. Identification of strategies and devices to prevent SVG failure represents a
pressing unmet clinical need. BioGraft will address this unmet need by developing an external biodegradable
scaffold device to prevent SVG failure. It is well established that mechanical loading contributes to the cellular
and structural changes leading to SVG failure. In current clinical practice, when the SVG is harvested and
implanted into the coronary circulation, it is subjected to an abrupt change in mechanical loading (20X change
in pressure, 4X change in flow-induced shear), triggering SVG wall remodeling and, often, maladaptation and
failure. 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 this
concept 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 biodegradable
scaffold, which we will refine and test in this proposal. To achieve our goals, we propose three specific aims. In
Aim 1, we will screen 3D-printed design candidates with ex vivo testing and degradation studies. This will allow
us to efficiently and inexpensively select designs matching desired targets. In Aim 2, we will perform pre-clinical
testing of the scaffold device in an established ovine carotid-jugular interpositional vein graft model of CABG
surgery. This will establish preliminary safety and efficacy. In Aim 3, we will characterize device performance
using mechanical testing and histopathology. These data will enable follow up fundraising, development of a
commercialization plan and initiation of FDA discussions. BioGraft’s founding team leverages a long-standing
engineering and clinical collaboration and recent partnerships with renowned investigators at Stanford and Duke
who 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.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.