(287k) Bioinspired Self-Healing and Acellular Vascular Grafts for Hemodialysis Applications

Cardiovascular and end-stage renal diseases (ESRD) are leading causes of mortality in the United States, with over 26 million adults affected by coronary artery disease, and more than 71% of 800,000 ESRD patients undergoing hemodialysis. Among ESRD patients, only 15.1% receive an arteriovenous fistula due to long waiting time, compliance mismatch between vein and arteries, and comorbid conditions such as diabetes and aging. The increasing demand for clinically viable vascular grafts necessitates the development of the next-generation constructs for bypass surgery and hemodialysis shunts. An ideal hemodialysis shunt should be robust and capable of maintaining long-term mechanical properties and patency without causing infection, clotting, and bleeding post-cannulation. But current synthetic grafts lack the ability to autonomously repair damage caused by repeated cannulation, increasing the risk of bleeding upon early cannulation or graft failure.

To address these challenges, we developed an innovative bilayer self-healing tissue-engineered vascular graft (SH-TEV) by electrospinning a polyurethane-based autonomous self-healing polymer, PU-DAA, around a nature biomaterial scaffold, small intestinal submucosa (SIS), that can be functionalized with biomolecules to recruit host cells and promote endothelialization. The self-healing ability of PU-DAA_x arises from a synergistic interplay between reversible H-bonds and dynamic oxime bonds, enabling the SH-TEV to exhibit both self-healing capability and mechanical strength. To optimize the balance between self-healing efficiency and mechanical strength, the ratio of [DAA]/[PTMG] was systematically tuned. PU-DAA_1.5 exhibited high strength (3.92 ±0.09 MPa), exceptional toughness (22.45±1.99 MJ/m3), and rapid autonomous self-healing (86.44±6.65 % after 12 hr) under physiological conditions. Additionally, PU-DAA_1.5 supported fibroblast attachment, spreading and proliferation in vitro, indicating excellent biocompatibility. Following implantation in a rat aortic interposition model, SH-TEVs remained patent without any thrombosis over 4 weeks (100% animal survival and 100% graft patency), exhibited native-like vascular remodeling and demonstrated needle resistance and extraordinary self-healing ability (hemostatic time < 40 sec). Notably, unlike most reported grafts, SH-TEVs achieved the outstanding performance without any anti-platelet treatment. Overall, the results demonstrated the self-healing capability, patency and clinical feasibility of the acellular SH-TEVs, highlighting their potential applications as a promising next-generation vascular graft for hemodialysis access.