VASCRAFT: a novel tissue-engineered human vascular graft for coronary artery bypass grafting (CABG)

Introduction Small-diameter vascular grafts are crucial for patients undergoing coronary artery bypass surgery. Inherent comorbidities and the absence of optimal autologous vessels have prompted the development of vascular grafts through tissue engineering; though a clinically translatable solution remains elusive. Purpose To develop and preclinically validate VasCraft, a bioengineered human vascular graft consisting of a decellularized human saphenous vein (DhSV) re-endothelialized with endothelial cells derived from umbilical cord blood (UCB-ECs), intended for coronary revascularization. Methods Human saphenous veins obtained from cadaveric donors were processed under Good Tissue Practice conditions using 11 decellularization protocols combining ionic agents, endonucleases, and/or detergents. Scaffolds were assessed for extracellular matrix preservation, residual nuclear and cytoplasmic material, DNA content, and cytotoxicity. The selected DhSV was seeded with UCB-ECs using a custom-engineered perfusion bioreactor with continuous flow to achieve luminal endothelialization. Ten immunosuppressed Large White × Landrace pigs (5 females) underwent femoral artery interposition grafting and were followed for 30 days. Graft performance was monitored by clinical assessment, weekly Doppler ultrasonography, and terminal angiography. Explanted grafts were analyzed by gross examination, histology, and immunofluorescence. Results All protocols significantly reduced residual DNA content (n = 11); however, a detergent-free protocol demonstrated superior preservation of collagen and elastin architecture. Cytotoxicity assays confirmed scaffold biocompatibility. The custom bioreactor enabled homogeneous endothelial coverage, confirmed by immunofluorescent staining of endothelial markers. All grafts were successfully implanted. Doppler ultrasonography demonstrated sustained blood flow in most animals, with 7/10 grafts remaining patent at day 21 and 5/10 at day 30, as confirmed by angiography. Histological evaluation showed preserved structural integrity, adventitial neovascularization, smooth muscle cell repopulation within the tunica media, and partial luminal endothelial coverage. Conclusion VasCraft demonstrates the feasibility of generating a biocompatible and surgically implantable human-derived vascular graft with short-term patency in an arterial large-animal model. The optimized decellularization strategy and bioreactor-based endothelialization support reproducible scaffold preparation and functional integration. These findings warrant long-term preclinical evaluation in coronary-relevant settings.