Preclinical validation of VasCraf: a human-derived decellularized and re-endothelialized tissue-engineered vascular graft in a porcine arterial model

Abstract Background Coronary artery bypass grafting (CABG) remains the gold-standard surgical intervention for advanced coronary artery disease, aiming to restore myocardial perfusion using vascular conduits. Although autologous grafts are widely employed, their use is limited by donor-site morbidity, reduced long-term patency, and the lack of suitable conduits in some patients. To overcome these challenges, tissue-engineered vascular grafts have emerged as promising small-diameter (6 mm) alternatives, but a clinically translatable and durable solution remains elusive. Purpose This study aims to preclinically validate VasCraft, a bioengineered human vascular graft composed of a decellularized human saphenous vein re-endothelialized with umbilical cord blood-derived endothelial cells, as a potential coronary bypass conduit. Methods Twelve immunosuppressed Large White × Landrace pigs underwent femoral artery interposition grafting with VasCraft, followed by a 30-day observation period. Postoperative recovery and graft performance were monitored through clinical assessment and imaging. Doppler ultrasonography was performed weekly to evaluate blood flow, and angiography at the endpoint confirmed patency. Explanted grafts underwent gross examination, histology, and immunofluorescence to assess structural integrity and cellular integration. Results All implantations were successfully completed (Fig1Ai), with uneventful postoperative recovery. Doppler ultrasonography revealed sustained blood flow and vascular continuity in 8 of 12 grafts, patent at day 21 (Fig1Aii). Final angiographic evaluation at day 30 confirmed patency in 6 subjects (Fig1Aiii). Macroscopic and histological analyses demonstrated preserved structural integrity (Fig1B), while immunohistochemistry revealed neovascularization in the adventitia, smooth muscle cell presence in the tunica media, and partial endothelial coverage of the luminal surface (Fig1C). Conclusions Preclinical assessment confirmed the surgical feasibility, short-term patency, and mechanical stability of the VasCraft graft within an arterial environment. The observed cellular integration and neovascularization supported its biocompatibility and potential for long-term functionality. These results provide a strong rationale for an extended evaluation in large-animal studies, advancing the clinical translation of this technology for coronary artery bypass grafting.Figure 1For image description, please refer to the figure legend and surrounding text.