VasCraft: a human decellularized and re-endothelialized tissue-engineered vascular graft for coronary arterial revascularization

Introduction

Coronary artery bypass grafting (CABG) remains the gold-standard surgical intervention for severe coronary artery disease. The lack of suitable autlogous vessels has driven the development of tissue-engineered grafts; though clinically translatable solution remains elusive.

Purpose

This study aimed to develop and preclinically validate VasCraft, a bioengineered human vascular graft composed of a decellularized human saphenous vein (DVSh) re-endothelialized with umbilical cord blood-drived endothelial cells (UCB-ECs), for coronary revascularization.

Methods

Following Good Tissue Practice standards, hSV from cadaveric donors underwent various decellularization protocols using ionic agents, endonucleases, and/or detergents. The DhSV were evaluated for extracellular matrix integrity, nuclear and cytoplasmic residues, an cytotoxicity to ensure biocompatibility. A 3D bioreactor was designed and optimized for UCB-EC seeding on the luminal surface of the optimal DVSh. 12 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 (IF) to assess structural integrity and cellular integration.

Results

All decellularization protocols (n=11) effectively reduced the residual DNA content; however, the detergent-free approach (Protocol 1) demonstrated superior preservation of collagen and elastin architecture. Cytotoxicity assays confirmed the biocompatibility of the resulting scaffolds.

The custom-engineered bioreactor (Figure 1A,i) enabled uniform endothelialization, as confirmed by IF staining for endothelial-specific markers (Figure 1A,ii). All surgical implantations were successfully performed (Figure 1B,i). Doppler ultrasonography revealed sustained blood flow in the majority of animals, with 8 of 12 grafts remaining patent at day 21 (Figure 1B,ii). Final angiographic assessment at day 30 confirmed patency in 6 subjects (4 males) (Figure 1B,iii). Anatomopathological inspection demonstrated preserved structural integrity (Figure 1C). IF analysis showed new formation of vasa vasorum in the adventitia, smooth muscle cells in tunica media, and partial endothelial coverage of the luminal surface (Figure 1D).

Conclusion

VasCraft demonstrates the feasibility of generating a biocompatible and surgically implantable human-derived vascular graft. The optimized decellularization strategy and bioreactor system enable reliable scaffold preparation and uniform endothelialization, while preclinical evaluation confirms short-term patency and safety within an arterial environment. These results support futher long-term assessment in large-animal preclinical studies.For image description, please refer to the figure legend and surrounding text.