Strategies in cell-free tissue-engineered vascular grafts

Cardiovascular diseases (CVD) remain the leading cause of morbidity and mortality in the world, among which coronary artery diseases (CAD) are the most common type of CVD. Coronary artery bypass grafting (CABG) using autologous vein and artery grafts is the typical surgical intervention for CAD patients. However, for patients whose autologous grafts are not available, there are no appropriate substitutes for vascular grafts. Investigation of tissue-engineered vascular graft (TEVG) has persisted over decades with significant advancement, utilizing different types of biomaterials. In the past two decades, a great number of studies based on cell-seeding strategies were reported. However, limitations of cell-based strategies made clinical application difficult. With the understanding of stem cells and tissue remodeling process, strategies without cell-seeding emerged as potential methods to achieve in situ regeneration. A cell-free graft may recruit host cells and guide their participation in vascular remodeling. The grafts modified by bio-active molecules showed good results in promoting in situ regeneration and exhibited potential to make the vascular grafts off-the-shelf. In this review, the strategies for cell-free TEVG manufacturing were discussed, including the materials for fabricating TEVGs, the methods of functionalization to promote in situ regeneration, the challenges researchers faced in TEVG investigation, and finally the prospects in TEVG design.