Anti-Sca-1 antibody-functionalized vascular grafts improve vascular regeneration via selective capture of endogenous vascular stem/progenitor cells

Small-diameter vascular grafts fabricated from synthetic biodegradable polymers exhibit beneficial mechanical properties but often face poor regenerative potential. Different tissue engineering approaches have been employed to improve tissue regeneration in vascular grafts, but there remains a requirement for a new generation of synthetic grafts that can orchestrate the host response to achieve robust vascular regeneration. Vascular stem/progenitor cells (SPCs) are mostly found in quiescent niches but can be activated in response to injury and participate in endothelium and smooth muscle regeneration during neo-artery formation. Here, we developed a functional vascular graft by surface immobilization of stem cell antigen-1 (Sca-1) antibody on an electrospun poly(ε-caprolactone) graft (PCL-Sca-1 Ab). PCL-Sca-1 Ab promoted capture and retainment of Sca-1(+) SPCs in vitro. In rat abdominal aorta replacement models, PCL-Sca-1 Ab stimulated in vivo recruitment of Sca-1(+) SPCs, and drove SPCs differentiation towards vascular cell lineages. The origin of infiltrated Sca-1(+) SPCs was further investigated using a bone marrow transplantation mouse model, which revealed that Sca-1(+) SPCs originating from the resident tissues and bone marrow contributed to rapid vascular regeneration of vascular grafts. Our data indicated that PCL-Sca-1 Ab vascular grafts may serve as a useful strategy to develop next generation cell-free vascular grafts.