Vascular grafts with a mimetic microenvironment extracted from extracellular matrix of adipocytes can promote endothelialization in vivo

Synthetic vascular substitutes are widely studied for small-caliber arteries replacement but their efficacy requires further improvement. Vascular tissue engineering holds great promise for preparing small-caliber vascular grafts with therapeutic effects, and previous work has demonstrated that the cellular layer at the luminal surface of vascular grafts has the potential to provide high functionality to vascular tissue. Improved endothelialization has been proven to be a key strategy for promoting the efficacy of vascular regeneration. However, there still remains a challenge of finding proper endothelialization methods or cell types to guarantee vascular grafts the long-term patency and functions. Herein, a biomimetic bilayer vascular graft was developed by 3D printing and electrospinning techniques. The electrospun PCL nanofiber was fabricated as the outer supporting layer while a biomimetic inner layer structure composed of cell extracellular matrix microenvironment was prepared by a decellularization process. This inner layer was designed to favor endothelial cell (EC) adhesion and enhance endothelialization on the surfaces of vascular grafts. Fibronectin, derived from adipocytes, provided a naturally occurring substrate for EC adhesion. The findings showed that by binding fibronectin, integrin α5β1 mediates EC adherence to the designed vascular graft. The bilayer graft with a mimetic microenvironment extracted from extracellular matrix of adipocytes can promote endothelialization and sustain good patency in vivo, which may represent a promising biomaterial for clinical vascular transplantation. STATEMENT OF SIGNIFICANCE: This study proposed a universal method for including any substrate type in vascular cell type-specific extracellular matrices (ECM) via regulating selective adhesion to promote vascular tissue regeneration. The reconstructed 3D ECM recapitulating a vascular-like microenvironment promoted the orderly regeneration and functional recovery of vascular tissues in vivo. The findings represent a proof of principle for vascular cell selectivity in cell type-specific ECM microenvironments, and provide a valuable perspective for further investigations on the controlled regeneration of heterogeneous tissues.