Regeneration deficiency is one of the main obstacles limiting the effectiveness of tissue-engineered scaffolds. To develop scaffolds that are capable of accelerating regeneration, we created a heparin/chitosan nanoparticle-immobilized decellularized bovine jugular vein scaffold to increase the loading capacity and allow for controlled release of vascular endothelial growth factor (VEGF). The vascularization of the scaffold was evaluated in vitro and in vivo. The functional nanoparticles were prepared by physical self-assembly with a diameter of 67–132 nm, positive charge, and a zeta potential of ∼30 mV and then the nanoparticles were successfully immobilized to the nanofibers of scaffolds by ethylcarbodiimide hydrochloride/hydroxysulfosuccinimide modification. The scaffolds immobilized with heparin/chitosan nanoparticles exhibited highly effective localization and sustained release of VEGF for several weeks in vitro. This modified scaffold significantly stimulated endothelial cells’ proliferation in vitro. Importantly, utilization of heparin/chitosan nanoparticles to localize VEGF significantly increased fibroblast infiltration, extracellular matrix production, and accelerated vascularization in mouse subcutaneous implantation model in vivo. This study provided a novel and promising system for accelerated regeneration of tissue-engineering scaffolds.

Biocompatibility and biomechanical stability are two of the main obstacles limiting the effectiveness of vascular scaffolds. To improve the biomechanical stability and biocompatibility of these scaffolds, we created a heparin-nanomodified acellular bovine jugular vein scaffold by alternating linkage of heparin and dihydroxy-iron via self-assembly. Features of the scaffold were evaluated in vitro and in vivo. Heparin was firmly linked to and formed nanoscale coatings around the fibers of the scaffold, and the amount of heparin linked was about 808 ± 86 µg/cm 2 (101 ± 11 USP/cm 2 ) per assembly cycle. The scaffolds showed significantly strengthened biomechanical stability with sustained release of heparin for several weeks in vitro. Importantly, the modified scaffolds showed significantly reduced platelet adhesion, stimulated proliferation of endothelial cells in vitro, and reduced calcification in a subcutaneous implantation rat model in vivo. Heparin nanomodification improves the biocompatibility and biomechanical stability of vascular scaffolds.