Vascular endothelial growth factor-loaded elastin-hydrogel modification of the pericardium improves endothelialization potential of bioprosthetic heart valves

摘要

Glutaraldehyde-fixed pericardium is widely used to replace human heart valves. The lack of endothelialization contributes to calcification and structural-valve deterioration, which is particularly significant in young patients where valve longevity is crucial. This current study demonstrates an optimized approach to improve endothelialization of glutaraldehyde-fixed pericardium. Vascular endothelial growth factor-loaded elastin-hydrogel-hybrid pericardium was developed by the crosslinking reaction between the amine groups of soluble elastin and hexamethylene diisocyanate. The elastin solution can penetrate the space of the pericardium. Vascular endothelial growth factor was loaded into the elastin hydrogel, which was hybridized with pericardium via in situ polymerization. We investigated the adhesion and growth potential of human umbilical vein endothelial cells on pericardia, platelet adhesion, and calcification via an in vivo rat model of subdermal implantation. Vascular endothelial growth factor-loaded elastin-hydrogel-hybrid pericardium showed improved human umbilical vein endothelial cell adhesion and proliferation, less platelet adhesion, and less calcification. Thus, the vascular endothelial growth factor-loaded elastin-hydrogel-hybrid pericardium is a promising approach to obtain valve bioprostheses for clinical applications with increased endothelialization, antithrombotic and anti-calcification potential.