Abstract
Vascularization is a major challenge in tissue engineering. The purpose of this study is to expedite the formation of blood vessels in porous polycaprolactone (PCL) scaffolds by the delivery of endothelial progenitor cells (EPCs). To establish a pro-angiogenic and pro-vasculogenic microenvironment, we employed EPCs seeded in PCL scaffold with surface-immobilized heparin and vascular endothelial growth factor (VEGF). EPCs seeded on scaffolds with VEGF exhibited phosphorylation of the receptor. After 7 days of subcutaneous implantation in immunodeficient mice, heparin-immobilized PCL scaffolds with VEGF induced significantly high density of blood vessel formation. The anastomosis of EPC-derived vessels with the host circulatory system was evident by the presence of murine erythrocytes in the lumen of human-CD31 positive vessels. A more uniform distribution of blood vessels was achieved within 2-mm thick scaffolds by seeding an optimal density of EPCs. The seeding of a higher density of EPC resulted in an increase in apoptosis and a concomitant decline in blood vessel formation at the scaffold's inner core. When co-seeded with other cells, the EPCs maintained the ability to accelerate vessel formation. The excessive expansion of EPCs in vitro was associated with a decline in their in vivo vasculogenic potential. EPCs accelerated the vascularization of heparin-immobilized PCL scaffolds in the presence of VEGF.