Electrospun vascular scaffold for cellularized small diameter blood vessels: A preclinical large animal study

摘要

The strategy of vascular tissue engineering is to create a vascular substitute by combining autologous vascular cells with a tubular-shaped biodegradable scaffold. We have previously developed a novel electrospun bilayered vascular scaffold that provides proper biological and biomechanical properties as well as structural configuration. In this study, we investigated the clinical feasibility of a cellularized vascular scaffold in a preclinical large animal model. We fabricated the cellularized vascular construct with autologous endothelial progenitor cell (EPC)-derived endothelial cells (ECs) and smooth muscle cells (SMCs) followed by a pulsatile bioreactor preconditioning. This fully cellularized vascular construct was tested in a sheep carotid arterial interposition model. After preconditioning, confluent and mature EC and SMC layers in the scaffold were achieved. The cellularized constructs sustained the structural integrity with a high degree of graft patency without eliciting an inflammatory response over the course of the 6-month period in sheep. Moreover, the matured EC coverage on the lumen and a thick smooth muscle layer were formed at 6 months after transplantation. We demonstrated that electrospun bilayered vascular scaffolds in conjunction with autologous vascular cells may be a clinically applicable alternative to traditional prosthetic vascular graft substitutes.