Dual-delivery of VEGF and PDGF by double-layered electrospun membranes for blood vessel regeneration

Abstract

Tissue engineering of small-diameter blood vessels is still challenging because of restenosis and burst. To prevent thrombosis, rapid endothelialization along the lumen of grafts is intended, followed by proliferation of vascular smooth muscle cells (VSMCs) around the exterior for compliance. To this goal, two modified coaxial electrospinning techniques were developed to encapsulate vascular endothelial growth factor (VEGF) and platelet-derived growth factor-bb (PDGF), respectively, to regulate proliferation of vascular endothelial cells (VECs) and VSMCs. Release profiles, in vitro cell proliferation and in vivo implantation of double-layered electrospun membranes were investigated, and what made it special was the electrospun membranes were composed of chitosan hydrogel/poly(ethylene glycol)-b-poly(l-lactide-co-caprolactone) (PELCL) electrospun membrane loaded with VEGF as the inner layer and emulsion/PELCL electrospun membrane-loaded PDGF as the outer. It was found that dual-release of VEGF and PDGF could accelerate VEC proliferation in the first 6 days, and modulate slow VSMC proliferation in the initial 3 days whereas generate rapid proliferation after day 6, which is of great benefit to blood vessel regeneration. Four weeks of in vivo replacement of rabbit carotid artery demonstrated that VECs and VSMCs developed on the lumen and exterior of vascular grafts, respectively, and no thrombus or burst appeared. It was concluded that dual-delivery of VEGF and PDGF by the modified electrospun membranes could facilitate revascularization.