Electrospun membranes of PELCL/PCL-REDV loading with miRNA-126 for enhancement of vascular endothelial cell adhesion and proliferation

Abstract

Surface modification for rapid endothelialization of vascular biomaterials is known as an important way to prevent thrombosis and intimal hyperplasia. Moreover, therapeutical manipulation of microRNAs (miRNAs) expression via local delivery of miRNA mimics or inhibitors by electrospun ultrafine fibers has demonstrated the promise in tissue regeneration. In this work, a dual-functional electrospun membrane was developed by combining Arg-Glu-Asp-Val (REDV) peptide-modification of the fiber surface to enhance vascular endothelial cell (VEC) adhesion and encapsulation of miRNA-126 (miR-126) complexes in the electrospun fibers to accelerate VEC proliferation. The electrospun membranes were specially prepared by emulsion electrospinning of poly(ethylene glycol)-b-poly(l-lactide-co-ε-caprolactone) (PELCL) and REDV-terminated polycaprolactone (PCL) (50/50 mass ratio), in which miR-126 was encapsulated via REDV peptide-modified trimethyl chitosan-g-poly(ethylene glycol). By introduction of REDV-terminated PCL with lower molecular weight, the obtained electrospun fibers could be modified by REDV on their surface, and also achieve a relatively fast release profile of miR-126 in favor of VEC proliferation. Results of direct seeding VECs on the electrospun membranes indicated the enhanced cell adhesion and proliferation. The combination of REDV peptide-modification of the electrospun fibrous membranes and controllable miRNA release may provide a synergistic strategy of surface guidance and biochemical signals to support and modulate VECs for vascular tissue regeneration.