Target regulation of both VECs and VSMCs by dual-loading miRNA-126 and miRNA-145 in the bilayered electrospun membrane for small-diameter vascular regeneration.

Clinical utility of small-diameter vascular grafts is still challenging in blood vessel regeneration owing to thrombosis and intimal hyperplasia. To cope with the issues, modulation of gene expression via microRNAs (miRNAs) could be a feasible approach by rational regulating physiological activities of both vascular endothelial cells (VECs) and vascular smooth muscle cells (VSMCs). Our previous studies demonstrated that individually loaded miRNA-126 (miR-126) or miRNA-145 (miR-145) in the electrospun membranes showed the tendency to promote vascular regeneration. In this work, the bilayered electrospun graft in 1.5-mm diameter was developed by emulsion electrospinning to dual-load miR-126 and miR-145 for target regulation of both VECs and VSMCs, respectively. Accelerated release of miR-126 was achieved by introducing poly(ethylene glycol) in the inner electrospun poly(ethylene glycol)-b-poly(l-lactide-co-caprolactone) ultrafine fibrous membrane, reaching 61.3 ± 1.2% of the cumulative release in the initial 10 days, whereas the outer electrospun poly(l-lactide-co-glycolide) membrane composed of microfibers fulfilled prolonged release of miR-145 for about 56 days. In vivo tests suggested that dual-loading with miR-126 and miR-145 in the bilayered electrospun membranes could modulate both VECs and VSMCs for rapid endothelialization and hyperplasia inhibition as well. It is reasonably expected that dual target-delivery of miR-126 and miR-145 in the electrospun vascular grafts has effective potential for small-diameter vascular regeneration. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 371-382, 2019.