As manipulation of gene expression by virtue of microRNAs (miRNAs) is one of the emerging strategies for cardiovascular disease remedy, local delivery of miRNAs to a specific vascular tissue is challenging. In this work, we developed an efficient delivery system composed of electrospun fibrous membranes and target carriers for the intracellular delivery of miRNA-126 (miR-126) to vascular endothelial cells (VECs) in the local specific vascular environment. A bilayer vascular scaffold was specially prepared via emulsion electrospinning of poly(ethylene glycol)-b-poly(L-lactide-co-epsilon-caprolactone) (PELCL) and dual-power electrospinning of poly(epsilon-caprolactone) (PCL) and gelatin. The inner layer of PELCL, which was loaded with complexes of miR-126 in REDV peptide-modified trimethyl chitosan-g-poly(ethylene glycol), regulated the response of VECs, while the outer layer of PCL/gelatin contributed to the mechanical stability. Biological activities of the miR-126-loaded electrospun membranes were evaluated by cell proliferation and SPRED-1 expression of a miR-126 target gene. By encapsulating targeting complexes of miR-126 in the electrospun membranes, a sustained release profile of miRNA was obtained for 56 days. Significant down-regulation of SPRED-1 gene expression in VECs was detected on day 3, and it was found that miR-126 released from the electrospun membranes accelerated VEC proliferation in the first 9 days. The bilayer vascular scaffold loaded with miR-126 complexes could also improve endothelialization in vivo. These results demonstrated the potential of this approach towards a new and more effective delivering system for local delivery of miRNAs to facilitate blood vessel regeneration. Statement of Significance Tissue engineering of small-diameter blood vessels is still challenging because of thrombosis and low long-term patency. The manipulation of gene expression by miRNAs could be a novel strategy in vascular regeneration. Here, we report an efficient delivery system of electrospun fibrous scaffold combined with REDV peptide-modified trimethyl chitosan for targeted intracellular delivery of miR-126 to VECs in the local vascular environment. Results exhibited that miR-126 released from the electrospun membrane could modulate VEC proliferation via down-regulation of SPRED-1 gene expression. The electrospun scaffolds loaded with target-delivery carriers may serve as an ideal platform for local delivery of miRNAs in the vascular tissue engineering. (C) 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

• Journal: Acta Biomaterialia
• Volume: 43
• Issue:
• Pages: 303-313
• ISSN: 1742-7061
• DOI: 10.1016/j.actbio.2016.07.048
• Year: 2016
• Number:
• Type: