Globally growing problems related to cardiovascular diseases lead to a considerable need for synthetic vascular grafts. For small-caliber vascular prosthesis, it remains essential to fulfill rapid endothelialization, inhibit intimal hyperplasia, and prevent calcification for keeping patency. To modulate vascular regeneration, herein, we developed a bioactive trilayered tissue-engineered vascular graft encapsulating both microRNA-126 and microRNA-145 in the fibrous inner and middle layers, respectively. In vitro cell activities demonstrated that the trilayered electrospun membranes had significant biological advantages in enhanced growth and intracellular nitric oxide production of vascular endothelial cells, modulation of phenotypes of vascular smooth muscle cells (SMCs), and restraint of calcium deposition through fast-releasing microRNA-126 and slow-releasing microRNA-145. Histological and immunofluorescent analyses of in vivo implantation in a rat abdominal aorta interposition model suggested that the dual-microRNA-loading trilayered electrospun graft exerted a positive effect on accelerating endothelialization, improving contractile SMC regeneration, and promoting normal extracellular matrix formation. Meanwhile, the local bioactivity of microRNA-126 and microRNA-145 in the trilayered vascular graft could regulate inflammation and depress calcification possibly by facilitating transformation of macrophages into the anti-inflammatory M2 phenotype. These findings indicated that the trilayered electrospun graft by local delivery of dual microRNAs could be possibly used as a bioactive substitute for replacement of artificial small-caliber blood vessels.

No abstract

No abstract

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.

No abstract