Local Delivery of Dual miRNAs in Trilayered Electrospun Grafts for Vascular Regeneration

Globally growing problems in cardiovascular diseases lead to a considerable need of 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 miRNA-126 and miRNA-145 in the fibrous inner and middle layers, respectively. In vitro cell activities demonstrated that the trilayered electrospun membranes had significantly 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 miRNA-126 and slow-releasing miRNA-145. Histological and immunofluorescent analyses of in vivo implantation in a rat abdominal aorta interposition model suggested that the dual-miRNA-loading tr...