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.
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