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

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.

Medienart:

E-Artikel

Erscheinungsjahr:

2020

Erschienen:

2020

Enthalten in:

Zur Gesamtaufnahme - volume:12

Enthalten in:

ACS applied materials & interfaces - 12(2020), 6 vom: 12. Feb., Seite 6863-6875

Sprache:

Englisch

Beteiligte Personen:

Wen, Meiling [VerfasserIn]
Zhi, Dengke [VerfasserIn]
Wang, Lina [VerfasserIn]
Cui, Ce [VerfasserIn]
Huang, Ziqi [VerfasserIn]
Zhao, Yunhui [VerfasserIn]
Wang, Kai [VerfasserIn]
Kong, Deling [VerfasserIn]
Yuan, Xiaoyan [VerfasserIn]

Links:

Volltext

Themen:

Journal Article
Local delivery
MIRN126 microRNA, rat
MIRN145 microRNA, rat
MicroRNAs
Polymers
Trilayered electrospun graft
Vascular Endothelial Growth Factor A
Vascular cells
Vascular regeneration

Anmerkungen:

Date Completed 07.12.2020

Date Revised 14.12.2020

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1021/acsami.9b19452

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM305560689