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

Abstract

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.

Inhibition of Lysyl Oxidase with β-aminopropionitrile Improves Venous Adaptation after Arteriovenous Fistula Creation

“…We then postulated that inhibition of LOX using BAPN, a natural irreversible inhibitor of LOX (29) and LOXL (14,30) Electrospun nanofibers have been widely used as vascular biomaterials due to their structural and mechanical properties which closely resemble the vascular ECM (34)(35)(36)(37). We developed an electrospun scaffold for perivascular delivery of BAPN to increase the effective drug concentration while minimizing off-target effects (38).…”

Surface Engineering of Cardiovascular Devices for Improved Hemocompatibility and Rapid Endothelialization

“…Reproduced with permission. [306] Copyright 2020, American Chemical Society. electrostatic interaction, our group used electrospinning and electrospraying techniques to introduce plasmid ZNF580-loaded complexes (positively charged) onto the surface of poly(lactideco-glycolide)/silk fibroin (PLGA/SF) nanofibrous scaffolds (negatively charged).…”

“…Given gene manipulation by miR-126 and miR-145 in vascular cells, Kong's group developed a trilayered vascular graft loaded with both miR-126 and miR-145 in the fibrous inner and middle layers, respectively. [306] The dual-miRNA-loading trilayered electrospun graft exerted significantly biological advantages in accelerated endothelialization and controlled SMC phenotypes owing to the bioactivities of miR-126 and miR-145 ( Figure 13B). The aforementioned results demonstrate the potential of dual-miRNA-loading electrospun graft towards a bioactive substitute for replacement of artificial small-caliber blood vessels.…”

Anti-Sca-1 antibody-functionalized vascular grafts improve vascular regeneration via selective capture of endogenous vascular stem/progenitor cells

“…To improve the performance of artificial small-diameter vascular grafts, considerations of capabilities of the material to induce tissue regeneration in situ for the rapid integration with host tissue and formation of functional blood vessels is imperative to achieve long-term patency. Rapid endothelialization [ 9 ], regeneration of contractile smooth muscle layers (SMCs) [ 10 ], and prolonged modulation of inflammation in vivo may be effectively achieved through the design of cell-free vascular grafts that invoke the host's own regenerative potential, to orchestrate cell responses and promote extracellular matrix (ECM) deposition and remodelling [ 11 ].…”