Performance of TMC-g-PEG-VAPG/miRNA-145 complexes in electrospun membranes for target-regulating vascular SMCs.

ABSTRACT

Restenosis is still one of the main challenges in small-diameter vascular regeneration, and effective modulation of vascular smooth muscle cells (SMCs) is essential to cope with the related issues. As one of microRNAs (miRNAs) in vascular systems, miRNA-145 can regulate SMCs in the normal contractile phenotype, and inhibit the excessive proliferation and intimal hyperplasia. Herein, VAPG peptide-modified trimethyl chitosan-g-poly(ethylene glycol) (TMC-g-PEG-VAPG) was developed specially for target-delivery of miRNA-145 to SMCs to fulfill the proper function. The TMC-g-PEG-VAPG/miRNA-145 complexes exhibited low cytotoxicity, and TMC-g-PEG-VAPG with relatively higher molecular weight of chitosan (50 kDa) could significantly enhance cellular uptake in SMCs. Moreover, loading with TMC-g-PEG-VAPG/miRNA-145 complexes, the electrospun membranes of poly(ethylene glycol)-b-poly(L-lactide-co-ε-caprolactone) were capable of controlling SMCs at gene and protein levels on day 3 by targeting Krüppel-like factor 4 to increase the expression of myocardin and α-smooth muscle actin. Furthermore, miRNA-145 released from the electrospun membranes also showed in vitro bioactivity of modulating the contractile phenotype of SMCs in the prolonged duration, at least 56 days. The functional electrospun membranes containing TMC-g-PEG-VAPG/miRNA-145 complexes may have a great potential in the application of small-diameter blood vessel regeneration.