Poly(amino acid-hydroxyethyl methacrylate)s with chiral lysine and/or leucine side moieties and their antibacterial abilities for biomedical applications.

Biomedical applications of the synthetic polymers with amino acid side moieties have been studied in light of their biocompatibility. In this work, poly(amino acid-hydroxyethyl methacrylate)s with lysine (Lys)/leucine side moieties were synthesized via reversible addition-fragmentation chain transfer polymerization, and were verified with intrinsic chirality. For biomedical uses, their antibacterial abilities as well as hemolysis and cytotoxicity were investigated. The results indicated that there were similar inhibitions for d- and l-enantiomeric polymers against Staphylococcus aureus when the polymer concentrations were lower than ~300µg/mL, while the polymer containing d-Lys moiety was more effective against Escherichia coli. The d-enantiomers at concentrations <500µg/mL showed relatively lower hemolysis, and all the polymers showed good in vitro cell viability with concentrations lower than 200µg/mL. It was indicated that the antibacterial amino acid-related synthetic polymers could be potentially applied for biomedical applications.

Nanofiber-mediated microRNA-126 delivery to vascular endothelial cells for blood vessel regeneration.

UNLABELLED: As manipulation of gene expression by virtue of microRNAs (miRNAs) is one of the emerging strategies for cardiovascular disease remedy, local delivery of miRNAs to a specific vascular tissue is challenging. In this work, we developed an efficient delivery system composed of electrospun fibrous membranes and target carriers for the intracellular delivery of miRNA-126 (miR-126) to vascular endothelial cells (VECs) in the local specific vascular environment. A bilayer vascular scaffold was specially prepared via emulsion electrospinning of poly(ethylene glycol)-b-poly(l-lactide-co-ε-caprolactone) (PELCL) and dual-power electrospinning of poly(ε-caprolactone) (PCL) and gelatin. The inner layer of PELCL, which was loaded with complexes of miR-126 in REDV peptide-modified trimethyl chitosan-g-poly(ethylene glycol), regulated the response of VECs, while the outer layer of PCL/gelatin contributed to the mechanical stability. Biological activities of the miR-126-loaded electrospun membranes were evaluated by cell proliferation and SPRED-1 expression of a miR-126 target gene. By encapsulating targeting complexes of miR-126 in the electrospun membranes, a sustained release profile of miRNA was obtained for 56days. Significant down-regulation of SPRED-1 gene expression in VECs was detected on day 3, and it was found that miR-126 released from the electrospun membranes accelerated VEC proliferation in the first 9days. The bilayer vascular scaffold loaded with miR-126 complexes could also improve endothelialization in vivo. These results demonstrated the potential of this approach towards a new and more effective delivering system for local delivery of miRNAs to facilitate blood vessel regeneration. STATEMENT OF SIGNIFICANCE: Tissue engineering of small-diameter blood vessels is still challenging because of thrombosis and low long-term patency. The manipulation of gene expression by miRNAs could be a novel strategy in vascular regeneration. Here, we report an efficient delivery system of electrospun fibrous scaffold combined with REDV peptide-modified trimethyl chitosan for targeted intracellular delivery of miR-126 to VECs in the local vascular environment. Results exhibited that miR-126 released from the electrospun membrane could modulate VEC proliferation via down-regulation of SPRED-1 gene expression. The electrospun scaffolds loaded with target-delivery carriers may serve as an ideal platform for local delivery of miRNAs in the vascular tissue engineering.