title: Nanofiber-mediated microRNA-126 delivery to vascular endothelial cells for blood vessel regeneration.
abstract: 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.
  
  
  
  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.
authors.affiliation: School of Materials Science and Engineering, and Tianjin Key Laboratory of Composite and Functional Materials, Tianjin University, Tianjin 300072, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Zhou
authors.affiliation: Key Laboratory for Biomechanics and Mechanobiology of Ministry of Education, School of Biological Science and Medical Engineering, Beihang University, Beijing 100083, China.
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Jia
authors.affiliation: School of Materials Science and Engineering, and Tianjin Key Laboratory of Composite and Functional Materials, Tianjin University, Tianjin 300072, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Key Laboratory for Biomechanics and Mechanobiology of Ministry of Education, School of Biological Science and Medical Engineering, Beihang University, Beijing 100083, China.
authors.forename: Qingmao
authors.initials: Q
authors.lastname: Yang
authors.affiliation: Key Laboratory for Biomechanics and Mechanobiology of Ministry of Education, School of Biological Science and Medical Engineering, Beihang University, Beijing 100083, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Gao
authors.affiliation: School of Materials Science and Engineering, and Tianjin Key Laboratory of Composite and Functional Materials, Tianjin University, Tianjin 300072, China.
authors.forename: Suli
authors.initials: S
authors.lastname: Hu
authors.affiliation: School of Materials Science and Engineering, and Tianjin Key Laboratory of Composite and Functional Materials, Tianjin University, Tianjin 300072, China.
authors.forename: Yunhui
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Key Laboratory for Biomechanics and Mechanobiology of Ministry of Education, School of Biological Science and Medical Engineering, Beihang University, Beijing 100083, China; National Research Center for Rehabilitation Technical Aids, Beijing 100176, China. Electronic address: yubofan@buaa.edu.cn.
authors.forename: Yubo
authors.initials: Y
authors.lastname: Fan
authors.affiliation: School of Materials Science and Engineering, and Tianjin Key Laboratory of Composite and Functional Materials, Tianjin University, Tianjin 300072, China. Electronic address: yuanxy@tju.edu.cn.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Yuan
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D001807:Blood Vessel Prosthesis; D001808:Blood Vessels / Q000502:physiology*; D049109:Cell Proliferation; D005455:Fluorescent Antibody Technique; D005786:Gene Expression Regulation; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D035683:MicroRNAs / Q000378:metabolism*; D057139:Nanofibers / Q000737:chemistry* / Q000648:ultrastructure; D010641:Phenotype; D011091:Polyesters / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D011817:Rabbits; D012038:Regeneration; D054457:Tissue Scaffolds / Q000737:chemistry
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D047908:Intracellular Signaling Peptides and Proteins; C527111:MIRN126 microRNA, human; D008565:Membrane Proteins; D035683:MicroRNAs; D011091:Polyesters; C504812:SPRED1 protein, human; C000617025:polycaprolactone-g-polyethylene glycol; D011092:Polyethylene Glycols
keywords: Bilayer vascular scaffold; Blood vessel regeneration; Electrospun membranes; miRNA-126