title: Instructive nanofiber scaffolds with VEGF create a microenvironment for arteriogenesis and cardiac repair.
abstract: Angiogenic therapy is a promising approach for tissue repair and regeneration. However, recent clinical trials with protein delivery or gene therapy to promote angiogenesis have failed to provide therapeutic effects. A key factor for achieving effective revascularization is the durability of the microvasculature and the formation of new arterial vessels. Accordingly, we carried out experiments to test whether intramyocardial injection of self-assembling peptide nanofibers (NFs) combined with vascular endothelial growth factor (VEGF) could create an intramyocardial microenvironment with prolonged VEGF release to improve post-infarct neovascularization in rats. Our data showed that when injected with NF, VEGF delivery was sustained within the myocardium for up to 14 days, and the side effects of systemic edema and proteinuria were significantly reduced to the same level as that of control. NF/VEGF injection significantly improved angiogenesis, arteriogenesis, and cardiac performance 28 days after myocardial infarction. NF/VEGF injection not only allowed controlled local delivery but also transformed the injected site into a favorable microenvironment that recruited endogenous myofibroblasts and helped achieve effective revascularization. The engineered vascular niche further attracted a new population of cardiomyocyte-like cells to home to the injected sites, suggesting cardiomyocyte regeneration. Follow-up studies in pigs also revealed healing benefits consistent with observations in rats. In summary, this study demonstrates a new strategy for cardiovascular repair with potential for future clinical translation.
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei 11574, Taiwan.
authors.forename: Yi-Dong
authors.initials: YD
authors.lastname: Lin
authors.forename: Chwan-Yau
authors.initials: CY
authors.lastname: Luo
authors.forename: Yu-Ning
authors.initials: YN
authors.lastname: Hu
authors.forename: Ming-Long
authors.initials: ML
authors.lastname: Yeh
authors.forename: Ying-Chang
authors.initials: YC
authors.lastname: Hsueh
authors.forename: Min-Yao
authors.initials: MY
authors.lastname: Chang
authors.forename: Da-Ching
authors.initials: DC
authors.lastname: Tsai
authors.forename: Jieh-Neng
authors.initials: JN
authors.lastname: Wang
authors.forename: Ming-Jer
authors.initials: MJ
authors.lastname: Tang
authors.forename: Erika I H
authors.initials: EI
authors.lastname: Wei
authors.forename: Matthew L
authors.initials: ML
authors.lastname: Springer
authors.forename: Patrick C H
authors.initials: PC
authors.lastname: Hsieh
mesh_terms: D000818:Animals; D008297:Male; D009203:Myocardial Infarction / Q000628:therapy; D009206:Myocardium / Q000473:pathology; D057139:Nanofibers / Q000737:chemistry*; D018919:Neovascularization, Physiologic / Q000187:drug effects; D051381:Rats; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds / Q000737:chemistry*; D042461:Vascular Endothelial Growth Factor A / Q000737:chemistry / Q000627:therapeutic use*
chemical_list: D042461:Vascular Endothelial Growth Factor A