Instructive nanofiber scaffolds with VEGF create a microenvironment for arteriogenesis and cardiac repair

Yi Dong Lin, Chwan Yau Luo, Yu Ning Hu, Ming Long Yeh, Ying Chang Hsueh, Min Yao Chang, Da Ching Tsai, Jieh Neng Wang, Ming Jer Tang, Erika I.H. Wei, Matthew L. Springer, Patrick C.H. Hsieh

Research output: Contribution to journalArticlepeer-review

109 Citations (Scopus)

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.

Original languageEnglish
Article number146ra109
JournalScience translational medicine
Volume4
Issue number146
DOIs
Publication statusPublished - 2012 Aug 8

All Science Journal Classification (ASJC) codes

  • Medicine(all)

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