Aligned-Braided Nanofibrillar Scaffold with Endothelial Cells Enhances Arteriogenesis

Karina H. Nakayama, Guosong Hong, Jerry C. Lee, Jay Patel, Bryan Edwards, Tatiana S. Zaitseva, Michael V. Paukshto, Hongjie Dai, John P. Cooke, Y. Joseph Woo, Ngan F. Huang

Research output: Contribution to journalArticle

36 Scopus citations

Abstract

The objective of this study was to enhance the angiogenic capacity of endothelial cells (ECs) using nanoscale signaling cues from aligned nanofibrillar scaffolds in the setting of tissue ischemia. Thread-like nanofibrillar scaffolds with porous structure were fabricated from aligned-braided membranes generated under shear from liquid crystal collagen solution. Human ECs showed greater outgrowth from aligned scaffolds than from nonpatterned scaffolds. Integrin α1 was in part responsible for the enhanced cellular outgrowth on aligned nanofibrillar scaffolds, as the effect was abrogated by integrin α1 inhibition. To test the efficacy of EC-seeded aligned nanofibrillar scaffolds in improving neovascularization in vivo, the ischemic limbs of mice were treated with EC-seeded aligned nanofibrillar scaffold; EC-seeded nonpatterned scaffold; ECs in saline; aligned nanofibrillar scaffold alone; or no treatment. After 14 days, laser Doppler blood spectroscopy demonstrated significant improvement in blood perfusion recovery when treated with EC-seeded aligned nanofibrillar scaffolds, in comparison to ECs in saline or no treatment. In ischemic hindlimbs treated with scaffolds seeded with human ECs derived from induced pluripotent stem cells (iPSC-ECs), single-walled carbon nanotube (SWNT) fluorophores were systemically delivered to quantify microvascular density after 28 days. Near infrared-II (NIR-II, 1000-1700 nm) imaging of SWNT fluorophores demonstrated that iPSC-EC-seeded aligned scaffolds group showed significantly higher microvascular density than the saline or cells groups. These data suggest that treatment with EC-seeded aligned nanofibrillar scaffolds improved blood perfusion and arteriogenesis, when compared to treatment with cells alone or scaffold alone, and have important implications in the design of therapeutic cell delivery strategies.

Original languageEnglish (US)
Pages (from-to)6900-6908
Number of pages9
JournalACS Nano
Volume9
Issue number7
DOIs
StatePublished - Jul 28 2015
Externally publishedYes

Keywords

  • angiogenesis
  • carbon nanotube
  • induced pluripotent stem cell
  • ischemia
  • nanofibrillar
  • peripheral arterial disease

ASJC Scopus subject areas

  • Engineering(all)
  • Materials Science(all)
  • Physics and Astronomy(all)

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  • Cite this

    Nakayama, K. H., Hong, G., Lee, J. C., Patel, J., Edwards, B., Zaitseva, T. S., Paukshto, M. V., Dai, H., Cooke, J. P., Woo, Y. J., & Huang, N. F. (2015). Aligned-Braided Nanofibrillar Scaffold with Endothelial Cells Enhances Arteriogenesis. ACS Nano, 9(7), 6900-6908. https://doi.org/10.1021/acsnano.5b00545