期刊
ACS NANO
卷 9, 期 7, 页码 6900-6908出版社
AMER CHEMICAL SOC
DOI: 10.1021/acsnano.5b00545
关键词
nanofibrillar; peripheral arterial disease; induced pluripotent stem cell; angiogenesis; carbon nanotube; ischemia
类别
资金
- US National Institutes of Health [HL098688, EB0202351, 1T32HL098049]
- US Army Medical Research and Materiel Command [W81XWH-12-C-0111]
- National Science Foundation [1249008]
- Stanford Chemistry Engineering & Medicine for Human Health
- Stanford Cardiovascular Institute
- Directorate For Engineering [1249008] Funding Source: National Science Foundation
- Div Of Industrial Innovation & Partnersh [1249008] Funding Source: National Science Foundation
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 alpha 1 was in part responsible for the enhanced cellular outgrowth on aligned nanofibrillar scaffolds, as the effect was abrogated by integrin a1 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.
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