Abstract 127: Collagen Nanopatterning Modulates Endothelial Cell Atheroprotective Function, Survival, and Angiogenesis
Vascular endothelial cells (ECs) are longitudinally oriented in regions of laminar flow, but randomly distributed in regions of disturbed flow. The unaligned ECs in disturbed flow fields manifest altered function and reduced survival that promote atherosclerotic lesion formation. We hypothesized that the alignment of the ECs may directly influence their biology, independent of fluid flow. We fabricated parallel-aligned nanofibrillar collagen scaffolds with that mimic the native structure of collagen extracellular matrix within blood vessels, and examined the effects of aligned collagen nanopatterning on EC alignment, function, and in vivo survival. The 30-nm diameter aligned nanofibrils reoriented F-actin assembly along the nanofibril direction. ECs cultured on aligned nanofibrils were also 50% less adhesive for monocytes than the ECs grown on randomly oriented fibrils. To test the efficacy of the aligned nanofibrillar scaffolds in improving neovascularization in vivo, we induced unilateral hindlimb ischemia in SCID mice by excising the superficial femoral artery. The mice received one of the following treatments at the site of the excised femoral artery: 1) aligned nanofibrillar scaffold seeded with human ECs; 2) non-patterned scaffold seeded with ECs; 3) EC delivery in saline; or 4) no treatment (n>4). After 14 days, laser Doppler blood spectroscopy demonstrated significant improvement in blood perfusion in the group treated with cell-seeded aligned nanofibrillar scaffolds, in comparison to the groups with no treatment or EC delivery in saline. Furthermore, based on non-invasive bioluminescence imaging, the transplanted ECs persisted for longer periods of time when cultured on aligned nanofibrillar scaffolds, in comparison to non-patterned scaffolds. Together, these studies demonstrate that 30-nm aligned nanofibrillar collagen scaffolds guide cellular organization, modulate endothelial inflammatory response, and enhance cell survival and angiogenesis after implantation in the ischemic hind limb. These results have important implications for therapeutic cell delivery approaches.
Author Disclosures: N.F. Huang: 2. Research Grant; Modest; National Institutes of Health, Department of Defense E. Lai: None. T. Zaitseva: 1. Employment; Modest; Fibralign Corporation. M.V. Paukshto: 1. Employment; Modest; Fibralign Corporation. 2. Research Grant; Modest; Department of Defense. J.P. Cooke: 2. Research Grant; Modest; National Institutes of Health.
- © 2014 by American Heart Association, Inc.