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Abstract 83: Nanopatterned Collagen Scaffolds Promote Blood Perfusion in the Ischemic Limb

Cell-based approaches to improve blood perfusion are promising for treatment of peripheral arterial disease (PAD). However, cell delivery alone is limited by poor cell survival and the lack of organization among newly formed vessels. We hypothesized that parallel-aligned nanofibrillar scaffolds may guide endothelial cell (EC) assembly and accelerate the formation of organized vascular networks that enhance blood perfusion, in comparison to cell delivery in saline. We fabricated nanofibrillar collagen scaffolds with parallel-oriented configuration or randomly oriented configuration. Primary human ECs aligned along the direction of the nanofibrils of the aligned nanofibrillar scaffold, as shown by scanning electron microscopy, where the arrow denotes the orientation of nanofibrils (Fig 1). The ECs also had organized cytoskeleton within 20 degrees from the direction of the aligned nanofibrils. 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) randomly oriented nanofibrillar 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. In summary, these results suggest that aligned nanofibrillar scaffolds regulate EC morphology as well as angiogenic potential. This work highlights the innovative use of biomaterial nanopatterning as a way to promote blood perfusion, and has implications in the treatment of patients with PAD.
 
 
