Fabrication of endothelial progenitor cell (EPC)-seeded intravascular stent devices and in vitro endothelialization on hybrid vascular tissue

Abstract

Rapid re-endothelialization at an atherosclerotic lesion after balloon inflation or stent deployment may be essential for reducing or preventing local thrombus formation and restenosis. In order to prevent these complications via enhanced rapid re-endothelialization, we fabricated two types of endothelial progenitor cell (EPC)-seeded intravascular stent devices. One was a photocured gelatin-coated metallic stent, and the other was a microporous thin segmented polyurethane (SPU) film-covered stent on which photocured gelatin was coated. Both devices were seeded with ex vivo expanded EPCs obtained from canine peripheral blood. Seeded EPCs formed confluent monolayers onto surfaces of both photocured gelatin-coated stent struts and SPU film, and a majority of cells remained on surfaces of stents after stent expansion. The EPC-seeded stent was expanded in a tubular hybrid vascular medial tissue composed of vascular smooth muscle cells and collagen as an arterial media mimic. After 7-day culture, EPCs, which migrated from the stent struts, proliferated and endothelialized the luminal surfaces of the hybrid vascular medial tissue. This in vitro pilot study prior to in vivo experiments suggests that on-stent cell delivery of EPCs may be novel therapeutic devices for re-endothelialization or endothelium lining or paving at an atherosclerotic arterial wall, resulting in the prevention of on-stent thrombus formation and in-stent restenosis, as well as the rapid formation of normal tissue architecture.