Intralumenal tissue-engineered therapeutic stent using endothelial progenitor cell-inoculated hybrid tissue and in vitro performance

Abstract

Rapid reendothelialization at an atherosclerotic lesion after balloon or stent inflation may be essential for maintaining homeostatic tissue function, which could reduce or prevent restenosis. We devised an endothelial progenitor cell (EPC)-enriched tubular hybrid tissue and mounted it on a small-diameter metallic stent (outer diameter, 1.5 mm), which is used for intravascular angioplasty to atherosclerotic lesions. This study addressed the fabrication technique and in vitro performance to verify lumenal endothelialization. A thin collagenous tubular tissue was prepared by contraction of collagen fibers by inoculated EPCs, which were isolated from canine peripheral blood and expanded ex vivo, in a collagen gel formed in a mold. An EPC-inoculated hybrid tissue-covered stent, loaded on a balloon catheter, was inserted into a tubular hybrid vascular medial tissue inoculated with smooth muscle cells (SMCs) as an arterial media mimic, and subjected to balloon inflation for enlargement (outer diameter, 3 mm), followed by balloon deflation. The EPC-inoculated hybrid tissue-covered stent tightly adhered to the lumenal surface of the hybrid medial tissue. On culture, EPCs in the hybrid tissue migrated and proliferated to form a completely endothelialized lumenal surface at stented sites as well as sites adjacent to the vascular hybrid medial tissue with the prolongation of culture. This in vitro pilot study before in vivo experiments suggests that an EPC-inoculated hybrid tissue-covered stent may be a novel therapeutic device for reendothelialization or paving with EPC-enriched tissue at an atherosclerotic arterial wall, resulting in the prevention of restenosis and the rapid formation of normal tissue.