Abstract

Small-diameter (<4 mm) vascular constructs are urgently needed for patients requiring replacement of their peripheral vessels. However, successful development of constructs remains a significant challenge. In this study, we successfully developed small-diameter vascular constructs with high patency using our integrally designed computer-controlled bioreactor system. This computer-controlled bioreactor system can confer physiological mechanical stimuli and fluid flow similar to physiological stimuli to the cultured grafts. The medium circulating system optimizes the culture conditions by maintaining fixed concentration of O2 and CO2 in the medium flow and constant delivery of nutrients and waste metabolites, as well as eliminates the complicated replacement of culture medium in traditional vascular tissue engineering. Biochemical and mechanical assay of newly developed grafts confirm the feasibility of the bioreactor system for small-diameter vascular engineering. Furthermore, the computer-controlled bioreactor is superior for cultured cell proliferation compared with the traditional non-computer-controlled bioreactor. Specifically, our novel bioreactor system may be a potential alternative for tissue engineering of large-scale small-diameter vascular vessels for clinical use.

Highlights

  • Peripheral vascular disease becomes an increasing health and socio-economic burden in most countries

  • As shown by HE staining (Fig. 5B), after 2-week culture, vascular grafts cultured in the dynamic bioreactor system showed normal appearing smooth muscle cells with circumferential orientation in the external areas of the graft and the endothelial layer appeared healthy and nearly confluent

  • Vascular tissues cultured in the dynamic bioreactor system showed more cell density of both aortic smooth muscle cells and endothelial cells than that of cells cultured under static conditions

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Summary

Introduction

Peripheral vascular disease becomes an increasing health and socio-economic burden in most countries. Usable vessels are not often available due to vascular disease, amputation, as well as previous harvest [1]. Smalldiameter (,4 mm) vascular substitutes are urgently needed for patients requiring replacement of their peripheral vessels. The most common alternative to autologous grafts is the use of synthetic small-diameter vascular grafts made of materials such as Dacron or expanded polytetrafluoroethylene [2]. The small-diameter arterials of low flow pose a different set of design criteria and introduce various problems including thrombogenicity not encountered in large-caliber vascular substitutes where these synthetic vascular grafts have succeed [3]. The main objective is to generate biological substitutes of small-diameter arterial conduits with functional characteristics of native vessels with cellular components

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