A double chamber rotating bioreactor for enhanced tubular tissue generation from human mesenchymal stem cells

摘要

Cardiovascular diseases represent a major global health burden, with high rates of mortality and morbidity. Autologous grafts are commonly used to replace damaged or failing blood vessels, however such approaches are hampered by the scarcity of suitable graft tissue, donor site morbidity and poor long-term stability. Tissue engineering has been investigated as a means by which exogenous vessel grafts can be produced, with varying levels of success to date, a result of mismatched mechanical properties of these vessel substitutes and inadequate ex vivo vessel tissue genesis. In this work, we describe the development of a novel multifunctional dual-phase (air/aqueous) bioreactor, designed to both rotate and perfuse small diameter tubular scaffolds and encourage enhanced tissue genesis throughout such scaffolds. Within this novel dynamic culture system, an elastomeric nanofibrous, microporous composite tubular scaffold, composed of Poly(caprolactone) and acrylated Poly(lactide-co-trimethylene-carbonate) and with mechanical properties approaching those of native vessels, was seeded with human mesenchymal stem cells and cultured for up to 14 days in inductive (smooth muscle) media. This scaffold/bioreactor combination provided a dynamic culture environment that enhanced (compared to static controls) scaffold colonisation, cell growth, extracellular matrix deposition, and in situ differentiation of the human mesenchymal stem cells into mature smooth muscle cells, representing a concrete step towards our goal of creating a mature ex vivo vascular tissue for implantation. This article is protected by copyright. All rights reserved.