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Cyclic Stretch and Perfusion Bioreactor for Conditioning Large Diameter Engineered Tissue Tubes

机译:循环拉伸和灌注生物反应器用于处理大直径工程组织管

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摘要

A cyclic stretch and perfusion bioreactor was designed to culture large diameter engineered tissue tubes for heart valve applications. In this bioreactor, tubular tissues consisting of dermal fibroblasts in a sacrificial fibrin gel scaffold were placed over porated latex support sleeves and mounted in a custom bioreactor. Pulsatile flow of culture medium into the system resulted in cyclic stretching as well as ablumenal, lumenal, and transmural flow (perfusion). In this study, lumenal remodeling, composition, and mechanical strength and stiffness were compared for tissues cyclically stretched in this bioreactor on either the porated latex sleeves or solid latex sleeves, which did not permit lumenal or transmural flow. Tissues cyclically stretched on porated sleeves had regions of increased lumenal remodeling and cellularity that were localized to the columns of pores in the latex sleeve. A CFD model was developed with COMSOL Multiphysics® to predict flow of culture medium in and around the tissue, and the predictions suggest that the enhanced lumenal remodeling was likely a result of elevated shear stresses and transmural velocity in these regions. This work highlights the beneficial effects of increased nutrient transport and flow stimulation for accelerating in vitro tissue remodeling.
机译:设计了一种循环拉伸和灌注生物反应器,以培养用于心脏瓣膜应用的大直径工程组织管。在该生物反应器中,将由牺牲性纤维蛋白凝胶支架中的真皮成纤维细胞组成的肾小管组织置于带孔的乳胶支撑套上,并安装在定制的生物反应器中。培养基的脉冲流进入系统会导致循环拉伸,以及渗出液,灌注液和透壁液。在这项研究中,比较了在该生物反应器中周期性循环拉伸的,在多孔乳胶套筒或固体乳胶套筒上不允许腔或透壁流动的组织的腔重塑,组成以及机械强度和刚度。在带孔套筒上周期性拉伸的组织具有增加的管腔重塑和细胞结构的区域,这些区域位于乳胶套筒的孔柱中。使用COMSOLMultiphysics®开发的CFD模型可预测组织内和周围组织的培养基流动,并且预测结果表明,腔内重塑的增强可能是这些区域内剪切应力和穿膜速度升高的结果。这项工作突出了增加营养物质运输和流动刺激对加速体外组织重塑的有益作用。

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