Transmural flow bioreactor for vascular tissue engineering.

Transmural flow bioreactor for vascular tissue engineering.
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DOI:
10.1002/bit.22475
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发表时间:
2009-12-15
影响因子:
3.8
通讯作者:
Tranquillo, Robert T.
Tranquillo, Robert T.
中科院分区:
工程技术2区
文献类型:
--
作者:
Bjork, Jason W.;Tranquillo, Robert T.

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营养转运限制仍然是工程组织体外培养的一个基本问题。在这项研究中,研究人员研究了灌注生物反应器的配置,以提供均匀的氧气输送到介质当量(MEs),这是组织工程动脉的基础。开发了生物反应器配置,以评估与完全跨壁流动(通过ME壁),完全轴向流动(通过管腔)以及这些流动的组合相关的氧气输送。此外,研究人员还分析了不同流动配置的输运模型,以确定整个组织中最均匀的氧气分布,包括组织水力传导性、细胞氧气消耗动力学、细胞密度以及ME物理尺寸的直接测量。模型结果表明,跨壁流和轴向流相结合时,溶解氧均匀性得到改善;然而,由于管腔压力超过破裂压力,或者由于过度的跨壁流速或由于ME压实导致的水力导电性降低而造成的破坏性间隙剪切应力,可能会产生有害影响。通过将预测的出口DO浓度与实际的出口DO浓度进行比较,验证了该模型。基于这些结果,控制跨壁流动与轴向流动的结合提出了一种有吸引力的方法,可以增加培养组织内营养物质向细胞的运输,以改善生长(增加细胞和细胞外基质浓度)以及均匀性。
Nutrient transport limitation remains a fundamental issue for in vitro culture of engineered tissues. In this study, perfusion bioreactor configurations were investigated to provide uniform delivery of oxygen to media equivalents (MEs) being developed as the basis for tissue-engineered arteries. Bioreactor configurations were developed to evaluate oxygen delivery associated with complete transmural flow (through the wall of the ME), complete axial flow (through the lumen), and a combination of these flows. In addition, transport models of the different flow configurations were analyzed to determine the most uniform oxygen profile throughout the tissue, incorporating direct measurements of tissue hydraulic conductivity, cellular O2 consumption kinetics, and cell density along with ME physical dimensions. Model results indicate that dissolved oxygen (DO) uniformity is improved when a combination of transmural and axial flow is implemented; however, detrimental effects could occur due to lumenal pressure exceeding the burst pressure or damaging interstitial shear stress imparted by excessive transmural flow rates or decreasing hydraulic conductivity due to ME compaction. The model was verified by comparing predicted with measured outlet DO concentrations. Based on these results, the combination of a controlled transmural flow coupled with axial flow presents an attractive means to increase the transport of nutrients to cells within the cultured tissue to improve growth (increased cell and extracellular matrix concentrations) as well as uniformity.
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