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首页> 外文学位 >Oxygen transport, shear stress, and metabolism in perfused hepatocyte-seeded scaffolds with radial pore architecture: Experimental and computational analyses.
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Oxygen transport, shear stress, and metabolism in perfused hepatocyte-seeded scaffolds with radial pore architecture: Experimental and computational analyses.

机译：具有径向孔结构的灌注肝细胞种子支架中的氧运输，切应力和代谢：实验和计算分析。

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摘要

Several modalities have been proposed as treatments or temporary stop-gap for patients suffering from liver failure until a suitable organ is available. However there is still an urgent need for an off-the-shelf device that can accommodate clinically relevant cell numbers, be cultured at physiological oxygen tensions and, can be fully integrated into and heal the injured hepatic space. In this study we investigated the effects that convective and direct oxygenation had on hepatocyte functionality, morphology and viability while cultured in bulk 3D chitosan scaffolds and perfusion bioreactor systems. Cylindrical chitosan scaffolds with radial directed pore structures were fabricated by a thermal gradient directed from the center to the periphery. Capillary-like direct oxygenation was facilitated by embedding gas permeable silicone tubing throughout the scaffold body. Three iterations of bioreactor design and optimization produced a perfusion system that could enable direct oxygenation, accommodate high density hepatocyte seeding (8x10-7 to 1x10-8 cells), ensure adequate mass transfer and induce sustainable metabolic outputs for a least 7 days at a flow rate of 10 ml/min. A computational fluid dynamics model of the internal scaffold pore structure infused with spheroids that resembled hepatocyte aggregates was utilized to understand how varying flow rates (5, 10, 15, 20 and 25 ml/min) effected fluid flow profiles, shear stress imposed on the cells and oxygen consumption within the microenvironment. The results showed that the volumetric flow rate 15 ml/min at the scaffold's central port inlet produced the best oxygen consumption profile with no damaging effects due to shear stress or eddies flow. The simulation was validated and showed good correlation to empirically derived data. Experimentally the flow rate of 15 ml/min induced the most favorable hepatic response out of the five experimental flow conditions and a static culture (only direct oxygenation). We also looked at how increasing cellular compactness, via reduced scaffold dimensions, would affect phenotypic expression and viability. It was discerned that increasing the cell packing density by 14% increased the rate of albumin and urea production by 79% and 40% respectively. In total the results show that the experimental measures conducted in this study enhanced hepatocyte metabolic performance, viability and morphological appearance.
机译：对于患有肝功能衰竭的患者，直到有合适的器官可用之前，已经提出了几种治疗方法或暂时性的治疗方法。然而，仍然迫切需要一种现成的设备，该设备可以容纳临床上相关的细胞数量，可以在生理氧气压力下进行培养，并且可以完全整合并治愈受伤的肝脏空间。在这项研究中，我们研究了在大量3D壳聚糖支架和灌注生物反应器系统中培养时，对流和直接氧合对肝细胞功能，形态和活力的影响。通过从中心到外围定向的热梯度来制备具有径向定向孔结构的圆柱形壳聚糖支架。通过将透气的硅胶管嵌入整个支架体内，可促进毛细管样直接氧合。生物反应器设计和优化的三次迭代产生了一个灌注系统，该灌注系统可实现直接充氧，容纳高密度肝细胞接种（8x10-7至1x10-8个细胞），确保足够的传质并在连续流动至少7天时诱导可持续的代谢输出速度为10毫升/分钟。利用注入类似于肝细胞聚集体的球状体的内部支架孔结构的计算流体动力学模型来了解变化的流速（5、10、15、20和25 ml / min）如何影响流体流动曲线，施加于流体的剪切应力微环境内的细胞和氧气消耗。结果表明，在支架的中心端口入口处的体积流量为15 ml / min，产生了最佳的耗氧量，而没有由于剪切应力或涡流而造成的破坏作用。该仿真已得到验证，并且与经验得出的数据具有良好的相关性。实验上，在五个实验流量条件和静态培养（仅直接氧化）中，15 ml / min的流速引起了最有利的肝反应。我们还研究了通过减小​​支架的尺寸来增加细胞紧密度将如何影响表型表达和生存能力。可以看出，将细胞堆积密度提高14％可使白蛋白和尿素的产生率分别提高79％和40％。总体而言，结果表明，在这项研究中进行的实验措施增强了肝细胞的代谢性能，生存能力和形态外观。

著录项

  • 作者

    Mbanu, Chijioke Anaele.;

  • 作者单位

    Wayne State University.;

  • 授予单位 Wayne State University.;
  • 学科 Biomedical engineering.;Cellular biology.;Biochemistry.
  • 学位 Ph.D.
  • 年度 2016
  • 页码 202 p.
  • 总页数 202
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

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