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首页> 外文期刊>Journal of Combinatorial Optimization >Modeling and in vitro and in vivo characterization of a tissue engineered pancreatic substitute
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Modeling and in vitro and in vivo characterization of a tissue engineered pancreatic substitute

机译：组织工程化胰腺替代物的建模以及体外和体内表征

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摘要

In designing appropriate devices for the development of a functional pancreatic substitute, computational models capable of accurately predicting cellular behavior constitute a critical aspect. This study investigated the model-based design, fabrication and in vitro and in vivo experimental characterization of a pancreatic substitute consisting of mouse insulinoma cells encapsulated in agarose in a disk-shaped construct. Two construct prototypes were examined: (i) a single disk construct comprised of agarose and βTC3 cells; and (ii) a buffered disk construct, consisting of agarose and βTC3 cells, coated with an additional layer of pure agarose. Diffusional studies of glucose and insulin were performed to characterize the transport properties of the material. Three dimensional oxygen diffusion-reaction models were used to predict the appropriate cell loadings for the two construct prototypes under varying external oxygen tensions. In vitro and in vivo experiments found the overall viable cell number for each construct prototype plateaued to the same value, regardless of the initial cell seeding number, when constructs were placed under identical environmental conditions. Furthermore, mathematical model calculations correlated well with experimental in vitro and in vivo results of cell viability, indicating oxygen tension to be the dominating factor in establishing total viable cell number in these constructs. These results indicate that the development of a computational model capable of accurately predicting overall cell viability is useful for the development of tissue engineered constructs, when permissive matrices and continuous cell lines are used. The applicability of this modeling and experimental methodology in the development of agarose-based constructs for use as a bioartificial pancreas is discussed.
机译：在设计用于开发功能性胰腺替代物的合适设备时，能够准确预测细胞行为的计算模型是一个关键方面。这项研究调查了胰腺替代品的基于模型的设计，制备以及体外和体内实验表征，该替代品由小鼠胰岛素瘤细胞包裹在琼脂糖中盘状构建而成。检查了两个构建体原型：（i）由琼脂糖和βTC3细胞组成的单盘构建体； （ii）由琼脂糖和βTC3细胞组成的缓冲盘构建体，其被另外的纯琼脂糖层覆盖。进行了葡萄糖和胰岛素的扩散研究以表征材料的传输特性。使用三维氧气扩散反应模型来预测在变化的外部氧气张力下两个构建体原型的合适细胞负荷。体外和体内实验发现，当将构建体置于相同的环境条件下时，无论初始细胞接种数如何，每个构建体原型的总体活细胞数均稳定在相同的值。此外，数学模型计算与细胞存活率的体外和体内实验结果高度相关，表明氧张力是在这些构建物中建立总存活细胞数的主要因素。这些结果表明，当使用允许的基质和连续细胞系时，能够准确预测总体细胞生存力的计算模型的开发对于组织工程构建体的开发是有用的。讨论了这种建模和实验方法在开发用作生物人工胰腺的基于琼脂糖的构建体中的适用性。

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  • 来源
    《Journal of Combinatorial Optimization》 |2009年第1期|54-73|共20页
  • 作者

    C. L. Stabler; C. Fraker; E. Pedraza; I. Constantinidis; A. Sambanis;

  • 作者单位

    Department of Biomedical Engineering University of Miami 219A McArthur Annex Coral Gables FL 33124-0621 USA;

    Department of Biomedical Engineering University of Miami 219A McArthur Annex Coral Gables FL 33124-0621 USA;

    Department of Biomedical Engineering University of Miami 219A McArthur Annex Coral Gables FL 33124-0621 USA;

    Division of Endocrinology Department of Medicine University of Florida PO Box 100226 Gainesville FL 32610-0226 USA;

    Department of Biomedical Engineering Georgia Institute of Technology/Emory University 313 Ferst Drive Atlanta GA 30332-0363 USA;

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  • 原文格式 PDF
  • 正文语种 eng
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  • 关键词

    Tissue construct modeling; Pancreatic substitute; Agarose; Encapsulated cells; βTC3 insulinoma cells;

    机译：组织构建模型;胰腺替代物;琼脂糖;包囊细胞;βTC3胰岛素瘤细胞;

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