组织工程支架作为机械和机械调制信号传递装置的设计。

Eric J Anderson, Melissa L Knothe Tate
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引用次数: 49

摘要

组织工程的新方法旨在利用内源性策略,如那些发生在产前发育和产后愈合期间重演。定义组织模板规格来模拟发育过程中浓缩间充质的环境,允许利用组织支架作为外部信号的传递装置,包括生化和机械信号,以驱动植入的间充质干细胞的命运。虽然已经确定了多种调节干细胞命运的生化信号,但有利于引导多能细胞向特定谱系发展的机械信号尚未得到很好的表征。此外,不仅对细胞的机械刺激的空间和时间控制具有挑战性,而且由于组织向内生长和/或支架降解,组织模板的几何形状也会随时间变化。因此,作为优化支架结构的第一步,进行了一个案例研究,分析了试验台支架的流动状况。施加压力梯度产生局部(纳米-微米)流场,有利于细胞的迁移、粘附、增殖和分化,以及整体流动参数(微米-毫米),包括流速和渗透率,以增强定向细胞浸润和增加质量运输。对流道尺寸进行迭代遮挡,以虚拟地预测时间几何变化(例如,由于组织发育和生长)对局部和全局机械信号传递的影响。此后,从案例研究中获得的见解被归纳为未来在体外或体内实施支架开发的优化方案。虽然很可能需要制造和测试来完成设计规范,但预计合理设计优化的使用将减少确定最终原型几何形状和流动条件所需的迭代次数。随着有利于引导细胞原位命运的机械信号范围的进一步阐明,这些改进的设计标准可以整合到一般的优化准则中,为在实验室或临床中利用自然的内源性组织工程策略进行靶向组织生成提供技术平台。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Design of tissue engineering scaffolds as delivery devices for mechanical and mechanically modulated signals.

New approaches to tissue engineering aim to exploit endogenous strategies such as those occurring in prenatal development and recapitulated during postnatal healing. Defining tissue template specifications to mimic the environment of the condensed mesenchyme during development allows for exploitation of tissue scaffolds as delivery devices for extrinsic cues, including biochemical and mechanical signals, to drive the fate of mesenchymal stem cells seeded within. Although a variety of biochemical signals that modulate stem cell fate have been identified, the mechanical signals conducive to guiding pluripotent cells toward specific lineages are less well characterized. Furthermore, not only is spatial and temporal control of mechanical stimuli to cells challenging, but also tissue template geometries vary with time due to tissue ingrowth and/or scaffold degradation. Hence, a case study was carried out to analyze flow regimes in a testbed scaffold as a first step toward optimizing scaffold architecture. A pressure gradient was applied to produce local (nm-micron) flow fields conducive to migration, adhesion, proliferation, and differentiation of cells seeded within, as well as global flow parameters (micron-mm), including flow velocity and permeability, to enhance directed cell infiltration and augment mass transport. Iterative occlusion of flow channel dimensions was carried out to predict virtually the effect of temporal geometric variation (e.g., due to tissue development and growth) on delivery of local and global mechanical signals. Thereafter, insights from the case study were generalized to present an optimization scheme for future development of scaffolds to be implemented in vitro or in vivo. Although it is likely that manufacture and testing will be required to finalize design specifications, it is expected that the use of the rational design optimization will reduce the number of iterations required to determine final prototype geometries and flow conditions. As the range of mechanical signals conducive to guiding cell fate in situ is further elucidated, these refined design criteria can be integrated into the general optimization rubric, providing a technological platform to exploit nature's endogenous tissue engineering strategies for targeted tissue generation in the lab or the clinic.

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来源期刊
Tissue engineering
Tissue engineering CELL & TISSUE ENGINEERING-BIOTECHNOLOGY & APPLIED MICROBIOLOGY
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