Remote-Controlled 3D Porous Magnetic Interface toward High-Throughput Dynamic 3D Cell Culture.

Remote-Controlled 3D Porous Magnetic Interface toward High-Throughput Dynamic 3D Cell Culture.
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远程控制的3D多孔磁性界面,用于高通量动态3D细胞培养。

DOI:
10.1021/acsbiomaterials.1c00459
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发表时间:
2021-09-13
影响因子:
5.8
通讯作者:
He, Mei
He, Mei
中科院分区:
工程技术2区
文献类型:
--
作者:
Stottlemire, Bryce J.;Chakravarti, Aparna R.;Whitlow, Jonathan W.;Berkland, Cory J.;He, Mei

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机械刺激已被证明在细胞行为中起重要作用,包括细胞生长、分化、形态、稳态和疾病。因此,开发能够为组织工程和疾病建模药物筛选创造复杂机械环境的生物反应器系统是有吸引力的。然而,许多现有的系统受到限制,由于其庞大的尺寸与外力发生器,破坏性的微环境控制,和低吞吐量。这些缺点已经在利用磁刺激响应材料之前,考虑到它们在微观尺度和宏观尺度水平上的不受约束、快速和可调的致动潜力,用于无缝整合到细胞培养威尔斯孔和微流体系统中。然而,用于细胞培养的磁性软材料由于不能开发出用于更复杂和生理相关的机械致动的良好限定的3D结构而受到限制。在此,我们介绍了一种简便的制造工艺,以开发磁性- PDMS(聚二甲基硅氧烷)多孔复合材料设计,其具有良好定义和可控的微观和宏观特征,以在规模上动态操纵3D细胞负载凝胶。磁性-PDMS多孔复合材料的固有刚度也被调制以控制变形潜力,以模拟生理相关的应变水平,在磁致动研究中观察到2.89至11%。在与磁性-PDMS多孔复合材料界面连接的3D细胞负载凝胶中培养人脂肪干细胞(hADMSC)和人脐带间充质干细胞(hUCMSC),实现了高细胞活力。此外,磁性-PDMS复合材料的高度互连的多孔网络促进了整个多孔结构的自由扩散,展示了在储液器和96孔板插入物设计中用于更复杂的动态机械致动的多表面接触3D多孔磁性结构的潜力。总之,这些研究提供了一种建立具有快速和可编程动态应变电位的生物相容性、可调磁性-PDMS多孔复合材料的方法,使其成为高通量、动态3D细胞培养的合适平台。
Mechanical stimuli have been shown to play a large role in cellular behavior, including cellular growth, differentiation, morphology, homeostasis, and disease. Therefore, developing bioreactor systems that can create complex mechanical environments for both tissue engineering and disease modeling drug screening is appealing. However, many of existing systems are restricted due to their bulky size with external force generators, destructive microenvironment control, and low throughput. These shortcomings have preceded to the utilization of magnetic stimuli responsive materials, given their untethered, fast, and tunable actuation potential at both the microscale and macroscale level, for seamless integration into cell culture wells and microfluidic systems. Nevertheless, magnetic soft materials for cell culture have been limited due to the inability to develop well-defined 3D structures for more complex and physiological relevant mechanical actuation. Herein, we introduce a facile fabrication process to develop magnetic- PDMS (polydimethylsiloxane) porous composite designs with both well-defined and controllable microlevel and macrolevel features to dynamically manipulate 3D cell-laden gel at the scale. The intrinsic stiffness of the magnetic-PDMS porous composites is also modulated to control the deformation potential to mimic physiological relevant strain levels, with 2.89 to 11% observed in magnetic actuation studies. High cell viability was achieved with the culturing of both human adipose stem cells (hADMSCs) and human umbilical cord mesenchymal stem cells (hUCMSCs) in 3D cell-laden gel interfaced with the magnetic-PDMS porous composite. Also, the highly interconnected porous network of the magnetic-PDMS composites facilitated free diffusion throughout the porous structure showcasing the potential of a multi-surface contact 3D porous magnetic structure in both reservoir and 96-well plate insert designs for more complex dynamic mechanical actuation. In conclusion, these studies provide a means for establishing a biocompatible, tunable magnetic-PDMS porous composite with fast and programmable dynamic strain potential making it a suitable platform for high-throughput, dynamic 3D cell culture.
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