Gupta Tamaghna, Aithal Srivatsa, Mishriki Sarah, Sahu Rakesh P, Geng Fei, Puri Ishwar K
ACS Biomater Sci Eng. 2020 Jul 13;6(7):4294-4303. doi: 10.1021/acsbiomaterials.0c00233. Epub 2020 Jun 5.
Controlled cell assembly is essential for fabricating in vitro 3D models that mimic the physiology of in vivo cellular architectures. Whereas tissue engineering techniques often rely on intrusive magnetic nanoparticles placed in cells and hydrogel encapsulation of cells to produce multilayered cellular constructs, we describe a high-throughput, label-free, and scaffold-free magnetic field-guided technique that assembles cells into a layered aggregate. An inhomogeneous magnetic field influences the diamagnetic cells suspended in a paramagnetic culture medium. Driven by the magnetic susceptibility difference and the field gradient, the cells are displaced toward the region of lowest field strength. Two cell lines are used to demonstrate the sequential assembly of layer-on-layer aggregates in microwells within 6 h. The effect of magnet size on the assembly dynamics is characterized and a microwell size criterion for the highest cell aggregation provided. Label-free magnetic-field-assisted assembly is relevant for on-demand scalable biofabrication of complex layered structures. Potential applications include drug discovery, developmental biology, lab-on-chip devices, and cancer research.
可控细胞组装对于构建模拟体内细胞结构生理学的体外3D模型至关重要。虽然组织工程技术通常依赖于置于细胞内的侵入性磁性纳米颗粒以及细胞的水凝胶封装来制备多层细胞构建体，但我们描述了一种高通量、无标记且无支架的磁场引导技术，该技术可将细胞组装成层状聚集体。不均匀磁场会影响悬浮在顺磁性培养基中的抗磁性细胞。在磁化率差异和场梯度的驱动下，细胞会朝着场强最低的区域移动。使用两种细胞系来证明在6小时内微阱中层状聚集体的逐层组装。表征了磁体尺寸对组装动力学的影响，并提供了实现最高细胞聚集的微阱尺寸标准。无标记磁场辅助组装与按需可扩展地生物制造复杂层状结构相关。潜在应用包括药物发现、发育生物学、芯片实验室设备和癌症研究。
