Karlsruhe Institute of Technology (KIT), Institute of Functional Interfaces, Hermann-von-Helmholtz-Platz 1, 76344, Eggenstein-Leopoldshafen, Germany.
Adv Healthc Mater. 2018 May;7(9):e1701403. doi: 10.1002/adhm.201701403. Epub 2018 Jan 19.
There is an urgent need for 3D cell culture systems that avoid the oversimplifications and artifacts of conventional culture in 2D. However, 3D culture within the cavities of porous biomaterials or large 3D structures harboring high cell numbers is limited by the needs to nurture cells and to remove growth-limiting metabolites. To overcome the diffusion-limited transport of such soluble factors in 3D culture, mixing can be improved by pumping, stirring or shaking, but this in turn can lead to other problems. Using pumps typically requires custom-made accessories that are not compatible with conventional cell culture disposables, thus interfering with cell production processes. Stirring or shaking allows little control over movement of scaffolds in media. To overcome these limitations, magnetic, macroporous hydrogels that can be moved or positioned within media in conventional cell culture tubes in a contactless manner are presented. The cytocompatibility of the developed biomaterial and the applied magnetic fields are verified for human hematopoietic stem and progenitor cells (HSPCs). The potential of this technique for perfusing 3D cultures is demonstrated in a proof-of-principle study that shows that controlled contactless movement of cell-laden magnetic hydrogels in culture media can mimic the natural influence of differently perfused environments on HSPCs.
目前非常需要 3D 细胞培养系统，以避免传统 2D 培养中的过度简化和人为假象。然而，在多孔生物材料的腔室内或容纳大量细胞的大型 3D 结构内进行 3D 培养受到需要滋养细胞和去除生长限制代谢物的限制。为了克服 3D 培养中这些可溶性因子的扩散限制传输，可以通过泵送、搅拌或摇动来改善混合，但这反过来又会导致其他问题。使用泵通常需要定制的附件，这些附件与传统的细胞培养一次性用品不兼容，从而干扰细胞生产过程。搅拌或摇动几乎无法控制支架在培养基中的运动。为了克服这些限制，提出了可以在传统细胞培养管中的培养基中以非接触方式移动或定位的磁、大孔水凝胶。为人类造血干细胞和祖细胞（HSPCs）验证了所开发生物材料的细胞相容性和应用磁场。在一项原理验证研究中证明了该技术用于 3D 培养物灌注的潜力，该研究表明，在培养物中对载细胞的磁性水凝胶进行受控的非接触式移动可以模拟不同灌注环境对 HSPCs 的自然影响。
