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Magnetic levitation assisted biofabrication, culture, and manipulation of 3D cellular structures using a ring magnet based setup
Biotechnology and Bioengineering ( IF 3.5 ) Pub Date : 2021-09-24 , DOI: 10.1002/bit.27941
Muge Anil-Inevi 1 , Kerem Delikoyun 1 , Gulistan Mese 2 , H Cumhur Tekin 1 , Engin Ozcivici 1
Affiliation  

Diamagnetic levitation is an emerging technology for remote manipulation of cells in cell and tissue level applications. Low-cost magnetic levitation configurations using permanent magnets are commonly composed of a culture chamber physically sandwiched between two block magnets that limit working volume and applicability. This work describes a single ring magnet-based magnetic levitation system to eliminate physical limitations for biofabrication. Developed configuration utilizes sample culture volume for construct size manipulation and long-term maintenance. Furthermore, our configuration enables convenient transfer of liquid or solid phases during the levitation. Before biofabrication, we first calibrated/ the platform for levitation with polymeric beads, considering the single cell density range of viable cells. By taking advantage of magnetic focusing and cellular self-assembly, millimeter-sized 3D structures were formed and maintained in the system allowing easy and on-site intervention in cell culture with an open operational space. We demonstrated that the levitation protocol could be adapted for levitation of various cell types (i.e., stem cell, adipocyte and cancer cell) representing cells of different densities by modifying the paramagnetic ion concentration that could be also reduced by manipulating the density of the medium. This technique allowed the manipulation and merging of separately formed 3D biological units, as well as the hybrid biofabrication with biopolymers. In conclusion, we believe that this platform will serve as an important tool in broad fields such as bottom-up tissue engineering, drug discovery and developmental biology.

中文翻译:

使用基于环形磁铁的设置磁悬浮辅助生物制造、培养和操作 3D 细胞结构

抗磁悬浮是一种新兴技术,用于在细胞和组织水平应用中远程操纵细胞。使用永磁体的低成本磁悬浮配置通常由物理上夹在两个块状磁体之间的培养室组成,这限制了工作体积和适用性。这项工作描述了一种基于单环磁铁的磁悬浮系统,以消除生物制造的物理限制。开发的配置利用样本培养体积进行构建大小操作和长期维护。此外,我们的配置能够在悬浮过程中方便地转移液相或固相。在生物制造之前,我们首先使用聚合物珠校准/悬浮平台,考虑到活细胞的单细胞密度范围。通过利用磁聚焦和细胞自组装,在系统中形成并维护了毫米大小的 3D 结构,从而可以在开放的操作空间中轻松地对细胞培养进行现场干预。我们证明了悬浮协议可以适用于悬浮代表不同密度的细胞的各种细胞类型(即干细胞、脂肪细胞和癌细胞),方法是通过修改顺磁离子浓度,也可以通过操纵介质的密度来降低该浓度。该技术允许操纵和合并单独形成的 3D 生物单元,以及与生物聚合物的混合生物制造。总之,我们相信该平台将成为自下而上的组织工程、药物发现和发育生物学等广泛领域的重要工具。
更新日期:2021-11-10
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