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基于环形磁铁装置的磁悬浮辅助三维细胞结构的生物制造、培养和操作。

Magnetic levitation assisted biofabrication, culture, and manipulation of 3D cellular structures using a ring magnet based setup.

机构信息

Department of Bioengineering, Izmir Institute of Technology, Izmir, Turkey.

Department of Molecular Biology and Genetics, Izmir Institute of Technology, Izmir, Turkey.

出版信息

Biotechnol Bioeng. 2021 Dec;118(12):4771-4785. doi: 10.1002/bit.27941. Epub 2021 Oct 5.

DOI:10.1002/bit.27941
PMID:34559409
Abstract

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.

摘要

抗磁性悬浮是一种新兴的技术,用于在细胞和组织水平的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一个培养室组成,该培养室物理上夹在两个块磁铁之间,这限制了工作体积和适用性。这项工作描述了一种基于单个环形磁铁的磁悬浮系统,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来操纵构建体的大小并进行长期维护。此外,我们的配置还可以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粒对平台进行悬浮校准,考虑到可行细胞的单细胞密度范围。通过利用磁聚焦和细胞自组装,毫米大小的 3D 结构在系统中形成并保持悬浮状态,允许在开放的操作空间中轻松进行现场细胞培养干预。我们证明,通过改变顺磁离子浓度,可以调整悬浮协议以适应不同密度的各种细胞类型(例如干细胞、脂肪细胞和癌细胞)的悬浮,也可以通过操纵介质密度来降低顺磁离子浓度。该技术允许单独形成的 3D 生物单元的操纵和合并,以及与生物聚合物的混合生物制造。总之,我们相信这个平台将在组织工程、药物发现和发育生物学等广泛领域发挥重要作用。

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