Magnetic Macroporous Hydrogels as a Novel Approach for Perfused Stem Cell Culture in 3D Scaffolds via Contactless Motion Control

Abstract

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.

Perfused 3D scaffolds promise to overcome the limitations of 2D culture systems. An innovative 3D magnetic hydrogel system that greatly improves the diffusion-limited nutrient transport in state-of-the-art approaches by moving the hydrogel contactless in conventional cell culture tubes is presented. The engineered system is verified with hematopoietic progenitor cell culture and shows the impact of perfused environments on cell behavior.

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