Remote Magnetic Microengineering and Alignment of Spheroids into 3D Cellular Fibers

摘要

Developing in vitro models that recapitulate the in vivo organization of livingcells in a 3D microenvironment is one of the current challenges in the fieldof tissue engineering. In particular for anisotropic tissues where alignmentof precursor cells is required for them to create functional structures. Herein,a new method is proposed that allows aligning in the direction of a uniformmagnetic field both individual cells (muscle, stromal, and stem cells) orspheroids in a thermoresponsive collagen hydrogel. In an all-in-one approach,spheroids are generated at high throughput by magnetic engineering usingmicrofabricated micromagnets and are used as building blocks to create 3Danisotropic tissue structures of different scales. The magnetic cells and spheroidsalignment process is optimized in terms of magnetic cell labeling, concentration,and size. Anisotropic structures are induced to form fibers in thedirection of the magnetic alignment, with the respective roles of the magneticfield, the mechanical stretching of hydrogel or co-culture of the aligned cellswith non-magnetic stromal cells, being investigated. Over days, spheroidsfuse into 3D tubular structures, oriented in the direction of the magneticalignment. Moreover, in the case of the muscle cells model, multinucleatedcells can be observed within the fibers.