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

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