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

• Published in: Advanced functional materials Vol. 32; no. 50
• Main Authors: Demri, Noam, Dumas, Simon, Nguyen, Manh‐Louis, Gropplero, Giacomo, Abou‐Hassan, Ali, Descroix, Stéphanie, Wilhelm, Claire
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc 01.12.2022; Wiley
• Subjects: 3D cell cultures; Alignment; Fibers; Hydrogels; Magnetic fields; magnetic forces; magnetic nanoparticles; Materials science; Microengineering; muscle tissue engineering; Muscles; organ on chip; Physics; Spheroids; Stem cells; Tissue engineering
• ISSN: 1616-301X; 1616-3028
• DOI: 10.1002/adfm.202204850

Developing 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. Spheroids are created by attracting magnetic muscle cells to micromagnets. They are next aligned in a 3D thermoresponsive collagen hydrogel between two strong magnets. As the gel polymerizes around the spheroids chains, they are trapped in an anisotropic organization. After differentiating for a couple of days, the spheroids fuse into 3D fiber‐like muscle structures.