Magnetic reconstruction of three-dimensional tissues from multicellular spheroids.

Multicellular spheroids are useful building blocks for tissue reconstruction. This study reports a simple technique called magnetic organoid patterning for assembly of spheroids into a complex tissue-mimicking construct. Spheroids were labeled magnetically using co-incubation of RGD peptide-conjugated magnetic microparticles and single cells in suspension culture. The labeled spheroids can be manipulated individually or in parallel with a magnet without producing apparent effects on cell growth and migration. Spheroid patterns such as rings, lines, and arrays can be efficiently generated using this method. The patterned spheroid can be immobilized in functional hydrogels, in which fusion of neighboring spheroids and tissue-specific features were observed. Spheroid patterns temporarily encapsulated in a thermal-responsive hydrogel can be stacked layer by layer to generate thick three-dimensional (3D) tissues. These results indicate that magnetic organoid patterning is useful for construction of complex 3D tissue and will find applications in cell-to-cell interaction research, drug screening, and regenerative medicine.