Template-based fabrication of spatially organized 3D bioactive constructs using magnetic low-concentration gelation methacrylate (GelMA) microfibers

Low concentrations of gelatin methacrylate (GelMA) microfibers are more favorable for cellular activity compared with high concentrations. However, applying low-concentration GelMA microfibers as building blocks for higher-order cellular assembly remains challenging owing to their poor mechanical properties. Herein, we report a new template-based method to solve this problem. GelMA microfibers (5%, w/v) containing magnetic nanoparticles were synthesized by a microfluidic spinning method. A 9 × 9 micropillar array surrounded by a magnetic substrate was constructed to form 8 × 8 microgaps arranged in a crisscross pattern as a magnetic template. In DMEM solution, magnetic attraction facilitated efficient arrangement of the microfibers according to the template with micron assembly accuracy, with a microgrid-like construct (microGC) generated after removing all micropillars. MicroGCs were shown to effectively support the activities of surface seeded or encapsulated cells and be flexibly constructed with various organized spatial patterns. Owing to the low mechanical property requirements of assembled microfibers and the easy-to-implement operation, the proposed method provides a versatile pathway for the assembly of various microfluidic spun microfibers. Furthermore, the resulting 3D microgrid-like cellular constructs with organized spatiotemporal composition offer a convenient platform for the study of tissue engineering.