hDPSC-laden GelMA microspheres fabricated using electrostatic microdroplet method for endodontic regeneration.

The microsphere system has attracted considerable attention as a stem-cell delivery vehicle in regeneration medicine owing to its injectability, fast substance transfer ability, and mimicry of the three-dimensional native environment. However, suitable biomaterials for preparation of microspheres optimal for endodontic regeneration are still being explored. Owing to its excellent bioactivity and biodegradability, gelatin methacryloyl (GelMA) was used to fabricate hydrogel microspheres by the electrostatic microdroplet method, and the potential of GelMA microspheres applied in endodontic regeneration was studied. The average size of GelMA microspheres encapsulating human dental pulp stem cells (hDPSCs) was ~200 μm, and the Young's modulus was approximately 582.8 ± 66.0 Pa, which was close to that of the natural human dental pulp. The encapsulated hDPSCs could effectively adhere, spread, proliferate, and secrete extracellular matrix proteins in the microspheres, and tended to occupy the outer layer. Moreover, the cell-laden GelMA microsphere system could withstand cryopreservation, and the thawed cells exhibited normal functions. After subcutaneous implantation in a nude mouse model, more vascularized pulp-like tissues were generated in the cell-laden GelMA microsphere group compared with that in the cell-laden bulk GelMA group, and this was accompanied by a suitable degradation rate. The GelMA microspheres showed remarkable performances and great potential as cell delivery vehicles in endodontic regeneration.