Cerium Oxide Nanoparticles-Reinforced GelMA Hydrogel Loading Bone Marrow Stem Cells with Osteogenic and Inflammatory Regulatory Capacity for Bone Defect Repair

Abstract

Effective bone defect repair has been a tough clinical challenge due to the complexity of the bone defect microenvironment. Hydrogels loaded with bone marrow mesenchymal stem cells (BMSCs) have been widely applied for bone regeneration. However, the low survival of BMSCs at the site of transplantation and lack of sufficient osteogenic induction capacity greatly limit their applications. In order to solve this puzzle, we fabricated gelatin methacryloyl (GelMA) hydrogels containing BMSCs with cerium oxide (CeO₂) nanoparticles via photo-cross-linking to endow the composite hydrogel with osteogenic induction ability and immune induction ability. In vitro results demonstrated that the GelMA-CeO₂-BMSC hydrogel presented with good biocompatibility and excellent osteogenic induction ability. In addition, the GelMA-CeO₂-BMSC hydrogel could inhibit M1 polarization and promote M2 polarization, providing a good environment for the growth and osteogenic differentiation of BMSCs. Besides, the GelMA-CeO₂-BMSC hydrogel was transplanted into critical-sized calvarial defects, and the results further confirmed its excellent bone regeneration capacity. In conclusion, the composite hydrogel provides a perspective for bone repair due to the remarkable potential for application in bone regeneration.

Keywords: bone defect repair; cerium oxide nanoparticle; hydrogel; immunomodulation; osteogenesis.