Abstract: The management of critical-size bone defects remains a significant clinical challenge due to the substantial volume involved and the limitations of current treatment methods such as autologous bone grafting, bone allografts, and metal implants. This study aims to develop a novel bone regeneration material by loading bone marrow-derived mesenchymal stem cells (BMSCs) microgels onto a 3D-printed scaffold composed of Si₃N₄ nanoparticles and poly (lactic-co-glycolic acid) (PLGA) copolymer. The scaffold was fabricated using high-temperature fused deposition modeling 3D printing technology. The addition of Si₃N₄ nanoparticles enhanced the scaffold’s hydrophilicity, mechanical properties, and biological activity. BMSCs microgels were prepared by encapsulating BMSCs in GelMA hydrogel to enhance cell survival rate and prevent the influence of immune response and mechanical stress. In vitro experiments demonstrated that the PS5@BM scaffold (PLGA scaffold with 5 % Si₃N₄ loaded with BMSCs microgels) significantly promoted osteogenic differentiation of BMSCs, anti-inflammatory effects, and angiogenesis. The in vivo study in rat femoral condyle defect models confirmed that within 8 weeks after surgery, the PS5@BM scaffold effectively improved the immune microenvironment at the bone defect site, thereby promoting bone regeneration and vascularization. Compared with the control group, the PS5@BM group had higher vascular regeneration efficiency and new bone content. The synergistic effect of Si⁴⁺ ions released from the scaffold and paracrine growth factors secreted by BMSCs microgels effectively modulated the immune microenvironment, promoting a favorable environment for bone regeneration. This study provides a promising solution for the treatment of critical bone defects, highlighting the potential of Si₃N₄ bioceramics in bone tissue engineering.

Key words: Si₃N₄ bioceramics, 3D-printed scaffolds, BMSCs microgels, Bone regeneration