Given that autologous bone graft for bone defects is limited by insufficient supply and morbidity at the donor site, developing biomimetic graft materials as an alternative has gained consistent attention. However, obstacles in designing bone-mimetic materials that could integrate the biomimetic nature of the bone extracellular matrix, osteogenic cells, and osteoinductive ingredients with a fast and convenient strategy still exist. Methods: This study designed and fabricated a mesenchymal stem cell (MSC)-laden, nanohydroxyapatite (HAP), and nanosilicate (SN)-loaded bone mimetic and injectable gelatin-methacryloyl hydrogel (GelMA-HAP-SN) system for bone tissue engineering, and systemically investigated the osteogenic capacity of GelMA-HAP-SN in vitro and in vivo. Results: Introducing HAP enhanced the compositional similarity to the natural bone extracellular matrix, and SN loading endowed the hydrogel with injectable and osteogenic ability. As a result, the GelMA-HAP-SN hydrogel demonstrated an increase in cellular viability, proliferation, and spreading behavior. The GelMA-HAP-SN hydrogel also amplified the embedded MSCs' osteogenic biomarkers' expression and matrix mineralization. Furthermore, the MSC-encapsulated GelMA-HAP-SN hydrogel was injected into rats' critical-sized calvaria defect, and micro-CT and histomorphometry staining results further confirmed its excellent bone regeneration ability. Conclusion: These MSC-loaded GelMA-HAP-SN hydrogels are potential graft materials for bone defect treatment.

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