An injectable multi-functional strontium based gentiopicroside hydrogel accelerates bone regeneration via immunomodulation and promoting osteo-/angiogenesis effects

The complex pathological microenvironment of bone defects (resulting from trauma, tumors, or infections) poses significant clinical challenges, wherein adverse conditions (e.g., inflammation and vascular damage) impede bone regeneration and complicate treatment. Although bone grafting remains the primary clinical approach, its therapeutic efficacy is limited under these circumstances. To address this, we developed a gentiopicroside-strontium complex (GPS-Sr) to leverage the synergistic effects of both components, subsequently encapsulating it within a gelatin methacrylate (GelMA) hydrogel to create an injectable GelMA/GPS-Sr system with sustained-release properties. In vitrostudies demonstrated that GPS-Sr promotes osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) via the PI3K/AKT pathway, polarizes M2 macrophages to mitigate inflammation, and enhances angiogenesis. These in vitrofindings were corroborated in vivo, where the GelMA/GPS-Sr hydrogel significantly enhanced bone regeneration in a rat defect model, exhibiting high biocompatibility and achieving a ~ 45% increase in bone volume fraction (BV/TV) compared to the control group, along with a ~ 30% improvement over single-component formulations (GelMA/Sr or GelMA/GPS) at 8 weeks post-implantation. This strategy offers a promising therapeutic approach for complex bone repair.