Abstract
The complex bone repair microenvironment remains a significant challenge in orthopedics. As pivotal regulators, bioactive metal ions can promote osseointegration by coordinating the bone immune microenvironment. To address this, we engineered Zn2+/Ce3+ double-doped whitlockite nanoparticles (Zn2+/Ce3+-WH) via a biomimetic GelMA template (GM&Zn2+/Ce3+-WH). These biomimetic GM&Zn2+/Ce3+-WH hydrogel scaffolds exhibit excellent antioxidant, significantly activated anti-inflammatory macrophage phenotypes and inhibited osteoclastogenesis. The resulting immune microenvironment favorably promoted osteogenic differentiation in vitro and facilitated implant-to-bone osteointegration in vivo. Additionally, the scaffolds demonstrated potential for post-operative anti-infection activity. Notably, GM&Zn2+/Ce3+-WH exhibited excellent overall performance. In summary, the natural bone-like Zn2+/Ce3+ co-doping strategy endows GM&Zn2+/Ce3+-WH with immunomodulatory, bacteriostatic, and osseointegrative properties, offering a distinctive and promising approach to re-establishing an immunoregulated osteogenic microenvironment for bone regeneration.