Immune regulative GelMA&Zn²⁺/Ce³⁺-whitlockite scaffolds with continuous ions release for bone regeneration.

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 <i>in vitro</i> and facilitated implant-to-bone osteointegration <i>in vivo</i>. 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.