Meiqi Jin, Miao Xia, Tianlin Wang, Yanan Zhao, Da-Li Xu, Dali Xu, Linxuan Wu, Taotao Liu, Leo Li, Dake Xu, Dake Xu, Huazhe Yang, Xiaoqian Xu
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 Zn 2+ /Ce 3+ double-doped whitlockite nanoparticles (Zn 2+ /Ce 3+ -WH) via a biomimetic GelMA template (GM&Zn 2+ /Ce 3+ -WH). These biomimetic GM&Zn 2+ /Ce 3+ -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&Zn 2+ /Ce 3+ -WH exhibited excellent overall performance. In summary, the natural bone-like Zn 2+ /Ce 3+ co-doping strategy endows GM&Zn 2+ /Ce 3+ -WH with immunomodulatory, bacteriostatic, and osseointegrative properties, offering a distinctive and promising approach to re-establishing an immunoregulated osteogenic microenvironment for bone regeneration. • Bioinspired Zn 2+ /Ce 3+ -WH minerals mimic bone, enabling effective osteoimmune regulation and bone regeneration. • Dual Zn 2+ /Ce 3+ ion doping, which remodels the bone immune microenvironment through modulation of the NF-κB signaling pathway. • Hydrogel-based delivery system offers sustaining released ions, fostering good microenvironment for bone regeneration.