Journal Article

Multifunctional polyoxomolybdate cluster loaded into hydrogel for augmented bone regeneration through synergistic immunomodulation and osteogenesis

Jia, Siming, Li, Kehao, Liu, Shihang, Xu, Fan, Chen, Yawen, Wang, Jing, Cao, Jingcheng, Chen, Wei, Zhang, Ya, Du, Xiaofeng, Zhang, Mo, Kang, Kai, Shi, Yuhang, Zhang, Tao

2026

Overview

Fracture nonunion or delayed union presents a significant challenge in orthopedic practice. Bone healing is a complex physiological process that initiates with the modulation of inflammatory immunity and progresses through critical stages, including angiogenesis, osteogenic differentiation, and biomineralization. The intrinsic link among immune homeostasis, bacterial clearance, and osteogenic microenvironments underscores the need for an integrated therapeutic strategy. To address these challenges, we developed a multifunctional molybdenum-based polyoxometalate cluster (Mo-POM) modified with gallic acid (GA). Theoretical and experimental evidence confirms that electron transfer from GA to the Mo-POM cluster narrows the HOMO-LUMO energy gap, enhancing its multi-enzyme mimetic activity for effective reactive oxygen species (ROS) scavenging, thereby remodeling the immune microenvironment. The Mo-POM also exhibits broad-spectrum antibacterial function through synergistic disruption of bacterial membranes and biofilms. To ensure practical applicability and sustained release, the Mo-POM was encapsulated within a gellan gum/nano-hydroxyapatite (GG/nHA) hydrogel scaffold. The resulting Mo-POM@GG/nHA system effectively coordinates early immunomodulation and antibacterial activity with enhanced biomineralization in the bone regeneration process. Although polyoxometalates have demonstrated versatile biochemical properties, their application in bone regeneration remains largely unexplored. This work demonstrates that a single Mo-POM cluster acts as a core modulator, achieving the “three birds with one stone” effect by eliminating inflammation, modulating the immune microenvironment, and boosting osteogenesis, thereby providing a new avenue for designing a new class of integrated biomaterials for orthopedic applications. [Display omitted] •A multifunctional Mo-POM@GG/nHA hydrogel was developed to orchestrate immunomodulation and osteogenesis for bone repair.•Gallic acid modification enhances the multi-enzyme mimicking activity of POM nanoclusters for effective ROS scavenging.•Mo-POM nanoclusters exert broad-spectrum antibacterial activity by disrupting bacterial membranes and biofilms.•The hydrogel provides a bioactive matrix for sustained release of Mo-POM NCs and promotes osteogenic mineralization.•Mo-POM@GG/nHA hydrogel promotes regeneration through immunomodulation, antibacterial activity, and biomineralization.

• Publisher: Elsevier B.V
• Subject: Antioxidative / Bone regeneration / Immunomodulatory / Osteogenic properties / Polyoxometalate