Under a high-sugar environment, the accumulation of AGEs and ROS causes osteogenesis-related cells to age and die, slowing down bone defect repair. Researchers assembled tannic acid, copper ions, and PTHrP-1 into TCP nanozymes, using a metal–polyphenol network to mimic multiple enzyme activities and enhance them under near-infrared light, achieving local sugar consumption and ROS clearing. They then loaded TCP into CAT hydrogels crosslinked with OSA and CMC-PBA. Using glucose/pH responsiveness and NIR triggering, Cu²⁺ and PTHrP-1 are released differently, aligning antibacterial, pro-angiogenic, and pro-osteogenic actions with the stages of repair, targeting the high-sugar bone defect microenvironment.  

In vitro, the CAT hydrogel maintained mitochondrial stability, reduced ROS, and helped BMSCs recover activity and osteogenic differentiation under high glucose. RNA sequencing suggested that the PI3K/AKT/mTOR pathway was involved, alleviating high-glucose damage and enhancing osteogenesis-related expression. In vivo, vascularized bone regeneration was faster, making diabetic bone defect repair more significant. Broadly, this platform combines nanozyme catalysis, photothermal regulation, and smart delivery—not just clearing ROS, but releasing active components in stages according to microenvironment signals, providing a useful combined approach for reshaping and regenerating local high-sugar bone defect microenvironments.  

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DOI:10.1016/j.cej.2026.179724