Bone loss represents a prevalent pathological feature in skeletal disorders, predominantly due to disrupted osteoclast/osteoblast activities at the bone matrix interface. Although interventions utilizing nanozymes to target reactive oxygen species (ROS) represent a promising therapeutic approach, they often suffer from off-target effects with their focus on the bone microenvironment rather than the cell-bone interface. Here, we proposed a "bone patching" to-stop "bone losing" strategy employing a tailored two-dimensional nanozyme patch (ezPatch) binding to the bone surface. The ezPatch integrates metal-phenolic network coordination and bone-binding ligand modification on copper nanosheets. This design confers high affinity for the bone surface, site-specific ROS scavenging, and oxygen generation via ligand-metal charge-transfer-driven nanozyme activity. In vitro experiments demonstrated that the ezPatch enhanced antioxidant defenses of osteoclasts by upregulating the expression of heme oxygenase 1 and SOD2 and suppressed osteoclastogenesis through inhibition of MAPK signaling and IFN-beta/STAT1/STAT2-mediated differentiation. In vivo assessments using murine models of osteoporosis and periodontitis revealed that ezPatch significantly attenuated proinflammatory cytokine levels and mitigated bone loss by restoring osteoclast/osteoblast homeostasis. This research introduces a bone-interface-targeted nanozyme-based therapeutic approach for treating bone loss-related pathologies.
[1]Shandong Univ, Sch & Hosp Stomatol, Cheeloo Coll Med, Dept Biomat Periodontol, Jinan, Peoples R China.
[2]Shandong Key Lab Oral Dis, Jinan, Peoples R China.
[3]Shandong Engn Res Ctr Dent Mat & Oral Tissue Regen, Jinan, Peoples R China.
[4]Shandong Prov Clin Res Ctr Oral Dis, Jinan, Peoples R China.
[5]Shandong Univ, Qilu Hosp, Cheeloo Coll Med, Adv Med Res Inst,Dept Orthopaed,Ctr Orthopaed, Jinan, Peoples R China.
[6]Nanyang Technol Univ, Sch Chem Chem Engn & Biotechnol, Singapore, Singapore.
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