Core-shell microneedles Co-loaded with simvastatin and doxycycline for combined anti-infection and osteogenesis in diabetic periodontitis

Diabetic periodontitis remains a formidable clinical challenge characterized by persistent infection, oxidative stress, and impaired alveolar bone regeneration. Here, we develop an intelligent core-shell microneedle (MN) patch that enables spatiotemporally programmed co-delivery of doxycycline and simvastatin to achieve synchronized antibacterial and osteogenic effects within periodontal lesions. The outer polyvinyl alcohol (PVA) shell rapidly dissolves upon insertion into gingival tissue, enabling burst release of doxycycline for immediate bacterial eradication. Subsequently, the polyvinylpyrrolidone (PVP) core, loaded with simvastatin-encapsulated polydopamine nanoparticles (Sim@PDA NPs), provides sustained release, leveraging the intrinsic reactive oxygen species (ROS)-scavenging capacity of PDA to mitigate local oxidative stress and promote osteogenic differentiation. A silk fibroin backing layer ensures long-term doxycycline release, preventing bacterial recolonization and maintaining a regenerative microenvironment. In vitro, Doxy/SIM-MNs exhibited potent antibacterial and antibiofilm activity against Porphyromonas gingivalis and Staphylococcus aureus, excellent cytocompatibility, and robust induction of alkaline phosphatase activity, mineralized nodule formation, and osteogenic gene expression in mesenchymal stem cells. In a rat model of diabetic periodontitis, Doxy/SIM-MNs markedly reduced inflammatory destruction, enhanced alveolar bone regeneration, and reestablished periodontal homeostasis by activating Wnt signaling while suppressing NF-κB–mediated apoptosis. This hierarchically staged microneedle platform offers a clinically translatable strategy for the integrated management of infection, inflammation, and bone regeneration in diabetes-associated periodontitis and other chronic inflammatory bone diseases.