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 have developed an engineered core-shell microneedle (MN) patch that enables the staged release of doxycycline and simvastatin to achieve coordinated 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 relieving negative regulation of Wnt signaling while suppressing NF-κB signaling and 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.