Design and construction of nanoengineered multifunctional microneedles with sustained-release properties for targeted microenvironment remodeling in diabetic bone regeneration

Chronic periodontitis associated with diabetes mellitus (CPDM) presents significant challenges due to an impaired tissue microenvironment characterized by persistent oxidative stress, chronic inflammation, and dysfunction of mesenchymal stem cells (MSCs). Nanotechnology-driven Met@ZIF-8@PDA microneedle (MN) therapeutic platform has been developed that integrates multiple functions and allows for precise modulation. The zeolite imidazolate framework-8 (ZIF-8), possessing an ultra-high specific surface area, serves as an effective drug carrier for loading metformin (Met). Subsequently, biomimetic modification using polydopamine (PDA) enhances both biocompatibility and antioxidant properties. The degradable microneedles integrated with nanoparticles facilitate targeted delivery within periodontal pockets while enabling the sustained release of Met and Zn²⁺ for up to 168 hours. In vitro and in vivo experiments demonstrated the remodeling of the damaged microenvironment through a triple synergistic mechanism: first, the phenolic hydroxyl structure of PDA directly scavenges excess reactive oxygen species (ROS); second, PDA and Met collaboratively enhance the M2/M1 macrophage ratio; third, localized drug delivery via microneedles aids in rescuing osteogenic differentiation of impaired MSCs. Mechanistically, this therapeutic paradigm shift from 'passive repair' to 'active regulation' arises from precise modulation of the JAK-STAT signaling pathway. In conclusion, the remarkable drug delivery capabilities of ZIF-8, when combined with the biomimetic functional modifications of PDAs and the targeted delivery advantages offered by microneedles, pave the way for advancements in CPDM therapy.