Microneedle patches with antimicrobial and immunomodulating properties for periodontal regeneration

• Development of a microneedle patch system for targeted delivery of therapeutic agents to periodontal tissues, enabling minimally invasive treatment. • Enhances tissue repair and regeneration by modulating the immune response, promoting a pro-healing environment in the periodontal pocket. • Combines antimicrobial and immunomodulating properties to address both infection control and tissue regeneration in periodontal disease. Periodontitis is a widespread chronic inflammatory disorder resulting from bacterial infection combined with immune response dysregulation, typically characterized by alveolar bone destruction and subsequent tooth displacement or loss. In this research, we engineered a multifunctional microneedle system integrating M2 macrophage-derived exosomes (M2-exos) with copper-doped zeolitic imidazolate framework-8 (Cu@ZIF-8) nanoparticles. This microneedle approach facilitates targeted delivery of therapeutic agents, thereby improving drug utilization efficiency and simultaneously mitigating potential systemic adverse effects. Meanwhile, Cu@ZIF-8 nanoparticles exhibit robust antimicrobial activity, significantly lowering bacterial populations within periodontal sites. Meanwhile, exosomes derived from M2 macrophages effectively induce macrophage polarization towards the anti-inflammatory M2 phenotype, consequently reducing the secretion of pro-inflammatory factors. This synergistic mechanism promotes a transition from a severe inflammatory microenvironment to a regenerative milieu favorable for periodontal bone tissue restoration. Both in vitro and in vivo results substantiate the promising application of microneedle systems in periodontal regeneration. Consequently, the integration of exosomes with nanotechnology holds great promise for addressing inflammation-related diseases and offers substantial theoretical foundations as well as technical support for future clinical applications.