Core–shell microneedles with MMP/pH-triggered release for periodontitis bone repair

Periodontitis is a localized inflammatory condition triggered by periodontal pathogens and marked by uneven loss of alveolar bone. The clash between the persistent inflammatory environment and requirement for bone regeneration complicates the treatment of periodontitis. To address this issue, we developed a core-shell microneedles drug delivery system responsive to both high matrix metalloproteinase (MMP) expression and a local acidic microenvironment, which are the pathological characteristics of periodontal lesions. This system utilizes a dual mechanism of MMP hydrolysis and pH triggering to achieve precise spatiotemporal release of therapeutic molecules and multimodal synergistic treatment. The microneedles system utilizes a layered core-shell design: the outer shell is loaded with glycyrrhizic-acid-functionalized MIL-101, which encapsulates the core layer containing mesenchymal stem cell-derived exosomes. In the initial treatment phase, when MMP levels are elevated and pH is low, the system rapidly releases drug-loaded nanoparticles from the microneedle shell, thereby significantly inhibiting the pro-inflammatory cytokine storm and alleviating excessive oxidative stress. Subsequently, exosomes released from the microneedles core in a sustained manner contribute to rebalancing the immune microenvironment and inducing new bone formation within periodontal defects. This novel drug delivery strategy combines precise drug delivery, immune regulation, and tissue regeneration of periodontitis-associated bone defects by integrating pathological microenvironmental responsiveness, thereby overcoming the challenge of graded drug release in the complex oral environment and providing an innovative therapeutic paradigm for clinical treatment.