Wireless flexible patch based on ultrasound-responsive SenA@ZIF-8 release for on-demand medication of periodontitis

Periodontitis is a prevalent chronic inflammatory disease that causes progressive periodontal tissue loss and systemic complications. However, conventional therapies often remove biofilms without fully resolving inflammation or regenerating tissue. Here, we report a flexible wireless ultrasonic patch loaded with ZIF-8 nanoparticles containing the anti-inflammatory antioxidant senkyunolide A (SenA@ZIF-8) for on-demand drug release. A piezoelectric transducer converts 1 MHz ultrasound into ≈ 10 V, 9 mA electrical output, heating a tridecanoic acid phase-change matrix to ≈ 43 °C to trigger SenA@ZIF-8 release. In vitro, SenA@ZIF-8 was biocompatible and outperformed free SenA in protecting periodontal ligament stem cells from H₂O₂-induced oxidative damage: it reduced intracellular ROS levels and restored the activity of antioxidant enzymes. In macrophages, ZIF-8 loading enhanced intracellular SenA uptake and markedly suppressed LPS-induced proinflammatory mediator expression while promoting M2 marker expression. In a rabbit model of ligature-induced periodontitis, repeated ultrasonic-triggered SenA@ZIF-8 delivery markedly reduced periodontal inflammation. Micro‑computed tomography (Micro-CT) and histology showed that the device-treated sites exhibited the greatest alveolar bone regeneration and collagen deposition, accompanied by minimal inflammation. This innovative MOF-based ultrasonic patch can relieve oxidative stress and inflammation through minimally invasive, precise, and on-demand drug delivery, thereby promoting periodontal regeneration. This approach has significant translational potential as an adjunct therapy to improve periodontal treatment outcomes and patient compliance.