Sustained‐Release Photothermal Microneedles for Postoperative Incisional Analgesia and Wound Healing via Hydrogen Therapy

Effective management of postoperative pain and wound healing presents significant challenges in clinical settings, driving the need for innovative therapeutic approaches. The analgesic and wound healing effects of hydrogen (H₂) have gradually been recognized; however, the lack of efficient hydrogen delivery systems remains a major limitation. This study introduces a novel transdermal drug delivery system, which utilizes sustained-release photothermal microneedles (MNs) to ameliorate incisional pain and accelerate wound healing. Polydopamine (PDA)-modified ZIF-8@ammonia borane (AB) nanoparticles with photothermal conversion properties are designed, along with temperature-responsive QX-314-loaded polycaprolactone (PCL) microspheres for controlled release, which are delivered in vivo by dissolvable MNs. In vitro results showed that PDA@ZIF-8@AB nanoparticles can release H₂ continuously for up to 5 days in an acidic microenvironment, while the photothermal properties of PDA facilitated controlled release of QX-314 through 6 cycles of near-infrared (NIR) exposure. In vivo experiments demonstrated that the MN system provided sustained analgesia for up to 5 days and promoted wound healing in the acidic microenvironment of postoperative incisions. Upon NIR exposure, the photothermal conversion of PDA activated membrane ion channels and induced thermally triggered deformation of PCL@QX-314 microspheres, allowing for on-demand release of QX-314 and targeted neuronal uptake, thus offering personalized analgesia. In vitro cell experiments and in vivo studies confirmed the biocompatibility of the system. This innovative approach not only highlights the dual role of H₂ in pain relief and wound healing but also provides a new personalized treatment strategy for postoperative pain management with promising clinical applications.