Photothermal-responsive dexmedetomidine-loaded MPDA-GelMA hydrogel promotes bone regeneration

The clinical demands for repairing bone defects have not been fully met, as conventional treatments are often limited by drawbacks such as burst drug release and immune rejection. The development of smart biomaterials enabling localized and controlled drug release represents a promising strategy to address these challenges. In this study, a photothermal-responsive hydrogel was fabricated by incorporating dexmedetomidine-loaded mesoporous polydopamine nanoparticles (DEX@MPDA) into gelatin methacryloyl (GelMA). The resulting composite hydrogel exhibited excellent shape adaptability and achieved precise drug release upon irradiation with an 808 nm near-infrared (NIR) laser. The system maintained a local temperature of 40-42 °C, and its photothermal performance showed no significant attenuation after multiple irradiation cycles, effectively overcoming the uncontrolled drug release commonly observed in conventional therapies. In vitro experiments demonstrated that DEX@MPDA exhibits good biocompatibility with rat bone marrow mesenchymal stem cells (rBMSCs) and that near-infrared irradiation effectively promotes cell adhesion and proliferation. Transcriptomic sequencing and western blot analyses further revealed that the composite hydrogel regulated osteogenic differentiation by activating the PI3K/AKT signalling pathway. In vivo evaluation using a rat calvarial defect model confirmed that the composite hydrogel achieved safe and efficient bone repair through its NIR-responsive photothermal properties. This innovative therapeutic strategy, characterised by superior plasticity, photothermal (PTT) performance, biocompatibility, and osteogenic potential, holds great promise for applications in bone tissue engineering and regenerative medicine.