Corynoline and Extracellular Vesicles Co-Loaded Scaffold Accelerates Vascularized Bone Regeneration with Photothermal Stimulation

Bone defect repair remains a major clinical challenge, and effective alternatives to autologous bone grafting are urgently needed due to limitations such as donor site scarcity, immune complications, and high long-term resorption rates. In this study, we developed a near-infrared (NIR)-responsive composite scaffold for the controlled and sustained delivery of corynoline (Cor) and extracellular vesicles (EVs) to enhance bone regeneration. The scaffold was constructed from β-tricalcium phosphate (β-TCP) and coated with bioinspired polydopamine (PDA), which enabled efficient immobilization of Cor and EVs via surface adsorption. The PDA layer endowed the scaffold with photothermal properties, allowing NIR irradiation to trigger and accelerate the release of bioactive factors in a sustained manner for at least 14 days. Cor promoted macrophage polarization from the pro-inflammatory M1 phenotype toward the anti-inflammatory M2 phenotype, thereby reducing excessive reactive oxygen species, while EVs derived from osteogenically induced umbilical cord mesenchymal stem cells enhanced angiogenesis and osteogenesis. The photothermal effect of PDA further synergized with these biofactors to modulate the local microenvironment. Under NIR stimulation, the composite scaffold effectively regulated the immune microenvironment and promoted vascularized bone regeneration. In vivo results demonstrated significantly enhanced new bone formation, accompanied by reduced inflammation, increased endogenous cell recruitment, and accelerated vascularization. Overall, this multifunctional, NIR-responsive scaffold provides a promising strategy for efficient and controlled bone defect repair.