Potential of Low-Dose Carbon Monoxide in Promoting Osseointegration.

Successful osseointegration is crucial for dental implant stability, yet it remains challenging due to adverse local microenvironments, particularly infection and inflammation. While carbon monoxide (CO) has been recognized as a promising gaseous signaling molecule with diverse therapeutic properties, its clinical application faces significant limitations due to dose control challenges. To address this issue, we developed a polyetheretherketone (PEEK)-based photo-responsive implant system with surface-immobilized manganese carbonyl nanocrystals, enabling precisely controlled near-infrared light-triggered CO release. The system demonstrated efficient photoresponsiveness, achieving 13.83 ± 1.16 μM CO release within 10 min under optimal illumination conditions. In vitro studies revealed that low-dose CO significantly enhanced bone marrow mesenchymal stem cell osteogenic differentiation with upregulated expression of key markers, including Runx2, ALP, and OCN. In a rat femoral defect model, implants with controlled CO release exhibited significantly improved osseointegration. Comprehensive biosafety assessments confirmed the system's excellent biocompatibility without detectable organ toxicity. This research provides compelling evidence for controlled low-dose CO as an innovative strategy to enhance osseointegration, offering new possibilities for dental and orthopedic implant development, particularly for challenging clinical scenarios with compromised bone healing.