Taurine-loaded covalent organic frameworks for alleviating post-radiation bone regeneration disorder

Radiation-induced jaw injury, characterized by inflammation, bone damage, and infection, is a frequent complication of radiotherapy for head and neck malignancies. However, effective biomaterials designed based on the microenvironmental characteristics of irradiated jaws for alleviating bone regeneration disorders remain lacking. Taurine (Tau) and hypotaurine metabolism are significantly upregulated in irradiated mandibular stromal cells, and orally administered Tau can markedly promote jaw regeneration. In order to increase local taurine accumulation and augment therapeutic outcomes, this study aimed to develop covalent organic frameworks (COFs) loaded with Tau (Tau-COFs) for localized application to irradiated jaws. Notably, Tau-COFs modulated bone homeostasis and downregulated tartrate-resistant acid phosphatase in the jaws (86.73 %, p<0.0001). Additionally, they promoted macrophage recruitment (49.34 %, p = 0.0026) and M2 polarization (725.11 %, p<0.0001) within irradiated tissues. Irradiated bone marrow mesenchymal stromal cells and macrophages exhibited endocytosis but unirradiated cells did not, suggesting its distinct role in post-irradiation bone repair. The results of plate count assays revealed that 50 μg/mL COFs significantly inhibited two specific pathogens of osteoradionecrosis of the jaws, Staphylococcus aureus (79.20 %, p = 0.0008) and Prevotella intermedia (84.27 %, p = 0.0238), demonstrating its antibacterial properties. Tau-COFs at the same concentration exhibited superior antibacterial abilities on S. aureus (92.80 %, p = 0.0004) and P. intermedia (95.63 %, p = 0.0006) than COFs. In vivo experiments further validated the osteogenic effects and biosafety of Tau-COFs. Overall, the findings of this study identify Tau-COFs as a promising biomaterial for improving radiation-induced bone regeneration disorders, offering significant potential for future clinical applications.