Multifunctional Metal-Phenolic Composites Promote Efficient Periodontitis Treatment via Antibacterial and Osteogenic Properties.

Periodontitis, a complex inflammatory disease initiated by bacterial infections, presents a significant challenge in public health. The increased levels of reactive oxygen species and the subsequent exaggerated immune response associated with periodontitis often lead to alveolar bone resorption and tooth loss. Herein, we develop multifunctional metal-phenolic composites (i.e., Au@MPN-BMP2) to address the complex nature of periodontitis, where gold nanoparticles (AuNPs) are coated by metal-phenolic networks (MPNs) and bone morphogenetic protein 2 (BMP2). In this design, MPNs exhibit remarkable antibacterial and antioxidant properties, and AuNPs and BMP2 promote osteogenic differentiation of bone marrow mesenchymal stem cells under inflammatory conditions. In a rat model of periodontitis, treatment with Au@MPN-BMP2 leads to notable therapeutic outcomes, including mitigated oxidative stress, reduced progression of inflammation, and the significant prevention of inflammatory bone loss. These results highlight the multifunctionality of Au@MPN-BMP2 nanoparticles as a promising therapeutic approach for periodontitis, addressing both microbial causative factors and an overactivated immune response. We envision that the rational design of metal-phenolic composites will provide versatile nanoplatforms for tissue regeneration and potential clinical applications.

Sema3A secreted by sensory nerve induces bone formation under mechanical loads.

Bone formation and deposition are initiated by sensory nerve infiltration in adaptive bone remodeling. Here, we focused on the role of Semaphorin 3A (Sema3A), expressed by sensory nerves, in mechanical loads-induced bone formation and nerve withdrawal using orthodontic tooth movement (OTM) model. Firstly, bone formation was activated after the 3rd day of OTM, coinciding with a decrease in sensory nerves and an increase in pain threshold. Sema3A, rather than nerve growth factor (NGF), highly expressed in both trigeminal ganglion and the axons of periodontal ligament following the 3rd day of OTM. Moreover, in vitro mechanical loads upregulated Sema3A in neurons instead of in human periodontal ligament cells (hPDLCs) within 24 hours. Furthermore, exogenous Sema3A restored the suppressed alveolar bone formation and the osteogenic differentiation of hPDLCs induced by mechanical overload. Mechanistically, Sema3A prevented overstretching of F-actin induced by mechanical overload through ROCK2 pathway, maintaining mitochondrial dynamics as mitochondrial fusion. Therefore, Sema3A exhibits dual therapeutic effects in mechanical loads-induced bone formation, both as a pain-sensitive analgesic and a positive regulator for bone formation.