Network Toxicology and Molecular Docking Analysis of Targets and Potential Mechanisms of PEEK-Induced Bone Resorption

Polyetheretherketone (PEEK), a high-performance thermoplastic, is utilized in bone tissue engineering due to its elastic modulus resembling that of human cortical bone. However, toxicological studies on PEEK remain limited. PEEK disrupts bone homeostasis by recruiting macrophages and inducing the aggregation of foreign body multinucleated giant cells, ultimately leading to bone resorption. The lack of effective therapeutic approaches underscores the importance of identifying novel treatments. This study systematically investigated the potential molecular mechanisms underlying PEEK-induced bone resorption using network toxicology, molecular docking techniques, and molecular dynamics simulations. We first conducted a network-based toxicological assessment based on the molecular structure of PEEK. By integrating and screening targets from multiple databases, we identified 139 potential targets associated with PEEK-induced bone resorption and constructed an interaction network diagram of these targets. Gene Ontology (GO)/KEGG enrichment analysis revealed that PEEK may induce bone resorption through pathways such as the PI3K-AKT signaling pathway and TNF signaling pathway. Further analysis using STRING and Cytoscape 3.9.0 software identified 53 core targets, including MAPK3, TNF, IL-6, AKT1, IL-1β, EGFR, and MMP9. We found that enriched highly correlated pathways encompassed core targets, supporting the scientific hypothesis that PEEK induces bone resorption. Furthermore, molecular docking and molecular dynamics simulation results confirmed that PEEK exhibits strong binding affinity with core targets, forming stable complexes. In summary, this study not only reveals the potential biological mechanisms underlying PEEK-induced bone resorption but also provides new evidence for future prevention and treatment of PEEK-induced bone imbalance.