The efficient prediction of inflammatory osteolysis caused by polylactic acid through network toxicology and...

Polylactic acid (PLA), as a bioplastic, is extensively utilized in bone tissue engineering for its biocompatibility, adaptability and affordability. However, the toxicological research of PLA is still limited. The hydrolysis products of PLA induced inflammatory response which caused inflammatory osteolysis mediated by oxidative damage through the recruitment of macrophages and the accumulation of foreign body multinucleated giant cells, ultimately leading to the failure of bone tissue regeneration. The lack of effective treatments highlights the importance of finding new therapies. This study systematically investigated the potential molecular mechanisms of PLA-induced inflammatory osteolysis by employing network toxicology and molecular docking techniques. We first conducted a network toxicology-based assessment according to the molecular structure of PLA. The result from integrating and screening targets from multiple databases identified 126 potential targets associated with PLA-induced inflammatory osteolysis, and then an interaction network diagram of the targets was constructed. Gene ontology (GO)/KEGG enrichment analysis clarified that PLA may cause inflammatory osteolysis via metabolic pathways and pathways in cancer, as well as lipid and atherosclerosis. Further analysis by STRING and Cytoscape software screened 25 core targets including HSP90AA1, AKT1, SRC, STAT1 and FYN. We found that the enriched highly correlated pathways covered 18 of the 25 core targets, supporting the scientific hypothesis that PLA induces inflammatory osteolysis. Moreover, the results of molecular docking confirmed that PLA displayed a strong binding ability with the core targets and formed stable binding. Taken together, this study not only revealed the potential biological mechanism of PLA-induced inflammatory osteolysis, but also provided new evidence for the future prevention and treatment of PLA-induced inflammation.