Emerging studies have shown that immune response to biomaterial implants plays a central role in bone healing. Ipriflavone is clinically used for osteoporosis. However, the mechanism of ipriflavone in immune response to implants in early stage of osseointegration remains unclear. In this study, we aimed to investigate the potential role of ipriflavone in early bone healing process and uncover the underlying mechanism.
Histological examination, proinflammatory cytokines, and NLRP3 inflammasome activation were analyzed in a tibial implantation mouse model with intraperitoneal injection of ipriflavone. In addition, we explored the mechanism of ipriflavone in the regulation of NLRP3 inflammasome activation in macrophages.
In vivo, ipriflavone ameliorated host inflammatory response related to NLRP3 inflammasome activation at implantation sites characterized by reductions of inflammatory cells infiltration and proinflammatory cytokine IL-1β levels. Ipriflavone treatment also showed beneficial effects on early osseointegration. Further investigations of the molecular mechanism showed that the suppression of NLRP3 inflammasome acts upstream of NLRP3 oligomerization through abrogating the production of reactive oxygen species (ROS).
These results revealed an anti-inflammatory role of ipriflavone in NLRP3 inflammasome activation through improving mitochondrial function. This research provides a new strategy for the development of immune-regulated biomaterials and treatment options for NLRP3-related diseases.

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