Ipriflavone suppresses NLRP3 inflammasome activation in host response to biomaterials and promotes early bone healing.

AIM: 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 stages 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. MATERIALS AND METHODS: We carried out histological examination as well as analysis of proinflammatory cytokines and NLRP3 inflammasome activation in a tibial implantation mouse model with intra-peritoneal injection of ipriflavone. In addition, we explored the mechanism of ipriflavone in the regulation of NLRP3 inflammasome activation in macrophages. RESULTS: In vivo, ipriflavone ameliorated host inflammatory response related to NLRP3 inflammasome activation at implantation sites, characterized by reductions of inflammatory cell infiltration and proinflammatory cytokine interleukin-1ß 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. CONCLUSIONS: These results revealed an anti-inflammatory role of ipriflavone in NLRP3 inflammasome activation through improving mitochondrial function. This study provides a new strategy for the development of immune-regulated biomaterials and treatment options for NLRP3-related diseases.

Mechanical and Morphological Analysis of Cancer Cells on Nanostructured Substrates.

Cancer metastasis is a major cause of cancer-induced deaths in patients. Mimicking nanostructures of an extracellular matrix surrounding cancer cells can provide useful clues for metastasis. This paper compares the morphology, proliferation, spreading, and stiffness of highly aggressive glioblastoma multiforme cancer cells and normal fibroblast cells seeded on a variety of ordered polymeric nanostructures (nanopillars and nanochannels). Both cell lines survive and proliferate on the nanostructured surface and show more similarity on nanostructured surfaces than on flat surfaces. Although both show similar stiffness on the nanochannel surface, glioblastomas are softer, spread to a larger area, and elongate less than fibroblasts. The nanostructured surfaces are useful for in vitro model of an extracellular matrix to study the cancer cell migratory phenotype.