Graphene oxide-decorated microporous sulfonated polyetheretherketone for guiding osteoporotic bone regeneration.

Recent studies have indicated that the nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome is an ideal therapeutic target for osteoporosis because it affects the differentiation of osteoblasts and osteoclasts. RNA sequencing utilizing multifunctional graphene oxide (GO) nanosheets revealed a correlation between GO nanomaterials and the NLRP3 inflammasome, as well as osteogenic genes in macrophages. This study aimed to construct a bone microenvironment-responsive multifunctional two-dimensional GO coating on the surface of microporous sulfonated polyetheretherketone (SPEEK) via polydopamine modification (SPEEK@PDA-GO). In vitro analysis showed that the SPEEK@PDA-GO implants weakened the STAT3-mediated NLRP3/caspase-1/IL-1β signaling pathway in macrophages and subsequently prevented the formation of an extracellular inflammatory microenvironment, which is crucial for osteoclastogenesis. SPEEK@PDA-GO displayed significantly higher expression of M2 macrophage markers and osteogenic genes, indicating that the multifunctional GO nanosheets could facilitate bone regeneration via their immunomodulatory properties. The ability of SPEEK@PDA-GO to stimulate new bone formation and block bone loss caused by estrogen loss due to ovariectomy was also analyzed. The findings of this study offer valuable information on the possible involvement of the NLRP3 inflammasome in the interaction between the immune system and bone health in patients with osteoporosis.