Specific biological responses of the synovial membrane to carbon nanotubes

Biological evaluation of carbon nanotubes (CNTs) is typically performed in the lung or abdominal cavity; however, biological reactions to CNTs are predicted to be markedly different in other tissues. In applications of CNTs as reinforcement for artificial joints and drug delivery systems, including their use in bone regeneration, the intra-articular synovial membrane makes contact with the CNTs. Herein, we analyzed the reaction of the synovial membrane with multiwalled CNTs (MWCNTs). Injection of MWCNTs into rat knee joints revealed their dose-dependent incorporation into deep synovial membranes and the formation of granulation tissue, without long-term inflammation. MWCNTs were incorporated into human fibroblast-like synoviocytes (HFLSs), with less cytotoxicity than that observed in macrophages (RAW264 cells). Moreover, MWCNTs inhibited the release of cytokines and chemokines from HFLSs. The reaction of the synovial membrane with MWCNTs differed from that observed in other tissues; thus, detailed biological evaluation at each target site is necessary for clinical applications.