title: A novel nano-copper-bearing stainless steel with reduced Cu(2+) release only inducing transient foreign body reaction via affecting the activity of NF-κB and Caspase 3.
abstract: Foreign body reaction induced by biomaterials is a serious problem in clinical applications. Although 317L-Cu stainless steel (317L-Cu SS) is a new type of implant material with antibacterial ability and osteogenic property, the foreign body reaction level still needs to be assessed due to its Cu(2+) releasing property. For this purpose, two macrophage cell lines were selected to detect cellular proliferation, apoptosis, mobility, and the secretions of inflammatory cytokines with the influence of 317L-Cu SS. Our results indicated that 317L-Cu SS had no obvious effect on the proliferation and apoptosis of macrophages; however, it significantly increased cellular migration and TNF-α secretion. Then, C57 mice were used to assess foreign body reaction induced by 317L-Cu SS. We observed significantly enhanced recruitment of inflammatory cells (primarily macrophages) with increased TNF-α secretion and apoptosis level in tissues around the materials in the early stage of implantation. With tissue healing, both inflammation and apoptosis significantly decreased. Further, we discovered that NF-κB pathway and Caspase 3 played important roles in 317L-Cu SS induced inflammation and apoptosis. We concluded that 317L-Cu SS could briefly promote the inflammation and apoptosis of surrounding tissues by regulating the activity of NF-κB pathway and Caspase 3. All these discoveries demonstrated that 317L-Cu SS has a great potential for clinical application.
authors.affiliation: Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedics, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, People's Republic of China.
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.affiliation: Institute of Metal Research, Chinese Academy of Sciences, Shenyang, People's Republic of China.
authors.forename: Ling
authors.initials: L
authors.lastname: Ren
authors.affiliation: Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedics, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, People's Republic of China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Tang
authors.affiliation: Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedics, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, People's Republic of China.
authors.forename: Kerong
authors.initials: K
authors.lastname: Dai
authors.affiliation: Institute of Metal Research, Chinese Academy of Sciences, Shenyang, People's Republic of China.
authors.forename: Ke
authors.initials: K
authors.lastname: Yang
authors.affiliation: Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedics, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, People's Republic of China.
authors.forename: Yongqiang
authors.initials: Y
authors.lastname: Hao
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism*; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003300:Copper / Q000737:chemistry*; D005549:Foreign-Body Reaction / Q000378:metabolism / Q000473:pathology*; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism*; D053758:Nanoparticles / Q000737:chemistry*; D019919:Prosthesis Implantation; D000067996:RAW 264.7 Cells; D015398:Signal Transduction / Q000187:drug effects; D013193:Stainless Steel / Q000737:chemistry*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D013193:Stainless Steel; D003300:Copper; D053148:Caspase 3
keywords: Caspase 3; NF-κB; apoptosis; foreign body reaction; inflammation; nano-copper