title: Influence of particulate and dissociated metal-on-metal hip endoprosthesis wear on mesenchymal stromal cells in vivo and in vitro.
abstract: In hip arthroplasty the implants' articulating surfaces can be made of a cobalt-chromium-molybdenum (CoCrMo) alloy. The use of these metal-on-metal (MoM) pairings can lead to the release of wear products such as metallic particles and dissociated metal species, raising concerns regarding their safety amongst orthopedic surgeons and the public. MoM-wear particles are reported to be heterogeneous in their physicochemical properties, are capable of inducing adverse effects on a cellular level and are thought to be involved in relevant clinical problems like aseptic osteolysis. Yet, it remains elusive how MoM-wear affects bone forming cells and their progenitors: bone marrow residing mesenchymal stromal cells (MSCs). This study introduces an assessment of the in vivo exposure to particulate and dissociated Co and Cr and evaluates the effects of MoM-wear on MSCs. The exposure to MoM-wear products in vivo and in vitro leads to a decrease in MSCs' osteogenic matrix mineralization and alkaline phosphatase activity on a cellular and systemic level. In conclusion, MoM-wear products are released in the periprosthetic region and elevate bone marrow Co and Cr concentrations towards levels that impair osteogenic differentiation of MSCs. Therefore, the ongoing use of CoCrMo alloys for articulating surfaces in joint replacement implants needs critical reconsideration.
authors.affiliation: Center for Musculoskeletal Surgery, Charité - Universitätsmedizin Berlin, 10117 Berlin, Germany.
authors.forename: Anastasia
authors.initials: A
authors.lastname: Rakow
authors.affiliation: Julius Wolff Institute, Charité - Universitätsmedizin Berlin, 13353 Berlin, Germany; Berlin-Brandenburg Center for Regenerative Therapies, Charité - Universitätsmedizin Berlin, 13353 Berlin, Germany.
authors.forename: Janosch
authors.initials: J
authors.lastname: Schoon
authors.affiliation: Julius Wolff Institute, Charité - Universitätsmedizin Berlin, 13353 Berlin, Germany; Berlin-Brandenburg Center for Regenerative Therapies, Charité - Universitätsmedizin Berlin, 13353 Berlin, Germany.
authors.forename: Anke
authors.initials: A
authors.lastname: Dienelt
authors.affiliation: Trauma Surgery and Orthopedics, DRK Kliniken Berlin Westend, 14050 Berlin, Germany.
authors.forename: Thilo
authors.initials: T
authors.lastname: John
authors.affiliation: Julius Wolff Institute, Charité - Universitätsmedizin Berlin, 13353 Berlin, Germany; Berlin-Brandenburg Center for Regenerative Therapies, Charité - Universitätsmedizin Berlin, 13353 Berlin, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Textor
authors.affiliation: Julius Wolff Institute, Charité - Universitätsmedizin Berlin, 13353 Berlin, Germany; Berlin-Brandenburg Center for Regenerative Therapies, Charité - Universitätsmedizin Berlin, 13353 Berlin, Germany; Berlin-Brandenburg School for Regenerative Therapies, Berlin, Charité - Universitätsmedizin Berlin, 13353 Berlin, Germany.
authors.forename: Georg
authors.initials: G
authors.lastname: Duda
authors.affiliation: Center for Musculoskeletal Surgery, Charité - Universitätsmedizin Berlin, 10117 Berlin, Germany; Berlin-Brandenburg Center for Regenerative Therapies, Charité - Universitätsmedizin Berlin, 13353 Berlin, Germany; Berlin-Brandenburg School for Regenerative Therapies, Berlin, Charité - Universitätsmedizin Berlin, 13353 Berlin, Germany. Electronic address: carsten.perka@charite.de.
authors.forename: Carsten
authors.initials: C
authors.lastname: Perka
authors.affiliation: Julius Wolff Institute, Charité - Universitätsmedizin Berlin, 13353 Berlin, Germany; Berlin-Brandenburg Center for Regenerative Therapies, Charité - Universitätsmedizin Berlin, 13353 Berlin, Germany; Berlin-Brandenburg School for Regenerative Therapies, Berlin, Charité - Universitätsmedizin Berlin, 13353 Berlin, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Schulze
authors.affiliation: Julius Wolff Institute, Charité - Universitätsmedizin Berlin, 13353 Berlin, Germany; Berlin-Brandenburg Center for Regenerative Therapies, Charité - Universitätsmedizin Berlin, 13353 Berlin, Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: Ode
mesh_terms: D000368:Aged; D000469:Alkaline Phosphatase / Q000097:blood; D001857:Bone Matrix / Q000378:metabolism; D002454:Cell Differentiation; D049109:Cell Proliferation; D002470:Cell Survival; D005260:Female; D006622:Hip Prosthesis / Q000009:adverse effects*; D006801:Humans; D008297:Male; D059630:Mesenchymal Stem Cells / Q000378:metabolism* / Q000473:pathology; D061825:Metal-on-Metal Joint Prostheses / Q000009:adverse effects*; D008875:Middle Aged; D008903:Minerals / Q000378:metabolism; D010012:Osteogenesis; D052638:Particulate Matter / Q000009:adverse effects*
chemical_list: D008903:Minerals; D052638:Particulate Matter; D000469:Alkaline Phosphatase
keywords: Biocompatibility; CoCrMo alloy; Mesenchymal stromal cells; Metal toxicity; Metal-on-metal wear; Total hip arthroplasty