title: Intramedullary Mg2Ag nails augment callus formation during fracture healing in mice.
abstract: Intramedullary stabilization is frequently used to treat long bone fractures. Implants usually remain unless complications arise. Since implant removal can become technically very challenging with the potential to cause further tissue damage, biodegradable materials are emerging as alternative options. Magnesium (Mg)-based biodegradable implants have a controllable degradation rate and good tissue compatibility, which makes them attractive for musculoskeletal research. Here we report for the first time the implantation of intramedullary nails made of an Mg alloy containing 2% silver (Mg2Ag) into intact and fractured femora of mice. Prior in vitro analyses revealed an inhibitory effect of Mg2Ag degradation products on osteoclast differentiation and function with no impair of osteoblast function. In vivo, Mg2Ag implants degraded under non-fracture and fracture conditions within 210days and 133days, respectively. During fracture repair, osteoblast function and subsequent bone formation were enhanced, while osteoclast activity and bone resorption were decreased, leading to an augmented callus formation. We observed a widening of the femoral shaft under steady state and regenerating conditions, which was at least in part due to an uncoupled bone remodeling. However, Mg2Ag implants did not cause any systemic adverse effects. These data suggest that Mg2Ag implants might be promising for intramedullary fixation of long bone fractures, a novel concept that has to be further investigated in future studies.
  
  
  
  Biodegradable implants are promising alternatives to standard steel or titanium implants to avoid implant removal after fracture healing. We therefore developed an intramedullary nail using a novel biodegradable magnesium-silver-alloy (Mg2Ag) and investigated the in vitro and in vivo effects of the implants on bone remodeling under steady state and fracture healing conditions in mice. Our results demonstrate that intramedullary Mg2Ag nails degrade in vivo over time without causing adverse effects. Importantly, radiographs, μCT and bone histomorphometry revealed a significant increase in callus size due to an augmented bone formation rate and a reduced bone resorption in fractures supported by Mg2Ag nails, thereby improving bone healing. Thus, intramedullary Mg2Ag nails are promising biomaterials for fracture healing to circumvent implant removal.
authors.affiliation: Helmholtz Virtual Institute for Magnesium-based Bio-degradable Materials, Germany; Heisenberg-Group for Molecular Skeletal Biology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; Department of Trauma, Hand and Reconstructive Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Jähn
authors.affiliation: Heisenberg-Group for Molecular Skeletal Biology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; Department of Trauma, Hand and Reconstructive Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Saito
authors.affiliation: Heisenberg-Group for Molecular Skeletal Biology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; Department of Trauma, Hand and Reconstructive Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Hanna
authors.initials: H
authors.lastname: Taipaleenmäki
authors.affiliation: Heisenberg-Group for Molecular Skeletal Biology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; Department of Trauma, Hand and Reconstructive Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Gasser
authors.affiliation: Helmholtz Virtual Institute for Magnesium-based Bio-degradable Materials, Germany; Institute of Materials Research, Helmholtz-Center Geesthacht, Geesthacht, Germany.
authors.forename: Norbert
authors.initials: N
authors.lastname: Hort
authors.affiliation: Helmholtz Virtual Institute for Magnesium-based Bio-degradable Materials, Germany; Institute of Materials Research, Helmholtz-Center Geesthacht, Geesthacht, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Feyerabend
authors.affiliation: Helmholtz Virtual Institute for Magnesium-based Bio-degradable Materials, Germany; Institute of Clinical Chemistry and Laboratory Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Hartmut
authors.initials: H
authors.lastname: Schlüter
authors.affiliation: Helmholtz Virtual Institute for Magnesium-based Bio-degradable Materials, Germany; Department of Trauma, Hand and Reconstructive Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Johannes M
authors.initials: JM
authors.lastname: Rueger
authors.affiliation: Helmholtz Virtual Institute for Magnesium-based Bio-degradable Materials, Germany; Department of Trauma, Hand and Reconstructive Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Lehmann
authors.affiliation: Helmholtz Virtual Institute for Magnesium-based Bio-degradable Materials, Germany; Institute of Materials Research, Helmholtz-Center Geesthacht, Geesthacht, Germany.
authors.forename: Regine
authors.initials: R
authors.lastname: Willumeit-Römer
authors.affiliation: Helmholtz Virtual Institute for Magnesium-based Bio-degradable Materials, Germany; Heisenberg-Group for Molecular Skeletal Biology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; Department of Trauma, Hand and Reconstructive Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; Department of Anatomy and Cell Biology, Indiana University School of Medicine, Indianapolis, USA. Electronic address: e.hesse@uke.de.
authors.forename: Eric
authors.initials: E
authors.lastname: Hesse
mesh_terms: D000497:Alloys / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D001858:Bone Nails; D002146:Bony Callus / Q000378:metabolism*; D005264:Femoral Fractures / Q000378:metabolism / Q000601:surgery; D017102:Fracture Healing; D008274:Magnesium / Q000737:chemistry / Q000494:pharmacology; D008297:Male; D008422:Materials Testing; D051379:Mice; D010006:Osteoblasts / Q000378:metabolism; D012834:Silver / Q000737:chemistry / Q000494:pharmacology; D013978:Tibial Fractures / Q000378:metabolism / Q000601:surgery
chemical_list: D000497:Alloys; D012834:Silver; D008274:Magnesium
keywords: Biodegradation; Bone healing; Callus formation; Intramedullary fracture fixation; Mg2Ag alloy