gms | German Medical Science

Deutscher Kongress für Orthopädie und Unfallchirurgie
73. Jahrestagung der Deutschen Gesellschaft für Unfallchirurgie
95. Tagung der Deutschen Gesellschaft für Orthopädie und Orthopädische Chirurgie
50. Tagung des Berufsverbandes der Fachärzte für Orthopädie und Unfallchirurgie

21. - 24.10.2009, Berlin

Histological and radiological characterisation of the MouseFix murine fracture model

Meeting Abstract

  • R. Steck - Queensland University of Technology, Institute of Health and Biomedical Innovation, Brisbane, Australia
  • M. Ueno - Kitasato University Hospital, Orthopaedica and Trauma Surgery, Kitasato, Japan
  • L. Gregory - Queensland University of Technology, Institute of Health and Biomedical Innovation, Brisbane, Australia
  • H. Minehara - Kitasato University Hospital, Emergency Center, Kitasato, Japan
  • M. A. Schuetz - Queensland University of Technology, Institute of Health and Biomedical Innovation, Brisbane, Australia
  • M. Itoman - Kitasato University Hospital, Orthopaedica and Trauma Surgery, Kitasato, Japan

Deutscher Kongress für Orthopädie und Unfallchirurgie. 73. Jahrestagung der Deutschen Gesellschaft für Unfallchirurgie, 95. Tagung der Deutschen Gesellschaft für Orthopädie und Orthopädische Chirurgie, 50. Tagung des Berufsverbandes der Fachärzte für Orthopädie. Berlin, 21.-24.10.2009. Düsseldorf: German Medical Science GMS Publishing House; 2009. DocPO17-326

DOI: 10.3205/09dkou676, URN: urn:nbn:de:0183-09dkou6764

Published: October 15, 2009

© 2009 Steck et al.
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Outline

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Problem: To study the molecular biology of fracture healing, murine fracture models are preferred due to the fully mapped genome and the availability of genetically modified mice. Unfortunately, the mechanics of most established fixation techniques for fractured mouse bones are ill-defined; therefore these models are not ideal to study the influence of the mechanical environment on fracture healing. The "MouseFix" internal fixator (AO Development Institute, Switzerland) appears promising to become a new standard implant to study the molecular biology of murine fracture healing in a well controlled mechanical environment. We performed a collaborative study with two series of experiments at two institutions in Australia and Japan, in order to characterise the new experimental model for its reliability and reproducibility, and with respect to the healing mechanisms and timing of the fracture healing cascade, based on a histological and radiological evaluation.

Methods: Femoral osteotomies were performed in 136 male C57BL/6 mice and stabilised with MouseFix implants in either stiff, or defined, flexible configurations. Healing progression was studied at 10 time points between 3 and 42 days post-surgery. After surgery and after sacrifice, mice were radiographed to confirm the correct implant positioning. After sacrifice, the extracted femora were scanned in a microCT (analysis of volume and distribution of mineralised callus) and processed for decalcified histology. Thin sections were taken as longitudinal, mid-shaft sections or as serial transverse sections for subsequent three-dimensional reconstruction.

Results and conclusion: The surgery was successful in 126 animals; only 10 (7.4%) animals had to be sacrificed due to complications during surgery. Radiographs demonstrated a high reproducibility of implant positioning after surgery and no implant failure or screw loosening during the experimental period. Mineralised callus volume measurements showed significantly higher values for the more flexibly fixed osteotomies (3.66 times greater at 21 days post-fracture, p<0.05), with this difference increasing with longer healing times. The histological evaluation confirmed the lack of a periosteal callus, and exclusively endosteal, intramembraneous bone formation in the bones stabilised with the stiff implants. The bones stabilised with the more flexible internal fixation showed endochondral ossification with extensive, highly asymmetrical, periosteal callus formation.

Our results demonstrate that the MouseFix murine fracture model leads to different healing patterns depending on the flexibility of the chosen plate system, which allows researchers to investigate the efficacy of fracture healing in different ossification modes by selection of the appropriate fixation. A key advantage over other mouse fracture healing models is the improved consistency in surgical technique leading to more uniform results, which may allow a reduction in the sample size needed in future fracture healing studies.