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Development and characterization of a predictive microCT-based non-union model in Fischer F344 rats

  • Orthopaedic Surgery
  • Published:
Archives of Orthopaedic and Trauma Surgery Aims and scope Submit manuscript

Abstract

Introduction

Non-unions remain a clinical problem and are characterised by the failure to heal after a defined period of time. Current preclinical non-union models apply a wide variety of techniques to diminish intrinsic healing potential deviating from the clinical situation. The aim of this study was to develop and characterise a non-union model in rats using internal plate fixation without the need for additional healing insults, whereby bone healing can be longitudinally assessed using microCT. It was hypothesized that healing/non-unions can be accurately predicted at early time points by microCT.

Materials and methods

Female, skeletally mature Fischer F344 rats received a 2 mm or 1 mm femoral osteotomy, stabilized with either a 2 mm thick plate or a 1.25 mm thick plate. Healing was monitored by microCT over 14 weeks and histological analysis at euthanasia. The mechanical environment was characterised using finite element (FE) modelling and biomechanical testing.

Results

The majority of animals receiving the 2 mm thick plate displayed poor healing responses in both the 2 mm and 1 mm defect size groups. Bone and cartilage formation were markedly improved using the 1.25 mm thick plate. MicroCT could accurately predict bone forming capacity at early time points (3–4 weeks).

Conclusions

The 2 mm thick plating system confers poor healing responses in female Fischer F344 rats, comparable to atrophic non-unions. By reducing plate thickness to increase interfragmentary strain within the defect site healing is improved, leading to borderline healing situations or increased abundance of cartilage tissue present in the defect site with ultimate failure to bridge the defect (hypertrophic non-union). Furthermore, microCT can reliably identify delayed/non-healing animals within 4 weeks, thereby allowing their selective targeting for the testing of novel, clinically relevant treatment strategies in different clinical situations aimed at restoring impaired bone healing.

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Acknowledgements

The authors would like to thank Dr Dirk Nehrbass, Ivan Zderic, Dr Peter Varga and all the members of the Preclinical Facility at ARI Davos for their help with this study. Prof Martin Stoddart is also acknowledged for helpful comments on the manuscript.

Funding

This research was funded by the AO Foundation.

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Author notes

  1. M. Herrmann

    Present address: IZKF Research Group Tissue Regeneration in Musculoskeletal Diseases, University Hospital Würzburg and Orthopedic Center for Musculoskeletal Research, University of Würzburg, Würzburg, Germany

  2. S. Zeiter and K. Thompson contributed equally to this manuscript.

Authors and Affiliations

  1. AO Research Institute Davos, Clavadelerstrasse 8, 7270, Davos-Platz, Switzerland

    M. Hildebrand, M. Herrmann, F. Gieling, D. Gehweiler, D. Mischler, S. Verrier, M. Alini, S. Zeiter & K. Thompson

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  1. M. Hildebrand
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Contributions

MHi, MHe, WAL, FG, DG, DM, SZ and KT conducted experiments, acquired data and performed data analysis. MHi, SV, MA, SZ and KT designed the study. MHi, SZ and KT wrote the manuscript. MA and SV critically revised the manuscript. All authors have read and approve the submitted version of the manuscript.

Corresponding author

Correspondence to K. Thompson.

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Hildebrand, M., Herrmann, M., Gieling, F. et al. Development and characterization of a predictive microCT-based non-union model in Fischer F344 rats. Arch Orthop Trauma Surg 142, 579–590 (2022). https://doi.org/10.1007/s00402-020-03680-4

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  • DOI: https://doi.org/10.1007/s00402-020-03680-4

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