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

M Hildebrand1, M Herrmann1,2, F Gieling1

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

Archives of Orthopaedic and Trauma Surgery
|November 11, 2020
PubMed
Summary

A novel rat model for studying bone non-unions was developed using internal plate fixation. This model accurately predicts healing outcomes with microcomputed tomography (microCT) at early time points.

Keywords:
Delayed unionFracture healingNon-unionOsteotomymicroCT

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Area of Science:

  • Orthopedic research
  • Biomaterials science
  • Skeletal biology

Background:

  • Non-unions represent a significant clinical challenge, characterized by the failure of bone to heal.
  • Existing preclinical models often deviate from clinical scenarios by artificially impairing healing potential.
  • There is a need for clinically relevant models to study non-union and test therapeutic strategies.

Purpose of the Study:

  • To develop and characterize a rat model of bone non-union using internal plate fixation.
  • To assess bone healing longitudinally using microcomputed tomography (microCT).
  • To determine if microCT can predict healing or non-union at early time points.

Main Methods:

  • A femoral osteotomy was created in skeletally mature female Fischer F344 rats.
  • Osteotomies were stabilized with either 2 mm or 1.25 mm thick plates.
  • Bone healing was monitored non-invasively using microCT over 14 weeks, with histological and biomechanical analysis at study endpoint.

Main Results:

  • The 2 mm thick plating system resulted in poor healing responses, mimicking atrophic non-unions.
  • Reducing plate thickness to 1.25 mm improved bone and cartilage formation, leading to borderline or hypertrophic non-unions.
  • MicroCT accurately predicted bone healing capacity by 3-4 weeks.

Conclusions:

  • The 2 mm plating system induces a non-union phenotype in this rat model.
  • Adjusting plate thickness influences healing outcomes and the type of non-union observed.
  • MicroCT is a reliable tool for early identification of delayed healing, enabling targeted interventions for novel treatments.