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Individualized cyclic mechanical loading improves callus properties during the remodelling phase of fracture healing in mice as assessed from time-lapsed in vivo imaging

View ORCID ProfileEsther Wehrle, Graeme R Paul, Duncan C Tourolle né Betts, Gisela A Kuhn, View ORCID ProfileRalph Müller
doi: https://doi.org/10.1101/2020.09.15.297861
Esther Wehrle
1Institute for Biomechanics, ETH Zurich, Zurich, Switzerland
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  • For correspondence: esther.wehrle@hest.ethz.ch ram@ethz.ch
Graeme R Paul
1Institute for Biomechanics, ETH Zurich, Zurich, Switzerland
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Duncan C Tourolle né Betts
1Institute for Biomechanics, ETH Zurich, Zurich, Switzerland
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Gisela A Kuhn
1Institute for Biomechanics, ETH Zurich, Zurich, Switzerland
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Ralph Müller
1Institute for Biomechanics, ETH Zurich, Zurich, Switzerland
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  • For correspondence: esther.wehrle@hest.ethz.ch ram@ethz.ch
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Abstract

Fracture healing is regulated by mechanical loading. Understanding the underlying mechanisms during the different healing phases is required for targeted mechanical intervention therapies. Here, the influence of individualized cyclic mechanical loading on the remodelling phase of fracture healing was assessed in a mouse femur defect model. After bridging of the defect, a loading group (n=10) received individualized cyclic mechanical loading (8-16 N, 10 Hz, 5 min, 3x/week) based on computed strain distribution in the callus using animal-specific real-time micro-finite element analysis. Controls (n=10) received 0 N treatment at the same post-operative time-points. By registration of consecutive scans, structural and dynamic callus morphometric parameters were followed in three callus sub-volumes and the adjacent cortex showing that the remodelling phase of fracture healing is highly responsive to cyclic mechanical loading with changes in dynamic parameters leading to significantly larger callus formation and mineralization. Loading-mediated maintenance of callus remodelling was associated with distinct effects on Wnt-signalling-associated molecular targets Sclerostin and RANKL in callus sub-regions and the adjacent cortex. Given these distinct local protein expression patterns induced by cyclic mechanical loading, the femur defect loading model with individualized load application seems suitable to understand the local spatio-temporal mechano-molecular regulation of the different fracture healing phases.

Competing Interest Statement

The authors have declared no competing interest.

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Posted September 19, 2021.
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Individualized cyclic mechanical loading improves callus properties during the remodelling phase of fracture healing in mice as assessed from time-lapsed in vivo imaging
Esther Wehrle, Graeme R Paul, Duncan C Tourolle né Betts, Gisela A Kuhn, Ralph Müller
bioRxiv 2020.09.15.297861; doi: https://doi.org/10.1101/2020.09.15.297861
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Individualized cyclic mechanical loading improves callus properties during the remodelling phase of fracture healing in mice as assessed from time-lapsed in vivo imaging
Esther Wehrle, Graeme R Paul, Duncan C Tourolle né Betts, Gisela A Kuhn, Ralph Müller
bioRxiv 2020.09.15.297861; doi: https://doi.org/10.1101/2020.09.15.297861

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