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The connection between cellular mechanoregulation and tissue patterns during bone healing

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Abstract

The formation of different tissues in the callus during secondary bone healing is at least partly influenced by mechanical stimuli. We use computer simulations to test the consequences of different hypotheses of the mechanoregulation at the cellular level on the patterns of tissues formed during healing. The computational study is based on an experiment on sheep, where after a tibial osteotomy, histological sections were harvested at different time points. In the simulations, we used a recently proposed basic phenomenological model, which allows ossification to occur either via endochondral or intramembranous ossification, but tries otherwise to employ a minimal number of simulation parameters. The model was extended to consider also the possibility of bone resorption and consequently allowing a description of the full healing progression till the restoration of the cortex. Specifically, we investigated how three changes in the mechanoregulation influence the resulting tissue patterns: (1) a time delay between stimulation of the cell and the formation of the tissue, (2) a variable mechanosensitivity of the cells, and (3) an independence of long time intervals of the soft tissue maturation from the mechanical stimulus. For all three scenarios, our simulations do not show qualitative differences in the time development of the tissue patterns. Largest differences were observed in the intermediate phases of healing in the amount and location of the cartilage. Interestingly, the course of healing was virtually unaltered in case of scenario (3) where tissue maturation proceeded independent of mechanical stimulation.

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Acknowledgments

This study was supported by a grant of the German Research Foundation (Collaborative Research Centre “Biomechanics and Biology of Musculoskeletal Regeneration—From Functional Assessment to Guided Tissue Formation”, SFB 760). The authors like to thank Maria Gómez-Benito and Philip Kollmannsberger for fruitful discussions and Oliver Sander for his support with the finite element solver.

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Correspondence to Felix Repp.

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Repp, F., Vetter, A., Duda, G.N. et al. The connection between cellular mechanoregulation and tissue patterns during bone healing. Med Biol Eng Comput 53, 829–842 (2015). https://doi.org/10.1007/s11517-015-1285-8

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