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Annals of Biomedical Engineering

, Volume 44, Issue 12, pp 3446–3459 | Cite as

Unravelling the Role of Mechanical Stimuli in Regulating Cell Fate During Osteochondral Defect Repair

  • Adam O’Reilly
  • Daniel J. Kelly
Article

Abstract

We have previously developed a computational mechanobiological model to explore the role of substrate stiffness and oxygen availability in regulating stem cell fate during spontaneous osteochondral defect repair. This model successfully simulated many aspects of the regenerative process, however it was unable to predict the spatial patterns of endochondral bone and fibrocartilaginous tissue formation observed during the latter stages of the repair process. It is hypothesised that this was because the mechanobiological model did not consider the role of tissue strain in regulating specific aspects of chondrocyte differentiation. To test this, our mechanobiological model was updated to include rules whereby intermediate levels of octahedral shear strain inhibited chondrocyte hypertrophy, while excessively high octahedral shear strains resulted in the formation of fibrocartilage. This model was used to simulate spontaneous osteochondral defect repair, where it correctly predicted the experimentally observed patterns of bone formation. Overall the results suggest that oxygen availability regulates chondrogenesis and endochondral ossification during the early phases of osteochondral defect repair, while direct mechanical cues play a greater role in regulating chondrocyte differentiation during the latter stages of this process. In particular, these results suggest that an appropriate loading regime can assist in promoting the development of stable hyaline cartilage during osteochondral defect repair.

Keywords

Osteochondral defect Spontaneous repair Computational modelling Tissue differentiation Mechanical stimuli 

Notes

Acknowledgments

Funding was provided by a European Research Council Starter Grant (StemRepair – No. 258463).

Conflict of Interest

Grants from the European Research Council are reported. There are no other conflicts of interest pertaining to this study.

Supplementary material

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Copyright information

© Biomedical Engineering Society 2016

Authors and Affiliations

  1. 1.Trinity Centre for Bioengineering, Trinity Biomedical SciencesTrinity College DublinDublinIreland
  2. 2.Department of Mechanical and Manufacturing Engineering, School of EngineeringTrinity College DublinDublinIreland
  3. 3.Advanced Materials and Bioengineering Research Centre (AMBER)Royal College of Surgeons in Ireland and Trinity College DublinDublinIreland

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