Variability observed in mechano-regulated in vivo tissue differentiation can be explained by variation in cell mechano-sensitivity

Research output: Contribution to journalArticle

Abstract

Computational simulations of tissue differentiation have been able to capture the main aspects of tissue formation/regeneration observed in animal experiments—except for the considerable degree of variability reported. Understanding and modelling the source of this variability is crucial if computational tools are to be developed for clinical applications. The objective of this study was to test the hypothesis that differences in cell mechano-sensitivity between individuals can explain the variability of tissue differentiation patterns observed experimentally. Simulations of an experiment of tissue differentiation in a mechanically loaded bone chamber were performed. Finite element analysis was used to determine the biophysical environment, and a lattice-modelling approach was used to simulate cell activity. Differences in cell mechano-sensitivity among individuals were modelled as differences in cell activity rates, with the activation of cell activities regulated by the mechanical environment. Predictions of the tissue distribution in the chambers produced the two different classes of results found experimentally: (i) chambers with a layer of bone across the chamber covered by a layer of cartilage on top and (ii) chambers with almost no bone, mainly fibrous tissue and small islands of cartilage. This indicates that the differing cellular response to the mechanical environment (i.e., subject-specific mechano-sensitivity) could be a reason for the different outcomes found when implants (or tissue engineered constructs) are used in a population.

Details

Authors
Organisations
External organisations
  • Trinity College Dublin
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Orthopedics

Keywords

  • Mechano-regulation, Mechanobiology, Inter-specimen variability, FE-model, Lattice model
Original languageEnglish
Pages (from-to)1051-1058
JournalJournal of Biomechanics
Volume44
Issue number6
Publication statusPublished - 2011
Publication categoryResearch
Peer-reviewedYes