Theories of mechanoregulation have been integrated in computational models of mechanobiological experiments to test hypotheses of mechanobiology. It is believed that computational models need to be improved by considering the variability reported in animal experiments in order to enhance corroboration of hypotheses and to enable the use of computational models in practical bioengineering applications.

The sources of variability in the mechanoregulated tissue differentiation process were investigated in simulations of a bone chamber experiment that allowed comparison with experimental data. The simulations predicted the load-dependent tissue differentiation process inside the chamber. However, environmental variation and stochastic cell activities could not capture the full variability found among the specimens in the experiment. Genetic variability was identified as variability in the expression of mechanosensitive genes, which control cell activities. The simulations captured the variability observed experimentally, suggesting that the differing cellular response to the mechanical environment could be a reason for the different outcomes found when tissue engineering constructs are used in a population.

Mechanoregulation at population level was investigated in an evolutionary simulation of the emergence of endochondral ossification. The results show that the emergence of mechanosensitive genes, when favoured by natural selection, could have led to the emergence and establishment of new differentiation processes such as the endochondral ossification pathway, which exists with variability in a population.

This work concludes that evolution has led to the rise of mechanosensitive genes which are the main source of variability in the mechanoregulated tissue differentiation process.