Characterising and engineering biomimetic materials for viscoelastic mechanotransduction studies.

The mechanical behaviour of soft tissue extracellular matrix is time dependent. Moreover, it evolves over time due to physiological processes as well as aging and disease. Measuring and quantifying the time-dependent mechanical behaviour of soft tissues and materials poses a challenge, partly because of their labile and hydrated nature but also because of the lack of a common definition of terms and understanding of models for characterising viscoelasticity. Here we review the most important measurement techniques and models used to determine the viscoelastic properties of soft hydrated materials - or hydrogels - underlining the difference between viscoelastic behaviour and the properties and descriptors used to quantify viscoelasticity. We then discuss the principal factors which determine tissue viscoelasticity in vivo and summarise what we currently know about cell response to time-dependent materials, outlining fundamental factors that have to be considered when interpreting results. Particular attention is given to the relationship between the different time scales involved (mechanical, cellular and observation time scales), as well as scaling principles, all of which must be considered when designing viscoelastic materials and performing experiments for biomechanics or mechanobiology applications. From this overview, key considerations and directions for furthering insights and applications in the emergent field of cell viscoelastic mechanotransduction are provided.