Characterising the elastic and viscoelastic interaction between the cell and its matrix in 3D: because it takes two to salsa dance

The extracellular matrix (ECM) is a three-dimensional, acellular component of all organs and tissues. The ECM has elastic and viscoelastic properties, quantified through the elastic modulus (i.e. stiffness) and stress relaxation, respectively, that guide cell fate. Stiffness and stress relaxation drive cellular plasticity in homeostasis and disease. Therefore, to represent the mechanics of the ECM in vitro it is necessary to employ models that recapitulate these properties. Among said models are hydrogels: polymeric networks whose mass mainly consists of water. Importantly, hydrogel viscoelasticity remains an understudied property, notably in cell-loaded materials. Hence, this thesis investigated the elastic and viscoelastic properties of diverse cell-free and cell-loaded hydrogels. The hydrogels evaluated in this thesis include organ-derived ECM, gelatine methacryloyl, agarose, human-derived platelet-poor plasma, alginate and pluronic. These hydrogels have tissue engineering and regenerative medicine (TERM) potential. Particular emphasis was placed on investigating and mathematically modelling the elastic and viscoelastic fate of cell-loaded hydrogels. Our data show that increasing polymer concentration tailored hydrogel elasticity and viscoelasticity. Hydrogel architecture, composition and the bonds forming the polymer network dictated hydrogel elasticity and viscoelasticity. Also, cells altered hydrogel stiffness and stress relaxation in a polymer type, hydrogel concentration and time-dependent manner. A generalised Maxwell model of viscoelasticity further revealed cell-induced changes in hydrogel time-dependent mechanics. Overall, this thesis furthers our understanding of cell-matrix biology in vitro. The data presented here also have implications for the TERM field and areas of hydrogel-based research for cellular applications