Chiara Pizzolitto received master’s degree in nanobiotechnology in 2019. Currently she is a second year PhD student at University of Trieste.
Dual cross-link hydrogels with tunable viscoelasticity control stem cell differentiation
Mechanotransduction recapitulates the conversion of external mechanical information into intracellular biochemical response. To this, it was recently recognized that stem cell fate can be markedly influenced by surrounding extracellular matrix (ECM) mechanics. Most of our knowledge in cell mechanobiology has been built using purely elastic materials as model of ECM. However, native tissues do not exhibit purely elastic response but manifest viscoelasticity, that is a time- and frequencydependence to loading. In fact, recent works have proved that stress-relaxation or plasticity, and more broadly, viscosity-driven processes can be considered as potent modulators of stem cell behavior. To recapitulate native tissue mechanics and provide a more realistic ECM model, here we present unprecedented viscoelastic substrates showing adaptable viscoelasticity. In particular, I will present an innovative dual cross-link gel system based on a chitosan derivative, shortly named CTL, assembled via both temporary and permanent cross-linkers. Concepts related to macromolecular chemistry and physics will be disclosed. Of note, temporary junctions are exploited to finely tune material viscoelasticity. I will show how resulting hydrogels result optimal substrates for cell anchoring upon coating with ECM proteins. Though endowed with similar elasticity, a viscositycell function relationship will be unveiled, identifying high viscosity hydrogels as superior materials in fostering stem cell differentiation toward a bone-like phenotype with respect to more elastic counterparts. Taken together, these results lay the groundwork for additional investigations on the role played by substrate viscoelasticity in directing cell-fate decisions.
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