Tuning mechanical properties of hydrogels
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Abstract
The properties of the cellular microenvironment are critical for cellular behaviour and are dynamically regulated in living tissues. The mechanical properties of the extracellular matrix (ECM), in particular, are relevant cues influencing attachment, spreading, and phenotypic differentiation of cells. These properties change during healing, aging, or disease states. Natural and synthetic hydrogels used to mimic the extracellular matrix in in vitro cultures need to capture the mechanical properties of the ECM and their changes. In this thesis, different strategies to adjust and dynamically tune the stiffness of synthetic poly(ethyleneglycol) and natural alginate based hydrogels within physiologically relevant ranges are presented. They include different tunable crosslinking mechanisms (catechol chemistry, ionic crosslinking and photoactivatable strategies), polymer architectures (single and interpenetrating networks) and morphologies (hydrogel films and 3D bioprinted scaffolds).
Catechol-terminated poly(ethyleneglycol) (PEG) hydrogels with tunable mechanical properties were developed by introducing electron-donating or electron-withdrawing substituents on the catechol ring. Gel mechanics during gelation was characterized by rheology measurements. The effect of substitution in the final stiffness and the crosslinking kinetics of the hydrogels was studied. Independently variation of these two parameters within desired ranges was successfully achieved by mixing different catechol derivatives and oxidative conditions.
Light-based dynamic regulation of the mechanical properties of catechol-derivatized PEG hydrogels was attempted using photosensitive nitrocatechol derivatives. Synthetic effort was devoted to obtain chromophores with high photosensitivity in order to allow changes in the mechanical properties in the presence of living cells without causing photodamage. Nitrobenzyl chemistry was also applied to dynamically regulate the mechanics of soft alginate hydrogels by using a phototunable calcium chelator. In situ variations in the ionic crosslinking degree of the alginate upon light-induced changes in the concentration of Ca2+ ions was demonstrated.
The long term mechanical stability of ionically crosslinked alginate in cell culture conditions was studied by rheology. Interpenetrating networks (IPNs) of ionically crosslinked alginate and covalently crosslinked polyacrylamide hydrogels with different compositions were developed and the mechanical properties during incubation in different conditions were studied. Stable network compositions with mechanical properties within physiologically relevant ranges were obtained.
Mechanically tunable 3D alginate scaffolds were developed by 3D bioprinting Alginate/Gelatin mixtures. Parameter windows for printability using different compositions, temperature and ionic concentration of the printing bath were identified. 3D scaffolds with enhanced stability in watery media were achieved by using chitosan to build polyionic complex coatings on the scaffold. The physical properties of scaffold were monitored over different temperature ranges.