Abstract:
Life is a complicated phenomenon assembled by complex biochemical and mechanical processes. Cells are the basic entities of a living organism. Studying the mechanical forces that affects cell behavior during various phases is essential for understanding developmental processes and disease progression. Moreover, such research can provide ways to restore or regenerate damaged organs which is one of the main goals of the tissue engineering field.
In vivo cells are located inside a three-dimensional extracellular matrix (ECM) that houses various proteins and proteoglycans. Cells and ECM exhibit a bidirectional relationship i.e., the properties of ECM affect cells and also the cells can synthesize various proteins which in turn affects the ECM. To control the cellular processes such as differentiation, synthetic mimics of ECMs are used.
Hydrogels are cross-linked networks of hydrophilic polymers that are commonly used as synthetic mimics of ECM. The mechanical properties and water content in hydrogels can be modulated by adjusting the cross-linking ratio. There is a need for development of hydrogel substrates with tunable dissipation properties to study how cells sense and respond to such substrates. Tuning of stiffness and toughness by using double network gels consisting of two polymer networks has been explored for such applications. However, the mechanical properties of such hydrogels are often hindered by swelling. Moreover, development of hydrogels with stable mechanical properties and tuning of dissipation in such hydrogels remains a challenge.
This thesis focusses on the development of hydrogels with tunable mechanical properties in which the elastic and viscous properties can be tuned independently. In this thesis, the influence of polymerizing monomers inside a cross-linked polymer network is explored. The second networks formed through this in-situ polymerization were designed to hydrogen bond with the first cross-linked polymer network. Specifically, acrylic acid and tannic acid as monomers, that polymerize inside a cross-linked gel to form linear poly(acrylic acid) chains and oligomeric poly(tannic acid) respectively were explored. The mechanical properties were investigated using a suite of mechanical characterization including rheology, compression and tensile testing. The structure-property relationships of the tannic acid monomer and oligomer incorporated gels were studied by performing small angle neutron scattering and rheology at different temperatures. The strain-induced birefringence of the gels were studied by performing polarized optical microscopy. Finally, the cytotoxicity of the gels was evaluated, and cell culture was performed on the optimized gels.
Overall, this thesis provides a simple approach to produce hydrogels with tunable dissipation properties and explores the spreading of cells in these gels. The results presented in this thesis has potential in further expanding the fundamental knowledge of cellular mechanotransduction.