Development of hydrogels and study the effect of their mechanical properties on podocyte behaviors

Overview & Synopsis

Extracellular matrix (ECM), non-cellular component, regulates and maintains the main biological activities of cells such as cellular survival, proliferation and differentiation. Recently, hydrogels scaffolds have shown a remarkable advancement as candidates for tissue engineering and regenerative medicine. Hydrogels are defined as hydrophilic polymer network having the ability to hold a large amount of water and biological fluid. Various natural and synthetic hydrogels have been studied and developed in many tissue regeneration purposes. They provide an appropriate mechanical support, chemical and biological cues mimicking the native extracellular matrix (ECM). These artificial matrices characteristics contribute to induce the cellular functions as adhesion, proliferation and differentiation. The thesis aim was to develop polymers based hydrogels and to study the effect of their physical properties on podocyte kidney cells. Synthetic hydrolyzed polyacrylamide based hydrogel (PAAm) was the choice of study where the physical properties can be tailored and tuned over a wide range. These scaffolds have provided elasticity similar to the in vivo glomerular basement membrane (GBM) and have shown a suitable candidate for the regulation of podocyte functions. Moreover, the development of synthetic and biologic hybrid hydrogels was able to mimic the biological and mechanical properties of native ECM. The combination of gelatin methacrylate and acrylamide (GelMA-AAm) based hydrogels have been investigated and has shown tunable mechanical properties mimicking the native kidney GBM elasticity and a significant attachment of podocytes without any surface functionalization with adhesion proteins. This work permits to investigate the cellular physiology and to develop kidney-on-chip in order to study the functions of kidney on both healthy and diseased states.