Biological activities of cells such as survival and differentiation processes are mainly maintained by a specific extracellular matrix (ECM). Hydrogels have recently been employed successfully in tissue engineering applications. In particular, scaffolds made of gelatin methacrylate-based hydrogels (GelMA) showed great potential due to their biocompatibility, biofunctionality, and low mechanical strength. The development of a hydrogel having tunable and appropriate mechanical properties as well as chemical and biological cues was the aim of this work. A synthetic and biological hybrid hydrogel was developed to mimic the biological and mechanical properties of native ECM. A combination of gelatin methacrylate and acrylamide (GelMA-AAm)-based hydrogels was studied, and it showed tunable mechanical properties upon changing the polymer concentrations. Different GelMA-AAm samples were prepared and studied by varying the concentrations of GelMA and AAm (AAm_2.5% + GelMA_3%, AAm_5% + GelMA_3%, and AAm_5% + GelMA_5%). The swelling behavior, biodegradability, physicochemical and mechanical properties of GelMA-AAm were also characterized. The results showed a variation of swelling capability and a tunable elasticity ranging from 4.03 to 24.98 kPa depending on polymer concentrations. Moreover, the podocyte cell morphology, cytoskeleton reorganization and differentiation were evaluated as a function of GelMA-AAm mechanical properties. We concluded that the AAm_2.5% + GelMA_3% hydrogel sample having an elasticity of 4.03 kPa can mimic the native kidney glomerular basement membrane (GBM) elasticity and allow podocyte cell attachment without the functionalization of the gel surface with adhesion proteins compared to synthetic hydrogels (PAAm). This work will further enhance the knowledge of the behavior of podocyte cells to understand their biological properties in both healthy and diseased states.

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