Balancing Charge Density and Hydrophobicity in Polysaccharide Biomaterials to Regulate Cell Behavior

Hydrogel surface properties play an important role in regulating cellular behavior for tissue engineering and biomedical device design application. Alterations in the biointerface can activate specific cellular signals, resulting in different physiological outcomes. Developing a hydrogel system where surface physiochemical characteristics such as stiffness, charge density, and hydrophobicity can be independently tuned would provide significant insights to tailor material-cell interactions at tissue interface for various therapeutic applications. In this study, we synthesized methacrylate and carboxylate dual-functionalized dextran derivatives, and investigated the impact of the intricate balance between hydrogel surface charge density and hydrophobicity on cell behavior. We are leveraging the defined chemical moieties and tunable surface properties of modified dextran hydrogels to probe the impact of our materials on regulating cell adhesion and spreading. By synthetically tuning these two parameters in dextran-based substrates, we revealed that increased surface charge density and decreased hydrophobicity enhance hydrogel surface wettability and prevent cell adhesion. On the contrary, increasing surface hydrophobicity facilitates the adsorption of fibronectin that supports cell adhesion. Our findings suggest an optimized balance between charge density and hydrophobicity that can be engineered to promote desired cell behavior. Imbalances between these two parameters resulted in an inhibition of cell attachment, emphasizing the importance of fine-tuning charge density and hydrophobicity in biomaterial design. This project will differentiate and identify critical chemical characteristics of hydrogel surface properties responsible for cell behaviors and develop a new class of synthetic polysaccharide biomaterials.