Biofunctional Polyacrylamide Hydrogels using Tetrazole‐Methylsulfone Comonomer for Thiol Conjugation

Abstract Biofunctionalized polyacrylamide (PAAm) hydrogels are important 2D substrates for studying cell physics and mechanobiology. In this work, an arylmethylsulfone (MS) comonomer is developed that can be incorporated into PAAm gels under aqueous radical polymerization conditions. The resulting hydrogels show similar properties to unmodified PAAm gels, indicating that the comonomer is incorporated without affecting PAAm physical properties. The MS‐containing PAAm hydrogels allow efficient conjugation of thiol derivatized biomolecules and require very low comonomer content (2 mM, 0.18 mol% relative to AAm) and thiol incubation amounts (≥ 0.15 µg per gel) to achieve functional densities that elicit cell responses. Compared to carboxyl‐functionalized PAAm hydrogels, a 10‐fold lower comonomer concentration and a 10‐fold lower ligand feed concentration are sufficient to achieve comparable cell adhesion responses. The new comonomer opens up possibilities for efficient and straightforward biofunctionalization of PAAm hydrogels used in cell biophysical studies.