Porosity-Tuned Chitosan–Polyacrylamide Hydrogel Microspheres for Improved Protein Conjugation

We report a robust method to manufacture polyacrylamide-based functional hydrogel microspheres with readily tunable macroporous structures by utilizing a simple micromolding-based technique. Specifically, surface tension-induced droplet formation of aqueous solutions of chitosan and acrylamide in 2D-shaped micromolds followed by photoinduced polymerization leads to monodisperse microspheres. Pore sizes of the microspheres can be readily tuned by simple addition of inert long-chain poly­(ethylene glycol) porogen at low content in the prepolymer solution. The as-prepared chitosan–polyacrylamide microspheres exhibit chemical functionality through chitosan’s primary amines, rapid protein conjugation with selective tetrazine–trans-cyclooctene reaction, and nonfouling property. Combined with the potential to create anisotropic network structures, we envision that our simple fabrication-conjugation method would offer a potent route to manufacture a variety of biofunctionalized hydrogel microentities.