Protein-Delivering Polyelectrolyte Complex Hydrogels: Structure, Swelling and Dissolution Characteristics, and...

We demonstrate triblock polyelectrolyte complex (PEC) hydrogels as a model platform for protein delivery and unveil their precisely tunable swelling behaviors. PEC hydrogels self-assemble in water, do not require UV light or organic solvents, and demonstrate easily tunable shear properties. However, for PEC hydrogels to be effectively designed as protein delivery vehicles, it is imperative to understand the influence of protein additives on their microstructure and swelling behavior. Herein, we utilize small-angle X-ray scattering to demonstrate that model proteins, including bovine serum albumin, lipase, human carbonic anhydrase II, and urease, do not perturb the PEC hydrogel microstructure at therapeutically relevant concentrations. The swelling and dissolution characteristics are shown to be precisely controlled by triblock polyelectrolyte (tbPE) end-block length and concentration. Moreover, we demonstrate that PEC hydrogel swelling and dissolution characteristics, as well as their shear moduli, are unaffected by protein inclusion. Finally, we demonstrate tunable protein release in PEC hydrogels by varying tbPE concentration and end-block length, mixing tbPEs of different lengths to create mixed PEC hydrogels, and incorporating a covalent interpenetrated network. Our work provides easily accessible design parameters to achieve the desired protein release characteristics in PEC hydrogels. At the same time, it also provides insights into the influence of charged macromolecules on the microstructure and dynamics of PEC-based self-assemblies.