Stimulation-Inhibition of Protein Release from Alginate Hydrogels Using Electrochemically Generated Local pH Changes

The electrochemically controlled release of proteins was studied in a Ca2+-cross-linked alginate hydrogel deposited on an electrode surface. The electrochemical oxidation of ascorbate or reduction of O-2 was achieved upon applying electrical potentials +0.6 or -0.8 V (vs Ag/AgCl/KCl 3 M), respectively, resulting in decreasing or increasing pH locally near an electrode surface. The obtained local acidic solution resulted in the protonation of carboxylic groups in the alginate hydrogel and, as a result, the formation of a hydrophobic shrunken hydrogel film. Conversely, the produced alkaline local environment resulted in a hydrophilic swollen hydrogel film. The release of the proteins was effectively inhibited from the shrunk hydrogel and activated from the swollen hydrogel film. Overall, the electrochemically produced local pH changes allowed control over the biomolecule release process. While the release inhibition by applying +0.6 V was always effective and could be maintained as long as the positive potential was applied, the release activation was different depending on the protein molecular size, being more effective for smaller species, and molecule charge, being more effective for negatively charged species. The repetitive change from the inhibited to stimulated state of the biomolecule release process was obtained upon cyclic application of oxidative and reductive potentials (+0.6 V <-> -0.8 V). The alginate hydrogel film shrinking-swelling as well as the protein release process were studied and visualized using a confocal fluorescent microscope. In order to be observed, an external surface of the alginate film and the loaded protein molecules were labeled with different fluorescent dyes, which then produced colored fluorescent images under a confocal microscope.

Automated summary

This study investigated the electrochemically controlled release of proteins in a Ca2+-cross-linked alginate hydrogel deposited on an electrode surface. By applying different electrical potentials, the pH of the hydrogel could be modified, resulting in the shrinkage or swelling of the hydrogel film. The release of proteins was inhibited or activated depending on the pH changes. The release inhibition was effective with the application of +0.6 V, while the release activation was influenced by the protein size and charge. Cyclic application of oxidative and reductive potentials allowed for the repetitive change between inhibition and activation states. The alginate hydrogel film shrinking-swelling and protein release process were studied using a confocal fluorescent microscope.