Emergence of Anionic Counterparts of Divalent Metal Salts as the Fine-Tuners of Alginate Hydrogel Properties for Tissue Engineering and Drug Delivery Applications

The role of anionic counter ions of divalent metal salts in alginate gelation and hydrogel properties was thoroughly investigated. Three anions were selected from the Hofmeister series viz. sulphates, acetates and chlorides paired in all permutations and combinations with calcium, zinc and copper divalent metals. Spectroscopic analysis revealed the presence of anions and their interaction with the metal atoms post-gelation. Data showed gelation time and other hydrogel properties were mostly governed by the cations. However, subtle yet significant variations in viscoelastic, water-uptake, drug-release and cytocompatibility properties were anion dependent in a cationic group. Computational modelling study showed metal-anion-alginate configurations were energetically more stable than metal-alginate models. The in vitro and in silico studies conclude that acetate anions precede the chlorides in the drug-delivery, swelling, and cytocompatibility fronts, followed by sulphate anions in each cationic group. Overall, the data provided affirmation that anions are integral part of the metal-alginate complex. Furthermore, anions offer a novel option to further fine-tune the properties of alginate hydrogels for tissue engineering and drug delivery applications. Moreover, extensive exploration of this novel avenue would enhance the usability of alginate polymers in pharma, environmental, biomedical and food industries.