Understanding the combinatorial impact of amino acids as bio-linker on rheological behavior of gellan hydrogel blends

Amino acids (AAs) can serve as essential bio-linkers due to their different functional groups, which may facilitate physical cross-linking in hydrogels. The mechanical properties of such hydrogels can be fine-tuned by varying the type and concentration of cross-linking agents. In this study, we developed novel gellan gum (GG) hydrogels by incorporating combinations of native AAs, including ʟ-Arginine, ʟ-Lysine, ʟ-Glutamic acid, and ʟ-Aspartic acid. These hydrogels exhibit thermo-reversible properties attributed to non-covalent interactions, enabling a gel-to-sol transition at temperatures above 37 °C owing to their upper critical solution temperature (UCST). Interestingly, these hydrogels were transparent, suggesting a uniform network structure. Moreover, they display a relatively low swelling capacity (10-25 %), indicating strong electrostatic interactions between AAs and GG. Rheological analyses highlight the significant role of AA combinations in modulating hydrogel behavior, showing improvements in shear-thinning, elasticity, self-healing, creep resistance, and overall mechanical performance. Mathematical modeling further supported these findings. Notably, mixtures containing ʟ-Aspartic acid and ʟ-Glutamic acid exhibited enhanced mechanical strength and stability, highlighting the importance of strategic cross-linker selection. These results demonstrate that tailoring cross-linkers can transform hydrogel properties, enabling the development of innovative materials for industrial applications.