Tailoring calcium-alginate hydrogels: a systematic study of molecular weight and concentration effects

Calcium-Alginate (Ca-Alg) hydrogels with tunable properties are increasingly desired across diverse applications, yet our understanding of how their structure–property relationships determine performance remains limited. Here, we systematically examined alginate molecular weight (Mw) and concentration (c) as key levers to modulate Ca-Alg hydrogel behaviour.Three alginates, spanning low to high viscosity, were fully characterized by Size-Exclusion Chromatography–Triple-Detector-Array (SEC-TDA), revealing distinct molecular weight distributions (Mw 123 ± 4 to 400 ± 20 kDa; Mw/Mn = 1.5–2.3). Ca-Alg hydrogel sponges were fabricated from these alginates at 10–40 g/L concentrations, and the impact of Mw and c on their properties was assessed. Polymer concentration primarily influenced sponge density, while the the 3D-microarchitecture became increasingly well-defined with Mw and c. Apparent porosity remained consistently high (>90%), whereas water-uptake (4–7 g/g) exhibited limited and inconsistent dependence on the parameters. In contrast, mechanical stiffness and degradation kinetics, two critical determinants of hydrogel performance, were strongly and predictably enhanced by higher Mw and c with G′ values in the range 4–260 kPa and residual mass after 30 days in Phosphate-Buffer-Saline varying from about 23% to 66%. Quantitative relationships correlating these properties to polymer chain-length and concentration were established, providing a predictive framework for rational hydrogel design.Biological evaluation demonstrated comparable human dermal fibroblast colonization, proliferation, and collagen-I expression in sponges with the most divergent physicochemical characteristics.Overall, these results offer valuable insights into the roles of alginate Mw and concentration in determining Ca-Alg hydrogel performance and provide mathematical correlations to guide optimization toward targeted applications.