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 (M w ) 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 (M w 123 ± 4 to 400 ± 20 kDa; M w /M n = 1.5–2.3). Ca-Alg hydrogel sponges were fabricated from these alginates at 10–40 g/L concentrations, and the impact of M w and c on their properties was assessed. Polymer concentration primarily influenced sponge density, while the the 3D-microarchitecture became increasingly well-defined with M w 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 M w 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 M w and concentration in determining Ca-Alg hydrogel performance and provide mathematical correlations to guide optimization toward targeted applications.