Crosslinking-Dependent Structure-Transport-Function Relationships in Gelatin-Hyaluronic Acid Hydrogels for Wound-Fluid Management

Effective wound-fluid management is essential in medical applications, as dressings must absorb, retain, and regulate excess blood, exudate, and other biological fluids. Gelatin-hyaluronic acid (Gel/HA) hydrogels are promising dressing materials because they provide a hydrated, tissue-mimetic environment and combine the biological functions of both polymers. Their performance depends strongly on the crosslinking strategy, which regulates network architecture, fluid transport, and mechanical integrity. Three Gel/HA networks were prepared by physical association (Network I), glutaraldehyde-mediated covalent crosslinking (Network II), and PEGDA-mediated interpenetrating-network formation (Network III). Molecular interactions, morphology, fluid uptake, and mechanical properties were evaluated within a structure-transport-function framework. The networks exhibited distinct pore structures, with average pore sizes of 21 ± 7, 2.3 ± 0.8, and 9 ± 3 μm and porosities of 74 ± 3, 59 ± 3, and 67 ± 3% for Networks I-III, respectively. Tensile strength increased from 62 ± 5 kPa for Network I to 127 ± 7 kPa for Network II and 215 ± 9 kPa for Network III, while elongation at break increased from 152 ± 9 to 257 ± 12 and 343 ± 14%, respectively. Simulated blood uptake at 240 min reached 483 ± 45, 842 ± 59, and 1285 ± 72% for Networks I-III, respectively. An integrated hydrogel performance index was used as a comparative dimensionless descriptor of selected transport and mechanical properties. Overall, the results show that network formulation yields distinct combinations of pore architecture, fluid transport, and mechanical performance, providing a basis for comparing Gel/HA hydrogel designs for wound management applications that balance fluid management and mechanical properties.