Fabrication and characterization of tetra-PEG-derived hydrogels of controlled softness

Tetra-PEG hydrogels are known for their exceptionally homogeneous network structure and high mechanical stability. In this study, we demonstrate how the tetra-PEG framework can be adapted to create hydrogels of widely variable softness, with elastic moduli as low as 1–10 Pa. This is achieved by systematically tuning the ratio of tetra-functional and linear PEG macromers, producing networks with long, linear polymer segments that are intermittently cross-linked. The resulting hydrogels may serve as simple model systems for more complex biological hydrogels. Using small-angle neutron scattering (SANS), dynamic light scattering (DLS), rheometry, and microrheology, we reveal how the ratio of linear and tetra-functional precursor macromers influences the network structure and mechanical properties. These hydrogels, with precisely controllable rheological and structural characteristics, offer a versatile platform for studying the structure–property relationship in hydrogels mimicking the properties of biological systems such as mucus. The introduced principles are general and provide a foundation for designing new hydrogel materials with tailored properties for biomedical applications.