Sterilization is essential for hydrogel-based biomaterials, but it can also determine the final material state. This study used ionically crosslinked alginate hydrogels as a model system to evaluate sterilization as a coupled process linking microbial inactivation and hydrogel structural reorganization. Steam sterilization, gamma irradiation, ethylene oxide (EtO), ultraviolet (UV) irradiation, and high hydrostatic pressure (HHP) treatment were assessed within the same model system. Microbiological effectiveness was assessed using surface- and matrix-associated contamination models, while structural responses were evaluated by rheology, dimensional changes, and swelling behavior. Steam sterilization, gamma irradiation, EtO, and selected HHP conditions resulted in no detectable microbial growth under the tested conditions, whereas UV irradiation was insufficient to eliminate detectable growth from matrix-associated contamination. However, microbiologically effective treatments produced distinct material profiles. Steam generated a compact and stiff hydrogel state, gamma irradiation produced softened but deformation-tolerant networks, EtO caused pronounced dimensional alteration and high deformability, and HHP produced softened, water-accessible hydrogels with parameter-dependent responses. These findings show that sterilization method selection should integrate microbial inactivation with the final structural state required for application-specific hydrogel performance.
Kaufelde et al. (2026) studied this question.