Redox-Active Hyaluronan-Ascorbate Hydrogel Shields β-Cells During Encapsulation and Transport-Mimetic Storage
This study reports the development of a redox-active hyaluronan-ascorbate conjugate (HA-Asc) as a building block for β-cell-supportive hydrogels. HA was functionalized with ascorbate via EDC/NHS coupling, retaining radical-scavenging activity and a dominant high-molecular-weight polymer population. In INS-1E β-cells, soluble HA-Asc improved bioenergetic resilience after H2O2 challenge, increasing basal, maximal, and ATP-linked respiration compared to HA and oxidant-only controls. Physically assembled HA/HA-Asc cell-laden hydrogels moderated intracellular oxidative activity after exogenous oxidant exposure. Under room-temperature transport-mimetic storage, HA/HA-Asc formulations reduced intracellular oxidative burden relative to HA alone, and oxygenated storage further limited lactate accumulation associated with hypoxia-driven glycolytic drift. The authors conclude that covalent ascorbate incorporation into HA creates a biofabrication-compatible redox microenvironment that combines HA processability with localized antioxidant function, providing a simple route to improve handling resilience of encapsulated β-cells in transport-relevant settings.