Boronate-crosslinked hyaluronic acid hydrogels with grafting-dependent mechano-redox properties

Reactive oxygen species (ROS) are key regulators of neuronal physiology but contribute to oxidative damage when dysregulated, as in traumatic, ischemic, and inflammatory conditions. Biomaterials capable of replicating the mechanical characteristics of brain extracellular matrix while modulating oxidative stress are therefore of significant interest for neural tissue engineering and in vitro disease modeling. In this study, we functionalized dynamic hyaluronic acid (Ha) hydrogels with 3-aminomethyl phenylboronic acid (PBA) and crosslinked with poly(vinyl alcohol) (PVA) via reversible boronic ester bonds to develop ROS-responsive scaffolds. By varying the degree of PBA grafting, we observed linked feedback governed the mechano-redox properties of Ha-based dynamic hydrogels with the functionalization degree, enabling simultaneous tuning of stiffness, viscoelastic behavior, and antioxidant activity. The developed materials provide a platform for investigating cell responses to mechanically and chemically defined microenvironments and may be useful for modeling oxidative stress-related neuropathological conditions.