A Degradable PEGDA-Dopamine Hydrogel with ROS Scavenging Capacity Supports Flexible Design for Nerve Repair

Peripheral nerve injury remains a significant clinical challenge, with current therapeutic material limited by inadequate degradation control, insufficient oxidative stress management, and poor adaptability to patient-specific contexts. We developed a degradable poly(ethylene glycol) diacrylate-dopamine-acrylamide hydrogel platform that addresses these limitations, enabling tunable bulk degradation with concomitant dopamine release. By systematically varying the ratio of degradable crosslinker poly(ethylene glycol) diacrylate-dopamine, we generated composition-defined degradation profiles spanning 2 months with corresponding dopamine release patterns. The hydrogels exhibited mechanical properties comparable to native peripheral nerves while maintaining exceptional flexibility through multiple bending and torsional cycles. In vitro validation demonstrated that dopamine-releasing hydrogels effectively scavenged intracellular reactive oxygen species in both human Schwann cells and endothelial cells under oxidative challenge, while modulating Schwann cell gene expression in a pattern consistent with a transition from repair toward a pro-remyelination transcriptional profile, and shifting endothelial gene expression toward a pro-angiogenic transcriptional pattern. Using digital light processing bioprinting we fabricated customizable nerve wraps, tubular structures, and microarchitectures with internal channels that directed cell alignment, while controlled FITC-dextran release validated localized delivery capabilities. These findings establish a multifunctional hydrogel platform combining programmable degradation, antioxidant functionality, and cellular microenvironment control for peripheral nerve repair applications.