ROS-Scavenging Selenium Nanoparticle Hydrogel Synergizes with Adipose-Derived Stem Cells to Promote Peripheral Nerve Repair

Abstract Peripheral nerve injury (PNI) remains challenging due to oxidative stress and inflammation limiting stem cell therapy. Here, we developed an injectable, ROS-scavenging selenium nanoparticle (SeNP) hydrogel (SeNP-Gel) to protect adipose-derived stem cells (ADSCs) and enhance peripheral nerve repair. SeNP-Gel exhibited excellent biocompatibility, a porous structure, and favorable mechanical properties, effectively scavenging hydrogen peroxide and reducing oxidative stress to improve ADSC survival. In vitro, the hydrogel promoted Schwann cell migration, angiogenesis, and M2 microglial polarization, thereby alleviating neuroinflammation. In a rat sciatic nerve injury model, the ADSCs/SeNP-Gel composite synergistically accelerated axonal regeneration, myelination, and functional recovery, outperforming either component alone. This strategy integrates SeNPs, hydrogel, and ADSCs to coordinate oxidative stress modulation and immune microenvironment remodeling for PNI treatment.