Recent advances in hydrogel therapy for traumatic brain injury

Traumatic brain injury (TBI) remains one of the most devastating neurological disorders, characterized by complex primary mechanical damage and secondary cascades involving inflammation, oxidative stress, and glial scar formation. Conventional therapies offer limited efficacy due to the blood-brain barrier, the inability to reconstruct tissue defects, and poor spatiotemporal drug control. Hydrogels have emerged as a versatile platform for brain repair owing to their high-water content, biocompatibility, tunable mechanics, and injectability. By tailoring their composition and crosslinking mechanisms, hydrogels can mimic the native brain extracellular matrix, fill irregular cavities, and provide mechanical support that matches neural tissue softness. More importantly, functional hydrogels serve as local delivery vehicles for neuroprotective drugs and growth factors, scaffolds for stem cell transplantation, and active regulators of the post-injury microenvironment. Recent advances include bioactive, conductive, and stimuli-responsive hydrogels capable of modulating immune polarization, enhancing angiogenesis, and promoting neurogenesis. Despite encouraging preclinical results, challenges remain in achieving long-term biocompatibility, precise degradation control, and scalable clinical translation. This review summarizes the current progress, underlying mechanisms, and emerging design strategies of hydrogel-based therapies for TBI, highlighting their potential as next-generation biomaterials for neuroregeneration and functional recovery.