Photocuring CsA and bFGF-embedded hemostatic hydrogel promotes recovery from TBI by mitigating ferroptosis and neuroinflammation.

Traumatic brain injury (TBI) causes focal intracranial hemorrhage, neuroinflammation, and gliosis, which contribute to motor dysfunction. Therapies addressing singular aspects of TBI damage have demonstrated limited efficacy in mitigating its comprehensive impact. Here, we investigated the therapeutic efficacy of a combination therapy comprising cyclosporine A (CsA) and basic fibroblast growth factor (bFGF) during the acute phase of TBI, delivered in a hemostatic hyaluronan-based hydrogel (OCHAMA). The OCHAMA hydrogel substantially reduced iron deposition and inhibited key drivers within the ferroptotic pathway in focal mechanical brain injury. CsA and bFGF-embedded OCHAMA (OCHAMA/CF) treatment resulted in a significant reduction in CD8(+) T lymphocyte infiltration and interferon-γ (IFN-γ) secretion, which correlated with attenuated neuroinflammation. TBI rats treated with OCHAMA/CF exhibited enhanced neuronal preservation and reduced lesion volume, which was associated with significant recovery of motor function. This therapeutic approach reshaped the peritraumatic neuroinflammatory microenvironment and facilitated neuron survival, underscoring its potential for widespread clinical applicability.