Lymphatic-Immune Microenvironment Engineering via Rapamycin-Eluting Nanofibers for Meningeal Repair and Neuroprotection in Traumatic Brain Injury Rats.

While current dural repair patches achieve mechanical sealing to prevent cerebrospinal fluid leakage, they fail to address the critical pathological cascades of traumatic brain injury, including structural disruption of meningeal lymphatic vessels and dysregulation of neuroimmune responses. Here, we break this therapeutic stalemate through lymphatic-immune microenvironment engineering using rapamycin-eluting poly(l-lactide-co-ε-caprolactone) nanofibers. This bioactive patch exerts its therapeutic effects through 3 mechanisms: (a) restoring immune homeostasis by modulating the T helper 17/regulatory T cell balance; (b) morphologically normalizing the meningeal lymphatic network; and (c) preventing cerebral tissue adhesion by suppressing fibroblasts proliferation. In rat traumatic brain injury models, 4% rapamycin-loaded poly(l-lactide-co-ε-caprolactone) nanofibers achieved much higher functional recovery and markedly reduced cerebral tissue loss compared to controls. Crucially, it reconstructed the immune microenvironment and normalized the morphology of the meningeal lymphatic system. This study represents a paradigm shift from passive dural closure to active neuroimmunomodulation, offering a neuroprotective therapeutic strategy for traumatic brain injury.