Abstract

Vascular compression and concomitant hypoxia exacerbate trigeminal neuralgia (TN), yet current therapies rarely target both pathologies. We developed a photosynthetic nerve guide conduit (SFM‐Gel) by embedding auto fluorescent microalgae in silk fibroin hydrogel, enabling simultaneous mechanical decompression and oxygen release. The construct exhibited suitable mechanical properties, tunable oxygen generation, and excellent biocompatibility. Under hypoxia, SFM‐Gel promoted neuronal cell proliferation and function by reducing ROS and restoring mitochondrial activity, while downregulating HIF‐1α and ATP/P2×3 pathways. In a rat TN model, auto fluorescent SFM‐Gel implantation alleviated mechanical allodynia, repaired nerve morphology, and suppressed BDNF/NGF and ATP/P2×3 inflammatory signaling. Transcriptomic analysis confirmed modulation of hypoxia/ROS/NF‐κB pathways during immune/inflammatory responses to compression. This integrated decompression‐oxygenation strategy offers a transformative therapy for TN.