Harnessing polysialic acid (PSA)-embedded exudate-absorbing hydrogel for on-demand trigeminal neuralgia treatment

A key characteristic of trigeminal neuralgia (TN) is cytokine-enriched exudate and a "reactive oxygen species (ROS) storm" generated from the inflammatory cascade, resulting in demyelination of the sensory root of the trigeminal nerve, tissue swelling, and intense electric shock-like pain. The clinically approved drug carbamazepine (CBZ) is capable of inhibiting pain, reducing inflammatory factors, and alleviating oxidative stress, but its clinical application is restricted by its systemic toxicity. Herein, we developed an exudate-absorbing hydrogel incorporating polysialic acid (PSA) and CBZ (F127@PSA@CBZ) for on-demand TN treatment. Owing to the strong water absorption properties of PSA and F127, the F127@PSA@CBZ hydrogel can quickly absorb the lesion exudate and swell into a larger volume with a looser structure, thus releasing payloads sustainably, such as CBZ and PSA, for approximately 7 days in vivo. The released CBZ can scavenges the ROS storm and inhibits the levels of proinflammatory factors. More importantly, the residual PSA was found to promoted the proliferation of Schwann cells by upregulating the expression of STAT3 and Ki67, contributing to enhanced myelin sheath regeneration in a rat TN model. These findings highlight that the PSA-embedded exudate-absorbing hydrogel has great potential for facilitating the repair of the trigeminal nerve myelin sheath.