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Liu, G.* ; Li, S.* ; Deng, B.* ; Huo, L.* ; Bai, H.* ; Jiang, S.* ; Zhou, Y.* ; Pei, Z.* ; Kimna, C. ; Zhao, Y.* ; Xu, L.* ; Li, J.* ; Mu, X.* ; Song, J.*

Phase-separated anisotropic PVA hydrogel loaded with tetramethylpyrazine for spinal cord injury repair.

Chem. Eng. J. 506:159944 (2025)

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Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.

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Spinal cord injury (SCI) is a severe central nervous system disorder that disrupts neural circuit integrity, leading to significant motor and sensory dysfunction or loss. Despite the urgent need, no effective treatments are currently available in clinical practice. Tetramethylpyrazine (TMP), a compound extracted from the plant Ligusticum wallichii, has shown therapeutic potential for SCI, but its efficacy is constrained by the blood-spinal cord barrier and a short half-life. To address this limitation, we developed a polyvinyl alcohol (PVA) hydrogel with an oriented porous structure (TMP/OPH) designed to achieve sustained, localized TMP delivery at the injury site. The TMP/OPH was synthesized via a combined sol–gel transition and freeze-casting method, which enables physical gelation of PVA without additional crosslinking agents, making it a simple, and safe approach that enables the gel to revert to sol upon heating for complete recyclability. TMP/OPH not only functions as a local drug delivery system but also features an anisotropic porous structure that supports axonal regeneration and synaptic reconstruction at the injury site. Mechanistic studies revealed that TMP/OPH, through the sustained TMP release in the early stages of SCI, regulates the TNF signaling pathway, promotes M2 polarization of microglia, suppresses neuroinflammation, and improves the local microenvironment, thus creating favorable conditions for nerve repair. Long-term therapeutic effects, including axonal regeneration, synaptic reconstruction, reduction of glial scar, and improved motor function further support TMP/OPH as a promising therapeutic strategy for SCI repair.

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