Remodeling of the Intra-Conduit Inflammatory Microenvironment to Improve Peripheral Nerve Regeneration with a Neuromechanical Matching Protein-Based Conduit,Advanced Science

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Remodeling of the Intra-Conduit Inflammatory Microenvironment to Improve Peripheral Nerve Regeneration with a Neuromechanical Matching Protein-Based Conduit
Advanced Science ( IF 14.3 ) Pub Date : 2024-03-02 , DOI: 10.1002/advs.202302988
Jia-Yi Wang ₁ , Ya Yuan _{1,

2} , Shu-Yan Zhang ₃ , Shun-Yi Lu ₁ , Guan-Jie Han ₁ , Meng-Xuan Bian ₁ , Lei Huang ₁ , De-Hua Meng ₁ , Di-Han Su ₁ , Lan Xiao _{4,

5} , Yin Xiao _{4,

5,

6} , Jian Zhang ₁ , Ning-Ji Gong ₇ , Li-Bo Jiang ₁

Affiliation

Peripheral nerve injury (PNI) remains a challenging area in regenerative medicine. Nerve guide conduit (NGC) transplantation is a common treatment for PNI, but the prognosis of NGC treatment is unsatisfactory due to 1) neuromechanical unmatching and 2) the intra-conduit inflammatory microenvironment (IME) resulting from Schwann cell pyroptosis and inflammatory-polarized macrophages. A neuromechanically matched NGC composed of regenerated silk fibroin (RSF) loaded with poly(3,4-ethylenedioxythiophene): poly(styrene sulfonate) (P:P) and dimethyl fumarate (DMF) are designed, which exhibits a matched elastic modulus (25.1 ± 3.5 MPa) for the peripheral nerve and the highest 80% elongation at break, better than most protein-based conduits. Moreover, the NGC can gradually regulate the intra-conduit IME by releasing DMF and monitoring sciatic nerve movements via piezoresistive sensing. The combination of NGC and electrical stimulation modulates the IME to support PNI regeneration by synergistically inhibiting Schwann cell pyroptosis and reducing inflammatory factor release, shifting macrophage polarization from the inflammatory M1 phenotype to the tissue regenerative M2 phenotype and resulting in functional recovery of neurons. In a rat sciatic nerve crush model, NGC promoted remyelination and functional and structural regeneration. Generally, the DMF/RSF/P:P conduit provides a new potential therapeutic approach to promote nerve repair in future clinical treatments.

中文翻译：

利用神经力学匹配的基于蛋白质的导管重塑导管内炎症微环境以改善周围神经再生

周围神经损伤（PNI）仍然是再生医学中的一个具有挑战性的领域。神经导管（NGC）移植是 PNI 的常见治疗方法，但 NGC 治疗的预后并不理想，原因是 1）神经力学不匹配和 2）雪旺细胞焦亡和炎症极化巨噬细胞导致的导管内炎症微环境（IME）。设计了一种神经力学匹配的 NGC，由负载有聚（3,4-乙烯二氧噻吩）：聚（苯乙烯磺酸）（P:P）和富马酸二甲酯（DMF）的再生丝素蛋白（RSF）组成，具有匹配的弹性模量（25.1 ± 3.5 MPa) 的周围神经和最高 80% 的断裂伸长率，优于大多数基于蛋白质的导管。此外，NGC 可以通过释放 DMF 逐渐调节导管内 IME，并通过压阻传感监测坐骨神经运动。 NGC 和电刺激的结合可调节 IME，通过协同抑制雪旺细胞焦亡和减少炎症因子释放，将巨噬细胞极化从炎症 M1 表型转变为组织再生 M2 表型，从而支持 PNI 再生，从而导致神经元功能恢复。在大鼠坐骨神经挤压模型中，NGC 促进髓鞘再生以及功能和结构再生。一般来说，DMF/RSF/P:P导管为未来临床治疗中促进神经修复提供了一种新的潜在治疗方法。

更新日期：2024-03-02

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