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可注射导电水凝胶重塑脊髓损伤后的微环境并模拟神经电信号传递。

Injectable conductive hydrogel remodeling microenvironment and mimicking neuroelectric signal transmission after spinal cord injury.

机构信息

Center for Regenerative Medicine, the Fourth Affiliated Hospital of School of Medicine, and International School of Medicine, International Institutes of Medicine, Zhejiang University, Yiwu, Zhejiang 322000, China.

Dr. Li Dak Sum & Yip Yio Chin Center for Stem Cells and Regenerative Medicine, and Department of Orthopedic Surgery of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310000, China; Zhejiang University-University of Edinburgh Institute, Zhejiang University, Hangzhou, Zhejiang, China 310000.

出版信息

J Colloid Interface Sci. 2024 Aug 15;668:646-657. doi: 10.1016/j.jcis.2024.04.209. Epub 2024 Apr 30.

Abstract

Severe spinal cord injury (SCI) leads to dysregulated neuroinflammation and cell apoptosis, resulting in axonal die-back and the loss of neuroelectric signal transmission. While biocompatible hydrogels are commonly used in SCI repair, they lack the capacity to support neuroelectric transmission. To overcome this limitation, we developed an injectable silk fibroin/ionic liquid (SFMA@IL) conductive hydrogel to assist neuroelectric signal transmission after SCI in this study. The hydrogel can form rapidly in situ under ultraviolet (UV) light. The mechanical supporting and neuro-regenerating properties are provided by silk fibroin (SF), while the conductive capability is provided by the designed ionic liquid (IL). SFMA@IL showed attractive features for SCI repair, such as anti-swelling, conductivity, and injectability. In vivo, SFMA@IL hydrogel used in rats with complete transection injuries was found to remodel the microenvironment, reduce inflammation, and facilitate neuro-fiber outgrowth. The hydrogel also led to a notable decrease in cell apoptosis and the achievement of scar-free wound healing, which saved 45.6 ± 10.8 % of spinal cord tissue in SFMA@IL grafting. Electrophysiological studies in rats with complete transection SCI confirmed SFMA@IL's ability to support sensory neuroelectric transmission, providing strong evidence for its signal transmission function. These findings provide new insights for the development of effective SCI treatments.

摘要

严重的脊髓损伤 (SCI) 会导致神经炎症失调和细胞凋亡,从而导致轴突退变和神经电信号传输的丧失。虽然生物相容性水凝胶常用于 SCI 修复,但它们缺乏支持神经电传输的能力。为了克服这一限制,我们开发了一种可注射的丝素蛋白/离子液体 (SFMA@IL) 导电水凝胶,以在 SCI 后协助神经电信号传输。该水凝胶可以在紫外 (UV) 光下迅速原位形成。丝素蛋白 (SF) 提供机械支撑和神经再生特性,而设计的离子液体 (IL) 提供导电能力。SFMA@IL 在 SCI 修复方面表现出了吸引人的特性,如抗肿胀、导电性和可注射性。在体内,SFMA@IL 水凝胶用于完全横断损伤的大鼠,发现其重塑了微环境,减轻了炎症,并促进了神经纤维的生长。水凝胶还导致细胞凋亡明显减少,并实现了无瘢痕的伤口愈合,在 SFMA@IL 移植中保留了 45.6±10.8%的脊髓组织。完全横断 SCI 大鼠的电生理研究证实了 SFMA@IL 支持感觉神经电传输的能力,为其信号传输功能提供了有力证据。这些发现为有效治疗 SCI 提供了新的思路。

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