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雪旺细胞衍生外泌体与甲泼尼龙复合贴剂修复脊髓损伤。

Schwann Cell-Derived Exosomes and Methylprednisolone Composite Patch for Spinal Cord Injury Repair.

机构信息

National Spinal Cord Injury International Cooperation Base, Tianjin Key Laboratory of Spine and Spinal Cord Injury, Department of Orthopedics, Tianjin Medical University General Hospital, Anshan Road 154, Heping District, Tianjin 300052, China.

Department of Orthopedics, Qilu Hospital of Shandong University, Shandong University Centre for Orthopedics, Advanced Medical Research Institute, Shandong University, Jinan, Shandong 250033, China.

出版信息

ACS Nano. 2023 Nov 28;17(22):22928-22943. doi: 10.1021/acsnano.3c08046. Epub 2023 Nov 10.

Abstract

Spinal cord injury (SCI) can cause permanent loss of sensory and motor function, and there is no effective clinical treatment, to date. Due to the complex pathological process involved after injury, synergistic treatments are very urgently needed in clinical practice. We designed a nanofiber scaffold hyaluronic acid hydrogel patch to release both exosomes and methylprednisolone to the injured spinal cord in a non-invasive manner. This composite patch showed good biocompatibility in the stabilization of exosome morphology and toxicity to nerve cells. Meanwhile, the composite patch increased the proportion of M2-type macrophages and reduced neuronal apoptosis in an in vitro study. In vivo, the functional and electrophysiological performance of rats with SCI was significantly improved when the composite patch covered the surface of the hematoma. The composite patch inhibited the inflammatory response through macrophage polarization from M1 type to M2 type and increased the survival of neurons by inhibition neuronal of apoptosis after SCI. The therapeutic effects of this composite patch can be attributed to TLR4/NF-κB, MAPK, and Akt/mTOR pathways. Thus, the composite patch provides a medicine-exosomes dual-release system and may provide a non-invasive method for clinical treatment for individuals with SCI.

摘要

脊髓损伤 (SCI) 可导致感觉和运动功能的永久性丧失,目前尚无有效的临床治疗方法。由于损伤后涉及的病理过程复杂,协同治疗在临床实践中非常迫切需要。我们设计了一种纳米纤维支架透明质酸水凝胶贴片,以非侵入性的方式向受伤的脊髓释放外泌体和甲泼尼龙。该复合贴片在稳定外泌体形态和毒性方面对神经细胞表现出良好的生物相容性。同时,在体外研究中,复合贴片增加了 M2 型巨噬细胞的比例,减少了神经元凋亡。在体内,当复合贴片覆盖血肿表面时,SCI 大鼠的功能和电生理性能得到了显著改善。复合贴片通过巨噬细胞从 M1 型向 M2 型极化抑制炎症反应,并通过抑制神经元凋亡增加神经元的存活。该复合贴片的治疗效果可归因于 TLR4/NF-κB、MAPK 和 Akt/mTOR 通路。因此,该复合贴片提供了一种药物-外泌体双重释放系统,可能为 SCI 患者的临床治疗提供一种非侵入性方法。

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