平滑肌细胞外基质修饰小肠粘膜下导管促进周围神经修复

IF 12.8 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials Pub Date : 2025-04-14 DOI:10.1016/j.biomaterials.2025.123346

Ya-Xing Li , Long-Mei Zhao , Xiu-Zhen Zhang , Xi-Kun Ma , Jing-Qi Liang , Ting-Jiang Gan , Heng Gong , Yan-Lin Jiang , Ye Wu , Yu-Ting Song , Yi Zhang , Yue Li , Xiao-Ting Chen , Cong-Hui Xu , Xiang-Yu Ouyang , Jesse Li-Ling , Hui Zhang , Hui-Qi Xie

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引用次数: 0

摘要

开发理想的无细胞神经引导导管（NGC）为快速、成功的神经再生提供良好的微环境仍然存在挑战。蛋白质组学分析显示，来源于平滑肌细胞（SMCs）的细胞外基质（ECM）富含神经相关活性蛋白，并显著丰富了参与神经再生的信号通路。然而，基于smcs衍生的ECM修饰策略的NGCs是否促进神经再生尚不清楚。在这项研究中，我们研究了smcs来源的ECM的神经再生作用，并通过将smcs来源的ECM包覆在小肠粘膜下层（SIS）上，开发了一种新的NGC （MyoNerve）。SMCs-ECM中含有丰富的神经营养因子，通过促进神经元维持相关基因的表达和激活参与神经再生的信号通路，赋予MyoNerve显著的神经再生能力。在体外实验中，MyoNerve在加速血管生成、调节巨噬细胞极化、促进雪旺细胞增殖、迁移和伸长、增强PC12细胞分化、诱导背根神经节神经突生长等方面表现出优异的生物活性。在大鼠坐骨神经10 mm缺损模型中，MyoNerve通过促进血管生成、雪旺细胞和神经元的增殖和迁移、轴突再生、髓鞘再生和神经功能恢复，显示出巨大的神经功能再生潜力。

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Smooth muscle extracellular matrix modified small intestinal submucosa conduits promote peripheral nerve repair

Challenges still exist to develop an ideal cell-free nerve guidance conduit (NGC) providing a favorable microenvironment for rapid and successful nerve regeneration. Proteomic analysis revealed that extracellular matrix (ECM) derived from smooth muscle cells (SMCs) was abundant in nerve-related active proteins and significantly enriched signaling pathways involved in nerve regeneration. However, whether NGCs based on SMCs-derived ECM modification strategy promote nerve regeneration remains unclear. In the study, we investigated the neuroregenerative effect of SMCs-derived ECM and developed a novel NGC (MyoNerve) by coating small intestinal submucosa (SIS) with SMCs-derived ECM. The SMCs-ECM was rich in neurotrophic factors, which endowed MyoNerve with remarkable neuroregenerative capabilities by promoting the expression of genes implicated in aspects of neuronal maintenance and activating signaling pathways involved in nerve regeneration. In vitro, MyoNerve exhibited excellent bioactivity for accelerating angiogenesis, regulating macrophages polarization, promoting the proliferation, migration and elongation of Schwann cells, enhancing differentiation of PC12 cells, and inducing the neurite outgrowth of dorsal root ganglia. In the model of rat sciatic nerve 10 mm defect, MyoNerve showed great potential for functional nerve regeneration by promoting angiogenesis, proliferation and migration of Schwann cells and neuron, axonal regeneration, remyelination, and neurological functional recovery.

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来源期刊

Biomaterials 工程技术-材料科学：生物材料

CiteScore

26.00

自引率

2.90%

发文量

565

审稿时长

46 days

期刊介绍： Biomaterials is an international journal covering the science and clinical application of biomaterials. A biomaterial is now defined as a substance that has been engineered to take a form which, alone or as part of a complex system, is used to direct, by control of interactions with components of living systems, the course of any therapeutic or diagnostic procedure. It is the aim of the journal to provide a peer-reviewed forum for the publication of original papers and authoritative review and opinion papers dealing with the most important issues facing the use of biomaterials in clinical practice. The scope of the journal covers the wide range of physical, biological and chemical sciences that underpin the design of biomaterials and the clinical disciplines in which they are used. These sciences include polymer synthesis and characterization, drug and gene vector design, the biology of the host response, immunology and toxicology and self assembly at the nanoscale. Clinical applications include the therapies of medical technology and regenerative medicine in all clinical disciplines, and diagnostic systems that reply on innovative contrast and sensing agents. The journal is relevant to areas such as cancer diagnosis and therapy, implantable devices, drug delivery systems, gene vectors, bionanotechnology and tissue engineering.