Bioinspired conductive oriented nanofiber felt with efficient ROS clearance and anti-inflammation for inducing M2 macrophage polarization and accelerating spinal cord injury repair

IF 18 1区医学 Q1 ENGINEERING, BIOMEDICAL Bioactive Materials Pub Date : 2024-12-13 DOI:10.1016/j.bioactmat.2024.12.009

Qingxia Zhang , Jiahe Zheng , Linlong Li , Jui-Ming Yeh , Xianrui Xie , Yuqing Zhao , Chengbo Li , Guige Hou , Huanhuan Yan

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Abstract

Complete spinal cord injury (SCI) causes permanent locomotor, sensory and neurological dysfunctions. Targeting complex immunopathological microenvironment at SCI sites comprising inflammatory cytokines infiltration, oxidative stress and massive neuronal apoptosis, the conductive oriented nanofiber felt with efficient ROS clearance, anti-inflammatory effect and accelerating neural regeneration is constructed by step-growth addition polymerization and electrostatic spinning technique for SCI repair. The formation of innovative Fe³⁺-PDA-PAT chelate in nanofiber felt enhances hydrophilic, antioxidant, antibacterial, hemostatic and binding factor capacities, thereby regulating immune microenvironment of SCI. With the capabilities of up-regulating COX5A and STAT6 expressions, down-regulating the expressions of IL1β, CD36, p-ERK, NFκB2 and NFκB signaling pathway proteins, the nanofiber felt attenuates oxidative stress injury, promotes M2 macrophage polarization and down-regulates inflammatory response. After implantation into complete transection SCI rats, the nanofiber felt is revealed to recruit endogenous NSCs, induce the differentiation of NSCs into neurons while inhibit astrocytes formation and inflammation, reduces glia scar, and promotes angiogenesis, remyelination and neurological functional recovery. Overall, this innovative strategy provides a facile immune regulatory system to inhibit inflammatory response and accelerate nerve regeneration after SCI, and its targeted proteins and mechanisms are first elucidated, which holds great application promise in clinical treatment of complete SCI.

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生物启发导电定向纳米纤维毡具有有效的ROS清除和抗炎症诱导M2巨噬细胞极化和加速脊髓损伤修复。

完全性脊髓损伤（SCI）会导致永久性的运动、感觉和神经功能障碍。针对脊髓损伤部位复杂的免疫病理微环境（包括炎症细胞因子浸润、氧化应激和大量神经元凋亡），通过阶跃生长加成聚合和静电纺丝技术构建了具有高效清除 ROS、抗炎和加速神经再生作用的导电定向纳米纤维毡，用于脊髓损伤修复。在纳米纤维毡中形成的创新型 Fe3+-PDA-PAT 螯合物增强了亲水、抗氧化、抗菌、止血和结合因子的能力，从而调节了 SCI 的免疫微环境。纳米纤维毡能上调 COX5A 和 STAT6 的表达，下调 IL1β、CD36、p-ERK、NFκB2 和 NFκB 信号通路蛋白的表达，从而减轻氧化应激损伤，促进 M2 巨噬细胞极化并下调炎症反应。将纳米纤维毡植入完全横断的 SCI 大鼠体内后，发现它能招募内源性 NSCs，诱导 NSCs 分化为神经元，同时抑制星形胶质细胞的形成和炎症反应，减少胶质瘢痕，促进血管生成、髓鞘再形成和神经功能恢复。总之，该创新策略提供了一种简便的免疫调节系统，可抑制炎症反应，加速脊髓损伤后的神经再生，并首次阐明了其靶向蛋白和机制，在完全性脊髓损伤的临床治疗中具有广阔的应用前景。

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来源期刊

Bioactive Materials Biochemistry, Genetics and Molecular Biology-Biotechnology

CiteScore

28.00

自引率

6.30%

发文量

436

审稿时长

20 days

期刊介绍： Bioactive Materials is a peer-reviewed research publication that focuses on advancements in bioactive materials. The journal accepts research papers, reviews, and rapid communications in the field of next-generation biomaterials that interact with cells, tissues, and organs in various living organisms. The primary goal of Bioactive Materials is to promote the science and engineering of biomaterials that exhibit adaptiveness to the biological environment. These materials are specifically designed to stimulate or direct appropriate cell and tissue responses or regulate interactions with microorganisms. The journal covers a wide range of bioactive materials, including those that are engineered or designed in terms of their physical form (e.g. particulate, fiber), topology (e.g. porosity, surface roughness), or dimensions (ranging from macro to nano-scales). Contributions are sought from the following categories of bioactive materials: Bioactive metals and alloys Bioactive inorganics: ceramics, glasses, and carbon-based materials Bioactive polymers and gels Bioactive materials derived from natural sources Bioactive composites These materials find applications in human and veterinary medicine, such as implants, tissue engineering scaffolds, cell/drug/gene carriers, as well as imaging and sensing devices.