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靶向纤维环缺陷中内源性活性氧的清除和调控再生微环境促进组织修复。

Targeting Endogenous Reactive Oxygen Species Removal and Regulating Regenerative Microenvironment at Annulus Fibrosus Defects Promote Tissue Repair.

机构信息

Orthopedic Institute, Department of Orthopaedic Surgery, The First Affiliated Hospital, School of Biology & Basic Medical Sciences, Suzhou Medical College, Soochow University, Suzhou, Jiangsu 215006, China.

Department of Forensic Medicine, School of Basic Medicine and Biological Sciences, Affiliated Guangji Hospital, Suzhou Medical College, Soochow University, Suzhou 215123, China.

出版信息

ACS Nano. 2023 Apr 25;17(8):7645-7661. doi: 10.1021/acsnano.3c00093. Epub 2023 Apr 6.

DOI:10.1021/acsnano.3c00093
PMID:37022700
Abstract

The excessive reactive oxygen species (ROS) level, inflammation, and weak tissue regeneration ability after annulus fibrosus (AF) injury constitute an unfavorable microenvironment for AF repair. AF integrity is crucial for preventing disc herniation after discectomy; however, there is no effective way to repair the AF. Herein, a composite hydrogel integrating properties of antioxidant, anti-inflammation, and recruitment of AF cells is developed through adding mesoporous silica nanoparticles modified by ceria and transforming growth factor β3 (TGF-β3) to the hydrogels. The nanoparticle loaded gelatin methacrylate/hyaluronic acid methacrylate composite hydrogels eliminate ROS and induce anti-inflammatory M2 type macrophage polarization. The released TGF-β3 not only plays a role in recruiting AF cells but is also responsible for promoting extracellular matrix secretion. The composite hydrogels can be solidified in the defect area to effectively repair AF in rats. The strategies targeting endogenous ROS removal and improving the regenerative microenvironment by the nanoparticle-loaded composite hydrogels have potential applications in AF repair and intervertebral disc herniation prevention.

摘要

纤维环(AF)损伤后,过量的活性氧(ROS)水平、炎症和薄弱的组织再生能力构成了不利于 AF 修复的微环境。AF 的完整性对于防止椎间盘切除术后椎间盘突出至关重要;然而,目前还没有有效的方法来修复 AF。在此,通过将载有氧化铈和转化生长因子β3(TGF-β3)的介孔硅纳米粒子添加到水凝胶中,开发了一种具有抗氧化、抗炎和募集 AF 细胞特性的复合水凝胶。负载纳米粒子的明胶甲基丙烯酰/透明质酸甲基丙烯酰复合水凝胶可消除 ROS,并诱导抗炎 M2 型巨噬细胞极化。释放的 TGF-β3 不仅可发挥募集 AF 细胞的作用,还可促进细胞外基质分泌。该复合水凝胶可在缺陷区域凝固,有效修复大鼠的 AF。该策略通过负载纳米粒子的复合水凝胶靶向内源性 ROS 清除和改善再生微环境,在 AF 修复和预防椎间盘突出方面具有潜在的应用价值。

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