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单宁酸/Sr 涂层丝/氧化石墨烯基半月板支架具有抗炎和抗 ROS 功能,可用于软骨保护和延缓骨关节炎。

Tannic acid/Sr-coated silk/graphene oxide-based meniscus scaffold with anti-inflammatory and anti-ROS functions for cartilage protection and delaying osteoarthritis.

机构信息

Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100871, China.

Department of Orthopedic Surgery, Beijing Jishuitan Hospital, Fourth Clinical College of Peking University, No. 31 Xinjiekou East Street, Xicheng District, Beijing, 100035, China.

出版信息

Acta Biomater. 2021 May;126:119-131. doi: 10.1016/j.actbio.2021.02.046. Epub 2021 Mar 5.

Abstract

Tissue engineering method provides a promising solution for meniscus repair and regeneration. However, the inflammatory environment that persists after meniscus injury in the knee joint impedes meniscus tissue regeneration. The purpose of this study was to investigate the applicability of silk/graphene oxide (GO)-based meniscus scaffold modified with tannic acid (TA)/Sr coating for the elimination of inflammatory cytokines and reactive oxygen species (ROS) under osteoarthritis (OA) environment along with cartilage protection by using a rat model. The self-assembled coating composed of a series of TA-Sr complex concentrations was formed by a facile, rapid, and efficient method on the scaffold. The phenolic hydroxyl groups on the coating endowed the meniscus scaffold with excellent anti-inflammatory and ROS scavenging capacities. We also found that the coating could promote cell migration in a mock wound model and could increase extracellular matrix secretion in vitro. Moreover, the coating components at a certain concentration played an effective role in delaying OA and providing cartilage protection in the rat model. The expression of inflammation cytokines (e.g., IL-6, IL-8, and MMPs) in rat knee tissue was significantly downregulated, and cartilage degeneration and OA damage were also inhibited according to tissue staining results and the OARSI (Osteoarthritis Research Society International) scoring system. Combining these performances, we suggest that this silk/GO-based scaffold modified with TA/Sr coating could have broader application prospects by virtue of its effective and user-friendly properties. STATEMENT OF SIGNIFICANCE: The biological properties of the meniscus play a role in activating and regulating the metabolic and inflammatory responses that influence the homeostasis of joint health and ultimately lead to knee osteoarthritis (OA). The inflammation condition of the knee joint may exacerbate the degeneration of meniscus and cartilage. The present study aimed to develop a functional coating composed of tannic acid/Sr complex on a silk/graphene oxide-based meniscus scaffold and to endow the scaffold with anti-inflammatory and ROS elimination capacities during the meniscus regeneration process to protect cartilage and delay OA development. The in vitro cytocompatibility study and the in vivo rat OA model study revealed that the coating was effective in promoting cell migration, facilitating ECM secretion, inhibiting inflammation, and delaying OA development.

摘要

组织工程方法为半月板修复和再生提供了有前途的解决方案。然而,膝关节半月板损伤后持续存在的炎症环境阻碍了半月板组织的再生。本研究旨在探讨基于丝/氧化石墨烯(GO)的半月板支架经单宁酸(TA)/Sr 涂层改性后在骨关节炎(OA)环境下消除炎症细胞因子和活性氧(ROS)并保护软骨的适用性,该研究使用大鼠模型进行。通过简便、快速、高效的方法,在支架上形成了由一系列 TA-Sr 络合物浓度组成的自组装涂层。涂层上的酚羟基基团赋予半月板支架优异的抗炎和 ROS 清除能力。我们还发现,该涂层可促进模拟伤口模型中的细胞迁移,并可增加体外细胞外基质的分泌。此外,在一定浓度下,涂层成分在大鼠模型中可有效延缓 OA 并提供软骨保护。根据组织染色结果和 OARSI(国际骨关节炎研究协会)评分系统,大鼠膝关节组织中炎症细胞因子(如 IL-6、IL-8 和 MMPs)的表达明显下调,软骨退变和 OA 损伤也得到抑制。综合这些表现,我们认为,基于丝/GO 的支架经 TA/Sr 涂层改性后,由于其有效且易于使用的特性,可能具有更广阔的应用前景。

意义声明

半月板的生物学特性在激活和调节代谢和炎症反应中发挥作用,这些反应影响关节健康的动态平衡,最终导致膝关节骨关节炎(OA)。膝关节的炎症状态可能会加剧半月板和软骨的退变。本研究旨在开发一种功能性涂层,由丝/氧化石墨烯基半月板支架上的单宁酸/Sr 络合物组成,并赋予支架在半月板再生过程中抗炎和消除 ROS 的能力,以保护软骨并延缓 OA 的发展。体外细胞相容性研究和体内大鼠 OA 模型研究表明,该涂层可有效促进细胞迁移,促进 ECM 分泌,抑制炎症,延缓 OA 进展。

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