Wu Jianjun, Qin Zainen, Jiang Xianfang, Fang Depeng, Lu Zhenhui, Zheng Li, Zhao Jinmin
Guangxi Engineering Center in Biomedical Materials for Tissue and Organ Regeneration, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, P.R. China.
Guangxi Collaborative Innovation Center for Biomedicine, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, P.R. China.
NPJ Regen Med. 2022 Nov 3;7(1):66. doi: 10.1038/s41536-022-00254-3.
Excessive reactive oxygen species (ROS) are one of the leading mechanisms in the initiation and development of osteoarthritis (OA). However, conventional injection of ROS-responsive drug delivery systems (DDSs) such as nanoparticles and hydrogels usually cannot provide effective treatment due to rapid clearance and degradation or low bioavailability. In this study, a ROS-responsive nanofiber membrane named PLA/PEGDA-EDT@rGO-Fucoxanthin (PPGF) is fabricated by electrospinning, wherein PEGDA-EDT served as the ROS-responsive motif, reduced graphene oxide (rGO) as the drug carrier and fucoxanthin (Fx) as the antioxidative and anti-inflammatory agent. The results demonstrated that the PPGF nanofiber membrane exhibited sustained and long-term Fx release behavior (at least 66 days) in response to hydrogen peroxide (HO) in vitro. With low cytotoxicity and smart ROS responsiveness, PPGF showed excellent anti-inflammatory and antioxidative effects on IL-1β-induced chondrocytes by potent ROS scavenging potential and upregulation of antioxidative enzymes. It also demonstrated the attenuation of OA progression with the reduced Osteoarthritis Research Society International (OARSI) score by 93.17% in 8 weeks. The smart ROS-responsive, biodegradable and biocompatible nanofiber membranes possess great potential for OA therapy under arthroscopy.
过量的活性氧（ROS）是骨关节炎（OA）发生和发展的主要机制之一。然而，传统的ROS响应性药物递送系统（DDSs）如纳米颗粒和水凝胶的注射，由于快速清除和降解或低生物利用度，通常不能提供有效的治疗。在本研究中，通过静电纺丝制备了一种名为PLA/PEGDA-EDT@rGO-岩藻黄质（PPGF）的ROS响应性纳米纤维膜，其中PEGDA-EDT作为ROS响应基序，还原氧化石墨烯（rGO）作为药物载体，岩藻黄质（Fx）作为抗氧化和抗炎剂。结果表明，PPGF纳米纤维膜在体外对过氧化氢（HO）表现出持续和长期的Fx释放行为（至少66天）。PPGF具有低细胞毒性和智能ROS响应性，通过强大的ROS清除潜力和抗氧化酶的上调，对IL-1β诱导的软骨细胞表现出优异的抗炎和抗氧化作用。它还证明了在8周内OA进展的减轻，国际骨关节炎研究学会（OARSI）评分降低了93.17%。这种智能ROS响应性、可生物降解和生物相容性的纳米纤维膜在关节镜下OA治疗中具有巨大潜力。
