Luo Huitong, Wang Zetao, He Zhichao, Ling Zemin, Wang Hao, Zhu Jiayi, Nie Jingjun, Chen Dafu, Feng Qi, Cao Xiaodong
Department of Biomedical Engineering, School of Materials Science and Engineering, South China University of Technology, Guangzhou, 510006, China.
National Engineering Research Center for Tissue Restoration and Reconstruction (NERC-TRR), South China University of Technology, Guangzhou, 510006, China.
Biomater Sci. 2023 May 16;11(10):3629-3644. doi: 10.1039/d3bm00359k.
Overactive inflammatory cascade accompanied by oxidative stress in the nucleus pulposus exacerbates intervertebral disc degeneration (IVDD). Hydrogels have been demonstrated to be promising in treating IVDD, yet they remain less efficacious in the case of anti-inflammation associated with antioxidation. In this study, we designed an injectable self-antioxidant hydrogel (HA/CS) with enhanced inflammation inhibitory performance for delivering chondroitin sulfate (CS) with well-documented anti-inflammatory property to treat IVDD. The hydrogel was rapidly formed dynamic boronate ester bonding between furan/phenylboronic acid and furan/dopamine-modified hyaluronic acid (HA), and mechanically enhanced by Diels-Alder reaction-induced secondary crosslinking, partial dopamine groups of which contribute to grafting phenylboronic acid-modified CS (CS-PBA). This hydrogel exhibits favorable injectability, mechanical property, and pH-responsive delivery behavior. The dopamine moiety endows the hydrogel with efficient antioxidative property. By sustained delivery of CS, the HA/CS hydrogel is well competent to inhibit inflammatory cytokine expression and maintain anabolic/catabolic balance in an inflammation-simulated environment. Most importantly, the HA/CS hydrogel significantly ameliorates degeneration in a puncture-induced IVDD rat model. The self-antioxidant HA/CS hydrogel designed in this work may serve as a novel and promising therapeutic platform for IVDD.
髓核中过度活跃的炎症级联反应伴有氧化应激，会加剧椎间盘退变（IVDD）。水凝胶已被证明在治疗IVDD方面具有潜力，但在与抗氧化相关的抗炎方面效果仍欠佳。在本研究中，我们设计了一种具有增强炎症抑制性能的可注射自抗氧化水凝胶（HA/CS），用于递送具有充分抗炎特性的硫酸软骨素（CS）以治疗IVDD。该水凝胶通过呋喃/苯硼酸与呋喃/多巴胺修饰的透明质酸（HA）之间的动态硼酸酯键快速形成，并通过狄尔斯-阿尔德反应诱导的二次交联进行机械增强，其中部分多巴胺基团有助于接枝苯硼酸修饰的CS（CS-PBA）。这种水凝胶具有良好的可注射性、机械性能和pH响应性释放行为。多巴胺部分赋予水凝胶高效的抗氧化性能。通过持续释放CS，HA/CS水凝胶能够有效抑制炎症细胞因子的表达，并在炎症模拟环境中维持合成代谢/分解代谢平衡。最重要的是，HA/CS水凝胶在穿刺诱导的IVDD大鼠模型中显著改善了退变情况。本研究设计的自抗氧化HA/CS水凝胶可能成为一种新型且有前景的IVDD治疗平台。
