Chen Tao, Qian Qiuping, Makvandi Pooyan, Zare Ehsan Nazarzadeh, Chen Qizhu, Chen Linjie, Zhang Zhiguang, Zhou Hao, Zhou Wenxian, Wang Hui, Wang Xiangyang, Chen Yu, Zhou Yunlong, Wu Aimin
Department of Orthopaedics, Key Laboratory of Orthopaedics of Zhejiang Province, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, China.
Zhejiang Engineering Research Center for Tissue Repair Materials, Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou, Zhejiang, 325000, China.
Bioact Mater. 2023 Jan 31;25:107-121. doi: 10.1016/j.bioactmat.2023.01.010. eCollection 2023 Jul.
Intervertebral disc degeneration (IVDD) is a leading cause of low back pain. The strategy of using functional materials to deliver nucleic acids provides a powerful tool for ameliorating IVDD. However, the immunogenicity of nucleic acid vectors and the poor mechanical properties of functional materials greatly limit their effects. Herein, antagomir-204-3p (AM) shows low immunogenicity and effectively inhibits the apoptosis of nucleus pulposus cells. Moreover, a high-strength biohydrogel based on zinc-oxidized sodium alginate-gelatin (ZOG) is designed as a multifunctional nucleic acid delivery platform. ZOG loaded with AM (ZOGA) exhibits great hygroscopicity, antibacterial activity, biocompatibility, and biodegradability. Moreover, ZOGA can be cross-linked with nucleus pulposus tissue to form a high-strength collagen network that improves the mechanical properties of the intervertebral disc (IVD). In addition, ZOGA provides an advantageous microenvironment for genetic expression in which AM can play an efficient role in maintaining the metabolic balance of the extracellular matrix. The results of the radiological and histological analyses demonstrate that ZOGA restores the height of the IVD, retains moisture in the IVD, and maintains the tissue structure. The ZOGA platform shows the sustained release of nucleic acids and has the potential for application to ameliorate IVDD, opening a path for future studies related to IVD.
椎间盘退变（IVDD）是下腰痛的主要原因。利用功能材料递送核酸的策略为改善IVDD提供了有力工具。然而，核酸载体的免疫原性和功能材料较差的力学性能极大地限制了它们的效果。在此，抗 miR-204-3p（AM）显示出低免疫原性，并能有效抑制髓核细胞的凋亡。此外，基于氧化锌海藻酸钠-明胶（ZOG）设计了一种高强度生物水凝胶作为多功能核酸递送平台。负载 AM 的 ZOG（ZOGA）具有很强的吸湿性、抗菌活性、生物相容性和生物降解性。此外，ZOGA 可与髓核组织交联形成高强度胶原网络，改善椎间盘（IVD）的力学性能。此外，ZOGA 为基因表达提供了有利的微环境，其中 AM 可在维持细胞外基质代谢平衡中发挥有效作用。影像学和组织学分析结果表明，ZOGA 可恢复 IVD 的高度，保持 IVD 中的水分，并维持组织结构。ZOGA 平台显示出核酸的持续释放，具有改善 IVDD 的应用潜力，为未来与 IVD 相关的研究开辟了道路。
