Engineered high-strength biohydrogel as a multifunctional platform to deliver nucleic acid for ameliorating intervertebral disc degeneration

Tao Chen; Qiuping Qian; Pooyan Makvandi; Ehsan Nazarzadeh Zare; Qizhu Chen; Linjie Chen; Zhiguang Zhang; Hao Zhou; Wenxian Zhou; Hui Wang; Xiangyang Wang; Yu Chen; Yunlong Zhou; Aimin Wu

doi:10.1016/j.bioactmat.2023.01.010

Engineered high-strength biohydrogel as a multifunctional platform to deliver nucleic acid for ameliorating intervertebral disc degeneration

Bioact Mater. 2023 Jan 31:25:107-121. doi: 10.1016/j.bioactmat.2023.01.010. eCollection 2023 Jul.

Authors

Tao Chen¹, Qiuping Qian², Pooyan Makvandi³, Ehsan Nazarzadeh Zare⁴, Qizhu Chen¹, Linjie Chen¹, Zhiguang Zhang¹, Hao Zhou¹, Wenxian Zhou⁵, Hui Wang⁵, Xiangyang Wang¹, Yu Chen⁶, Yunlong Zhou², Aimin Wu¹

Affiliations

¹ 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.
² Zhejiang Engineering Research Center for Tissue Repair Materials, Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou, Zhejiang, 325000, China.
³ Institute for Bioengineering, School of Engineering, The University of Edinburgh, Edinburgh, EH9 3FB, UK.
⁴ School of Chemistry, Damghan University, Damghan, 36716-45667, Iran.
⁵ Wenzhou Medical University, Wenzhou, Zhejiang, 325000, China.
⁶ Materdicine Lab, School of Life Sciences, Shanghai University, Shanghai, 200444, China.

Abstract

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.

Keywords: Delivery; Extracellular matrix; Hydrogel; Intervertebral disc degeneration; MicroRNA; Nucleic acid.