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

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.