Abstract
Intervertebral disc degeneration (IDD) is widely recognized as the primary culprit of chronic low back pain. Restoring deteriorated intervertebral disc (IVD) and alleviating IDD-induced low back pain are remaining enormous challenges. There is a genetic susceptibility to IDD, and gene therapy has some therapeutic potential. However, traditional gene therapy still has certain drawbacks, including host immunity, temporary release, and suppression of gene medication function. Although regenerative materials can effectively improve the local microenvironment, they cannot treat IDD from the root. Gene-functionalized regenerative material (GRM) is constructed based on physical embedding or forming chemical bonds by introducing particular genes, such as pDNA, siRNA, mRNA, and miRNA, into the regenerated materials. The findings demonstrate that GRM not only enhances the safety and controllability of gene therapy, but also effectively repairs IDD by overcoming the constraint that simple regenerative materials cannot reverse the disease's progression from the root. This article provided a brief overview of the physiological and pathological features of the IVD, genetic susceptibility to IDD, available treatment options, and their limitations. Then, the significance of GRM-based treatment of IDD is proposed, and the future challenges and development in this field are finally prospected.