Biomaterials and Noncoding RNA: The "Repair-Alliance" Perspective in Intervertebral Disc Degeneration.

Intervertebral disc degeneration (IVDD) is a common condition causing chronic back pain and functional impairment, which severely reduces patients' quality of life. Traditional treatments only relieve symptoms without addressing the underlying pathology, highlighting the need for new therapies that repair IVDD at a mechanistic level. Recent progress shows biomaterials can support structure and boost tissue regeneration by mimicking the native extracellular matrix (ECM) of the nucleus pulposus. They also act as delivery systems for bioactive molecules, extending their retention at the target site to enhance efficacy. Meanwhile, noncoding RNA (ncRNA) regulates IVDD pathogenesis by modifying genes linked to inflammation, cellular homeostasis, and ECM metabolism, opening new avenues for gene therapy. Thus, combining biomaterials with ncRNA delivery creates a synergistic IVDD treatment. Over the past decade, research has focused on designing nanoparticles to encapsulate ncRNAs, enabling precise targeting of specific cells in degenerated discs. This study outlines IVDD's physiological/pathological features, existing therapies and their limits, and recent advances in biomaterials and ncRNA for IVDD treatment. We propose that future research should develop multifunctional biomaterial platforms that provide structural support and targeted gene therapy to improve disc regeneration and clinical outcomes for IVDD patients.