Integrating cells, scaffolds, and molecular regulation: a mechanobiological and translational review of bioengineering therapies for intervertebral disc degeneration

Intervertebral disc degeneration (IDD) is a primary cause of chronic low back pain, severely impacting patients' quality of life. Conventional treatments focus on symptom relief but fail to restore disc structure and function. Recent bioengineering advances offer regenerative solutions, integrating cell therapy, tissue-engineered scaffolds, gene therapy, and mechanobiology. Cell therapy leverages mesenchymal stem cells (MSCs) from bone marrow, adipose tissue, or umbilical cord blood, with biomaterial carriers enhancing survival in the harsh disc microenvironment. Scaffolds-natural (collagen, chitosan) or synthetic (PLGA, PCL)-mimic native extracellular matrix (ECM) and provide mechanical support, often combined with growth factors for controlled release. Gene therapy targets ECM synthesis, inflammation, and degradation pathways via viral or non-viral vectors, while mechanobiology reveals how mechanical forces regulate disc cell behavior, guiding scaffold design. Animal models validate these therapies, and early clinical trials show promise in pain reduction and disc height restoration. However, challenges remain, including low cell survival, scaffold mechanical adaptation, and gene delivery safety. Multidisciplinary collaboration is key to translating preclinical progress into effective clinical interventions, addressing the unmet medical need for IDD treatment.