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Low back pain is the leading cause of work absences and years lived with disability, and it is often associated with degenerative disc disease. In recent years, biological treatment approaches such as the use of growth factors, cell injections, annulus fibrosus (AF) repair, nucleus pulposus replacement, and tissue-engineered discs have been explored as means for preventing or reversing degenerative disc disease. Both animal and clinical studies have shown promising results for cell-based therapy on the grounds of its regenerative potential. Clinical data also indicate that stem cell injection is safe when appropriately performed, albeit its long-term safety and efficacy are yet to be explored. Numerous challenges also remain to be overcome, such as isolating, differentiating, and preconditioning the disc cells, as well as managing the nutrient-deficient and oxygen-deficient micromilieu of the intervertebral disc (IVD). AF repair methods including devices used in clinical trials have shown success in decreasing reherniation rates and improving overall clinical outcomes. In addition, recent studies that combined AF repair and nucleus pulposus replacement have shown improved biomechanical stability in IVDs after the combined treatment. Tissue-engineered IVDs for total disc replacement are still being developed, and future studies are necessary to overcome the challenges in their delivery, efficacy, and safety.

Lumbar disc degeneration is one of the leading causes of chronic low back pain. The degenerative cascade is often initiated by an imbalance between catabolic and anabolic processes in the intervertebral discs. As a consequence of extracellular matrix degradation, neoinnervation and neovascularization take place. Ultimately, this degenerative process results in disc bulging and loss of nucleus pulposus and water content and subsequent loss of disc height. Most patients respond to conservative management and surgical interventions well initially, yet a significant number of patients continue to suffer from chronic low back pain. Because of the high prevalence of long-term discogenic pain, regenerative biological therapies, including gene therapies, growth factors, cellular-based injections, and tissue-engineered constructs, have attracted significant attention in light of their potential to directly address the degenerative process. Understanding the pathophysiology of degenerative disc disease is important in both refining existing technologies and developing innovative techniques to reverse the degenerative processes in the discs. In this review, we aimed to cover the underlying pathophysiology of degenerative disc disease as well as its associated risk factors and give a comprehensive summary about the developmental, structural, radiological, and biomechanical properties of human intervertebral discs.

The human intervertebral disc (IVD) is a complex organ composed of fibrous and cartilaginous connective tissues, and it serves as a boundary between 2 adjacent vertebrae. It provides a limited range of motion in the torso as well as stability during axial compression, rotation, and bending. Adult IVDs have poor innate healing potential due to low vascularity and cellularity. Degenerative disc disease (DDD) generally arises from the disruption of the homeostasis maintained by the structures of the IVD, and genetic and environmental factors can accelerate the progression of the disease. Impaired cell metabolism due to pH alteration and poor nutrition may lead to autophagy and disruption of the homeostasis within the IVD and thus plays a key role in DDD etiology. To develop regenerative therapies for degenerated discs, future studies must aim to restore both anatomical and biomechanical properties of the IVDs. The objective of this review is to give a detailed overview about anatomical, radiological, and biomechanical features of the IVDs as well as discuss the structural and functional changes that occur during the degeneration process.