Intervertebral disc (IVD) degeneration is a major contributing factor for discogenic low back pain (LBP), causing a significant global disability. The IVD consists of an inner core proteoglycan-rich nucleus pulposus (NP) and outer lamellae collagen-rich annulus fibrosus (AF) and is confined by a cartilage end plate (CEP), providing structural support and shock absorption against mechanical loads. Changes to degenerative cascades in the IVD cause dysfunction and instability in the lumbar spine. Various treatments include pharmacological, rehabilitation or surgical interventions that aim to relieve pain; however, these modalities do not halt the pathologic events of disc degeneration or promote tissue regeneration. Loss of stem and progenitor markers, imbalance of the extracellular matrix (ECM), increase of inflammation, sensory hyperinnervation and vascularization, and associated signaling pathways have been identified as the onset and progression of disc degeneration. To better understand the pain originating from IVD, our review focuses on the anatomy of IVD and the pathophysiology of disc degeneration that contribute to the development of discogenic pain. We highlight the key mechanisms and associated signaling pathways underlying disc degeneration causing discogenic back pain, current clinical treatments, clinical perspective and directions of future therapies. Our review comprehensively provides a better understanding of healthy IVD and degenerative events of the IVD associated with discogenic pain, which helps to model painful disc degeneration as a therapeutic platform and to identify signaling pathways as therapeutic targets for the future treatment of discogenic pain.

Intervertebral disc degeneration is a common cause of discogenic low back pain resulting in significant disability. Current conservative or surgical intervention treatments do not reverse the underlying disc degeneration or regenerate the disc. Biomaterial‐based tissue engineering strategies exhibit the potential to regenerate the disc due to their capacity to modulate local tissue responses, maintain the disc phenotype, attain biochemical homeostasis, promote anatomical tissue repair, and provide functional mechanical support. Despite preliminary positive results in preclinical models, these approaches have limited success in clinical trials as they fail to address discogenic pain. This review gives insights into the understanding of intervertebral disc pathology, the emerging concept of precision medicine, and the rationale of personalized biomaterial‐based tissue engineering tailored to the severity of the disease targeting early, mild, or severe degeneration, thereby enhancing the efficacy of the treatment for disc regeneration and ultimately to alleviate discogenic pain. Further research is required to assess the relationship between disc degeneration and lower back pain for developing future clinically relevant therapeutic interventions targeted towards the subgroup of degenerative disc disease patients.

Hyaluronic acid hydrogel alleviated inflammatory pain, altered glycosylation, and regulated matrix components for disc repair.

The advancement of natural-based biomaterials in providing a carrier has revealed a wide range of benefits in the biomedical sciences, particularly in wound healing, tissue engineering and regenerative medicine. Incorporating nanoparticles within polymer composites has been reported to enhance scaffolding performance, cellular interactions and their physico-chemical and biological properties in comparison to analogue composites without nanoparticles. This review summarized the current knowledge of nanoparticles incorporated into natural-based biomaterials with effects on their cellular interactions in wound healing. Although the mechanisms of wound healing and the function of specific cells in wound repair have been partially described, many of the underlying signaling pathways remain unknown. We also reviewed the current understanding and new insights into the wingless/integrated (Wnt)/β-catenin pathway and other signaling pathways of transforming growth factor beta (TGF-β), Notch, and Sonic hedgehog during wound healing. The findings demonstrated that most of the studies reported positive outcomes of biomaterial scaffolds incorporated with nanoparticles on cell attachment, viability, proliferation, and migration. Combining therapies consisting of nanoparticles and biomaterials could be promising for future therapies and better outcomes in tissue engineering and regenerative medicine.