Abstract
Intervertebral disc degeneration (IDD) is caused by genetics, aging, and environmental factors and is one of the leading causes of low back pain. The treatment of IDD presents many challenges. Hydrogels are biomaterials that possess properties similar to those of the natural extracellular matrix and have significant potential in the field of regenerative medicine. Hydrogels with various functional qualities have recently been used to repair and regenerate diseased intervertebral discs. Here, we review the mechanisms of intervertebral disc homeostasis and degeneration and then discuss the applications of hydrogel-mediated repair and intervertebral disc regeneration. The classification of artificial hydrogels and natural hydrogels is then briefly introduced, followed by an update on the development of functional hydrogels, which include noncellular therapeutic hydrogels, cellular therapeutic hydrogel scaffolds, responsive hydrogels, and multifunctional hydrogels. The challenges faced and future developments of the hydrogels used in IDD are discussed as they further promote their clinical translation.
Highlights
Low back pain is a leading cause of musculoskeletal disability and places a heavy burden on global healthcare systems
We discuss the development of multifunctional hydrogels for Intervertebral disc degeneration (IDD) and regeneration: (1) we introduce the concepts of homeostasis and degeneration of the intervertebral disc and the types of hydrogels used in the treatment of IDD; (2) we classify and summarize the advantages of multifunctional hydrogels in IDD and regeneration; (3) we emphasize the principles behind the use of hydrogels in the treatment of IDD and the high standards of regenerative medicine by customizing their functions
An ideal hydrogel for regenerating the Intervertebral Disc (IVD) should have the following properties: (1) good biocompatibility and biodegradability; (2) injectability so it can be used as adjuvant therapy for conservative treatment or minimally invasive surgery; (3) in situ curing to avoid leakage; (4) strong biomechanical properties, which improve the differentiation of nucleus pulposus cells; (5) good drug carrying and sustained-release capacity to extend the duration of treatment; (6) can integrate and adhere with the target to prevent poor localization and treatment failure; and (7) can encapsulate stem cells and retain the extracellular matrix (ECM) to promote IVD regeneration
Summary
Low back pain is a leading cause of musculoskeletal disability and places a heavy burden on global healthcare systems. The various forms of IVD homeostasis are closely related and maintain a dynamic physiologic balance that changes as the host ages: (1) immune homeostasis means that immune cells are not found in the IVD under normal circumstances due to the annulus fibrosus, cartilage endplates and the protection of FasL and other molecular mechanisms; (2) cellular homeostasis plays a central role in the maintenance of IVD physiology. As the human body grows older, IVD homeostasis gradually becomes unbalanced and damaged Various pathologic changes such as the accumulation of inflammatory mediators, the formation of cell clusters, nucleus pulposus fibrosis, annulus fibrosus rupture, and cartilaginous endplate calcification can be observed in the aging IVD [28]. Hydrogels, which are analogs of the ECM, provide structural support for the regeneration of nucleus pulposus cells, guide the differentiation of nucleus pulposus cells and the production of ECM, and act as a carrier of drugs or stem cells, and are lead candidate materials for the treatment of IDD
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