Importance of Matrix Cues on Intervertebral Disc Development, Degeneration, and Regeneration

Abstract

Back pain is one of the leading causes of disability worldwide and is frequently caused by degeneration of the intervertebral discs. The discs’ development, homeostasis, and degeneration are driven by a complex series of biochemical and physical extracellular matrix cues produced by and transmitted to native cells. Thus, understanding the roles of different cues is essential for designing effective cellular and regenerative therapies. Omics technologies have helped identify many new matrix cues; however, comparatively few matrix molecules have thus far been incorporated into tissue engineered models. These include collagen type I and type II, laminins, glycosaminoglycans, and their biomimetic analogues. Modern biofabrication techniques, such as 3D bioprinting, are also enabling the spatial patterning of matrix molecules and growth factors to direct regional effects. These techniques should now be applied to biochemically, physically, and structurally relevant disc models incorporating disc and stem cells to investigate the drivers of healthy cell phenotype and differentiation. Such research will inform the development of efficacious regenerative therapies and improved clinical outcomes.

Wharton's jelly‐derived multifunctional hydrogels: New tools to promote intervertebral disc regeneration in vitro and ex vivo

“…Based on the evidences here obtained, it will be necessary components and mechanical properties of the ECM of the discal tissue vary depending on the anatomical site within the spine. 6 The future direction is precisely to develop personalized biomaterials tailored to match the unique signature of ECM associated to the different IDD subtypes (disc fibrosis, disc calcification and disc herniations) to halt disease progression, promote tissue regeneration, and relieve the symptom, that is, discogenic low back pain. 49 We would like to conclude that, considering their versatility, the WJMs proposed here are also good candidates for the treatment of degenerative joint diseases such as osteoarthritis or various traumas that can affect the joints.…”

Tissue-mimetic hybrid bioadhesives for intervertebral disc repair

“…The values are within the range for the non-degenerate human NP reported in previous studies. 31,32 Together, the resulting NP glue is bioadhesive, injectable, and viscoelastic.…”

Natural products can modulate inflammation in intervertebral disc degeneration

“…Indeed, the dysregulation of ECM anabolism and catabolism, and the absence of crucial components, such as proteoglycans and type II collagen, are typical pathological changes in IDD. Matrix metalloproteinases (MMPs), and a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTSs), are two families of enzymes that regulate the ECM ( Kibble et al, 2022 ). Inflammatory factors not only accelerate the catabolism of key substances, but also downregulate their source synthesis and expression.…”

“…In addition to IL-1β, Séguin et al ( Séguin et al, 2005 ) also reported that TNF-α increased the expression levels of MMP-1, -3, -13, ADAMTS-4, and -5, and reduced the expression of type II collagen and proteoglycan genes in NP cells. The development of proteomics and transcriptomics is expected to reveal more detailed changes in the expression and synthesis of substances at the spatiotemporal level ( Eckersley et al, 2021 ; Kibble et al, 2022 ). Overall, the close relationship between inflammation and other mechanisms further indicates that controlling inflammation has great potential for the treatment of IDD.…”