Intervertebral disc degeneration and regeneration: a motion segment perspective

Abstract

Back and neck pain have become primary reasons for disability and healthcare spending globally. While the causes of back pain are multifactorial, intervertebral disc degeneration is frequently cited as a primary source of pain. The annulus fibrosus (AF) and nucleus pulposus (NP) subcomponents of the disc are common targets for regenerative therapeutics. However, disc degeneration is also associated with degenerative changes to adjacent spinal tissues, and successful regenerative therapies will likely need to consider and address the pathology of adjacent spinal structures beyond solely the disc subcomponents. This review summarises the current state of knowledge in the field regarding associations between back pain, disc degeneration, and degeneration of the cartilaginous and bony endplates, the AF-vertebral body interface, the facet joints and spinal muscles, in addition to a discussion of regenerative strategies for treating pain and degeneration from a whole motion segment perspective.

Figure 1.

Schematic of (A) coronal and (B) axial crossections of the spinal motion segment, demonstrating relevant anatomical regions. VB = vertebral body, NP = nucleus pulposus, AF = annulus fibrosus.

Figure 2.

(A) μCT scan of the rabbit lumbar spine perfused with microFil (scale = 5 mm). Dashed box highlights the boney endplate region shown in B and C.(Ashinsky et al.,2020) (B) Mallory-Heidenhain trichrome stain of a sagittal section of the rabbit endplate-NP interface. Yellow arrows denote vessels (scale = 100 μm).(Ashinsky et al., 2020) (C) Scanning electron micrograph of a cast of the rabbit endplate vasculature.(Oki et al., 1996) Images reproduced with permissions.

Figure 3.

Histology sections stained with the Mallory-Heidenhain trichrome stain of healthy and degenerative human intervertebral disc interfaces. CEP = cartilage endplate, AF = annulus fibrosus, VB = vertebral body. CEP scale = 200μm, AF-VB scale = 800μm.

Figure 4.

μCT scans of human facet joints (arrows) adjacent to the (A) L1-L2 disc, Pfirmman grade 5, from a 66 year old female, and (B) the L1-L2 disc, Pfirrmann grade 3, from a 65 year old male. Scale = 5mm.

Figure 5.

Examples of tissue engineered disc implants with endplate interfaces from the literature. (A) Endplate-modified disc-like angle ply structures after 20 weeks implantation in the rat tail.(Gullbrand et al., 2018b) (B) A tissue engineered CEP-AF interface. S = scaffold, # = outer AF, * = cartilage, yellow arrow heads = directional orientation of outer AF cells. (Chong et al., 2020) (C) A tissue engineered whole disc replacement with an osteochondral endplate component.(Chik et al., 2015) Images reproduced with permission.