Disordered Mechanical Stress and Tissue Engineering Therapies in Intervertebral Disc Degeneration

Abstract

Low back pain (LBP), commonly induced by intervertebral disc degeneration, is a lumbar disease with worldwide prevalence. However, the mechanism of degeneration remains unclear. The intervertebral disc is a nonvascular organ consisting of three components: Nucleus pulposus, annulus fibrosus, and endplate cartilages. The disc is structured to support our body motion and endure persistent external mechanical pressure. Thus, there is a close connection between force and intervertebral discs in LBP. It is well established that with aging, disordered mechanical stress profoundly influences the fate of nucleus pulposus and the alignment of collagen fibers in the annulus fibrosus. These support a new understanding that disordered mechanical stress plays an important role in the degeneration of the intervertebral discs. Tissue-engineered regenerative and reparative therapies are being developed for relieving disc degeneration and symptoms of lower back pain. In this paper, we will review the current literature available on the role of disordered mechanical stress in intervertebral disc degeneration, and evaluate the existing tissue engineering treatment strategies of the current therapies.

Extracellular Matrix From Decellularized Wharton’s Jelly Improves the Behavior of Cells From Degenerated Intervertebral Disc

“…In particular, several studies aim at developing innovative bio-inspired scaffolds, in order to counteract extracellular matrix (ECM) loss following degeneration/inflammation, and support functional recovery by endogenous damaged microenvironment (Coogan et al, 2016;Van Uden et al, 2017;Gullbrand et al, 2018). In this scenario, decellularized ECM deriving from autologous or non-autologous tissues represents an important advance in this field, as ideal system to deliver chemokines and growth factors, and provides adequate biomechanical microarchitecture also in the damaged IVD microenvironment (D'Este et al, 2018;Hensley et al, 2018;Liu et al, 2019;Ventre et al, 2019;Zhao et al, 2019). Obviously, obtaining autologous ECM from human IVD is not feasible, but recent evidences based on decellularized ECM from IVD of animal origin are encouraging (Illien-Jünger et al, 2016;Lin et al, 2016;Zhou et al, 2018;Xu et al, 2019).…”

Nuclear factor erythroid-2 related factor 2 inhibits human disc nucleus pulpous cells apoptosis induced by excessive hydrogen peroxide

“…The medullar cells were inoculated at a density of 5×10 3 Hoechst 3258 living cell staining The density of nucleus pulpous cells was 1.5×10 5 cells per pore in the 6-well plate, cultured for 48 hours. After H 2 O 2 and SFN treatment, the original solution was removed, PBS was washed twice, Hoechst 33258 diluted at 1:1000 was added and placed in a wet incubator at 37°C for 20 minutes.…”

“…Degeneration is a chronic disease with high incidence 1 and is considered to be one of the main causes of chronic back pain 2, 3 . Due to the change of the material and structure inside the intervertebral disc, the disc becomes unstable and its function is changed.…”

Structure Design and Optimization of the C5–C6 Cervical Intervertebral Fusion Cage Using the Anterior Cervical Plate and Cage Fixation System

“…The discs contain 2 different structural elements – the annulus fibrous and the nucleus pulposus. From the viewpoint of material mechanics, the annulus fibrous is flexible protein, and the nucleus pulposus is a gelatinous solid that is always regarded as an impressible material [ 19 , 20 ]. Cages designed using hard materials such as titanium/titanium alloy/PEEK provide sufficient mechanical support but have less flexibility compared with human tissue.…”