Pathomechanism and Biomechanics of Degenerative Disc Disease: Features of Healthy and Degenerated Discs

Kırnaz, Sertaç; Capadona, Charisse; Lintz, Marianne; Kim, Byumsu; Yerden, Rachel; Goldberg, Jacob L.; Medary, Branden; Sommer, Fabian; McGrath, Lynn B.; Bonassar, Lawrence J.; Härtl, Roger

doi:10.14444/8052

Cited by 35 publications

(20 citation statements)

References 170 publications

(192 reference statements)

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“…The relationship between mechanical loading and disc health has long been studied [ 48 , 49 ]. Mechanical factors have been demonstrated to significantly affect cellular function [ 50 , 51 ].…”

Section: Discussionmentioning

confidence: 99%

Regenerating and repairing degenerative intervertebral discs by regulating the micro/nano environment of degenerative bony endplates based on low-tension mechanics

Jing

Guo

Hao

et al. 2022

BMC Musculoskelet Disord

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Background Conservative treatment is the recommended first-line treatment for degenerative disc diseases. Traction therapy has historically been one of the most common clinical methods to address this, but the clinical effect remains controversial. Methods Forty-two six-month-old male Sprague-Dawley rats were randomly divided into six groups: the model group (Group A, four coccyx vertebrae (Co7-Co10) were fixed with customized external fixators, and the vertebral disc degeneration model was constructed by axial compression of the target segment Co8 - Co9 for 4 weeks), the experimental control group (Group B, after successful modeling, the external fixation device was removed and self-rehabilitation was performed) and four intervention groups (Groups C to F): Groups C and E: Co8 - Co9 vertebrae compressed for 4 weeks followed by two or 4 weeks of high tension traction (HTT), respectively, and Groups D and F: vertebrae compressed for 4 weeks followed by two or 4 weeks of low-tension traction (LTT), respectively. Imaging tests (X-ray and MRI) were performed to assess disc height and T2 signal intensity at each time point. After the experiment, the animals were euthanized, and the caudal vertebrae were collected for analysis of intervertebral disc histopathology, proteoglycan content, and micronanostructure of the annulus fibrosus, nucleus pulposus and bony endplate. Results Signs of tissue regeneration were apparent in all four intervention groups. After two to 4 weeks of intervention (HTT and LTT), the morphology of pores in the bony endplate, their number, and diameter had recovered significantly compared with those in Group A. The LTT group was superior to the HTT group, and the 4w in situ group was significantly superior to the 2w group. Meanwhile, the histological scores of discs, the mean fibril diameter and modulus of annulus fibrosus were significantly improved compared with the control groups, and the LTT group was superior to HTT group. Conclusions Low-tension traction better promotes active reconstruction of bony endplates and improves the elastic modulus and micro/nanostructure of the disc. Thus, it further promotes the regeneration and repair of intervertebral discs.

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Section: Discussionmentioning

confidence: 99%

Regenerating and repairing degenerative intervertebral discs by regulating the micro/nano environment of degenerative bony endplates based on low-tension mechanics

Jing

Guo

Hao

et al. 2022

BMC Musculoskelet Disord

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“…The delivery of Anakinra through TARP implantation also provided several benefits with potential to prolong disc health after injury. Some of the main hallmarks of disc degeneration include the depletion of NP proteoglycan content and a loss of the NP/AF boundary (34)(35)(36).…”

Section: Discussionmentioning

confidence: 99%

Anti-Inflammatory Tension-Activated Repair Patches Improve Repair After Intervertebral Disc Herniation

Peredo

Gullbrand

Friday

et al. 2022

Preprint

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Conventional treatment for intervertebral disc herniation alleviates pain but does not repair the annulus fibrosus (AF), resulting in a high incidence of recurrent herniation and persistent disfunction. The lack of repair and the acute inflammation that arise after injury further compromises the disc and can result in disc-wide degeneration in the long term. To address this clinical need, we developed tension-activated repair patches (TARPs) for annular repair and the local delivery of bioactive anti-inflammatory factors. TARPs transmit physiologic strains to mechanically-activated microcapsules (MAMCs) embedded within, which activate and release encapsulated biomolecules in response to physiologic loading. Here, we demonstrate that the TARP design modulates implant biomechanical properties and regulates MAMC mechano-activation. Next, the FDA-approved anti-inflammatory molecule, interleukin 1 receptor antagonist, Anakinra, was loaded in TARPs and the effects of TARP-mediated annular repair and Anakinra delivery was evaluated in a model of annular injury in the goat cervical spine. TARPs showed robust integration with the native tissue and provided structural reinforcement at the injury site that prevented disc-wide aberrant remodeling resulting from AF detensioning. The delivery of Anakinra via TARP implantation improved the retention of disc biochemical composition through increased matrix deposition and retention at the site of annular injury. Anakinra delivery additionally attenuated the inflammatory response associated by scaffold implantation, decreasing osteolysis in adjacent vertebrae and preserving disc cellularity and matrix organization throughout the AF. These results demonstrate the translational and therapeutic potential of this novel TARP system for the treatment of intervertebral disc herniations.One Sentence SummaryTension-activated repair patches delivering bioactive anti-inflammatory factors improve healing in an in vivo goat cervical disc injury model.

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“…DDD is considered to be linked to genes that influence IVD structure, catabolic cytokines polymorphisms, and inflammatory cascade cytokine polymorphisms [7]. Variations in the genes producing Type II collagen, a key component of the NP and inner AF extracellular matrix (ECM) [8].…”

Section: Genetics and Degenerated Discmentioning

confidence: 99%

“…Polymorphisms in the growth differentiation of factor 5, vitamin D receptor, and matrix degradative protease genes, among others, have been associated with IVD. however, the amount of each genes effect on the illness remains unclear [8].…”

Section: Vitamin D and Degenerated Discmentioning

confidence: 99%

“…This change in collagen types in the NP and inner AF is followed by a reduction in aggrecan concentration, resulting in disc hydration and turgor pressure loss Excessive pressures on the weaker outer AF lamellae eventually result in the creation of cracks and fissures, which increases the possibility of NP material seeping into the outer AF. Furthermore, these defects in the degenerated discs outer AF enable neoinnervation and angiogenesis within the IVD [8].…”

Section: Aging and Degenerated Discmentioning

confidence: 99%

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An Overview in the Management of Lumbar Degenerative Disc Diseases: Review Article

Albaker

Younis

Hafiz

et al. 2021

JPRI

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The degenerative disease of the intervertebral disc and back pain are chronic conditions that are caused by several factors and represent an important cause of morbidity and mortality in everyday clinical practice. The study aims to summarize the updated evidence regards epidemiology, pathophysiology, clinical manifestation, diagnosis, and management of degenerative disc diseases. The incidence of low back pain, which is the main symptom in Intervertebral Disc (IVD) disease, varies widely among different reports. It is the fifth most common cause for the visit to the doctor and affects 7.6 to 37% of patients. IVD degeneration is attributed to a complex interplay between environmental and genetic factors. DDD is a process that includes a progressive decrease in disk nutrient supply and changes in extracellular matrix (ECM) composition, which weakens the tissue strength and alters the cell metabolism.Degenerative lumb disc disease patients typically present with mechanical lower back pain, which is worse on forward flexion and when carrying heavy load. The pain is relieved with rest. Diagnosis of DDD is done by various methods, computed tomography (CT) scan, magnetic resonance imaging (MRI), and provocative discography. These methods should be used in conjunction with the patient history, physical examination and specific biomarker to monitor the response to treatment. There are three major lines of management of DDD; Treatment Options for Relief of Pain in Conservative Therapy.Treatment with Aims of Restoration, Repair, and Regeneration of Intervertebral Disc Diseases: Molecular Therapy. Reconstructive Strategies: Percutaneous Intervertebral Disc Techniques. Definitive Treatment for Intervertebral Disc Diseases :( surgical management).

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Pathomechanism and Biomechanics of Degenerative Disc Disease: Features of Healthy and Degenerated Discs

Cited by 35 publications

References 170 publications

Regenerating and repairing degenerative intervertebral discs by regulating the micro/nano environment of degenerative bony endplates based on low-tension mechanics

Regenerating and repairing degenerative intervertebral discs by regulating the micro/nano environment of degenerative bony endplates based on low-tension mechanics

Anti-Inflammatory Tension-Activated Repair Patches Improve Repair After Intervertebral Disc Herniation

An Overview in the Management of Lumbar Degenerative Disc Diseases: Review Article

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