IVD Degeneration and Repair

“Having a spine” is to be able to have tenacity. Just as the metaphor suggests, the spine does indeed support us and when problems arise with it, disaster occurs. One of these problems is herniation. The mechanism behind herniations is a complex topic, and researchers are now increasingly concerned with studying the gelatinous discs in our backs in order to find innovative ways to repair ruptures.

Composition and organization of the IVD

The spine is composed of 33 vertebrae with gelatinous discs that act as shock cushions in between each bone segment. These discs are known as the intervertebral discs (IVD) and are composed of a three-joint complex that includes two adjacent vertebral bodies (Bowles, 2017). The IVD is composed of two distinct tissues: the outer, type I collagen-rich annulus fibrosus (AF), and the inner, type II collagen-rich nucleus pulposus (NP). It is also the largest avascular — meaning  lacking blood vessels — organ in the body (Urban, 2005).

The AF is fibrocartilaginous, meaning it is composed of highly-ordered collagen fibers that give rise to anisotropic effects. This simply means that the mechanical properties of the tissue will differ depending on the orientation of the disc (Bowles, 2017). Under conditions of high tensile stress, for instance, AF tissues are able to withstand a great degree of pressure. However, in the process of degeneration which accelerates with age, the collagen of the AF becomes disordered and self-reparation is difficult due to the avascular nature of the AF tissue and its relatively low cell density. As a result, the AF becomes more susceptible to tears and fissures which can ultimately cause herniation and displacement of IVD fragments (Bowles, 2017). The NP, in contrast, is a highly hydrated gelatinous tissue but is plagued by similar problems. It too suffers from low cell density. In addition, high proteoglycan density is imperative for the proper functioning of NP tissues, yet it tends to decrease with age (Bowles, 2017). Therefore, the elderly are at higher risk for NP tissue degeneration.

The degeneration of IVD eventually lead to more serious conditions including herniation. Herniation occurs when the NP protrudes through AF defects or fissures, and applies pressure on surrounding nerves, causing pain (Sloan, 2018). Current discectomy procedures treat only the symptoms of acute herniation and pain but do not repair the AF tissues at the root of the problem (Bowles, 2017). As a result, a considerable number of patients that receive treatment are at high risk for reoperation. Among the 3-4 million people who experience sciatica in the U.S. annually, around 300,000 – 400,000 receive a discectomy (Hagon, 2017). Among them, 30-40% are considered at a high risk of reoperation (Hagon, 2017) These statistics are not ideal, suggesting that a new standard of care is necessary that targets the causal root and mitigates the chances for repeated treatment. 

Herniation of the nucleus pulposus impinging on a nerve.

There are two alternative options that  have received increasingly large amounts of attention. These methods are X-Close® and Barricaid®, both focusing on mechanical means of closing AF fissures. X-Close®, for instance, embeds four anchor points around the AF fissure and “stitches” the fissure closed (Sharifi, 2014). However, problems persist even with this method.  X-Close may close the tear in the AF, but it fails to restore the native flexible properties of healthy AF tissues (Sharifi, 2014). The use of anchor points also creates weak spots in the AF tissue, which may lead to additional tears (Sharifi, 2014). Barricaid®, the other mechanical method, inserts a metal implement into the patient’s herniated IVD to provide support to the surrounding vertebrae in a similar manner to the IVD. However, if the device were to undergo deformation, it could potentially further complicate the injury (Hagon, 2017). Both of these methods, while an improvement, fail to reduce peak concentration stresses because they are unable to restore the native mechanical properties of AF tissues. However, these mechanical methods remain appealing to device creators due to their simplicity and rapid application during surgery.

Another method that has garnered significant attention is the use of hydrogels in a void-fill type repair. An ideal AF repair would rejuvenate the tissues’ original mechanical properties and promote long-term healing within the region (Long, 2016). Hydrogels in particular may be quite useful for such repairs since they can be tuned to mimic AF properties and can potentially be adapted for surgical implementation. However, limitations still abound. As aforementioned, IVD fibers are anisotropic, and for the largely isotropic/uniform hydrogels, they would be unable to completely mimic the physical properties of the intervertebral disc (Long, 2016).

Tissue engineering is another possible method and is currently being tested for IVD repair. The goal of tissue engineering is to create structures or constructs that will mend damaged AF tissue by replicating the highly-ordered nature of the intervertebral disc. This can be achieved through methods such as electrospinning, where fibers are essentially spun through an electric field, thereby specifying their orientation. The only downside is that these materials cannot be injected into wounds and can only be implemented via invasive surgical techniques (Long, 2016).

When considering IVD repair, it is important to not only consider the mechanical aspects of the disc but the cellular components as well. The combination of low cellularity and lack of vascularity, results in extremely poor regenerative properties so the maintenance of the tissue during treatment is imperative to mitigate further damage (Bowles, 2017). The materials used must be biocompatible and harmless to the cells. Cytotoxicity materials could very well cause further disc degeneration by damaging the surrounding healthy tissue (Adams and Roughly, 2006).

All of the aforementioned methods are being actively studied by private and public entities alike in an effort to create a viable standard-of-care for IVD rehabilitation. It is unlikely that a truly comprehensive strategy will emerge via a single method alone. Instead, it will most likely be through a combination of methods that we reach a final conclusion.

Edited by Thalia Le

References

Adams, M. A., & Roughley, P. J. (2006). What is Intervertebral Disc Degeneration, and What Causes It? Spine, 31(18), 2151–2161. doi: 10.1097/01.brs.0000231761.73859.2c

Anderson, J. M., Rodriguez, A., & Chang, D. T. (2008). Foreign body reaction to biomaterials. Seminars in Immunology, 20(2), 86–100. doi: 10.1016/j.smim.2007.11.004

Bowles, R+. (2017). Biomaterials for Intervertebral Disc Regeneration and Repair. Biomaterials.

Hagon, Cary. (2017). Barricaid Annular Closure Device. FDA Review.

Helmus, M. N., Gibbons, D. F., & Cebon, D. (2008). Biocompatibility: Meeting a Key Functional Requirement of Next-Generation Medical Devices. Toxicologic Pathology, 36(1), 70–80. doi: 10.1177/0192623307310949 

Long, R+. (2016). Design Requirements for Annulus Fibrosus Repair: Review of Forces, 

Displacements, and Material Properties of the Intervertebral Disk and a Summary of Candidate Hydrogels for Repair. JBME.

Sharifi, S+. (2014). Treatment of the Degenerated Intervertebral Disc; Closure, Repair and Regeneration of the Annulus Fibrosus. Tissue of Regenerative Medicine. 

Sloan, S+. (2018). Biologic Annulus Fibrosus Repair: A Review of Preclinical In Vivo Investigations. Tissue Engineering.

Urban, J. P., Smith, S., & Fairbank, J. C. (2004). Nutrition of the Intervertebral Disc. Spine, 29(23), 2700–2709. doi: 10.1097/01.brs.0000146499.97948.52Tissue Engineering and Regenerative Medicine. (n.d.). Retrieved from https://www.nibib.nih.gov/science-education/science-topics/tissue-engineering-and-regenerative-medicine.

Image References

Intervertebral disc. (2019, September 17). Retrieved from https://en.wikipedia.org/wiki/Intervertebral_disc

Logic, P. (2016, December 30). What is a Herniated Disc?: Physio Logic Downtown Brooklyn Blog. Retrieved from https://physiologicnyc.com/treatment-for-herniated-disc/

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