Recent advances in biological therapies for disc degeneration: tissue engineering of the annulus fibrosus, nucleus pulposus and whole intervertebral discs

2013 ◽  
Vol 24 (5) ◽  
pp. 872-879 ◽  
Author(s):  
Katherine D Hudson ◽  
Marjan Alimi ◽  
Peter Grunert ◽  
Roger Härtl ◽  
Lawrence J Bonassar
Keyword(s):  
Tissue Engineering ◽  
Nucleus Pulposus ◽  
Disc Degeneration ◽  
Annulus Fibrosus ◽  
Intervertebral Discs ◽  
Biological Therapies ◽  
Recent Advances

scholarly journals Disordered Mechanical Stress and Tissue Engineering Therapies in Intervertebral Disc Degeneration

Polymers ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 1151 ◽  
Author(s):  
Runze Zhao ◽  
Wanqian Liu ◽  
Tingting Xia ◽  
Li Yang
Keyword(s):  
Tissue Engineering ◽  
Back Pain ◽  
Intervertebral Disc ◽  
Mechanical Stress ◽  
Nucleus Pulposus ◽  
Disc Degeneration ◽  
Annulus Fibrosus ◽  
Intervertebral Disc Degeneration ◽  
Intervertebral Discs ◽  
Body Motion

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.

scholarly journals Evaluation of apoptotic cell death in normal and chondrodystrophic canine intervertebral discs

2012 ◽  
Vol 2 (1) ◽  
pp. 6 ◽  
Author(s):  
Marie Klauser ◽  
Franck Forterre ◽  
Marcus Doherr ◽  
Andreas Zurbriggen ◽  
David Spreng ◽  
...  
Keyword(s):  
Nucleus Pulposus ◽  
Disc Degeneration ◽  
Annulus Fibrosus ◽  
Caspase 3 ◽  
Apoptotic Cell ◽  
Intervertebral Discs ◽  
Discogenic Pain ◽  
Age Related ◽  
Chondroid Metaplasia ◽  
Related Increase

Disc degeneration occurs commonly in dogs. A variety of factors is thought to contribute an inappropriate disc matrix that isolate cells in the disc and lead to apoptosis. Disc herniation with radiculopathy and discogenic pain are the results of the degenerative process. The objective of this prospective study was to determine the extent of apoptosis in intact and herniated intervertebral discs of chondrodystrophic dogs and non-chondrodystrophic dogs. In addition, the nucleus pulposus (NP) was histologically compared between non-chondrodystrophic and chondrodystrophic dogs. Thoracolumbar intervertebral discs and parts of the extruded nucleus pulposus were harvested from 45 dogs. Samples were subsequently stained with haematoxylin-eosin and processed to detect cleaved caspase-3 and poly(ADP-ribose) polymerase. A significant greater degree of apoptosis was observed in herniated NPs of chondrodystrophic dogs compared to non- chondrodystrophic dogs with poly (ADP-ribose) polymerase and cleaved caspase- 3 detection. Within the group of chondrodystrophic dogs, dogs with an intact disc and younger than 6 years showed a significant lower incidence of apoptosis in the NP compared to the herniated NP of chondrodystrophic dogs. The extent of apoptosis in the annulus fibrosus was not different between the intact disc from chondrodystrophic and non- chondrodystrophic dogs. An age-related increase of apoptotic cells in NP and annulus fibrosus was found in the intact non-herniated intervertebral discs. Histologically, absence of notochordal cells and occurrence of chondroid metaplasia were observed in the nucleus pulposus of chondrodystrophic dogs. As a result, we found that apoptosis plays a role in disc degeneration in chondrodystrophic dogs.

scholarly journals Intervertebral Disc Degeneration in Warmblood Horses: Morphology, Grading, and Distribution of Lesions

2018 ◽  
Vol 55 (3) ◽  
pp. 442-452 ◽  
Author(s):  
Wilhelmina Bergmann ◽  
Niklas Bergknut ◽  
Stefanie Veraa ◽  
Andrea Gröne ◽  
Hans Vernooij ◽  
...  
Keyword(s):  
Intervertebral Disc ◽  
Nucleus Pulposus ◽  
Disc Degeneration ◽  
Clinical Relevance ◽  
Annulus Fibrosus ◽  
Intervertebral Disc Degeneration ◽  
Thoracolumbar Spine ◽  
Intervertebral Discs ◽  
Vertebral Bone ◽  
Cleft Formation

Equine intervertebral disc degeneration is thought to be rare and of limited clinical relevance, although research is lacking. To objectively assess pathological changes of the equine intervertebral disc and their clinical relevance, description of the normal morphology and a practical, biologically credible grading scheme are needed. The objectives of this study are to describe the gross and histological appearance of the equine intervertebral discs and to propose a grading scheme for macroscopic degeneration. Spinal units from 33 warmblood horses were grossly analyzed and scored. Of the 286 intervertebral discs analyzed, 107 (37%) were assigned grade 1 and grade 2 (considered normal) and were analyzed histologically. A nucleus pulposus and an annulus fibrosus could be identified macroscopically and histologically. Histologically, the nucleus pulposus was composed of a cartilaginous matrix and the annulus fibrosus of parallel collagenous bands. A transition zone was also histologically visible. Intra- and inter-observer reliability scores were high for all observers. Higher grades were associated with greater age. Gross changes associated with equine intervertebral disc degeneration (grades 3–5)—that is, yellow discoloration, cleft formation (tearing), and changes in consistency of the nucleus pulposus—were largely similar to those in humans and dogs and were most prevalent in the caudal cervical spine. Equine intervertebral disc degeneration was not associated with osteophyte formation. Changes of the vertebral bone were most common in the thoracolumbar spine but were not correlated with higher grades of intervertebral disc degeneration. Thus, changes of the vertebral bone should be excluded from grading for equine intervertebral disc degeneration.

The Influence of Axial Compression on the Cellular and Mechanical Function of Spinal Tissues; Emphasis on The Nucleus Pulposus and Annulus Fibrosus

2021 ◽  
Author(s):  
John McMorran ◽  
Diane Gregory
Keyword(s):  
Intervertebral Disc ◽  
Nucleus Pulposus ◽  
Axial Compression ◽  
Disc Degeneration ◽  
Annulus Fibrosus ◽  
Intervertebral Disc Degeneration ◽  
Chronic Back Pain ◽  
Physiological State ◽  
Movement Pattern ◽  
Mechanical Function

Abstract In light of the correlation between chronic back pain and intervertebral disc degeneration, this literature review seeks to illustrate the importance of the hydraulic response across the nucleus pulposus- annulus fibrosus interface, by synthesizing current information regarding injurious biomechanics of the spine, stemming from axial compression. Damage to vertebrae, endplates, the nucleus pulposus, and the annulus fibrosus, can all arise from axial compression, depending on the segment's posture, the manner in which it is loaded, and the physiological state of tissue. Therefore, this movement pattern was selected to illustrate the importance of the bracing effect of a pressurized nucleus pulposus on the annulus fibrosus, and how injuries interrupting support to the annulus fibrosus may contribute to intervertebral disc degeneration.

Mesenchymal Stem Cell-Seeded High-Density Collagen Gel for Annular Repair: 6-Week Results From In Vivo Sheep Models

Neurosurgery ◽  
2018 ◽  
Vol 85 (2) ◽  
pp. E350-E359 ◽  
Author(s):  
Ibrahim Hussain ◽  
Stephen R Sloan ◽  
Christoph Wipplinger ◽  
Rodrigo Navarro-Ramirez ◽  
Micaella Zubkov ◽  
...  
Keyword(s):  
Nucleus Pulposus ◽  
Annulus Fibrosus ◽  
Perioperative Complications ◽  
Collagen Gel ◽  
Intervertebral Discs ◽  
High Density ◽  
Sheep Model ◽  
Gel Treatment ◽  
Pfirrmann Grade

AbstractBACKGROUNDOur group has previously demonstrated in vivo annulus fibrosus repair in animal models using an acellular, riboflavin crosslinked, high-density collagen (HDC) gel.OBJECTIVETo assess if seeding allogenic mesenchymal stem cells (MSCs) into this gel yields improved histological and radiographic benefits in an in vivo sheep model of annular injury.METHODSFifteen lumbar intervertebral discs (IVDs) were randomized into 4 groups: intact, injury only, injury + acellular gel treatment, or injury + MSC-seeded gel treatment. Sheep were sacrificed at 6 wk. Disc height index (DHI), Pfirrmann grade, nucleus pulposus area, and T2 relaxation time (T2-RT) were calculated for each IVD and standardized to healthy controls from the same sheep. Quantitative histological assessment was also performed using the Han scoring system.RESULTSAll treated IVDs retained gel plugs on gross assessment and there were no adverse perioperative complications. The MSC-seeded gel treatment group demonstrated statistically significant improvement over other experimental groups in DHI (P = .002), Pfirrmann grade (P < .001), and T2-RT (P = .015). There was a trend for greater Han scores in the MSC-seeded gel-treated discs compared with injury only and acellular gel-treated IVDs (P = .246).CONCLUSIONMSC-seeded HDC gel can be delivered into injured IVDs and maintained safely in live sheep to 6 wk. Compared with no treatment and acellular HDC gel, our data show that MSC-seeded HDC gel improves outcomes in DHI, Pfirrmann grade, and T2-RT. Histological analysis shows improved annulus fibrosus and nucleus pulposus reconstitution and organization over other experimental groups as well.

scholarly journals Early differentation of lamellar structure of the intervertebral disc in staged human embryos

2015 ◽  
Vol 84 (3) ◽  
pp. 157-166
Author(s):  
Witold Woźniak ◽  
Małgorzata Grzymisławska ◽  
Joanna Łupicka ◽  
Małgorzata Bruska ◽  
Adam Piotrowski ◽  
...  
Keyword(s):  
Intervertebral Disc ◽  
Nucleus Pulposus ◽  
Annulus Fibrosus ◽  
Developmental Stages ◽  
Intervertebral Discs ◽  
Human Embryos ◽  
Lateral Zone ◽  
Vast Literature ◽  
Dense Zone

Introduction. In the vast literature concerning the development of the intervertebral discs controversies exist as to the period of differentiation and structure of the nucleus pulposus and annulus fibrosus. These controversies result from different determination of age of the investigated embryos. Aim. Using embryos from departmental collection age of which was established according to international Carnegie staging and expressed in postfertilizational days, the differentiation of the intervertebral discs was traced. Material and methods. Study was performed on 34 embryos at developmental stages 13–23 (32–56 days). Embryos were serially sectioned in sagittal, frontal and horizontal planes. Sections were stained with various histological methods and impregnated with silver.Results. Division of sclerotomes into loose cranial and dense caudal zones (sclerotomites) was observed in embryos aged 32 days (stage 13). The intervertebral disc developed from the dense zone of sclerotome and was well recognized in embryos aged 33 days (stage 14). At the end of fifth week (embryos at stage 15, 36 days) the annulus fibrosus and the nucleus pulposus were seen. The annulus fibrosus differentiated into lateral and medial zones. Within the lateral zone cells were arranged into circular rows. These rows were considered as the first stage of laminar structure. In further developmental stages the laminae occupied both zones of the annulus fibrosus.Conclusions. The intervertebral discs develop from the dense zone of the sclerotome which is evident in embryos at stage 13 (32 days). Discs differentiate in embryos aged 33 days, when the nucleus pulposus and annulus fibrosus are recognized. In embryos aged 36 days in the annulus fibrosus circular rows forming laminar arrangement are seen.

Effects of Swelling Conditions on the Compressive Properties of Nucleus Pulposus From Bovine Intervertebral Discs

2004 ◽  
Author(s):  
David T. Korda ◽  
Delphine Perie ◽  
James C. Iatridis
Keyword(s):  
Intervertebral Disc ◽  
Water Content ◽  
Nucleus Pulposus ◽  
Annulus Fibrosus ◽  
Compressive Loading ◽  
Collagen Matrix ◽  
High Water ◽  
Intervertebral Discs ◽  
High Water Content ◽  
Outer Annulus Fibrosus

The intervertebral disc provides flexibility and load support for the spine. It consists of two main regions; the outer annulus fibrosus which is a highly organized collagen matrix and the inner nucleus pulposus which (in a healthy disc) is a proteoglycan rich gelatinous material. The predominant mode of loading on the intervertebral disc is axial compression, which generates hydrostatic pressures within the disc. The high water content of the nucleus plays a major role in supporting these loads. With age and degeneration, the water content of the nucleus changes, and is believed to significantly impact its ability to bear load. The purpose of this study therefore, was to define the effects of swelling conditions (which affect disc hydration) on the material properties of the disc under compressive loading.

Reactive changes in the adolescent porcine spine with disc degeneration due to endplate injury

2007 ◽  
Vol 20 (01) ◽  
pp. 12-17 ◽  
Author(s):  
A. Baranto ◽  
A. Kaigle Holm ◽  
L. Ekström ◽  
L. Swärd ◽  
T. Hansson ◽  
...  
Keyword(s):  
Blood Vessels ◽  
Nucleus Pulposus ◽  
Disc Degeneration ◽  
Annulus Fibrosus ◽  
Scar Tissue ◽  
Vertebral Endplate ◽  
Lumbar Intervertebral Disc ◽  
Physiological Loading ◽  
Reactive Changes ◽  
Chronic Inflammatory Reaction

SummaryDegenerative and reactive structural alterations occurring after experimentally-induced disc degeneration were evaluated using a porcine model. A cranial perforation was made through the L4 vertebral endplate into the nucleus pulposus. Three months later, the lumbar intervertebral disc and adjacent vertebrae were dissected, fixed in formalin and further processed for histopathological analyses. The results showed that there were nucleus pulposus fragments, rather than a distinct border between the nucleus and annulus fibrosus. The central lamellae were distorted and delamination of the outer anterior layers was observed. Blood vessels emerged from the adjacent tissue, penetrated the annulus and branched into the residues of the nucleus. Nerve fibres accompanying the blood vessels could be recognized in the disc within the connective scar tissue. The epiphyseal cartilage plates in the vertebrae were hypertrophic in several areas and there was bone formation directed towards the centre of the vertebral body and the disc. Hypertrophic hyaline cartilage, newly formed bone and scar tissue filled the injury canal. A slight chronic inflammatory reaction was evident along vascular buds. The reactive changes dominated over the degenerated features in the operated disc. Physiological loading enhanced the infiltration of various tissue types characterizing immature cartilage formation. Prominent neovascularisation of the central parts of the disc is likely to be of key importance in turning the degenerative features of the remaining tissue into reactive healthy structures.

scholarly journals Combined Nucleus Pulposus Augmentation and Annulus Fibrosus Repair Prevents Intervertebral Disc Degeneration After Discectomy

Neurosurgery ◽  
2019 ◽  
Vol 66 (Supplement_1) ◽  
Author(s):  
Sertac Kirnaz ◽  
Stephen Sloan ◽  
Christoph Wipplinger ◽  
Franziska Anna Schmidt ◽  
Roger Hartl ◽  
...  
Keyword(s):  
Nucleus Pulposus ◽  
Disc Degeneration ◽  
Annulus Fibrosus ◽  
Combined Treatment ◽  
Disc Height ◽  
Histological Evaluation ◽  
Sheep Model ◽  
Mri Scans ◽  
The Individual

Abstract INTRODUCTION The objective of the current study is to assess the efficacy of combined annulus fibrosus (AF) using a high-density collagen (HDC) gel and nucleus pulposus (NP) repair using a hyaluronic acid (HA) gel in an in Vivo sheep model. METHODS We performed an anterolateral, retroperitoneal prepsoas approach to access the IVDs L1-6 in a total of 8 skeletally mature Finn sheep. IVDs were randomized into 5 groups: (1) intact, (2) injured via 3 × 10 mm box annulotomy and removal of 200 mg of NP, (3) injury and HDC gel patch for AF repair, (4) injury and injection of a HA gel into the NP, and (5) injury and HDC AF repair and NP HA replacement. At 6 wk postoperatively, sheep were sacrificed and underwent postmortem 3T-MRI scans as well as gross anatomical and histological evaluation. Disc height index (DHI) analysis and Pfirrmann grading (PG) were performed on each segment using MR images. RESULTS Intact control discs were not degenerated and had an average PG of 1 while injured, and untreated discs had a significant degeneration with an average PG of 3. Discs receiving the combined injection and collagen AF patch individually showed fewer signs of degeneration than injured alone, and the combined treatment resulted in the least amount of degeneration with PG not significantly different from the intact controls. DHI confirmed the trends seen in the PG, where injured discs lost 20% of the intact disc height, the individual NP and AF repairs restored 5% to 10% of intact disc height, and the combined repairs preserved 90% of the intact disc height. CONCLUSION PG and DHI results demonstrate that individual NP and AF repairs are able to prevent disc degeneration better than no treatment at all; however, the greatest preservation of disc health was seen with combined AF and NP repairs.

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