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      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

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          Abstract

          <p class="first" id="d9891312e235">There is currently a lack of clinically available solutions to restore functionality to the intervertebral disk (IVD) following herniation injury to the annulus fibrosus (AF). Microdiscectomy is a commonly performed surgical procedure to alleviate pain caused by herniation; however, AF defects remain and can lead to accelerated degeneration and painful conditions. Currently available AF closure techniques do not restore mechanical functionality or promote tissue regeneration, and have risk of reherniation. This review determined quantitative design requirements for AF repair materials and summarized currently available hydrogels capable of meeting these design requirements by using a series of systematic PubMed database searches to yield 1500+ papers that were screened and analyzed for relevance to human lumbar in vivo measurements, motion segment behaviors, and tissue level properties. We propose a testing paradigm involving screening tests as well as more involved in situ and in vivo validation tests to efficiently identify promising biomaterials for AF repair. We suggest that successful materials must have high adhesion strength (∼0.2 MPa), match as many AF material properties as possible (e.g., approximately 1 MPa, 0. 3 MPa, and 30 MPa for compressive, shear, and tensile moduli, respectively), and have high tensile failure strain (∼65%) to advance to in situ and in vivo validation tests. While many biomaterials exist for AF repair, few undergo extensive mechanical characterization. A few hydrogels show promise for AF repair since they can match at least one material property of the AF while also adhering to AF tissue and are capable of easy implantation during surgical procedures to warrant additional optimization and validation. </p>

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          Most cited references115

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          New in vivo measurements of pressures in the intervertebral disc in daily life.

          We conducted intradiscal pressure measurements with one volunteer performing various activities normally found in daily life, sports, and spinal therapy. The goal of this study was to measure intradiscal pressure to complement earlier data from Nachemson with dynamic and long-term measurements over a broad range of activities. Loading of the spine still is not well understood. The most important in vivo data are from pioneering intradiscal pressure measurements recorded by Nachemson during the 1960s. Since that time, there have been few data to corroborate or dispute those findings. Under sterile surgical conditions, a pressure transducer with a diameter of 1.5 mm was implanted in the nucleus pulposus of a nondegenerated L4-L5 disc of a male volunteer 45-years-old and weighing 70 kg. Pressure was recorded with a telemetry system during a period of approximately 24 hours for various lying positions; sitting positions in a chair, in an armchair, and on a pezziball (ergonomic sitting ball); during sneezing, laughing, walking, jogging, stair climbing, load lifting during hydration over 7 hours of sleeping, and others. The following values and more were measured: lying prone, 0.1 MPa; lying laterally, 0.12 MPa; relaxed standing, 0.5 MPa; standing flexed forward, 1.1 MPa; sitting unsupported, 0.46 MPa; sitting with maximum flexion, 0.83 MPa; nonchalant sitting, 0.3 MPa; and lifting a 20-kg weight with round flexed back, 2.3 MPa; with flexed knees, 1.7 MPa; and close to the body, 1.1 MPa. During the night, pressure increased from 0.1 to 0.24 MPa. Good correlation was found with Nachemson's data during many exercises, with the exception of the comparison of standing and sitting or of the various lying positions. Notwithstanding the limitations related to the single-subject design of this study, these differences may be explained by the different transducers used. It can be cautiously concluded that the intradiscal pressure during sitting may in fact be less than that in erect standing, that muscle activity increases pressure, that constantly changing position is important to promote flow of fluid (nutrition) to the disc, and that many of the physiotherapy methods studied are valid, but a number of them should be re-evaluated.
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            A novel rabbit model of mild, reproducible disc degeneration by an anulus needle puncture: correlation between the degree of disc injury and radiological and histological appearances of disc degeneration.

            An in vivo study to radiographically and histologically assess a new method of induction of disc degeneration. OBJECTIVE.: To establish a reproducible rabbit model of disc degeneration by puncturing the anulus with needles of defined gauges and to compare it to the classic stab model. New treatment approaches to disc degeneration are of great interest. Although animal models for disc degenerative disease exist, the quantitative measurement of disease progression remains difficult. A reproducible, progressive disc degeneration model, which can be induced in a reasonable time frame, is essential for development of new therapeutic interventions. The classic anular stab model and the new needle puncture model were used in the rabbit. For the needle puncture model, 3 different gauges of needle (16G, 18G, and 21G) were used to induce an injury to the disc to a depth of 5 mm. Radiographic and histologic analyses were performed; magnetic resonance images were also assessed in the needle puncture model. Significant disc space narrowing was observed as early as 2 weeks after stabbing in the classic stab model; there was no further narrowing of the disc space. In the needle puncture model, all needle sizes tested induced a slower and more progressive decrease in disc height than in the classic stab model. The magnetic resonance imaging supported the results of disc height data. The needle puncture approach, using 16G to 21G needles, resulted in a reproducible decrease of disc height and magnetic resonance imaging grade. The ease of the procedure and transfer of the methodology will benefit researchers studying disc degeneration.
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              Stem cell therapy for intervertebral disc regeneration: obstacles and solutions.

              Intervertebral disc (IVD) degeneration is frequently associated with low back and neck pain, which accounts for disability worldwide. Despite the known outcomes of the IVD degeneration cascade, the treatment of IVD degeneration is limited in that available conservative and surgical treatments do not reverse the pathology or restore the IVD tissue. Regenerative medicine for IVD degeneration, by injection of IVD cells, chondrocytes or stem cells, has been extensively studied in the past decade in various animal models of induced IVD degeneration, and has progressed to clinical trials in the treatment of various spinal conditions. Despite preliminary results showing positive effects of cell-injection strategies for IVD regeneration, detailed basic research on IVD cells and their niche indicates that transplanted cells are unable to survive and adapt in the avascular niche of the IVD. For this therapeutic strategy to succeed, the indications for its use and the patients who would benefit need to be better defined. To surmount these obstacles, the solution will be identified only by focused research, both in the laboratory and in the clinic.
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                Author and article information

                Journal
                Journal of Biomechanical Engineering
                J Biomech Eng
                ASME International
                0148-0731
                February 01 2016
                January 27 2016
                : 138
                : 2
                : 021007
                Affiliations
                [1 ]Icahn School of Medicine at Mount Sinai, Leni and Peter W. May Department of Orthopaedics, New York, NY 10029;
                [2 ]Collaborative Research Partner Annulus Fibrosus Rupture Program of AO Foundation, Davos 7270, Switzerland e-mail: rose.long@mssm.edu
                [3 ]Icahn School of Medicine at Mount Sinai, Leni and Peter W. May Department of Orthopaedics, One Gustave Levy Place, Box 1188, New York, NY 10029 e-mail: olivia.torre@icahn.mssm.edu
                [4 ]Icahn School of Medicine at Mount Sinai, Leni and Peter W. May Department of Orthopaedics, One Gustave Levy Place, Box 1188, New York, NY 10029 e-mail: warren.hom@mssm.edu
                [5 ]Icahn School of Medicine at Mount Sinai, Leni and Peter W. May Department of Orthopaedics, One Gustave Levy Place, Box 1188, New York, NY 10029 e-mail: dylan.assael@icahn.mssm.edu
                [6 ]Icahn School of Medicine at Mount Sinai, Leni and Peter W. May Department of Orthopaedics, One Gustave Levy Place, Box 1188, New York, NY 10029;
                [7 ]Collaborative Research Partner Annulus Fibrosus Rupture Program of AO Foundation, Davos 7270, Switzerland e-mail: james.iatridis@mssm.edu
                Article
                10.1115/1.4032353
                4844119
                26720265
                fbc5c681-7f28-473f-a5b3-7a5354c06e1f
                © 2016
                History

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