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      Mimicking the Annulus Fibrosus Using Electrospun Polyester Blended Scaffolds

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          Abstract

          Treatments to alleviate chronic lower back pain, caused by intervertebral disc herniation as a consequence of degenerate annulus fibrosus (AF) tissue, fail to provide long-term relief and do not restore tissue structure or function. This study aims to mimic the architecture and mechanical environment of AF tissue using electrospun fiber scaffolds made from synthetic biopolymers-poly(ε-caprolactone) (PCL) and poly(L-lactic) acid (PLLA). Pure polymer and their blends (PCL%:PLLA%; 80:20, 50:50, and 20:80) are studied and material properties-fiber diameter, alignment, % crystallinity, tensile strength, and water contact angle-characterized. Tensile properties of fibers angled at 0°, 30°, and 60° (single layer scaffolds), and ±0°, ±30°, and ±60° (bilayer scaffolds) yield significant differences, with PCL being significantly stiffer with the addition of PLLA, and bilayer scaffolds considerably stronger. Findings suggest PCL:PLLA 50:50 fibers are similar to human AF properties. Furthermore, in vitro culture of AF cells on 50:50 fibers demonstrates attachment and proliferation over seven days. The optimal polymer composition for production of scaffolds that closely mimic AF tissue both structurally, mechanically, and which also support and guide favorable cell phenotype is identified. This study takes a step closer towards successful AF tissue engineering and a long-term treatment for sufferers of chronic back pain.

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          Most cited references49

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          A Review of Animal Models of Intervertebral Disc Degeneration: Pathophysiology, Regeneration, and Translation to the Clinic

          Lower back pain is the leading cause of disability worldwide. Discogenic pain secondary to intervertebral disc degeneration is a significant cause of low back pain. Disc degeneration is a complex multifactorial process. Animal models are essential to furthering understanding of the degenerative process and testing potential therapies. The adult human lumbar intervertebral disc is characterized by the loss of notochordal cells, relatively large size, essentially avascular nature, and exposure to biomechanical stresses influenced by bipedalism. Animal models are compared with regard to the above characteristics. Numerous methods of inducing disc degeneration are reported. Broadly these can be considered under the categories of spontaneous degeneration, mechanical and structural models. The purpose of such animal models is to further our understanding and, ultimately, improve treatment of disc degeneration. The role of animal models of disc degeneration in translational research leading to clinical trials of novel cellular therapies is explored.
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            Investigation of the laminate structure of lumbar disc anulus fibrosus.

            The structure of the lumbar disc anulus fibrosus was investigated using a layer-by-layer peeling technique and microscopic examination of various cut surfaces. Anulus specimens from spines of two different age groups and from two levels, L2-3 and L4-5, were examined. The vertebra-disc-vertebra units were subjected to intentional controlled dehydration to enhance the visual contrast between the white opaque fiber bundles and the translucent ground substance. The variations of the anulus structure with circumferential and radial locations were studied. The following principal structural features were quantified: 1) the anulus, excluding the transition zone, consists of 15 to 25 distinct layers, depending on the circumferential location, the spine level, and the specimen age; 2) in any 20 degrees circumferential sector, nearly half of the layers terminate or originate, thereby causing local laminate irregularities; 3) there are two identifiable mechanisms of layer interruption at these irregularities; 4) the thickness of individual layers varies both circumferentially and radially and increases markedly with age; and 5) the number of fiber bundles over the total height of the disc varies from 20 to 62, with an average interbundle spacing of 0.22 mm.
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              NANOFIBROUS BIOLOGIC LAMINATES REPLICATE THE FORM AND FUNCTION OF THE ANNULUS FIBROSUS

              Successful engineering of load-bearing tissues requires recapitulation of their complex mechanical functions. Given the intimate relationship between function and form, biomimetic materials that replicate anatomic form are of great interest for tissue engineering applications. However, for complex tissues such as the annulus fibrosus, scaffolds have failed to capture their multi-scale structural hierarchy. Consequently, engineered tissues have yet to reach functional equivalence with their native counterparts. Here we present a novel strategy for annulus fibrosus tissue engineering that replicates this hierarchy with anisotropic nanofibrous laminates seeded with mesenchymal stem cells. These scaffolds directed the deposition of organized, collagen-rich extracellular matrix that mimicked the angle-ply, multi-lamellar architecture and achieved mechanical parity with native tissue after 10 weeks of in vitro culture. Further, we identified a novel role for inter-lamellar shearing in reinforcing the tensile response of biologic laminates, a mechanism that has not previously been considered for these tissues.
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                Author and article information

                Journal
                Nanomaterials (Basel)
                Nanomaterials (Basel)
                nanomaterials
                Nanomaterials
                MDPI
                2079-4991
                03 April 2019
                April 2019
                : 9
                : 4
                : 537
                Affiliations
                [1 ]School of Materials, Faculty of Science and Engineering, The University of Manchester, Oxford Road, Manchester M13 9PL, UK; alyahhhh.shamsah@ 123456postgrad.manchester.ac.uk (A.H.S.); sarah.cartmell@ 123456manchester.ac.uk (S.H.C.)
                [2 ]School of Biology, Faculty of Biology, Medicine and Health, The University of Manchester, Oxford Road, Manchester M13 9PL, UK; s.richardson@ 123456manchester.ac.uk
                [3 ]Department of Eye and Vision Science, Institute of Ageing and Chronic Disease, 6 West Derby Street, University of Liverpool, Liverpool L7 8TX, UK
                Author notes
                [* ]Correspondence: lucy.bosworth@ 123456liverpool.ac.uk ; Tel.: +44-(0)151-794-9009
                Author information
                https://orcid.org/0000-0001-6864-0846
                https://orcid.org/0000-0002-6726-4663
                Article
                nanomaterials-09-00537
                10.3390/nano9040537
                6523918
                30987168
                e6c689d0-f1f9-403c-be7a-41f13f7d0da1
                © 2019 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 28 February 2019
                : 30 March 2019
                Categories
                Article

                electrospinning,intervertebral discs,annulus fibrosus,polycaprolactone,poly(l-lactic) acid

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