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      A Clinical, Biological, and Biomaterials Perspective into Tendon Injuries and Regeneration

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          Abstract

          Tendon injury is common and debilitating, and it is associated with long-term pain and ineffective healing. It is estimated to afflict 25% of the adult population and is often a career-ending disease in athletes and racehorses. Tendon injury is associated with high morbidity, pain, and long-term suffering for the patient. Due to the low cellularity and vascularity of tendon tissue, once damage has occurred, the repair process is slow and inefficient, resulting in mechanically, structurally, and functionally inferior tissue. Current treatment options focus on pain management, often being palliative and temporary and ending in reduced function. Most treatments available do not address the underlying cause of the disease and, as such, are often ineffective with variable results. The need for an advanced therapeutic that addresses the underlying pathology is evident. Tissue engineering and regenerative medicine is an emerging field that is aimed at stimulating the body's own repair system to produce de novo tissue through the use of factors such as cells, proteins, and genes that are delivered by a biomaterial scaffold. Successful tissue engineering strategies for tendon regeneration should be built on a foundation of understanding of the molecular and cellular composition of healthy compared with damaged tendon, and the inherent differences seen in the tissue after disease. This article presents a comprehensive clinical, biological, and biomaterials insight into tendon tissue engineering and regeneration toward more advanced therapeutics.

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          Most cited references100

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          Structure of the tendon connective tissue.

          P Kannus (2000)
          Tendons consist of collagen (mostly type I collagen) and elastin embedded in a proteoglycan-water matrix with collagen accounting for 65-80% and elastin approximately 1-2% of the dry mass of the tendon. These elements are produced by tenoblasts and tenocytes, which are the elongated fibroblasts and fibrocytes that lie between the collagen fibers, and are organized in a complex hierarchical scheme to form the tendon proper. Soluble tropocollagen molecules form cross-links to create insoluble collagen molecules which then aggregate progressively into microfibrils and then into electronmicroscopically clearly visible units, the collagen fibrils. A bunch of collagen fibrils forms a collagen fiber, which is the basic unit of a tendon. A fine sheath of connective tissue called endotenon invests each collagen fiber and binds fibers together. A bunch of collagen fibers forms a primary fiber bundle, and a group of primary fiber bundles forms a secondary fiber bundle. A group of secondary fiber bundles, in turn, forms a tertiary bundle, and the tertiary bundles make up the tendon. The entire tendon is surrounded by a fine connective tissue sheath called epitenon. The three-dimensional ultrastructure of tendon fibers and fiber bundles is complex. Within one collagen fiber, the fibrils are oriented not only longitudinally but also transversely and horizontally. The longitudinal fibers do not run only parallel but also cross each other, forming spirals. Some of the individual fibrils and fibril groups form spiral-type plaits. The basic function of the tendon is to transmit the force created by the muscle to the bone, and, in this way, make joint movement possible. The complex macro- and microstructure of tendons and tendon fibers make this possible. During various phases of movements, the tendons are exposed not only to longitudinal but also to transversal and rotational forces. In addition, they must be prepared to withstand direct contusions and pressures. The above-described three-dimensional internal structure of the fibers forms a buffer medium against forces of various directions, thus preventing damage and disconnection of the fibers.
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            Tendon injury and tendinopathy: healing and repair.

            Tendon disorders are frequent and are responsible for substantial morbidity both in sports and in the workplace. Tendinopathy, as opposed to tendinitis or tendinosis, is the best generic descriptive term for the clinical conditions in and around tendons arising from overuse. Tendinopathy is a difficult problem requiring lengthy management, and patients often respond poorly to treatment. Preexisting degeneration has been implicated as a risk factor for acute tendon rupture. Several physical modalities have been developed to treat tendinopathy. There is limited and mixed high-level evidence to support the, albeit common, clinical use of these modalities. Further research and scientific evaluation are required before biological solutions become realistic options.
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              Viral vectors for gene therapy: the art of turning infectious agents into vehicles of therapeutics.

              Considered by some to be among the simpler forms of life, viruses represent highly evolved natural vectors for the transfer of foreign genetic information into cells. This attribute has led to extensive attempts to engineer recombinant viral vectors for the delivery of therapeutic genes into diseased tissues. While substantial progress has been made, and some clinical successes are over the horizon, further vector refinement and/or development is required before gene therapy will become standard care for any individual disorder.
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                Author and article information

                Journal
                Tissue Eng Part B Rev
                Tissue Eng Part B Rev
                teb
                Tissue Engineering. Part B, Reviews
                Mary Ann Liebert, Inc. (140 Huguenot Street, 3rd FloorNew Rochelle, NY 10801USA )
                1937-3368
                1937-3376
                01 February 2017
                01 February 2017
                01 February 2017
                : 23
                : 1
                : 44-58
                Affiliations
                [ 1 ]School of Pharmacy, University of East Anglia , Norwich, United Kingdom.
                [ 2 ]Norfolk and Norwich University Hospital , Norwich, United Kingdom.
                [ 3 ]Norwich Medical School, University of East Anglia , Norwich, United Kingdom.
                [ 4 ]Neotherix Limited , York, United Kingdom.
                [ 5 ]University of Leeds , Leeds, United Kingdom.
                [ 6 ]School of Biological Sciences, University of East Anglia , Norwich, United Kingdom.
                Author notes
                Address correspondence to: Aram Saeed, PhD, School of Pharmacy, University of East Anglia Norwich, United Kingdom

                E-mail: aram.saeed@ 123456uea.ac.uk
                Article
                10.1089/ten.teb.2016.0181
                10.1089/ten.teb.2016.0181
                5312458
                27596929
                32ff4887-1a7f-465f-8a2b-8cba439dbf2f
                © Grace Walden et al., 2017; Published by Mary Ann Liebert, Inc.

                This Open Access article is distributed under the terms of the Creative Commons License ( http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited.

                History
                : 06 May 2016
                : 22 August 2016
                Page count
                Figures: 2, Tables: 4, References: 121, Pages: 15
                Categories
                Review Articles

                tendon injury,tissue engineering,tendinopathy,tendon rupture,injectable scaffold,implant

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