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      Effect of Uniaxial Tensile Cyclic Loading Regimes on Matrix Organization and Tenogenic Differentiation of Adipose-Derived Stem Cells Encapsulated within 3D Collagen Scaffolds

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          Abstract

          Adipose-derived mesenchymal stem cells have become a popular cell choice for tendon repair strategies due to their relative abundance, ease of isolation, and ability to differentiate into tenocytes. In this study, we investigated the solo effect of different uniaxial tensile strains and loading frequencies on the matrix directionality and tenogenic differentiation of adipose-derived stem cells encapsulated within three-dimensional collagen scaffolds. Samples loaded at 0%, 2%, 4%, and 6% strains and 0.1 Hz and 1 Hz frequencies for 2 hours/day over a 7-day period using a custom-built uniaxial tensile strain bioreactor were characterized in terms of matrix organization, cell viability, and musculoskeletal gene expression profiles. The results displayed that the collagen fibers of the loaded samples exhibited increased matrix directionality with an increase in strain values. Gene expression analyses demonstrated that ASC-encapsulated collagen scaffolds loaded at 2% strain and 0.1 Hz frequency showed significant increases in extracellular matrix genes and tenogenic differentiation markers. Importantly, no cross-differentiation potential to osteogenic, chondrogenic, and myogenic lineages was observed at 2% strain and 0.1 Hz frequency loading condition. Thus, 2% strain and 0.1 Hz frequency were identified as the appropriate mechanical loading regime to induce tenogenic differentiation of adipose-derived stem cells cultured in a three-dimensional environment.

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          Most cited references 56

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          NIH Image to ImageJ: 25 years of image analysis.

          For the past 25 years NIH Image and ImageJ software have been pioneers as open tools for the analysis of scientific images. We discuss the origins, challenges and solutions of these two programs, and how their history can serve to advise and inform other software projects.
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            Biology of tendon injury: healing, modeling and remodeling.

             P Sharma,  N Maffulli (2015)
            Tendon disorders are frequent, and are responsible for much morbidity both in sport and the workplace. Although the presence of degenerative changes does not always lead to symptoms, pre-existing degeneration has been implicated as a risk factor for acute tendon rupture. The term tendinopathy is a generic descriptor of the clinical conditions in and around tendons arising from overuse. The terms "tendinosis" and "tendinitis/tendonitis" should only be used after histopathological examination. Disordered healing is seen in tendinopathy, and inflammation is not typically seen. In acute injuries, the process of tendon healing is an indivisible process that can be categorized into three overlapping phases for descriptive purposes. Tendon healing can occur intrinsically, via proliferation of epitenon and endotenon tenocytes, or extrinsically, by invasion of cells from the surrounding sheath and synovium. Despite remodeling, the biochemical and mechanical properties of healed tendon tissue never match those of intact tendon. Tendon injuries account for considerable morbidity, and often prove disabling for several months, despite what is considered appropriate management. Chronic problems caused by overuse of tendons probably account for 30% of all running-related injuries, and the prevalence of elbow tendinopathy in tennis players can be as high as 40%. The basic cell biology of tendons is still not fully understood, and the management of tendon injury poses a considerable challenge for clinicians. This article describes the structure of tendons, and reviews the pathophysiology of tendon injury and healing.
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              Tendon: biology, biomechanics, repair, growth factors, and evolving treatment options.

              Surgical treatment of tendon ruptures and lacerations is currently the most common therapeutic modality. Tendon repair in the hand involves a slow repair process, which results in inferior repair tissue and often a failure to obtain full active range of motion. The initial stages of repair include the formation of functionally weak tissue that is not capable of supporting tensile forces that allow early active range of motion. Immobilization of the digit or limb will promote faster healing but inevitably results in the formation of adhesions between the tendon and tendon sheath, which leads to friction and reduced gliding. Loading during the healing phase is critical to avoid these adhesions but involves increased risk of rupture of the repaired tendon. Understanding the biology and organization of the native tendon and the process of morphogenesis of tendon tissue is necessary to improve current treatment modalities. Screening the genes expressed during tendon morphogenesis and determining the growth factors most crucial for tendon development will likely lead to treatment options that result in superior repair tissue and ultimately improved functional outcomes.
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                Author and article information

                Contributors
                Journal
                Stem Cells Int
                Stem Cells Int
                SCI
                Stem Cells International
                Hindawi
                1687-966X
                1687-9678
                2017
                11 December 2017
                : 2017
                Affiliations
                1Department of Bioengineering, University of Toledo, Toledo, OH 43606, USA
                2Department of Orthopedic Surgery, University of Toledo Health Sciences Campus, Toledo, OH 43614, USA
                Author notes

                Academic Editor: Heinrich Sauer

                Article
                10.1155/2017/6072406
                5742457
                Copyright © 2017 Gayathri Subramanian et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                Categories
                Research Article

                Molecular medicine

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