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      Tendon-Inspired Nanotopographic Scaffold for Tissue Regeneration in Rotator Cuff Injuries

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          Abstract

          Acute and chronic rotator cuff (RC) tears are common etiologies of shoulder disabilities. Despite the advanced surgical techniques and graft materials available for tendon repair, the high re-tear rate remains a critical challenge in RC healing. Inspired by the highly organized nanotopography of the extracellular matrix (ECM) in tendon tissue of the shoulder, nanotopographic scaffolds are developed using polycaprolactone for the repair and regeneration of RC tendons. The scaffolds show appropriate flexibility and mechanical properties for application in tendon tissue regeneration. It is found that the highly aligned nanotopographic cues of scaffolds could sensitively control and improve the morphology, attachment, proliferation, and differentiation of tendon-derived cells as well as promote their wound healing capacity in vitro. In particular, this study showed that the scaffolds could promote tendon regeneration along the direction of the nanotopography in the rabbit models of acute and chronic RC tears. Nanotopographic scaffold-augmented rotator cuff repair showed a more appropriate healing pattern compared to the control groups in a rabbit RC tear model. We demonstrated that the tendon ECM-like nanoscale structural cues of the tendon-inspired patch may induce the more aligned tissue regeneration of the underlying tissues including tendon-to-bone interface.

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          Most cited references50

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          The outcome and repair integrity of completely arthroscopically repaired large and massive rotator cuff tears.

          The impact of a recurrent defect on the outcome after rotator cuff repair has been controversial. The purpose of this study was to evaluate the functional and anatomic results after arthroscopic repair of large and massive rotator cuff tears with use of ultrasound as an imaging modality to determine the postoperative integrity of the repair. Eighteen patients who had complete arthroscopic repair of a tear measuring >2 cm in the transverse dimension were evaluated at a minimum of twelve months after surgery and again at two years after surgery. The evaluation consisted of a standardized history and physical examination as well as calculation of the preoperative and postoperative shoulder scores according to the system of the American Shoulder and Elbow Surgeons. The strength of both shoulders was quantitated postoperatively with use of a portable dynamometer. Ultrasound studies were performed with use of an established and validated protocol at a minimum of twelve months after surgery. Recurrent tears were seen in seventeen of the eighteen patients. Despite the absence of healing at twelve months after surgery, thirteen patients had an American Shoulder and Elbow Surgeons score of >/=90 points. Sixteen patients had an improvement in the functional outcome score, which increased from an average of 48.3 to 84.6 points. Sixteen patients had a decrease in pain, and twelve had no pain. Although eight patients had preoperative forward elevation to /=90 points, and six patients had a score of /=80.
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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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              Is Open Access

              Matrix nanotopography as a regulator of cell function

              The architecture of the extracellular matrix (ECM) directs cell behavior by providing spatial and mechanical cues to which cells respond. In addition to soluble chemical factors, physical interactions between the cell and ECM regulate primary cell processes, including differentiation, migration, and proliferation. Advances in microtechnology and, more recently, nanotechnology provide a powerful means to study the influence of the ECM on cell behavior. By recapitulating local architectures that cells encounter in vivo, we can elucidate and dissect the fundamental signal transduction pathways that control cell behavior in critical developmental, physiological, and pathological processes.
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                Author and article information

                Journal
                ACS Omega
                ACS Omega
                ao
                acsodf
                ACS Omega
                American Chemical Society
                2470-1343
                02 June 2020
                16 June 2020
                : 5
                : 23
                : 13913-13925
                Affiliations
                []Department of Rural and Biosystems Engineering, Chonnam National University , 77, Yongbong-ro, Buk-gu, Gwangju 61186, Republic of Korea
                []Department of Pathology, Chonnam National University Hospital , 42, Jebong-ro, Dong-gu, Gwangju 61649, Republic of Korea
                [§ ]Department of Orthopedics, Chonnam National University Hospital , 42, Jebong-ro, Dong-gu, Gwangju 61649, Republic of Korea
                Author notes
                Article
                10.1021/acsomega.0c01328
                7301599
                32566858
                b3f3fd98-95c4-4f08-a76f-36bda0630e17
                Copyright © 2020 American Chemical Society

                This is an open access article published under an ACS AuthorChoice License, which permits copying and redistribution of the article or any adaptations for non-commercial purposes.

                History
                : 25 March 2020
                : 19 May 2020
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