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      Evaluation of in Vivo Response of Three Biphasic Scaffolds for Osteochondral Tissue Regeneration in a Sheep Model

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          Abstract

          Osteochondral defects are a common problem in both human medicine and veterinary practice although with important limits concerning the cartilaginous tissue regeneration. Interest in the subchondral bone has grown, as it is now considered a key element in the osteochondral defect healing. The aim of this work was to generate and to evaluate the architecture of three cell-free scaffolds made of collagen, magnesium/hydroxyapatite and collagen hydroxyapatite/wollastonite to be implanted in a sheep animal model. Scaffolds were designed in a bilayer configuration and a novel “Honey” configuration, where columns of hydroxyapatite were inserted within the collagen matrix. The use of different types of scaffolds allowed us to identify the best scaffold in terms of integration and tissue regeneration. The animals included were divided into four groups: three were treated using different types of scaffold while one was left untreated and represented the control group. Evaluations were made at 3 months through CT analysis. The novel “Honey” configuration of the scaffold with hydroxyapatite seems to allow for a better reparative process, although we are still far from obtaining a complete restoration of the defect at this time point of follow-up.

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          The role of synovitis in pathophysiology and clinical symptoms of osteoarthritis.

          Osteoarthritis (OA), one of the most common rheumatic disorders, is characterized by cartilage breakdown and by synovial inflammation that is directly linked to clinical symptoms such as joint swelling, synovitis and inflammatory pain. The gold-standard method for detecting synovitis is histological analysis of samples obtained by biopsy, but the noninvasive imaging techniques MRI and ultrasonography might also perform well. The inflammation of the synovial membrane that occurs in both the early and late phases of OA is associated with alterations in the adjacent cartilage that are similar to those seen in rheumatoid arthritis. Catabolic and proinflammatory mediators such as cytokines, nitric oxide, prostaglandin E(2) and neuropeptides are produced by the inflamed synovium and alter the balance of cartilage matrix degradation and repair, leading to excess production of the proteolytic enzymes responsible for cartilage breakdown. Cartilage alteration in turn amplifies synovial inflammation, creating a vicious circle. As synovitis is associated with clinical symptoms and also reflects joint degradation in OA, synovium-targeted therapy could help alleviate the symptoms of the disease and perhaps also prevent structural progression.
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            The bone-cartilage unit in osteoarthritis.

            Osteoarthritis (OA) refers to a group of mechanically-induced joint disorders to which both genetic and acquired factors contribute. Current pathophysiological concepts focus on OA as a disease of the whole joint. Within these models, the functional unit formed by the articular cartilage and the subchondral bone seems to be of particular interest. Cartilage and bone receive and dissipate the stress associated with movement and loading, and are therefore continuously challenged biomechanically. Recent data support the view that cartilage and bone can communicate over the calcified tissue barrier; vessels reach out from bone into the cartilage zone, patches of uncalcified cartilage are in contact with bone, and microcracks and fissures further facilitate transfer of molecules. Several molecular signaling pathways such as bone morphogenetic proteins and Wnts are hypothesized to have a role in OA and can activate cellular and molecular processes in both cartilage and bone cells. In addition, intracellular activation of different kinase cascades seems to be involved in the molecular crosstalk between cartilage and bone cells. Further research is required to integrate these different elements into a comprehensive approach that will increase our understanding of the disease processes in OA, and that could lead to the development of specific therapeutics or treatment strategies.
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              The basic science of the subchondral bone.

              In the past decades, considerable efforts have been made to propose experimental and clinical treatments for articular cartilage defects. Yet, the problem of cartilage defects extending deep in the underlying subchondral bone has not received adequate attention. A profound understanding of the basic anatomic aspects of this particular site, together with the pathophysiology of diseases affecting the subchondral bone is the key to develop targeted and effective therapeutic strategies to treat osteochondral defects. The subchondral bone consists of the subchondral bone plate and the subarticular spongiosa. It is separated by the cement line from the calcified zone of the articular cartilage. A variable anatomy is characteristic for the subchondral region, reflected in differences in thickness, density, and composition of the subchondral bone plate, contour of the tidemark and cement line, and the number and types of channels penetrating into the calcified cartilage. This review aims at providing insights into the anatomy, morphology, and pathology of the subchondral bone. Individual diseases affecting the subchondral bone, such as traumatic osteochondral defects, osteochondritis dissecans, osteonecrosis, and osteoarthritis are also discussed. A better knowledge of the basic science of the subchondral region, together with additional investigations in animal models and patients may translate into improved therapies for articular cartilage defects that arise from or extend into the subchondral bone.
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                Author and article information

                Journal
                Vet Sci
                Vet Sci
                vetsci
                Veterinary Sciences
                MDPI
                2306-7381
                09 November 2019
                December 2019
                : 6
                : 4
                : 90
                Affiliations
                [1 ]Department of Emergency and Organ Transplantation, University of Bari Aldo Moro, 70010 Bari, Italy
                [2 ]Department of Veterinary Medicine, University of Milan, 20122 Milano, Italy; alessia.digiancamillo@ 123456unimi.it (A.D.G.); davide.zani@ 123456unimi.it (D.Z.); mauro.digiancamillo@ 123456unimi.it (M.D.G.)
                [3 ]Department of Engineering for Innovation, University of Salento, 73100 Lecce, Italy; francesca.gervaso@ 123456unisalento.it (F.G.); francesca.scalera@ 123456unisalento.it (F.S.); barbara.palazzo@ 123456unisalento.it (B.P.); danielaizzo84@ 123456gmail.com (D.I.); alessandro.sannino@ 123456unisalento.it (A.S.)
                [4 ]CNR NANOTEC, Institute of Nanotechnology c/o Campus Ecotekne, via Monteroni, 73100 Lecce, Italy
                [5 ]IRCCS Istituto Ortopedico Galeazzi, Via R. Galeazzi 4, Milan, 20122 Milano, Italy; laura.mangiavini@ 123456unimi.it (L.M.); marcoagno@ 123456hotmail.it (M.A.); sosiocor@ 123456gmail.com (C.S.); giuseppe.peretti@ 123456unimi.it (G.M.P.)
                [6 ]Department of Biomedical Sciences for Health, University of Milan, 20122 Milan, Italy
                [7 ]Residency Program in Orthopaedics and Traumatology, University of Milan, 20122 Milan, Italy; marcodomen@ 123456gmail.com
                Author notes
                [* ]Correspondence: alberto.crovace@ 123456libero.it ; Tel.: +39-3208239830
                Author information
                https://orcid.org/0000-0002-8644-1653
                Article
                vetsci-06-00090
                10.3390/vetsci6040090
                6958333
                31717551
                2893da24-c367-4a52-8917-60a2939ea2ac
                © 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 May 2019
                : 23 October 2019
                Categories
                Article

                osteochondral defects,scaffold,biomaterials
                osteochondral defects, scaffold, biomaterials

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