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      Micro-computed Tomography-Based Collagen Orientation and Anisotropy Analysis of Rabbit Articular Cartilage

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          Abstract

          The collagen network is the highly organized backbone of articular cartilage providing tissue tensile stiffness and restricting proteoglycan bleaching out of the tissue. Osteoarthritis (OA) diminishes proper collagen network adaptation. Our aim was to provide quantitative three-dimensional (3D) information of the cartilage collagen network adaptation in early osteoarthritis using high resolution micro-computed tomography ( µCT)-imaging. Osteochondral samples from the femoral condyles were collected from healthy ( N = 8, both legs) and experimental OA rabbit model with anterior cruciate ligament transection ( N = 14, single leg). Samples were processed for cartilage µCT-imaging and histological evaluation with polarized light microscopy (PLM). Structure tensor analysis was used to analyse the collagen fibre orientation and anisotropy of the µCT-images, and PLM was used as a validation for structural changes. Depth-wise comparison of collagen fibre orientation acquired with µCT-imaging and PLM correlated well, but the values obtained with PLM were systematically greater than those measured with µCT-imaging. Structure tensor analysis allowed for 3D quantification of collagen network anisotropy. Finally, µCT-imaging revealed only minor differences between the control and experimental groups.

          Supplementary Information

          The online version contains supplementary material available at 10.1007/s10439-023-03183-4.

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          Most cited references41

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          A Threshold Selection Method from Gray-Level Histograms

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            The OARSI histopathology initiative - recommendations for histological assessments of osteoarthritis in the rabbit.

            The primary goal of this body of work is to suggest a standardized system for histopathological assessment of experimental surgical instability models of osteoarthritis (OA) in rabbits, building on past experience, to achieve comparability of studies from different centres. An additional objective is to review methodologies that have been employed in the past for assessing OA in rabbits with particular reference to the surgical anterior cruciate ligament transection (ACLT) model. A panel of scientists and clinician-scientists with recognized expertise in assessing rabbit models of OA reviewed the literature to provide a critical appraisal of the methods that have been employed to assess both macroscopic and microscopic changes occurring in rabbit joint tissues in experimental OA. In addition, a validation of the proposed histologic histochemical grading system was performed. The ACLT variant of the surgical instability model in skeletally mature rabbits is the variation most capable of reproducing the entire range of cartilage, synovial and bone lesions recognized to be associated with OA. These lesions can be semiquantitatively graded using macroscopic and microscopic techniques. Further, as well as cartilage lesions, this ACLT model can produce synovial and bone lesions similar to that of human OA. The ACLT variant of the surgical instability model in rabbits is a reproducible and effective model of OA. The cartilage lesions in this model and their response to therapy can be graded according to an adapted histological and histochemical grading system, though also this system is to some extent subjective and, thus, neither objective nor entirely reproducible. Copyright © 2010 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.
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              Models of osteoarthritis: the good, the bad and the promising

              Summary Osteoarthritis (OA) is a chronic degenerative disease of diarthrodial joints most commonly affecting people over the age of forty. The causes of OA are still unknown and there is much debate in the literature as to the exact sequence of events that trigger the onset of the heterogeneous disease we recognise as OA. There is currently no consensus model for OA that naturally reflects human disease. Existing ex-vivo models do not incorporate the important inter-tissue communication between joint components required for disease progression and differences in size, anatomy, histology and biomechanics between different animal models makes translation to the human model very difficult. This narrative review highlights the advantages and disadvantages of the current models used to study OA. It discusses the challenges of producing a more reliable OA-model and proposes a direction for the development of a consensus model that reflects the natural environment of human OA. We suggest that a human osteochondral plug-based model may overcome many of the fundamental limitations associated with animal and in-vitro models based on isolated cells. Such a model will also provide a platform for the development and testing of targeted treatment and validation of novel OA markers directly on human tissues.
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                Author and article information

                Contributors
                simo.ojanen@uef.fi
                Journal
                Ann Biomed Eng
                Ann Biomed Eng
                Annals of Biomedical Engineering
                Springer International Publishing (Cham )
                0090-6964
                1573-9686
                1 April 2023
                1 April 2023
                2023
                : 51
                : 8
                : 1769-1780
                Affiliations
                [1 ]GRID grid.9668.1, ISNI 0000 0001 0726 2490, Department of Technical Physics, , University of Eastern Finland, ; P.O. Box 1627, 70210 Kuopio, Finland
                [2 ]GRID grid.10858.34, ISNI 0000 0001 0941 4873, Research Unit of Health Sciences and Technology, , University of Oulu, ; Oulu, Finland
                [3 ]GRID grid.22072.35, ISNI 0000 0004 1936 7697, Human Performance Laboratory, Faculty of Kinesiology, , University of Calgary, ; Calgary, AB Canada
                [4 ]GRID grid.412326.0, ISNI 0000 0004 4685 4917, Department of Diagnostic Radiology, , Oulu University Hospital, ; Oulu, Finland
                Author notes

                Associate Editor Stefan M. Duma oversaw the review of this article.

                Author information
                http://orcid.org/0000-0003-4386-0716
                Article
                3183
                10.1007/s10439-023-03183-4
                10326148
                37005948
                dcdaedf5-a4fa-4c93-89ad-bc35e43529f9
                © The Author(s) 2023

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 22 October 2021
                : 27 February 2023
                Funding
                Funded by: Saastamoinen Foundation
                Funded by: FundRef http://dx.doi.org/10.13039/501100004212, Päivikki ja Sakari Sohlbergin Säätiö;
                Funded by: FundRef http://dx.doi.org/10.13039/501100005432, Pohjois-Savon Rahasto;
                Award ID: 65171624
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/501100003125, Suomen Kulttuurirahasto;
                Award ID: 00180796
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/501100004756, Emil Aaltosen Säätiö;
                Funded by: The Canadian Institutes of Health Research (CIHR)
                Funded by: The Canada Research Chair Programme
                Funded by: The Killam Foundation
                Funded by: The Nigg Chair at the University of Calgary
                Funded by: The Arthritis Society, Canada
                Funded by: FundRef http://dx.doi.org/10.13039/501100002341, Academy of Finland;
                Award ID: 268378
                Award ID: 303786
                Award ID: 324529
                Award Recipient :
                Funded by: European Research Council under the European Union’s Seventh Framework Programme (FP/2007–2013)/ERC Grant Agreement
                Award ID: 336267
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/501100006306, Sigrid Juséliuksen Säätiö;
                Funded by: University of Eastern Finland (UEF) including Kuopio University Hospital
                Categories
                Original Article
                Custom metadata
                © Biomedical Engineering Society 2023

                Biomedical engineering
                anterior cruciate ligament transection,animal model,early osteoarthritis,hexamethyldisilazane,structure tensor analysis,polarized light microscopy

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