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      The benefits and limitations of animal models for translational research in cartilage repair

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          Abstract

          Much research is currently ongoing into new therapies for cartilage defect repair with new biomaterials frequently appearing which purport to have significant regenerative capacity. These biomaterials may be classified as medical devices, and as such must undergo rigorous testing before they are implanted in humans. A large part of this testing involves in vitro trials and biomechanical testing. However, in order to bridge the gap between the lab and the clinic, in vivo preclinical trials are required, and usually demanded by regulatory approval bodies. This review examines the in vivo models in current use for cartilage defect repair testing and the relevance of each in the context of generated results and applicability to bringing the device to clinical practice. Some of the preclinical models currently used include murine, leporine, ovine, caprine, porcine, canine, and equine models. Each of these has advantages and disadvantages in terms of animal husbandry, cartilage thickness, joint biomechanics and ethical and licencing issues. This review will examine the strengths and weaknesses of the various animal models currently in use in preclinical studies of cartilage repair.

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          Most cited references81

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          Outcomes of microfracture for traumatic chondral defects of the knee: average 11-year follow-up.

          In this study, we measured functional outcomes of patients treated arthroscopically with microfracture for full-thickness traumatic defects of the knee. A case series of patients with 7 to 17 years' follow-up. Between 1981 and 1991, a total of 72 patients (75 knees) met the following inclusion criteria: (1) traumatic full-thickness chondral defect, (2) no meniscus or ligament injury, and (3) age 45 years and younger (range, 13 to 45 years). Seventy-one knees (95%) were available for final follow-up (range, 7 to 17 years). All patients completed self-administered questionnaires preoperatively and postoperatively. The following results were significant at the P <.05 level. Significant improvement was recorded for both Lysholm (scale 1 to 100; preoperative, 59; final follow-up, 89) and Tegner (1 to 10; preoperative, 3; final follow-up, 6) scores. At final follow-up, the SF-36 and WOMAC scores showed good to excellent results. At 7 years after surgery, 80% of the patients rated themselves as "improved." Multivariate analysis revealed that age was a predictor of functional improvement. Over the 7- to 17-year follow-up period (average, 11.3 years), patients 45 years and younger who underwent the microfracture procedure for full-thickness chondral defects, without associated meniscus or ligament pathology, showed statistically significant improvement in function and indicated that they had less pain.
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            Osteochondral tissue engineering: current strategies and challenges.

            Osteochondral defect management and repair remain a significant challenge in orthopedic surgery. Osteochondral defects contain damage to both the articular cartilage as well as the underlying subchondral bone. In order to repair an osteochondral defect the needs of the bone, cartilage and the bone-cartilage interface must be taken into account. Current clinical treatments for the repair of osteochondral defects have only been palliative, not curative. Tissue engineering has emerged as a potential alternative as it can be effectively used to regenerate bone, cartilage and the bone-cartilage interface. Several scaffold strategies, such as single phase, layered, and recently graded structures have been developed and evaluated for osteochondral defect repair. Also, as a potential cell source, tissue specific cells and progenitor cells are widely studied in cell culture models, as well with the osteochondral scaffolds in vitro and in vivo. Novel factor strategies being developed, including single factor, multi-factor, or controlled factor release in a graded fashion, not only assist bone and cartilage regeneration, but also establish osteochondral interface formation. The field of tissue engineering has made great strides, however further research needs to be carried out to make this strategy a clinical reality. In this review, we summarize current tissue engineering strategies, including scaffold design, bioreactor use, as well as cell and factor based approaches and recent developments for osteochondral defect repair. In addition, we discuss various challenges that need to be addressed in years to come. Copyright © 2012 Elsevier Inc. All rights reserved.
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              A comparative anatomical study of the human knee and six animal species.

              Animal models are an indispensable tool for developing and testing new clinical applications regarding the treatment of acute injuries and chronic diseases of the knee joint. Therefore, the purpose of this study was to compare the anatomy of the intra-articular structures of the human knee to species commonly used in large animal research studies. Fresh frozen cow (n=4), sheep (n=3), goat (n=4), dog (n=4), pig (n=5), rabbit (n=5), and human (n=4) cadaveric knees were used. Passive range of motion and intra-articular structure sizes of the knees were measured, the structure sizes normalized to the tibial plateau, and compared among the species. Statistically significant differences in the range of motion and intra-articular structure sizes were found among all the species. Only the human knee was able to attain full extension. After normalization, only the pig ACL was significantly longer than the human counterpart. The tibial insertion site of the ACL was split by the anterior lateral meniscus attachment in the cow, sheep, and pig knees. The sheep PCL had two distinct tibial insertion sites, while all the other knees had only one. Furthermore, only in human knees, both lateral meniscal attachments were located more centrally than the medial meniscal attachments. Despite the relatively preserved dimensions of the cruciate ligaments, menisci, and intercondylar notch amongst human and animals, structural differences in the cruciate ligament attachment sites and morphology of the menisci between humans and animals are important to consider when selecting an animal model. Copyright © 2011 Elsevier B.V. All rights reserved.
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                Author and article information

                Contributors
                +353 (0)1-402-8574 , tanyalevingstone@rcsi.ie
                Journal
                J Exp Orthop
                J Exp Orthop
                Journal of Experimental Orthopaedics
                Springer Berlin Heidelberg (Berlin/Heidelberg )
                2197-1153
                6 January 2016
                6 January 2016
                December 2016
                : 3
                : 1
                Affiliations
                [ ]Tissue Engineering Research Group, Department of Anatomy, Royal College of Surgeons in Ireland, 123 St. Stephen’s Green, Dublin 2, Ireland
                [ ]Trinity Centre for Bioengineering, Trinity College Dublin, Dublin 2, Ireland
                [ ]Advanced Materials and Bioengineering Research (AMBER) Centre, RCSI & TCD, Dublin, Ireland
                [ ]Section of Veterinary Clinical Sciences, School of Veterinary Medicine, University College Dublin, Dublin, Ireland
                [ ]Cappagh National Orthopaedic Hospital, Finglas, Dublin 11, Ireland
                Article
                37
                10.1186/s40634-015-0037-x
                4703594
                26915001
                f2c62709-80cc-4923-b414-86b653cf9465
                © Moran et al. 2016

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

                History
                : 2 September 2015
                : 28 December 2015
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100001590, Health Research Board (IE);
                Award ID: TRA/2011/19
                Award Recipient :
                Categories
                Review
                Custom metadata
                © The Author(s) 2016

                tissue engineering,collagen,in vivo,osteochondral,cartilage
                tissue engineering, collagen, in vivo, osteochondral, cartilage

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