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      International Journal of Nanomedicine (submit here)

      This international, peer-reviewed Open Access journal by Dove Medical Press focuses on the application of nanotechnology in diagnostics, therapeutics, and drug delivery systems throughout the biomedical field. Sign up for email alerts here.

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      Noninvasive visualization of early osteoarthritic cartilage using targeted nanosomes in a destabilization of the medial meniscus mouse model

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          Abstract

          Background

          Early stage osteoarthritis (OA) is clinically asymptomatic due to the avascular and the aneural nature of the cartilage tissue. Nevertheless, early detection of cartilage tissue is critical in order to impede the progression of OA. Hence, in order to develop effective preventive therapy for OA, diagnosis in the early stages is necessary.

          Methods

          To achieve this goal, we have developed targeted, fluorescent nanosomes conjugated with monoclonal anti-type II collagen antibodies (MabCII) for diagnosis of early OA. The MabCII-coated nanosomes (targeted-nanosomes) bind to the damaged cartilage explants in vitro and in vivo in an OA mouse model that mimics early stage OA. The OA mouse model was induced by destabilization of the medial meniscus (DMM) in 9–10 weeks old C57Bl/6 mice.

          Results

          The targeted-nanosomes enhanced the binding specificity to the cartilage tissue according to the severity of damage.

          Conclusion

          We show that MabCII-nanosomes can precisely detect early stage OA in the DMM mouse model. Thus, MabCII-nanosomes have the potential to be used as a non-invasive method for diagnosing the early osteoarthritic lesions.

          Most cited references31

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          Pre-clinical whole-body fluorescence imaging: Review of instruments, methods and applications.

          Fluorescence sampling of cellular function is widely used in all aspects of biology, allowing the visualization of cellular and sub-cellular biological processes with spatial resolutions in the range from nanometers up to centimeters. Imaging of fluorescence in vivo has become the most commonly used radiological tool in all pre-clinical work. In the last decade, full-body pre-clinical imaging systems have emerged with a wide range of utilities and niche application areas. The range of fluorescent probes that can be excited in the visible to near-infrared part of the electromagnetic spectrum continues to expand, with the most value for in vivo use being beyond the 630 nm wavelength, because the absorption of light sharply decreases. Whole-body in vivo fluorescence imaging has not yet reached a state of maturity that allows its routine use in the scope of large-scale pre-clinical studies. This is in part due to an incomplete understanding of what the actual fundamental capabilities and limitations of this imaging modality are. However, progress is continuously being made in research laboratories pushing the limits of the approach to consistently improve its performance in terms of spatial resolution, sensitivity and quantification. This paper reviews this imaging technology with a particular emphasis on its potential uses and limitations, the required instrumentation, and the possible imaging geometries and applications. A detailed account of the main commercially available systems is provided as well as some perspective relating to the future of the technology development. Although the vast majority of applications of in vivo small animal imaging are based on epi-illumination planar imaging, the future success of the method relies heavily on the design of novel imaging systems based on state-of-the-art optical technology used in conjunction with high spatial resolution structural modalities such as MRI, CT or ultrasound. Published by Elsevier B.V.
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            In vivo T(1rho) and T(2) mapping of articular cartilage in osteoarthritis of the knee using 3 T MRI.

            Evaluation and treatment of patients with early stages of osteoarthritis (OA) is dependent upon an accurate assessment of the cartilage lesions. However, standard cartilage dedicated magnetic resonance (MR) techniques are inconclusive in quantifying early degenerative changes. The objective of this study was to determine the ability of MR T1rho (T(1rho)) and T(2) mapping to detect cartilage matrix degeneration between normal and early OA patients. Sixteen healthy volunteers (mean age 41.3) without clinical or radiological evidence of OA and 10 patients (mean age 55.9) with OA were scanned using a 3Tesla (3T) MR scanner. Cartilage volume and thickness, and T(1rho) and T(2) values were compared between normal and OA patients. The relationship between T(1rho) and T(2) values, and Kellgren-Lawrence scores based on plain radiographs and the cartilage lesion grading based on MR images were studied. The average T(1rho) and T(2) values were significantly increased in OA patients compared with controls (52.04+/-2.97ms vs 45.53+/-3.28ms with P=0.0002 for T(1rho), and 39.63+/-2.69ms vs 34.74+/-2.48ms with P=0.001 for T(2)). Increased T(1rho) and T(2) values were correlated with increased severity in radiographic and MR grading of OA. T(1rho) has a larger range and higher effect size than T(2), 3.7 vs 3.0. Our results suggest that both in vivo T(1rho) and T(2) relaxation times increase with the degree of cartilage degeneration. T(1rho) relaxation time may be a more sensitive indicator for early cartilage degeneration than T(2). The ability to detect early cartilage degeneration prior to morphologic changes may allow us to critically monitor the course of OA and injury progression, and to evaluate the success of treatment to patients with early stages of OA.
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              Osteoarthritis.

              Osteoarthritis (OA), the syndrome of joint pain and dysfunction caused by joint degeneration, affects more people than any other joint disease. In most instances joint degeneration develops in the absence of an identifiable cause, but increasing age, excessive joint loading, and joint abnormalities and insults increase the risk of OA. Articular surface contact stress that causes tissue damage and compromises that ability of chondrocytes to maintain and restore the tissue has an important role in the development of joint degeneration Current methods of attempting to restore an articular surface in osteoarthritic joints include penetrating subchondral bone, altering joint loading, osteotomies and insertion of soft tissue grafts. Dramatic advances in the prevention and treatment of OA are likely to stem from better understanding of the role of mechanical forces in the initiation and progression of joint degeneration.
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                Author and article information

                Journal
                Int J Nanomedicine
                Int J Nanomedicine
                International Journal of Nanomedicine
                International Journal of Nanomedicine
                Dove Medical Press
                1176-9114
                1178-2013
                2018
                01 March 2018
                : 13
                : 1215-1224
                Affiliations
                [1 ]Department of Orthopaedic Surgery and Biomedical Engineering, University of Tennessee Health Science Center–Campbell Clinic
                [2 ]Veterans Affairs Medical Center, Memphis, TN, USA
                [3 ]Department of Molecular Science and Technology, Ajou University
                [4 ]Cell Therapy Center, Ajou University Hospital, Suwon
                [5 ]Department of Biomedical Engineering, Pukyong National University, Nam-Gu, Busan
                [6 ]Department of Orthopedic Surgery, School of Medicine, Ajou University, Suwon, Republic of Korea
                Author notes
                Correspondence: Byoung-Hyun Min, Department of Orthopedic Surgery, Ajou University School of Medicine, 164 Worldcup-ro, Yongtong-gu, Suwon 16499, Republic of Korea, Tel +82 31 219 5225, Fax +82 31 219 1504, Email bhmin@ 123456ajou.ac.kr
                Karen A Hasty, Department of Orthopaedic Surgery and Biomedical Engineering University of Tennessee Health Science Center–Campbell Clinic Research Service 151, VA Medical Center, 1030 Jefferson Avenue, Memphis, TN 38104, USA, Tel +1 901 523 8990 ext 6175, Fax +1 901 577 7273, Email khasty@ 123456uthsc.edu
                [*]

                These authors contributed equally to this work

                Article
                ijn-13-1215
                10.2147/IJN.S149375
                5841948
                29535518
                63d1b441-3012-475f-8f3d-aaf54040cded
                © 2018 Cho et al. This work is published and licensed by Dove Medical Press Limited

                The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

                History
                Categories
                Original Research

                Molecular medicine
                osteoarthritis,nanosome,diagnosis,oa score,destabilization of the medial meniscus,matrix metalloproteinases,monoclonal anti-type ii collagen antibody

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