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            "title": "The mechanical behaviour of chondrocytes predicted with a micro-structural model of articular cartilage",
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                    "firstName": "S-K",
                    "lastName": "Han"
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                    "firstName": "S",
                    "lastName": "Federico"
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                    "firstName": "A",
                    "lastName": "Grillo"
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                    "lastName": "Giaquinta"
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            "abstractNote": "The integrity of articular cartilage depends on the proper functioning and mechanical stimulation of chondrocytes, the cells that synthesize extracellular matrix and maintain tissue health. The biosynthetic activity of chondrocytes is influenced by genetic factors, environmental influences, extracellular matrix composition, and mechanical factors. The mechanical environment of chondrocytes is believed to be an important determinant for joint health, and chondrocyte deformation in response to mechanical loading is speculated to be an important regulator of metabolic activity. In previous studies of chondrocyte deformation, articular cartilage was described as a biphasic material consisting of a homogeneous, isotropic, linearly elastic solid phase, and an inviscid fluid phase. However, articular cartilage is known to be anisotropic and inhomogeneous across its depth. Therefore, isotropic and homogeneous models cannot make appropriate predictions for tissue and cell stresses and strains. Here, we modelled articular cartilage as a transversely isotropic, inhomogeneous (TI) material in which the anisotropy and inhomogeneity arose naturally from the microstructure of the depth-dependent collagen fibril orientation and volumetric fraction, as well as the chondrocyte shape and volumetric fraction. The purpose of this study was to analyse the deformation behaviour of chondrocytes using the TI model of articular cartilage. In order to evaluate our model against experimental results, we simulated indentation and unconfined compression tests for nominal compressions of 15%. Chondrocyte deformations were analysed as a function of location within the tissue. The TI model predicted a non-uniform behaviour across tissue depth: in indentation testing, cell height decreased by 43% in the superficial zone and between 11 and 29% in the deep zone. In unconfined compression testing, cell height decreased by 32% in the superficial zone, 25% in the middle, and 18% in the deep zones. This predicted non-uniformity is in agreement with experimental studies. The novelty of this study is the use of a cartilage material model accounting for the intrinsic inhomogeneity and anisotropy of cartilage caused by its microstructure.",
            "publicationTitle": "Biomechanics and Modeling in Mechanobiology",
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            "date": "Apr 2007",
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            "pages": "139-150",
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            "journalAbbreviation": "Biomech Model Mechanobiol",
            "DOI": "10.1007/s10237-006-0016-3",
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                    "tag": "Anisotropy"
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                {
                    "tag": "Biomechanics"
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                {
                    "tag": "Biophysics"
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                {
                    "tag": "Cartilage, Articular"
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                {
                    "tag": "Chondrocytes"
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                {
                    "tag": "Collagen"
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                {
                    "tag": "Compressive Strength"
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                {
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            "itemType": "journalArticle",
            "title": "Characterization of apoptosis in articular cartilage derived from the knee joints of patients with osteoarthritis",
            "creators": [
                {
                    "creatorType": "author",
                    "firstName": "Giuseppe",
                    "lastName": "Musumeci"
                },
                {
                    "creatorType": "author",
                    "firstName": "Carla",
                    "lastName": "Loreto"
                },
                {
                    "creatorType": "author",
                    "firstName": "Maria Luisa",
                    "lastName": "Carnazza"
                },
                {
                    "creatorType": "author",
                    "firstName": "Giuseppa",
                    "lastName": "Martinez"
                }
            ],
            "abstractNote": "PURPOSE: The present study was conduced in order to analyse the molecular changes during the apoptotic cascade in knee articular cartilage of patients with OA. METHOD: Articular cartilage specimens were assessed by histology (Haematoxylin and Eosin), histochemistry (Masson's Trichromic and Alcian Blue), immunohistochemistry through TRAIL, DR5 and Caspase-3, TUNEL and Hoechst staining in fresh isolated chondrocytes. RESULTS: Histology results demonstrated the structural alterations in the articular knee cartilage with OA, and histochemistry results demonstrated the presence of matrix calcification and a proteoglycans reduction. Immunohistochemistry staining showed that structural alterations, matrix calcification and a proteoglycans reduction coincided with an increase in apoptotic cells when compared to normal cartilage; however, this cellular mechanism of death was demonstrated by TUNEL and Hoechst 33258 staining in fresh isolated chondrocytes. CONCLUSION: In this study, we demonstrated an apoptosis activation by the extrinsic pathway in OA cartilage. The apoptosis-positive cells might be due to a protection mechanism after sublethal injury, in particular, represented by an increased survival of chondrocytes that are able to participate in the repair process.",
            "publicationTitle": "Knee Surgery, Sports Traumatology, Arthroscopy: Official Journal of the ESSKA",
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            "journalAbbreviation": "Knee Surg Sports Traumatol Arthrosc",
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            "creatorSummary": "Gilmore and Palfrey",
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            "title": "Chondrocyte distribution in the articular cartilage of human femoral condyles.",
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                    "creatorType": "author",
                    "firstName": "R S",
                    "lastName": "Gilmore"
                },
                {
                    "creatorType": "author",
                    "firstName": "A J",
                    "lastName": "Palfrey"
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            ],
            "abstractNote": "The distribution of chondrocytes throughout the total thickness of articular cartilage from the femoral condyles of infants, children and adults has been studied using serial sections cut parallel as well as perpendicular to the articular surface. The thickness of the articular cartilage was estimated in fixed sections. In one of the adult specimens, the thickness of the articular cartilage was estimated firstly by direct measurement of the cut surfaces of a series of blocks cut from both condyles and then from the number of parallel sections of the cartilage prepared from those blocks. Cell density was highest in the superficial zone of all specimens examined, declining to lower values in the deep zone of the cartilage. Within this pattern the infant specimens had the highest values for cell density and the adults the lowest, with values for children in an intermediate range. There was no significant variation in cell density across the condyles of the selected adult specimen. The absolute values for cartilage thickness depended on the method used, but in general total thickness was found to approximately double from late gestation to maturity. In the selected adult specimen, the cartilage was thickest just anterior and posterior to the main weight-bearing area of the condyles.",
            "publicationTitle": "Journal of Anatomy",
            "publisher": "",
            "place": "",
            "date": "1988-4",
            "volume": "157",
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            "partNumber": "",
            "partTitle": "",
            "pages": "23-31",
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            "itemType": "journalArticle",
            "title": "Interspecies comparisons of in situ intrinsic mechanical properties of distal femoral cartilage",
            "creators": [
                {
                    "creatorType": "author",
                    "firstName": "K A",
                    "lastName": "Athanasiou"
                },
                {
                    "creatorType": "author",
                    "firstName": "M P",
                    "lastName": "Rosenwasser"
                },
                {
                    "creatorType": "author",
                    "firstName": "J A",
                    "lastName": "Buckwalter"
                },
                {
                    "creatorType": "author",
                    "firstName": "T I",
                    "lastName": "Malinin"
                },
                {
                    "creatorType": "author",
                    "firstName": "V C",
                    "lastName": "Mow"
                }
            ],
            "abstractNote": "We measured the in situ biomechanical properties of knee joint cartilage from five species (bovine, canine, human, monkey, and rabbit) to examine the biomechanical relevance of animal models of human knee joint injuries and osteoarthritis. In situ biphasic creep indentation experiments were performed to simultaneously determine all three intrinsic material coefficients (aggregate modulus, Poisson's ratio, and permeability) of the cartilage as represented by the linear KLM biphasic model. In addition, we also assessed the effects of load bearing on these intrinsic properties at \"high\" and \"low\" weight-bearing regions on the distal femur. Our results indicate that significant differences exist in some of these material properties among species and sites. The aggregate modulus of the anterior patellar groove within each species is the lowest among all sites tested, and the permeability of the patellar groove cartilage is the highest and does not vary among species. Similarly, the Poison's ratio in the patellar groove is the lowest in all species, except in the rabbit. These results lead to the conclusion that patellar groove cartilage can undergo greater and faster compression. Thus, under high compressive loads, the cartilage of the patellar groove surface can more rapidly compress to create a congruent patellofemoral joint articulation. For any given location, no differences were found in the aggregate modulus among all the species, and no correlation was found between aggregate modulus and thickness at the test site. Thus, in the process of selecting a suitable experimental animal model of human articular cartilage, it is essential to consider the significant interspecies differences of the mechanical properties.",
            "publicationTitle": "Journal of Orthopaedic Research: Official Publication of the Orthopaedic Research Society",
            "publisher": "",
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            "date": "May 1991",
            "volume": "9",
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            "pages": "330-340",
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            "journalAbbreviation": "J. Orthop. Res",
            "DOI": "10.1002/jor.1100090304",
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            "creatorSummary": "Gervaso et al.",
            "parsedDate": "2007",
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            "version": 3606,
            "itemType": "journalArticle",
            "title": "Effect of geometrical imperfections in confined compression tests on parameter evaluation of hydrated soft tissues",
            "creators": [
                {
                    "creatorType": "author",
                    "firstName": "Francesca",
                    "lastName": "Gervaso"
                },
                {
                    "creatorType": "author",
                    "firstName": "Giancarlo",
                    "lastName": "Pennati"
                },
                {
                    "creatorType": "author",
                    "firstName": "Federica",
                    "lastName": "Boschetti"
                }
            ],
            "abstractNote": "Experimental tests, such as the confined and unconfined compression and the indentation tests, are traditionally used to determine the poroelastic properties of hydrated soft tissues (HSTs). The purpose of this study was to quantitatively evaluate the reliability of H(A) and K values as identified from experimental confined test data, estimating the errors that could occur in several situations with more realistic sample geometry and boundary conditions. Finite element models of the step-wise stress-relaxation confined compression tests on HSTs were developed including geometrical imperfections of the sample and the presence of a gap between the piston and the confining chamber. The errors occurring when H(A) and K were estimated by means of the analytical solution of the 1-D confined compression problem were assessed. Results of the analysis indicate that errors in the parameter estimation due to geometrical inaccuracies of the sample can be eliminated by applying a 5% strain pre-compression to the sample. Gap errors are negligible for H(A), can reach 20% for K, and cannot be eliminated by a pre-compression of the sample.",
            "publicationTitle": "Journal of Biomechanics",
            "publisher": "",
            "place": "",
            "date": "2007",
            "volume": "40",
            "issue": "13",
            "section": "",
            "partNumber": "",
            "partTitle": "",
            "pages": "3041-3044",
            "series": "",
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            "journalAbbreviation": "J Biomech",
            "DOI": "10.1016/j.jbiomech.2007.02.020",
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            "url": "http://www.ncbi.nlm.nih.gov/pubmed/17418850",
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            "language": "",
            "libraryCatalog": "NCBI PubMed",
            "callNumber": "",
            "rights": "",
            "extra": "",
            "tags": [
                {
                    "tag": "Compressive Strength",
                    "type": 1
                },
                {
                    "tag": "Computer Simulation",
                    "type": 1
                },
                {
                    "tag": "Models, Biological",
                    "type": 1
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                    "type": 1
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            },
            "creatorSummary": "Michalek and Iatridis",
            "parsedDate": "2007",
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        "data": {
            "key": "Q4EIC5NE",
            "version": 3607,
            "itemType": "journalArticle",
            "title": "A numerical study to determine pericellular matrix modulus and evaluate its effects on the micromechanical environment of chondrocytes",
            "creators": [
                {
                    "creatorType": "author",
                    "firstName": "Arthur J",
                    "lastName": "Michalek"
                },
                {
                    "creatorType": "author",
                    "firstName": "James C",
                    "lastName": "Iatridis"
                }
            ],
            "abstractNote": "Chondrocyte biosynthesis is highly sensitive to mechanical strain. A thin pericellular matrix (PCM) surrounds the cell and plays an important role in mechanotransduction. PCM material properties are difficult to measure directly because of its size and connectivity to both cell and extracellular matrix (ECM). The purpose of this study was to develop a method of calculating linear elastic properties of the PCM using an inverse finite element approach with experimental properties of cell and chondron taken from the literature. Finite element models were constructed of both the equivalent chondron case and the chondrocyte-PCM structure, and a Fibonacci search obtained PCM moduli that matched the ECM strain field between the two cases. The most important result was that ECM strain adjacent to a chondron inclusion was sensitive to the chondron properties and may be used to calculate PCM mechanical properties, consistent with our strain field hypotheses. PCM moduli obtained through this method range from 43 to 240 kPa, were significantly higher than previously published but resulted in only a 0.5-21% decrease in relative effective cell strain. Similarities between effective strain ratios led to the conclusion that matching experimental techniques used to measure cell and PCM properties was more important than absolute values of the properties.",
            "publicationTitle": "Journal of Biomechanics",
            "publisher": "",
            "place": "",
            "date": "2007",
            "volume": "40",
            "issue": "6",
            "section": "",
            "partNumber": "",
            "partTitle": "",
            "pages": "1405-1409",
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            "seriesText": "",
            "journalAbbreviation": "J Biomech",
            "DOI": "10.1016/j.jbiomech.2006.05.025",
            "citationKey": "",
            "url": "http://www.ncbi.nlm.nih.gov/pubmed/16867304",
            "accessDate": "2010-09-30T18:01:45Z",
            "PMID": "16867304",
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            "ISSN": "0021-9290",
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            "archiveLocation": "",
            "shortTitle": "",
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            "libraryCatalog": "NCBI PubMed",
            "callNumber": "",
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            "tags": [
                {
                    "tag": "Animals",
                    "type": 1
                },
                {
                    "tag": "Biomechanics",
                    "type": 1
                },
                {
                    "tag": "Cells, Cultured",
                    "type": 1
                },
                {
                    "tag": "Chondrocytes",
                    "type": 1
                },
                {
                    "tag": "Chondrogenesis",
                    "type": 1
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                {
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                    "type": 1
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                {
                    "tag": "Elasticity",
                    "type": 1
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                {
                    "tag": "Extracellular Matrix",
                    "type": 1
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                {
                    "tag": "Humans",
                    "type": 1
                },
                {
                    "tag": "Mechanotransduction, Cellular",
                    "type": 1
                },
                {
                    "tag": "Models, Biological",
                    "type": 1
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                {
                    "tag": "Stress, Mechanical",
                    "type": 1
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    {
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            "creatorSummary": "Chen et al.",
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            "version": 3606,
            "itemType": "journalArticle",
            "title": "Time, stress, and location dependent chondrocyte death and collagen damage in cyclically loaded articular cartilage",
            "creators": [
                {
                    "creatorType": "author",
                    "firstName": "Chih Tung",
                    "lastName": "Chen"
                },
                {
                    "creatorType": "author",
                    "firstName": "Madhu",
                    "lastName": "Bhargava"
                },
                {
                    "creatorType": "author",
                    "firstName": "Peggy M",
                    "lastName": "Lin"
                },
                {
                    "creatorType": "author",
                    "firstName": "Peter A",
                    "lastName": "Torzilli"
                }
            ],
            "abstractNote": "We investigated the effect of light (0.1 MPa), moderate (1 MPa) or heavy (5 MPa) cyclical stresses applied continuously or intermittently for 0 to 72 h on cell death and collagen damage in adult bovine cartilage explants. No increase in cell death was observed in the cartilage loaded with a continuous cyclic stress at 0.1 MPa for up to 72 h. Cell death occurred in the uppermost superficial tangential zone (STZ) of explants after loading for 1 h at 1 MPa, and reached a maximum depth of 61+/-23 micro m by 6 h (at the rate of 9+/-6 micro m/h). At 5 MPa, cell death occurred in the STZ after as little as 1 min (30 cycles) of loading, and reached a maximum depth of 70+/-2 micro m by 60 min (47+/-8 micro m/h). When an intermittent (with 2 s on, 2 s off) stress of 5 MPa was applied, cell death appeared in the STZ after 2 min (30 cycles) and increased to a depth of 63+/-2 micro m at 60 min (45+/-11 micro m/h). No significant differences were observed between the continuous and intermittent loading conditions. Both collagenase-cleaved and denatured collagen fibers were found in the STZ of explants loaded at 1 and 5 MPa. We concluded that load-induced cell death depends on load duration and magnitude, and that the chondrocytes in the STZ are more vulnerable to load-induced injury than those in the middle and deep zones.",
            "publicationTitle": "Journal of Orthopaedic Research: Official Publication of the Orthopaedic Research Society",
            "publisher": "",
            "place": "",
            "date": "Sep 2003",
            "volume": "21",
            "issue": "5",
            "section": "",
            "partNumber": "",
            "partTitle": "",
            "pages": "888-898",
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            "seriesText": "",
            "journalAbbreviation": "J. Orthop. Res",
            "DOI": "10.1016/S0736-0266(03)00050-0",
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            "url": "http://www.ncbi.nlm.nih.gov/pubmed/12919878",
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            "tags": [
                {
                    "tag": "Animals",
                    "type": 1
                },
                {
                    "tag": "Cartilage, Articular",
                    "type": 1
                },
                {
                    "tag": "Cattle",
                    "type": 1
                },
                {
                    "tag": "Cell Death",
                    "type": 1
                },
                {
                    "tag": "Chondrocytes",
                    "type": 1
                },
                {
                    "tag": "Collagen",
                    "type": 1
                },
                {
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                    "type": 1
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                {
                    "tag": "Immunohistochemistry",
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                {
                    "tag": "Periodicity",
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                    "type": 1
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    {
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            "creatorSummary": "Guilak and Mow",
            "parsedDate": "2000-12",
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        },
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            "itemType": "journalArticle",
            "title": "The mechanical environment of the chondrocyte: a biphasic finite element model of cell-matrix interactions in articular cartilage",
            "creators": [
                {
                    "creatorType": "author",
                    "firstName": "F",
                    "lastName": "Guilak"
                },
                {
                    "creatorType": "author",
                    "firstName": "V C",
                    "lastName": "Mow"
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            ],
            "abstractNote": "Mechanical compression of the cartilage extracellular matrix has a significant effect on the metabolic activity of the chondrocytes. However, the relationship between the stress-strain and fluid-flow fields at the macroscopic \"tissue\" level and those at the microscopic \"cellular\" level are not fully understood. Based on the existing experimental data on the deformation behavior and biomechanical properties of articular cartilage and chondrocytes, a multi-scale biphasic finite element model was developed of the chondrocyte as a spheroidal inclusion embedded within the extracellular matrix of a cartilage explant. The mechanical environment at the cellular level was found to be time-varying and inhomogeneous, and the large difference ( approximately 3 orders of magnitude) in the elastic properties of the chondrocyte and those of the extracellular matrix results in stress concentrations at the cell-matrix border and a nearly two-fold increase in strain and dilatation (volume change) at the cellular level, as compared to the macroscopic level. The presence of a narrow \"pericellular matrix\" with different properties than that of the chondrocyte or extracellular matrix significantly altered the principal stress and strain magnitudes within the chondrocyte, suggesting a functional biomechanical role for the pericellular matrix. These findings suggest that even under simple compressive loading conditions, chondrocytes are subjected to a complex local mechanical environment consisting of tension, compression, shear, and fluid pressure. Knowledge of the local stress and strain fields in the extracellular matrix is an important step in the interpretation of studies of mechanical signal transduction in cartilage explant culture models.",
            "publicationTitle": "Journal of Biomechanics",
            "publisher": "",
            "place": "",
            "date": "Dec 2000",
            "volume": "33",
            "issue": "12",
            "section": "",
            "partNumber": "",
            "partTitle": "",
            "pages": "1663-1673",
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            "seriesText": "",
            "journalAbbreviation": "J Biomech",
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            "citationKey": "",
            "url": "http://www.ncbi.nlm.nih.gov/pubmed/11006391",
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            "PMID": "11006391",
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            "ISSN": "0021-9290",
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            "shortTitle": "The mechanical environment of the chondrocyte",
            "language": "",
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            "tags": [
                {
                    "tag": "Biomechanics",
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                {
                    "tag": "Cartilage, Articular",
                    "type": 1
                },
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                    "tag": "Chondrocytes",
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                    "type": 1
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    {
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                }
            },
            "creatorSummary": "Ofek et al.",
            "parsedDate": "2009-05-11",
            "numChildren": 0
        },
        "data": {
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            "version": 3606,
            "itemType": "journalArticle",
            "title": "In situ mechanical properties of the chondrocyte cytoplasm and nucleus",
            "creators": [
                {
                    "creatorType": "author",
                    "firstName": "Gidon",
                    "lastName": "Ofek"
                },
                {
                    "creatorType": "author",
                    "firstName": "Roman M",
                    "lastName": "Natoli"
                },
                {
                    "creatorType": "author",
                    "firstName": "Kyriacos A",
                    "lastName": "Athanasiou"
                }
            ],
            "abstractNote": "The way in which the nucleus experiences mechanical forces has important implications for understanding mechanotransduction. Knowledge of nuclear material properties and, specifically, their relationship to the properties of the bulk cell can help determine if the nucleus directly experiences mechanical loads, or if it is a signal transduction mechanism secondary to cell membrane deformation that leads to altered gene expression. Prior work measuring nuclear material properties using micropipette aspiration suggests that the nucleus is substantially stiffer than the bulk cell [Guilak, F., Tedrow, J.R., Burgkart, R., 2000. Viscoelastic properties of the cell nucleus. Biochem. Biophys. Res. Commun. 269, 781-786], whereas recent work with unconfined compression of single chondrocytes showed a nearly one-to-one correlation between cellular and nuclear strains [Leipzig, N.D., Athanasiou, K.A., 2008. Static compression of single chondrocytes catabolically modifies single-cell gene expression. Biophys. J. 94, 2412-2422]. In this study, a linearly elastic finite element model of the cell with a nuclear inclusion was used to simulate the unconfined compression data. Cytoplasmic and nuclear stiffnesses were varied from 1 to 7 kPa for several combinations of cytoplasmic and nuclear Poisson's ratios. It was found that the experimental data were best fit when the ratio of cytoplasmic to nuclear stiffness was 1.4, and both cytoplasm and nucleus were modeled as incompressible. The cytoplasmic to nuclear stiffness ratio is significantly lower than prior reports for isolated nuclei. These results suggest that the nucleus may behave mechanically different in situ than when isolated.",
            "publicationTitle": "Journal of Biomechanics",
            "publisher": "",
            "place": "",
            "date": "May 11, 2009",
            "volume": "42",
            "issue": "7",
            "section": "",
            "partNumber": "",
            "partTitle": "",
            "pages": "873-877",
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            "journalAbbreviation": "J Biomech",
            "DOI": "10.1016/j.jbiomech.2009.01.024",
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            "callNumber": "",
            "rights": "",
            "extra": "",
            "tags": [
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                    "tag": "Cell Nucleus",
                    "type": 1
                },
                {
                    "tag": "Chondrocytes",
                    "type": 1
                },
                {
                    "tag": "Cytoplasm",
                    "type": 1
                },
                {
                    "tag": "Finite Element Analysis",
                    "type": 1
                },
                {
                    "tag": "Stress, Mechanical",
                    "type": 1
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    {
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            },
            "creatorSummary": "Clements et al.",
            "parsedDate": "2001-07",
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            "version": 3606,
            "itemType": "journalArticle",
            "title": "How severe must repetitive loading be to kill chondrocytes in articular cartilage?",
            "creators": [
                {
                    "creatorType": "author",
                    "firstName": "K M",
                    "lastName": "Clements"
                },
                {
                    "creatorType": "author",
                    "firstName": "Z C",
                    "lastName": "Bee"
                },
                {
                    "creatorType": "author",
                    "firstName": "G V",
                    "lastName": "Crossingham"
                },
                {
                    "creatorType": "author",
                    "firstName": "M A",
                    "lastName": "Adams"
                },
                {
                    "creatorType": "author",
                    "firstName": "M",
                    "lastName": "Sharif"
                }
            ],
            "abstractNote": "OBJECTIVE: Little is known about the effects of severe repetitive loading on articular cartilage chondrocytes, even though epidemiological studies associate this type of loading with osteoarthritis. We hypothesize that repetitive loading can kill cartilage chondrocytes in a dose-related manner. DESIGN: Large cartilage-on-bone specimens were cut from the patella groove of bovine knees obtained directly from a slaughterhouse. Cartilage was loaded using a flat impermeable indenter in such a manner that the loaded region was supported naturally by surrounding cartilage and subchondral bone. Specimens received 3600 cycles of compressive loading at 1 Hz, with the peak load lying in the range 1-70% of the force required to damage cartilage in a single loading cycle (35 MPa). Cell viability was assessed in thick sections of loaded and control cartilage using a paravital staining method: fluorescein diacetate stained live cells green, and propidium iodide stained dead cells red. The assay was validated on cartilage which had been subjected to repeated freeze-thaw cycles to kill the chondrocytes. RESULTS: Paravital staining revealed 100% cell death after one freeze-thaw cycle at -196 degrees C and three cycles at -20 degrees C. Baseline chondrocyte viability was 80% in unloaded cartilage, and viability decreased when applied compressive loading exceeded 6 MPa. Above this threshold, cell viability was inversely proportional to applied stress. When gross damage to the cartilage surface first became evident, above 14 MPa, 40% of cells remained viable. Load-induced chondrocyte death was greatest in the surface zone, and extended beyond the loaded area. Electron micrographs indicated that some cells were dying by apoptosis. CONCLUSIONS: Some chondrocytes are much more vulnerable to repetitive mechanical loading than others, suggesting that vigorous activity may lead to cell death in articular cartilage.",
            "publicationTitle": "Osteoarthritis and Cartilage / OARS, Osteoarthritis Research Society",
            "publisher": "",
            "place": "",
            "date": "Jul 2001",
            "volume": "9",
            "issue": "5",
            "section": "",
            "partNumber": "",
            "partTitle": "",
            "pages": "499-507",
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            "seriesTitle": "",
            "seriesText": "",
            "journalAbbreviation": "Osteoarthr. Cartil",
            "DOI": "10.1053/joca.2000.0417",
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            "creators": [
                {
                    "creatorType": "author",
                    "firstName": "Jiang",
                    "lastName": "Yao"
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                {
                    "creatorType": "author",
                    "firstName": "Jason",
                    "lastName": "Snibbe"
                },
                {
                    "creatorType": "author",
                    "firstName": "Michael",
                    "lastName": "Maloney"
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                    "firstName": "Amy L",
                    "lastName": "Lerner"
                }
            ],
            "abstractNote": "The menisci are believed to play a stabilizing role in the ACL-deficient knee, and are known to be at risk for degradation in the chronically unstable knee. Much of our understanding of this behavior is based on ex vivo experiments or clinical studies in which we must infer the function of the menisci from external measures of knee motion. More recently, studies using magnetic resonance (MR) imaging have provided more clear visualization of the motion and deformation of the menisci within the tibio-femoral articulation. In this study, we used such images to generate a finite element model of the medial compartment of an ACL-deficient knee to reproduce the meniscal position under anterior loads of 45, 76, and 107 N. Comparisons of the model predictions to boundaries digitized from images acquired in the loaded states demonstrated general agreement, with errors localized to the anterior and posterior regions of the meniscus, areas in which large shear stresses were present. Our model results suggest that further attention is needed to characterize material properties of the peripheral and horn attachments. Although overall translation of the meniscus was predicted well, the changes in curvature and distortion of the meniscus in the posterior region were not captured by the model, suggesting the need for refinement of meniscal tissue properties.",
            "publicationTitle": "Journal of Biomechanical Engineering",
            "publisher": "",
            "place": "",
            "date": "Feb 2006",
            "volume": "128",
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            "pages": "135-141",
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            "journalAbbreviation": "J Biomech Eng",
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                    "firstName": "Yuhua",
                    "lastName": "Song"
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                {
                    "creatorType": "author",
                    "firstName": "Richard E",
                    "lastName": "Debski"
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                    "creatorType": "author",
                    "firstName": "Savio L-Y",
                    "lastName": "Woo"
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            ],
            "abstractNote": "In this study, the force and stress distribution within the anteromedial (AM) and posterolateral (PL) bundles of the anterior cruciate ligament (ACL) in response to an anterior tibial load with the knee at full extension was calculated using a validated three-dimensional finite element model (FEM) of a human ACL. The interaction between the AM and PL bundles, as well as the contact and friction caused by the ACL wrapping around the bone during knee motion, were included in the model. The AM and PL bundles of the ACL were simulated as incompressible homogeneous and isotropic hyperelastic materials. The multiple-degrees-of-freedom (DOF) knee kinematics of a cadaveric knee were first obtained using a robotic/universal force-moment sensor testing system. These data were used as the boundary conditions for the FEM of the ACL to calculate the forces in the ACL. The calculated forces were compared to the in situ force in the ACL, determined experimentally, to validate the model. The validated FEM was then used to calculate the force and stress distribution within the ACL under an anterior tibial load at full extension. The AM and PL bundles shared the force, and the stress distribution was non-uniform within both bundles with the highest stress localized near the femoral insertion site. The contact and friction caused by the ACL wrapping around the bone during knee motion played the role of transferring the force from the ACL to the bone, and had a direct effect on the force and stress distribution of the ACL. This validated model will enable the analysis of force and stress distribution in the ACL in response to more complex loading conditions and has the potential to help design improved surgical procedures following ACL injuries.",
            "publicationTitle": "Journal of Biomechanics",
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            "creatorSummary": "Youn et al.",
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        "data": {
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            "version": 3607,
            "itemType": "journalArticle",
            "title": "Zonal variations in the three-dimensional morphology of the chondron measured in situ using confocal microscopy",
            "creators": [
                {
                    "creatorType": "author",
                    "firstName": "I",
                    "lastName": "Youn"
                },
                {
                    "creatorType": "author",
                    "firstName": "J B",
                    "lastName": "Choi"
                },
                {
                    "creatorType": "author",
                    "firstName": "L",
                    "lastName": "Cao"
                },
                {
                    "creatorType": "author",
                    "firstName": "L A",
                    "lastName": "Setton"
                },
                {
                    "creatorType": "author",
                    "firstName": "F",
                    "lastName": "Guilak"
                }
            ],
            "abstractNote": "OBJECTIVE: Chondrocytes in articular cartilage are surrounded by a narrow pericellular matrix (PCM), which together with the enclosed cell(s) are termed the \"chondron\". Although the precise function of this tissue region is unknown, previous studies provide indirect evidence that the PCM plays an important role in governing the local mechanical environment of chondrocytes. In particular, theoretical models of the chondron under mechanical loading suggest that the shape, size, and biomechanical properties of the PCM significantly influence the stress-strain and fluid flow environment of the cell. The goal of this study was to quantify the three-dimensional morphology of chondron in situ using en bloc immunolabeling of type VI collagen coupled with fluorescence confocal microscopy. METHODS: Three-dimensional reconstructions of intact, fluorescently labeled chondrons were made from stacks of confocal images recorded in situ from the superficial, middle, and deep zones of porcine articular cartilage of the medial femoral condyle. RESULTS: Significant variations in the shape, size, and orientation of chondrocytes and chondrons were observed with depth from the tissue surface, revealing flattened discoidal chondrons in the superficial zone, rounded chondrons in the middle zone, and elongated, multicellular chondrons in the deep zone. CONCLUSIONS: The shape and orientation of the chondron appear to reflect the local collagen architecture of the interterritorial matrix, which varies significantly with depth. Quantitative measurements of morphology of the chondron and its variation with site, disease, or aging may provide new insights into the influence of this structure on physiology and the pathology of articular cartilage.",
            "publicationTitle": "Osteoarthritis and Cartilage / OARS, Osteoarthritis Research Society",
            "publisher": "",
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            "date": "Sep 2006",
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            "pages": "889-897",
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                {
                    "tag": "Cartilage, Articular",
                    "type": 1
                },
                {
                    "tag": "Chondrocytes",
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            "publicationTitle": "Nuclear Instruments and Methods in Physics Research Section B: Beam Interactions with Materials and Atoms",
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            "title": "Variation of cell and matrix morphologies in articular cartilage among locations in the adult human knee",
            "creators": [
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                    "creatorType": "author",
                    "firstName": "Thomas M",
                    "lastName": "Quinn"
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                {
                    "creatorType": "author",
                    "firstName": "Ernst B",
                    "lastName": "Hunziker"
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                    "firstName": "Hans-Jörg",
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            "abstractNote": "OBJECTIVE: Understanding of articular cartilage physiology, remodelling mechanisms, and evaluation of tissue engineering repair methods requires reference information regarding normal structural organization. Our goals were to examine the variation of cartilage cell and matrix morphology in different topographical areas of the adult human knee joint. METHODS: Osteochondral explants were acquired from seven distinct anatomical locations of the knee joints of deceased persons aged 20-40 years and prepared for analysis of cell, matrix and tissue morphology using confocal microscopy and unbiased stereological methods. Differences between locations were identified by statistical analysis. RESULTS: Medial femoral condyle cartilage had relatively high cell surface area per unit tissue volume in the superficial zone. In the transitional zone, meniscus-covered lateral tibia cartilage showed elevated chondrocyte densities compared to the rest of the knee while lateral femoral condyle cartilage exhibited particularly large chondrocytes. Statistical analyses indicated highly uniform morphology throughout the radial zone (lower 80% of cartilage thickness) in the knee, and strong similarities in cell and matrix morphologies among cartilage from the femoral condyles and also in the mediocentral tibial plateau. Throughout the adult human knee, the mean matrix volume per chondron was remarkably constant at approximately 224,000 microm(3), corresponding to approximately 4.6 x 10(6) chondrons per cm(3). CONCLUSIONS: The uniformity of matrix volume per chondron throughout the adult human knee suggests that cell-scale biophysical and metabolic constraints may place limitations on cartilage thickness, mechanical properties, and remodelling mechanisms. Data may also aid the evaluation of cartilage tissue engineering treatments in a site-specific manner. Results indicate that joint locations which perform similar biomechanical functions have similar cell and matrix morphologies; findings may therefore also provide clues to understanding conditions under which focal lesions leading to osteoarthritis may occur.",
            "publicationTitle": "Osteoarthritis and Cartilage / OARS, Osteoarthritis Research Society",
            "publisher": "",
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            "date": "Aug 2005",
            "volume": "13",
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            "pages": "672-678",
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            "journalAbbreviation": "Osteoarthr. Cartil",
            "DOI": "10.1016/j.joca.2005.04.011",
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                    "tag": "Adult",
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                    "tag": "Cartilage, Articular",
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                },
                {
                    "tag": "Cell Count",
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                },
                {
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                },
                {
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                {
                    "tag": "Knee Joint",
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                },
                {
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                    "type": 1
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                    "tag": "Menisci, Tibial",
                    "type": 1
                },
                {
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            "title": "Biomechanics of single chondrocytes under direct shear",
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                    "creatorType": "author",
                    "firstName": "Gidon",
                    "lastName": "Ofek"
                },
                {
                    "creatorType": "author",
                    "firstName": "Enda P",
                    "lastName": "Dowling"
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                {
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                    "firstName": "Robert M",
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                    "firstName": "Kyriacos A",
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            "abstractNote": "Articular chondrocytes experience a variety of mechanical stimuli during daily activity. One such stimulus, direct shear, is known to affect chondrocyte homeostasis and induce catabolic or anabolic pathways. Understanding how single chondrocytes respond biomechanically and morphologically to various levels of applied shear is an important first step toward elucidating tissue level responses and disease etiology. To this end, a novel videocapture method was developed in this study to examine the effect of direct shear on single chondrocytes, applied via the controlled lateral displacement of a shearing probe. Through this approach, precise force and deformation measurements could be obtained during the shear event, as well as clear pictures of the initial cell-to-probe contact configuration. To further study the non-uniform shear characteristics of single chondrocytes, the probe was positioned in three different placement ranges along the cell height. It was observed that the apparent shear modulus of single chondrocytes decreased as the probe transitioned from being close to the cell base (4.1 +/- 1.3 kPa), to the middle of the cell (2.6 +/- 1.1 kPa), and then near its top (1.7 +/- 0.8 kPa). In addition, cells experienced the greatest peak forward displacement (approximately 30% of their initial diameter) when the probe was placed low, near the base. Forward cell movement during shear, regardless of its magnitude, continued until it reached a plateau at ~35% shear strain for all probe positions, suggesting that focal adhesions become activated at this shear level to firmly adhere the cell to its substrate. Based on intracellular staining, the observed height-specific variation in cell shear stiffness and plateau in forward cell movement appeared to be due to a rearrangement of focal adhesions and actin at higher shear strains. Understanding the fundamental mechanisms at play during shear of single cells will help elucidate potential treatments for chondrocyte pathology and loading regimens related to cartilage health and disease.",
            "publicationTitle": "Biomechanics and Modeling in Mechanobiology",
            "publisher": "",
            "place": "",
            "date": "Apr 2010",
            "volume": "9",
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            "pages": "153-162",
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            "journalAbbreviation": "Biomech Model Mechanobiol",
            "DOI": "10.1007/s10237-009-0166-1",
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            "title": "Biomechanics of articular cartilage and determination of material properties",
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                    "firstName": "Xin L",
                    "lastName": "Lu"
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                    "lastName": "Mow"
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            "abstractNote": "Descriptions of the mechanical behaviors of articular cartilage and their correlations with collagen, proteoglycan, water, and ions are summarized, with particular emphasis on understanding the osmotic effect inside the tissue. First, a descriptive explanation is presented of the biphasic theory required to understand how interstitial water contributes toward the viscoelastic behavior of any hydrated soft tissue. Then, the famous osmotic effect in charged, hydrated soft tissue is interpreted in light of the triphasic mixture theory framework. In the introduction of mechanical testing methods, our emphasis is on the popular indentation technique, which can determine the material properties of cartilage in situ or in vivo. The widely accepted indentation analysis solutions in cartilage biomechanics history are summarized and evaluated. At the end of this paper, a new generalized correspondence principle between charged, hydrated soft tissue and linear, isotropic, elastic material (i.e., elasticity theory) is introduced. This principle makes the employment of triphasic theory as straightforward as using an elasticity theory to solve any equilibrium problem where the elasticity theory can be used to model the material. By using this generalized correspondence principle, the fixed charge density of bovine cartilage has been simply and conveniently calculated from the indentation testing data. The results of proteoglycan content from this mechanical test are remarkably consistent with those from standard biochemical assay. This new correspondence principle significantly improves the power of indentation tests in the determination of mechanoelectrochemical properties of articular cartilage.",
            "publicationTitle": "Medicine and Science in Sports and Exercise",
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            "date": "Feb 2008",
            "volume": "40",
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            "pages": "193-199",
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            "title": "Zonal changes in the three-dimensional morphology of the chondron under compression: the relationship among cellular, pericellular, and extracellular deformation in articular cartilage",
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                {
                    "creatorType": "author",
                    "firstName": "Jae Bong",
                    "lastName": "Choi"
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                {
                    "creatorType": "author",
                    "firstName": "Inchan",
                    "lastName": "Youn"
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                {
                    "creatorType": "author",
                    "firstName": "Li",
                    "lastName": "Cao"
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                {
                    "creatorType": "author",
                    "firstName": "Holly A",
                    "lastName": "Leddy"
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                {
                    "creatorType": "author",
                    "firstName": "Christopher L",
                    "lastName": "Gilchrist"
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                {
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                    "firstName": "Lori A",
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            "abstractNote": "The pericellular matrix (PCM) is a narrow region of tissue that completely surrounds chondrocytes in articular cartilage. Previous theoretical models of the \"chondron\" (the PCM with enclosed cells) suggest that the structure and properties of the PCM may significantly influence the mechanical environment of the chondrocyte. The objective of this study was to quantify changes in the three-dimensional (3D) morphology of the chondron in situ at different magnitudes of compression applied to the cartilage extracellular matrix. Fluorescence immunolabeling for type-VI collagen was used to identify the boundaries of the cell and PCM, and confocal microscopy was used to form 3D images of chondrons from superficial, middle, and deep zone cartilage in explants compressed to 0%, 10%, 30%, and 50% surface-to-surface strain. Lagrangian tissue strain, determined locally using texture correlation, was highly inhomogeneous and revealed depth-dependent compressive stiffness and Poisson's ratio of the extracellular matrix. Compression significantly decreased cell and chondron height and volume, depending on the zone and magnitude of compression. In the superficial zone, cellular-level strains were always lower than tissue-level strains. In the middle and deep zones, however, tissue strains below 25% were amplified at the cellular level, while tissue strains above 25% were decreased at the cellular level. These findings are consistent with previous theoretical models of the chondron, suggesting that the PCM can serve as either a protective layer for the chondrocyte or a transducer that amplifies strain, such that cellular-level strains are more homogenous throughout the tissue depth despite large inhomogeneities in local ECM strains.",
            "publicationTitle": "Journal of Biomechanics",
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            "shortTitle": "Zonal changes in the three-dimensional morphology of the chondron under compression",
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                    "creatorType": "author",
                    "firstName": "M A",
                    "lastName": "Martínez"
                },
                {
                    "creatorType": "author",
                    "firstName": "M",
                    "lastName": "Doblaré"
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            ],
            "abstractNote": "We present here a three-dimensional FE model of the healthy human knee that included the main structures of the joint: bones, all the relevant ligaments and patellar tendon, menisci and articular cartilages. Bones were considered to be rigid, articular cartilage and menisci linearly elastic, isotropic and homogeneous and ligaments hyperelastic and transversely isotropic. Initial strains on the ligaments and patellar tendon were also considered. This model was validated using experimental and numerical results obtained by other authors. Our main goal was to analyze the combined role of menisci and ligaments in load transmission and stability of the human knee. The results obtained reproduce the complex, nonuniform stress and strain fields that occur in the biological soft tissues involved and the kinematics of the human knee joint under a physiological external load.",
            "publicationTitle": "Journal of Biomechanics",
            "publisher": "",
            "place": "",
            "date": "2006",
            "volume": "39",
            "issue": "9",
            "section": "",
            "partNumber": "",
            "partTitle": "",
            "pages": "1686-1701",
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            "seriesTitle": "",
            "seriesText": "",
            "journalAbbreviation": "J Biomech",
            "DOI": "10.1016/j.jbiomech.2005.04.030",
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            "url": "http://www.ncbi.nlm.nih.gov/pubmed/15993414",
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            "tags": [
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                    "tag": "Finite Element Analysis",
                    "type": 1
                },
                {
                    "tag": "Health",
                    "type": 1
                },
                {
                    "tag": "Humans",
                    "type": 1
                },
                {
                    "tag": "Imaging, Three-Dimensional",
                    "type": 1
                },
                {
                    "tag": "Knee Joint",
                    "type": 1
                },
                {
                    "tag": "Rotation",
                    "type": 1
                },
                {
                    "tag": "Stress, Mechanical",
                    "type": 1
                },
                {
                    "tag": "Tensile Strength",
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            "creatorSummary": "Papaioannou et al.",
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        "data": {
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            "itemType": "journalArticle",
            "title": "Patient-specific knee joint finite element model validation with high-accuracy kinematics from biplane dynamic Roentgen stereogrammetric analysis",
            "creators": [
                {
                    "creatorType": "author",
                    "firstName": "G",
                    "lastName": "Papaioannou"
                },
                {
                    "creatorType": "author",
                    "firstName": "G",
                    "lastName": "Nianios"
                },
                {
                    "creatorType": "author",
                    "firstName": "C",
                    "lastName": "Mitrogiannis"
                },
                {
                    "creatorType": "author",
                    "firstName": "D",
                    "lastName": "Fyhrie"
                },
                {
                    "creatorType": "author",
                    "firstName": "S",
                    "lastName": "Tashman"
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                {
                    "creatorType": "author",
                    "firstName": "K H",
                    "lastName": "Yang"
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            ],
            "abstractNote": "Little is known about in vivo menisci loads and displacements in the knee during strenuous activities. A new method that combines high-speed kinematics measured with biplane dynamic Roentgen stereogrammetric analysis (DRSA) and a subject-specific finite element (FE) model for studying in vivo meniscal behavior is presented here. Further model calibration in a very controlled uniaxial low and high-rate compression loading condition is presented by comparing the model behavior against the measured high-accuracy menisci DRSA kinematics and direct tibio-femoral pressure measurement from a K-scan sensor. It is apparent that certain model aspects such as removing of the pressure sensor from the model can result in relatively large errors (14%) in contact parameters that are not reflected in the change of the measured meniscal kinematics. Changing mesh size to 1mm by 1mm elements increased the magnitude of all but one of the contact variables by up to 45%. This local validation using accurate localized patient-specific geometry and meniscal kinematics was needed to enhance model fidelity at the level of contact between menisci and cartilage.",
            "publicationTitle": "Journal of Biomechanics",
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            "place": "",
            "date": "Aug 28, 2008",
            "volume": "41",
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            "pages": "2633-2638",
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            "journalAbbreviation": "J Biomech",
            "DOI": "10.1016/j.jbiomech.2008.06.027",
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            "url": "http://www.ncbi.nlm.nih.gov/pubmed/18675422",
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                {
                    "tag": "Knee Joint",
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                },
                {
                    "tag": "Male",
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                },
                {
                    "tag": "Menisci, Tibial",
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                },
                {
                    "tag": "Pressure",
                    "type": 1
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                {
                    "tag": "Radiographic Image Interpretation, Computer-Assisted",
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                    "tag": "Reproducibility of Results",
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    {
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            "creatorSummary": "Moglo and Shirazi-Adl",
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        "data": {
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            "itemType": "journalArticle",
            "title": "Cruciate coupling and screw-home mechanism in passive knee joint during extension--flexion",
            "creators": [
                {
                    "creatorType": "author",
                    "firstName": "K E",
                    "lastName": "Moglo"
                },
                {
                    "creatorType": "author",
                    "firstName": "A",
                    "lastName": "Shirazi-Adl"
                }
            ],
            "abstractNote": "The screw-home mechanism and coupling between forces in cruciate ligaments during passive knee joint flexion were investigated for various boundary conditions, flexion axis alignments and posterior cruciate ligaments (PCL)/anterior cruciate ligament (ACL) conditions. A developed non-linear 3D finite element model was used to perform detailed elasto-static response analyses of the human tibiofemoral joint as a function of flexion angle varying from 10 degrees hyper-extension to 90 degrees flexion. The tibia rotated internally as the femur flexed and externally as the femur extended. The re-alignment of the flexion axis by +/-5 degrees rotation about the axial (distal-proximal) axis, transection of the ACL and changes in cruciate ligament initial strains substantially influenced the 'screw-home' motion. On the other hand, restraint on this coupled rotation diminished ACL forces in flexion. A remarkable coupling was predicted between ACL and PCL forces in flexion; forces in both cruciate ligaments increased as the initial strain or pretension in one of them increased whereas they both diminished as one of them was cut or became slack. This has important consequences in joint functional biomechanics following a ligament injury or replacement surgery and, hence, in the proper management of joint disorders.",
            "publicationTitle": "Journal of Biomechanics",
            "publisher": "",
            "place": "",
            "date": "May 2005",
            "volume": "38",
            "issue": "5",
            "section": "",
            "partNumber": "",
            "partTitle": "",
            "pages": "1075-1083",
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            "seriesTitle": "",
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            "journalAbbreviation": "J Biomech",
            "DOI": "10.1016/j.jbiomech.2004.05.033",
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            "url": "http://www.ncbi.nlm.nih.gov/pubmed/15797589",
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                    "tag": "Anterior Cruciate Ligament",
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                    "tag": "Movement",
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                },
                {
                    "tag": "Posterior Cruciate Ligament",
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                {
                    "tag": "Range of Motion, Articular",
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                {
                    "tag": "Stress, Mechanical",
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]