Sample records for acetabular articular cartilage

  1. Magnetic resonance imaging with gadolinium arthrography to assess acetabular cartilage delamination.

    PubMed

    Zaragoza, Edward; Lattanzio, Pierre-Jean; Beaule, Paul E

    2009-01-01

    Recent reports have demonstrated magnetic resonance imaging (MRI) as a promising technique in detecting articular cartilage lesions of the hip joint. The purpose of our study was to evaluate the diagnostic performance of MRI with gadolinium arthrography in detecting acetabular cartilage delamination in patients with pre-arthritic hip pain. 46 patients (48 hips) underwent surgical dislocation of the hip. Mean age was 38.8 (range 17-56). There were 26 males and 20 females. All patients had Magnetic Resonance Imaging with gadolinium arthrography (MRA) before undergoing open hip surgery where the acetabular cartilage was inspected. Acetabular cartilage delamination on MRA was seen on sagittal images as a linear intra-articular filling defect of low signal intensity >1mm in thickness on T1 weighted images and surrounded by contrast. On MRA all hips had a labral tear confirmed at surgery. At surgery 30 hips had evidence of acetabular cartilage delamination, 4 hips had ulceration and 14 had no articular cartilage damage. The majority of labral tears and cartilage damage were located in the antero-superior quadrant. The sensitivity and specificity of MRA detection of cartilage delamination confirmed at surgery were 97% and 84%, respectively. The positive and negative predictive values of the MRA finding were 90% and 94%, respectively. The presence of the acetabular cartilage delamination represents an early stage of articular cartilage degeneration. When evaluating a young adult with hip pain, labral tears in association with cartilage delamination should be considered. MRA represents an effective diagnostic tool.

  2. Evaluation of articular cartilage following rotational acetabular osteotomy for hip dysplasia using T2 mapping MRI.

    PubMed

    Shoji, Takeshi; Yamasaki, Takuma; Izumi, Soutaro; Sawa, Mikiya; Akiyama, Yuji; Yasunaga, Yuji; Adachi, Nobuo

    2018-04-27

    Rotational acetabular osteotomy (RAO) is one of the surgical treatments for acetabular dysplasia, and satisfactory results have been reported. We evaluated the postoperative changes of articular cartilage and whether the pre-operative condition of the articular cartilage influences the clinical results using T2 mapping MRI. We reviewed 31 hips with early stage osteoarthritis in 31 patients (mean age, 39.6 years), including three men and 28 women who underwent RAO for hip dysplasia. Clinical evaluations including Japanese Orthopedic Association (JOA) score and Japanese Orthopedic Association Hip Disease Evaluation Questionnaire (JHEQ), and radiographical evaluations on X-ray were performed. Longitudinal qualitative assessment of articular cartilage was also performed using 3.0-T MRI with T2 mapping technique preoperatively, 6 months, and at 1 and 2 years postoperatively. There was no case with progression of osteoarthritis. The mean JOA score improved from 70.1 to 93.4 points, the mean postoperative JHEQ score was 68.8 points, and radiographical data also improved postoperatively. We found that the T2 values of the cartilage at both femoral head and acetabulum increased at 6 months on coronal and sagittal views. However, they significantly decreased 1 and 2 years postoperatively. The T2 values of the center to anterolateral region of acetabulum negatively correlated with postoperative JHEQ score, particularly in pain score. This study suggests that biomechanical and anatomical changes could apparently cause decreased T2 values 1-2 years postoperatively compared with those preoperatively. Furthermore, preoperative T2 values of the acetabulum can be prognostic factors for the clinical results of RAO.

  3. Multi-pelvis characterisation of articular cartilage geometry.

    PubMed

    Gillard, Faye C; Dickinson, Alexander S; Schneider, Urs; Taylor, Andrew C; Browne, Martin

    2013-12-01

    The shape of the acetabular cartilage follows the contact stress distribution across the joint. Accurate characterisation of this geometry may be useful for the development of acetabular cup devices that are more biomechanically compliant. In this study, the geometry of the acetabular cartilage was characterised by taking plaster moulds of the acetabulum from 24 dry bone human pelvises and digitising the mould shapes using a three-dimensional laser scanner. The articular bone surface geometry was analysed, and the shape of the acetabulum was approximated by fitting a best-fit sphere. To test the hypothesis that the acetabulum is non-spherical, a best-fit ellipsoid was also fitted to the geometry. In each case, points around the acetabular notch edge that disclosed the articular surface geometry were identified, and vectors were drawn between these and the best-fit sphere or ellipsoid centre. The significantly larger z radii (into the pole) of the ellipsoids indicated that the acetabulum was non-spherical and could imply that the kinematics of the hip joint is more complex than purely rotational motion, and the traditional ball-and-socket replacement may need to be updated to reflect this motion. The acetabular notch edges were observed to be curved, with males exhibiting deeper, wider and shorter notches than females, although the difference was not statistically significant (mean: p = 0.30) and supports the use of non-gender-specific models in anatomical studies.

  4. Arthroscopic repair of delaminated acetabular articular cartilage using fibrin adhesive. Results at one to three years.

    PubMed

    Stafford, Giles H; Bunn, Jonathan R; Villar, Richard N

    2011-01-01

    We describe one- to three-year results of a novel use of fibrin glue in the treatment of cartilage damage by arthroscopy in the hip. This technique uses the microfracture technique and fibrin adhesive to bond delaminated articular cartilage to the underlying subchondral bone. This is generally performed in conjunction with treatment of underlying pathology such as femoroacetabular impingement. Patients were assessed using the modified Harris Hip Score (MHHS) pre- and post-operatively, and statistical significance determined by Student's t-test. We report the mid-term results of 43 patients with femoroacetabular impingement who have undergone this technique for re-attachment of delaminated chondral flaps. There was a statistically significant improvement in MHHS at a mean of 28 months (16 to 42 months) after surgery (p<0.0001). The MHHS for pain improved significantly from 21.8 (95% CI 19.0 to 24.7) pre-operatively to 35.8 (95% CI 32.6 to 38.9) post-operatively (p<0.0001). The MHHS for function also showed significant, although more modest, improvements from 40.0 (95% CI 37.7 to 42.3) pre-operatively to 43.6 (95% CI 41.4 to 45.8) post-operatively (p=0.0006). There were three patients who had early (within 12 months of the index procedure) revision arthroscopy for iliopsoas pathology. Arthroscopic repair of delaminated acetabular articular cartilage using fibrin adhesive is a useful technique in the treatment of early cartilage damage. We have seen encouraging mid-term results, although further studies are warranted.

  5. Computed tomography arthrography with traction in the human hip for three-dimensional reconstruction of cartilage and the acetabular labrum

    PubMed Central

    Henak, C.R.; Abraham, C.L.; Peters, C.L.; Sanders, R.K.; Weiss, J.A.; Anderson, A.E.

    2014-01-01

    AIM To develop and demonstrate the efficacy of a computed tomography arthrography (CTA) protocol for the hip that enables accurate three-dimensional reconstructions of cartilage and excellent visualization of the acetabular labrum. MATERIALS AND METHODS Ninety-three subjects were imaged (104 scans); 68 subjects with abnormal anatomy, 11 patients after periacetabular osteotomy surgery, and 25 subjects with normal anatomy. Fifteen to 25 ml of contrast agent diluted with lidocaine was injected using a lateral oblique approach. A Hare traction splint applied traction during CT. The association between traction force and intra-articular joint space was assessed qualitatively under fluoroscopy. Cartilage geometry was reconstructed from the CTA images for 30 subjects; the maximum joint space under traction was measured. RESULTS Using the Hare traction splint, the intra-articular space and boundaries of cartilage could be clearly delineated throughout the joint; the acetabular labrum was also visible. Dysplastic hips required less traction (~5 kg) than normal and retroverted hips required (>10 kg) to separate the cartilage. An increase in traction force produced a corresponding widening of the intra-articular joint space. Under traction, the maximum width of the intra-articular joint space during CT ranged from 0.98–6.7 mm (2.46 ± 1.16 mm). CONCLUSIONS When applied to subjects with normal and abnormal hip anatomy, the CTA protocol presented yields clear delineation of the cartilage and the acetabular labrum. Use of a Hare traction splint provides a simple, cost-effective method to widen the intra-articular joint space during CT, and provides flexibility to vary the traction as required. PMID:25070373

  6. Towards Regeneration of Articular Cartilage

    PubMed Central

    Iwamoto, Masahiro; Ohta, Yoichi; Larmour, Colleen; Enomoto-Iwamoto, Motomi

    2014-01-01

    Articular cartilage is classified into permanent hyaline cartilage and has significant differences in structure, extracelluar matrix components, gene expression profile, and mechanical property from transient hyaline cartilage found in growth plate. In the process of synovial joint development, articular cartilage is originated from the interzone, developing at the edge of the cartilaginous anlagen, it establishes zonal structure over time and supports smooth movement of the synovial joint through life. The cascade actions of key regulators such as Wnts, GDF5, Erg, and PTHLH coordinate sequential steps of articular cartilage formation. Articular chondrocytes are restrictedly controlled not to differentiate into a hypertrophic stage by autocrine and paracrine factors and extracerllular matrix microenvironment, but retain potential to undergo hypertrophy. The basal calcified zone of articular cartilage is connected with subchondral bone, but not invaded by blood vessels nor replaced by bone, which is highly contrasted with the growth plate. Articular cartilage has limited regenerative capacity, but likely possesses and potentially uses intrinsic stem cell source in the superficial layer, Ranvier’s groove, the intra-articular tissues such as synovium and fat pad, and marrow below the subchondral bone. Considering the biological views on articular cartilage, several important points are raised for regeneration of articular cartilage. We should evaluate the nature of regenerated cartilage as permanent hyaline cartilage and not just hyaline cartilage. We should study how a hypertrophic phenotype of transplanted cells can be lastingly suppressed in regenerating tissue. Further, we should develop the methods and reagents to activate recruitment of intrinsic stem/progenitor cells into the damaged site. PMID:24078496

  7. Calcification of the acetabular labrum of the hip: prevalence in the general population and relation to hip articular cartilage and fibrocartilage degeneration.

    PubMed

    Hawellek, Thelonius; Hubert, Jan; Hischke, Sandra; Krause, Matthias; Bertrand, Jessica; Schmidt, Burkhard C; Kronz, Andreas; Püschel, Klaus; Rüther, Wolfgang; Niemeier, Andreas

    2018-05-30

    Meniscal calcification is considered to play a relevant role in the pathogenesis of osteoarthritis of the knee. Little is known about the biology of acetabular labral disease and its importance in hip pathology. Here, we analyze for the first time the calcification of the acetabular labrum of the hip (ALH) and its relation to hip cartilage degeneration. In this cross-sectional post-mortem study of an unselected sample of the general population, 170 ALH specimens and 170 femoral heads from 85 donors (38 female, 47 male; mean age 62.1 years) were analyzed by high-resolution digital contact radiography (DCR) and histological degeneration grade. The medial menisci (MM) from the same 85 donors served as an intra-individual reference for cartilage calcification (CC). Scanning electron microscopy (SEM), energy dispersive analysis (ED) and Raman spectroscopy were performed for characterization of ALH CC. The prevalence of CC in the ALH was 100% and that in the articular cartilage of the hip (ACH) was 96.5%. Quantitative analysis revealed that the amount of ALH CC was higher than that in the ACH (factor 3.0, p < 0.001) and in the MM (factor 1.3, p < 0.001). There was significant correlation between the amount of CC in the fibrocartilage of the left and right ALH (r = 0.70, p < 0.001). Independent of age, the amount of ALH CC correlated with histological degeneration of the ALH (Krenn score) (r = 0.55; p < 0.001) and the ACH (Osteoarthritis Research Society International (OARSI), r = 0.69; p < 0.001). Calcification of the ALH was characterized as calcium pyrophosphate dihydrate deposition. The finding that ALH fibrocartilage is a strongly calcifying tissue is unexpected and novel. The fact that ALH calcification correlates with cartilage degeneration independent of age is suggestive of an important role of ALH calcification in osteoarthritis of the hip and renders it a potential target for the prevention and treatment of hip joint degeneration.

  8. Engineering Lubrication in Articular Cartilage

    PubMed Central

    McNary, Sean M.; Athanasiou, Kyriacos A.

    2012-01-01

    Despite continuous progress toward tissue engineering of functional articular cartilage, significant challenges still remain. Advances in morphogens, stem cells, and scaffolds have resulted in enhancement of the bulk mechanical properties of engineered constructs, but little attention has been paid to the surface mechanical properties. In the near future, engineered tissues will be able to withstand and support the physiological compressive and tensile forces in weight-bearing synovial joints such as the knee. However, there is an increasing realization that these tissue-engineered cartilage constructs will fail without the optimal frictional and wear properties present in native articular cartilage. These characteristics are critical to smooth, pain-free joint articulation and a long-lasting, durable cartilage surface. To achieve optimal tribological properties, engineered cartilage therapies will need to incorporate approaches and methods for functional lubrication. Steady progress in cartilage lubrication in native tissues has pushed the pendulum and warranted a shift in the articular cartilage tissue-engineering paradigm. Engineered tissues should be designed and developed to possess both tribological and mechanical properties mirroring natural cartilage. In this article, an overview of the biology and engineering of articular cartilage structure and cartilage lubrication will be presented. Salient progress in lubrication treatments such as tribosupplementation, pharmacological, and cell-based therapies will be covered. Finally, frictional assays such as the pin-on-disk tribometer will be addressed. Knowledge related to the elements of cartilage lubrication has progressed and, thus, an opportune moment is provided to leverage these advances at a critical step in the development of mechanically and tribologically robust, biomimetic tissue-engineered cartilage. This article is intended to serve as the first stepping stone toward future studies in functional

  9. Supporting Biomaterials for Articular Cartilage Repair

    PubMed Central

    Duarte Campos, Daniela Filipa; Drescher, Wolf; Rath, Björn; Tingart, Markus

    2012-01-01

    Orthopedic surgeons and researchers worldwide are continuously faced with the challenge of regenerating articular cartilage defects. However, until now, it has not been possible to completely mimic the biological and biochemical properties of articular cartilage using current research and development approaches. In this review, biomaterials previously used for articular cartilage repair research are addressed. Furthermore, a brief discussion of the state of the art of current cell printing procedures mimicking native cartilage is offered in light of their use as future alternatives for cartilage tissue engineering. Inkjet cell printing, controlled deposition cell printing tools, and laser cell printing are cutting-edge techniques in this context. The development of mimetic hydrogels with specific biological properties relevant to articular cartilage native tissue will support the development of improved, functional, and novel engineered tissue for clinical application. PMID:26069634

  10. Fat-suppressed 3D spoiled gradient-echo MRI and MDCT arthrography of articular cartilage in patients with hip dysplasia.

    PubMed

    Nishii, Takashi; Tanaka, Hisashi; Nakanishi, Katsuyuki; Sugano, Nobuhiko; Miki, Hidenobu; Yoshikawa, Hideki

    2005-08-01

    Our objective was to assess the diagnostic ability of MDCT arthrography for acetabular and femoral cartilage lesions in patients with hip dysplasia. A disorder of the articular cartilage was evaluated in 20 hips of 18 patients with acetabular dysplasia who did not have osteoarthritis or who had early stage osteoarthritis before undergoing pelvic osteotomy surgery. The findings on fat-suppressed 3D fast spoiled gradient-echo MRI and MDCT arthrography of the hip were evaluated by two independent observers, and sensitivity, specificity, and accuracy were determined using arthroscopic findings as the standard of reference. Kappa values were calculated to quantify the level of interobserver agreement. The sensitivity and specificity for the detection of any cartilage disorder (grade 1 or higher) were (observer 1/observer 2) 49%/67% and 89%/76%, respectively, on MRI, and 67%/67% and 89%/82%, respectively, on CT arthrography. The sensitivity and specificity for the detection of cartilage lesions with substance loss (grade 2 or higher) were (observer 1/observer 2) 47%/53% and 92%/87%, respectively, on MRI, and 70%/79% and 93%/94%, respectively, on CT arthrography. CT arthrography provided significantly higher sensitivity in the detection of grade 2 or higher lesions than MRI for both observers. Interobserver agreement in the detection of grade 2 or higher cartilage lesions was moderate (kappa = 0.53) on MRI and substantial (kappa = 0.78) on CT. MDCT arthrography is a sensitive and reproducible method for assessing articular cartilage lesions with substance loss in patients with hip dysplasia.

  11. [Research progress of articular cartilage scaffold for tissue engineering].

    PubMed

    Liu, Qingyu; Wang, Fuyou; Yang, Liu

    2012-10-01

    To review the research progress of articular cartilage scaffold materials and look into the future development prospects. Recent literature about articular cartilage scaffold for tissue engineering was reviewed, and the results from experiments and clinical application about natural and synthetic scaffold materials were analyzed. The design of articular cartilage scaffold for tissue engineering is vital to articular cartilage defects repair. The ideal scaffold can promote the progress of the cartilage repair, but the scaffold materials still have their limitations. It is necessary to pay more attention to the research of the articular cartilage scaffold, which is significant to the repair of cartilage defects in the future.

  12. Acetabular cartilage defects cause altered hip and knee joint coordination variability during gait.

    PubMed

    Samaan, Michael A; Teng, Hsiang-Ling; Kumar, Deepak; Lee, Sonia; Link, Thomas M; Majumdar, Sharmila; Souza, Richard B

    2015-12-01

    Patients with acetabular cartilage defects reported increased pain and disability compared to those without acetabular cartilage defects. The specific effects of acetabular cartilage defects on lower extremity coordination patterns are unclear. The purpose of this study was to determine hip and knee joint coordination variability during gait in those with and without acetabular cartilage defects. A combined approach, consisting of a semi-quantitative MRI-based quantification method and vector coding, was used to assess hip and knee joint coordination variability during gait in those with and without acetabular cartilage lesions. The coordination variability of the hip flexion-extension/knee rotation, hip abduction-adduction/knee rotation, and hip rotation/knee rotation joint couplings were reduced in the acetabular lesion group compared to the control group during loading response of the gait cycle. The lesion group demonstrated increased variability in the hip flexion-extension/knee rotation and hip abduction-adduction/knee rotation joint couplings, compared to the control group, during the terminal stance/pre-swing phase of gait. Reduced variability during loading response in the lesion group may suggest reduced movement strategies and a possible compensation mechanism for lower extremity instability during this phase of the gait cycle. During terminal stance/pre-swing, a larger variability in the lesion group may suggest increased movement strategies and represent a compensation or pain avoidance mechanism caused by the load applied to the hip joint. Copyright © 2015 Elsevier Ltd. All rights reserved.

  13. New trends in articular cartilage repair.

    PubMed

    Cucchiarini, Magali; Henrionnet, Christel; Mainard, Didier; Pinzano, Astrid; Madry, Henning

    2015-12-01

    Damage to the articular cartilage is an important, prevalent, and unsolved clinical issue for the orthopaedic surgeon. This review summarizes innovative basic research approaches that may improve the current understanding of cartilage repair processes and lead to novel therapeutic options. In this regard, new aspects of cartilage tissue engineering with a focus on the choice of the best-suited cell source are presented. The importance of non-destructive cartilage imaging is highlighted with the recent availability of adapted experimental tools such as Second Harmonic Generation (SHG) imaging. Novel insights into cartilage pathophysiology based on the involvement of the infrapatellar fat pad in osteoarthritis are also described. Also, recombinant adeno-associated viral vectors are discussed as clinically adapted, efficient tools for potential gene-based medicines in a variety of articular cartilage disorders. Taken as a whole, such advances in basic research in diverse fields of articular cartilage repair may lead to the development of improved therapies in the clinics for an improved, effective treatment of cartilage lesions in a close future.

  14. The influence of the acetabular labrum seal, intact articular superficial zone and synovial fluid thixotropy on squeeze-film lubrication of a spherical synovial joint.

    PubMed

    Hlavácek, M

    2002-10-01

    A model of synovial fluid (SF) filtration by articular cartilage (AC) in a step-loaded spherical synovial joint at rest is presented. The effects of joint pathology (such as a depleted acetabular labrum, a depleted cartilage superficial zone consistent with early osteoarthritis and an inflammatory SF) on the squeezed synovial film are also investigated. Biphasic mixture models for AC (ideal fluid and elastic porous transversely isotropic two-layer matrix) and for SF (ideal and thixotropic fluids) are applied and the following results are obtained. If the acetabular labrum is able to seal the pressurised SF between the articular surfaces (as in the normal hip joint), the fluid in the synovial film and in the cartilage within the labral ring is homogeneously pressurised. The articular surfaces remain separated by a fluid film for minutes. If the labrum is destroyed or absent and the SF can escape across the contact edge, the fluid pressure is non-homogeneous and with a small jump at the articular surface at the very moment of load application. The ensuing synovial film filtration by porous cartilage is lower for the normal cartilage (with the intact superficial zone) than if this zone is already depleted or rubbed off as in the early stage of primary osteoarthritis. Compared with the inflammatory (Newtonian) SF, the normal (thixotropic) fluid applies favourably in the squeezed film near the contact centre only, yielding a thicker SF film there, but not affecting the minimum thickness in the fluid film profile at a fixed time. For all that, in the unsealed case for both the normal and pathological joint, the macromolecular concentration of the hyaluronic acid-protein complex in the synovial film quickly increases due to the filtration in the greater part of the contact. A stable synovial gel film, thick on the order of 10(-7)m, protecting the articular surfaces from the intimate contact, is formed within a couple of seconds. Boundary lubrication by the synovial gel is

  15. MRI of articular cartilage at microscopic resolution

    PubMed Central

    Xia, Y.

    2013-01-01

    This review briefly summarises some of the definitive studies of articular cartilage by microscopic MRI (µMRI) that were conducted with the highest spatial resolutions. The article has four major sections. The first section introduces the cartilage tissue, MRI and µMRI, and the concept of image contrast in MRI. The second section describes the characteristic profiles of three relaxation times (T1, T2 and T1ρ) and self-diffusion in healthy articular cartilage. The third section discusses several factors that can influence the visualisation of articular cartilage and the detection of cartilage lesion by MRI and µMRI. These factors include image resolution, image analysis strategies, visualisation of the total tissue, topographical variations of the tissue properties, surface fibril ambiguity, deformation of the articular cartilage, and cartilage lesion. The final section justifies the values of multidisciplinary imaging that correlates MRI with other technical modalities, such as optical imaging. Rather than an exhaustive review to capture all activities in the literature, the studies cited in this review are merely illustrative. PMID:23610697

  16. Non-Contact Evaluation for Articular Cartilage Using Ultrasound

    NASA Astrophysics Data System (ADS)

    Mori, Koji; Nakagawa, Yasuaki; Kuroki, Hiroshi; Nakashima, Keisuke; Ikeuchi, Ken; Mine, Takatomo; Nakamura, Takashi; Kawai, Shinya; Saito, Takashi

    In orthopedic field, various new treatments of articular cartilage defect, for example autogenous osteochondral grafts, have been developed. With the spread of these treatments, orthopedists began to focus on the mechanical properties of recovered articular cartilage. The quantitative evaluation of articular cartilage before and after these treatments gives orthopedists the important information to improve these treatments and develop new treatments. We have been investigating the non-contact ultrasonic evaluation for articular cartilage under arthroscopy. In this paper, it was hypothesized that the ultrasonic evaluation depended on the collagen fiber in cartilage. The enzymatically degradation of collagen fiber in cartilage surface was performed. The effect of the degradation on sound velocity, attenuation coefficient and signal intensity, which is the index of cartilage stiffness calculated from the proposed method, was measured. The numerical analysis was performed to clear the relation between the cartilage character and ultrasonic parameters. Experimental and numerical results suggest that the present method can be expanded the sensitive evaluation for cartilage disease in clinical field.

  17. Use magnetic resonance imaging to assess articular cartilage

    PubMed Central

    Wang, Yuanyuan; Wluka, Anita E.; Jones, Graeme; Ding, Changhai

    2012-01-01

    Magnetic resonance imaging (MRI) enables a noninvasive, three-dimensional assessment of the entire joint, simultaneously allowing the direct visualization of articular cartilage. Thus, MRI has become the imaging modality of choice in both clinical and research settings of musculoskeletal diseases, particular for osteoarthritis (OA). Although radiography, the current gold standard for the assessment of OA, has had recent significant technical advances, radiographic methods have significant limitations when used to measure disease progression. MRI allows accurate and reliable assessment of articular cartilage which is sensitive to change, providing the opportunity to better examine and understand preclinical and very subtle early abnormalities in articular cartilage, prior to the onset of radiographic disease. MRI enables quantitative (cartilage volume and thickness) and semiquantitative assessment of articular cartilage morphology, and quantitative assessment of cartilage matrix composition. Cartilage volume and defects have demonstrated adequate validity, accuracy, reliability and sensitivity to change. They are correlated to radiographic changes and clinical outcomes such as pain and joint replacement. Measures of cartilage matrix composition show promise as they seem to relate to cartilage morphology and symptoms. MRI-derived cartilage measurements provide a useful tool for exploring the effect of modifiable factors on articular cartilage prior to clinical disease and identifying the potential preventive strategies. MRI represents a useful approach to monitoring the natural history of OA and evaluating the effect of therapeutic agents. MRI assessment of articular cartilage has tremendous potential for large-scale epidemiological studies of OA progression, and for clinical trials of treatment response to disease-modifying OA drugs. PMID:22870497

  18. Locating articular cartilage in MR images

    NASA Astrophysics Data System (ADS)

    Folkesson, Jenny; Dam, Erik; Pettersen, Paola; Olsen, Ole F.; Nielsen, Mads; Christiansen, Claus

    2005-04-01

    Accurate computation of the thickness of the articular cartilage is of great importance when diagnosing and monitoring the progress of joint diseases such as osteoarthritis. A fully automated cartilage assessment method is preferable compared to methods using manual interaction in order to avoid inter- and intra-observer variability. As a first step in the cartilage assessment, we present an automatic method for locating articular cartilage in knee MRI using supervised learning. The next step will be to fit a variable shape model to the cartilage, initiated at the location found using the method presented in this paper. From the model, disease markers will be extracted for the quantitative evaluation of the cartilage. The cartilage is located using an ANN-classifier, where every voxel is classified as cartilage or non-cartilage based on prior knowledge of the cartilage structure. The classifier is tested using leave-one-out-evaluation, and we found the average sensitivity and specificity to be 91.0% and 99.4%, respectively. The center of mass calculated from voxels classified as cartilage are similar to the corresponding values calculated from manual segmentations, which confirms that this method can find a good initial position for a shape model.

  19. Leptin plays a catabolic role on articular cartilage.

    PubMed

    Bao, Jia-peng; Chen, Wei-ping; Feng, Jie; Hu, Peng-fei; Shi, Zhong-li; Wu, Li-dong

    2010-10-01

    Leptin has been shown to play a crucial role in the regulation of body weight. There is also evidence that this adipokine plays a key role in the process of osteoarthritis. However, the precise role of leptin on articular cartilage metabolism is not clear. We investigate the role of leptin on articular cartilage in vivo in this study. Recombinant rat leptin (100 μg) was injected into the knee joints of rats, 48 h later, messenger RNA (mRNA) expression and protein levels of basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF), matrix metalloproteinases 2 and 9 (MMP-2, MMP-9), cathepsin D, and collagen II from articular cartilage were analyzed by real-time quantitative polymerase chain reaction (PCR) and western blot. Two important aggrecanases ADAMTS-4 and -5 (a disintegrin and metalloproteinase with thrombospondin motifs 4 and 5) were also analyzed by real-time quantitative PCR. Besides, articular cartilage was also assessed for proteoglycan/GAG content by Safranin O staining. Leptin significantly increased both gene and protein levels of MMP-2, MMP-9, cathepsin D, and collagen II, while decreased bFGF markedly in cartilage. Moreover, the gene expression of ADAMTS-4 and -5 were markedly increased, and histologically assessed depletion of proteoglycan in articular cartilage was observed after treatment with leptin. These results strongly suggest that leptin plays a catabolic role on cartilage metabolism and may be a disadvantage factor involve in the pathological process of OA.

  20. The effects of exercise on human articular cartilage

    PubMed Central

    Eckstein, F; Hudelmaier, M; Putz, R

    2006-01-01

    The effects of exercise on articular hyaline articular cartilage have traditionally been examined in animal models, but until recently little information has been available on human cartilage. Magnetic resonance imaging now permits cartilage morphology and composition to be analysed quantitatively in vivo. This review briefly describes the methodological background of quantitative cartilage imaging and summarizes work on short-term (deformational behaviour) and long-term (functional adaptation) effects of exercise on human articular cartilage. Current findings suggest that human cartilage deforms very little in vivo during physiological activities and recovers from deformation within 90 min after loading. Whereas cartilage deformation appears to become less with increasing age, sex and physical training status do not seem to affect in vivo deformational behaviour. There is now good evidence that cartilage undergoes some type of atrophy (thinning) under reduced loading conditions, such as with postoperative immobilization and paraplegia. However, increased loading (as encountered by elite athletes) does not appear to be associated with increased average cartilage thickness. Findings in twins, however, suggest a strong genetic contribution to cartilage morphology. Potential reasons for the inability of cartilage to adapt to mechanical stimuli include a lack of evolutionary pressure and a decoupling of mechanical competence and tissue mass. PMID:16637874

  1. The effects of exercise on human articular cartilage.

    PubMed

    Eckstein, F; Hudelmaier, M; Putz, R

    2006-04-01

    The effects of exercise on articular hyaline articular cartilage have traditionally been examined in animal models, but until recently little information has been available on human cartilage. Magnetic resonance imaging now permits cartilage morphology and composition to be analysed quantitatively in vivo. This review briefly describes the methodological background of quantitative cartilage imaging and summarizes work on short-term (deformational behaviour) and long-term (functional adaptation) effects of exercise on human articular cartilage. Current findings suggest that human cartilage deforms very little in vivo during physiological activities and recovers from deformation within 90 min after loading. Whereas cartilage deformation appears to become less with increasing age, sex and physical training status do not seem to affect in vivo deformational behaviour. There is now good evidence that cartilage undergoes some type of atrophy (thinning) under reduced loading conditions, such as with postoperative immobilization and paraplegia. However, increased loading (as encountered by elite athletes) does not appear to be associated with increased average cartilage thickness. Findings in twins, however, suggest a strong genetic contribution to cartilage morphology. Potential reasons for the inability of cartilage to adapt to mechanical stimuli include a lack of evolutionary pressure and a decoupling of mechanical competence and tissue mass.

  2. Techniques and Applications of in vivo Diffusion Imaging of Articular Cartilage

    PubMed Central

    Raya, José G.

    2014-01-01

    Early in the process of osteoarthritis (OA) the composition (water, proteoglycan [PG], and collagen) and structure of articular cartilage is altered leading to changes in its mechanical properties. A technique that can assess the composition and structure of the cartilage in vivo can provide insight in the mechanical integrity of articular cartilage and become a powerful tool for the early diagnosis of OA. Diffusion tensor imaging (DTI) has been proposed as a biomarker for cartilage composition and structure. DTI is sensitive to the PG content through the mean diffusivity (MD) and to the collagen architecture through the fractional anisotropy (FA). However, the acquisition of DTI of articular cartilage in vivo is challenging due to the short T2 of articular cartilage (~40 ms at 3 T) and the high resolution needed (0.5–0.7 mm in plane) to depict the cartilage anatomy. We describe the pulse sequences used for in vivo DTI of articular cartilage and discus general strategies for protocol optimization. We provide a comprehensive review of measurements of DTI of articular cartilage from ex vivo validation experiments to its recent clinical applications. PMID:25865215

  3. Articular Cartilage Repair of the Knee in Children and Adolescents

    PubMed Central

    Salzmann, Gian M.; Niemeyer, Philipp; Hochrein, Alfred; Stoddart, Martin J.; Angele, Peter

    2018-01-01

    Articular cartilage predominantly serves a biomechanical function, which begins in utero and further develops during growth and locomotion. With regard to its 2-tissue structure (chondrocytes and matrix), the regenerative potential of hyaline cartilage defects is limited. Children and adolescents are increasingly suffering from articular cartilage and osteochondral deficiencies. Traumatic incidents often result in damage to the joint surfaces, while repetitive microtrauma may cause osteochondritis dissecans. When compared with their adult counterparts, children and adolescents have a greater capacity to regenerate articular cartilage defects. Even so, articular cartilage injuries in this age group may predispose them to premature osteoarthritis. Consequently, surgery is indicated in young patients when conservative measures fail. The operative techniques for articular cartilage injuries traditionally performed in adults may be performed in children, although an individualized approach must be tailored according to patient and defect characteristics. Clear guidelines for defect dimension–associated techniques have not been reported. Knee joint dimensions must be considered and correlated with respect to the cartilage defect size. Particular attention must be given to the subchondral bone, which is frequently affected in children and adolescents. Articular cartilage repair techniques appear to be safe in this cohort of patients, and no differences in complication rates have been reported when compared with adult patients. Particularly, autologous chondrocyte implantation has good biological potential, especially for large-diameter joint surface defects. PMID:29568785

  4. The Effect of Intra-articular Corticosteroids on Articular Cartilage

    PubMed Central

    Wernecke, Chloe; Braun, Hillary J.; Dragoo, Jason L.

    2015-01-01

    Background: Intra-articular (IA) corticosteroid therapy has been used for the treatment of inflammation and pain in the knee since the 1950s. Purpose: To review the current literature on the effects of IA corticosteroids on articular cartilage. Study Design: Systematic review. Methods: A MEDLINE and SCOPUS database search was performed, and studies were selected for basic science and clinical trial research on corticosteroids with direct outcome measures of cartilage health. Preliminary searches yielded 1929 articles, and final analysis includes 40 studies. Results: Methylprednisolone, dexamethasone, hydrocortisone, betamethasone, prednisolone, and triamcinolone were reported to display dose-dependent deleterious effects on cartilage morphology, histology, and viability in both in vitro and in vivo models. The beneficial animal in vivo effects of methylprednisolone, hydrocortisone, and triamcinolone occurred at low doses (usually <2-3 mg/dose or 8-12 mg/cumulative total dose in vivo), at which increased cell growth and recovery from damage was observed; the single human clinical trial indicated a beneficial effect of triamcinolone. However, at higher doses (>3 mg/dose or 18-24 mg/cumulative total dose in vivo), corticosteroids were associated with significant gross cartilage damage and chondrocyte toxicity. Dose and time dependency of corticosteroid chondrotoxicity was supported in the in vitro results, however, without clear dose thresholds. Conclusion: Corticosteroids have a time- and dose-dependent effect on articular cartilage, with beneficial effects occurring at low doses and durations and detrimental effects at high doses and durations. Clinically, beneficial effects are supported for IA administration, but the lowest efficacious dose should be used. PMID:26674652

  5. Analysis of friction between articular cartilage and polyvinyl alcohol hydrogel artificial cartilage.

    PubMed

    Li, Feng; Wang, Anmin; Wang, Chengtao

    2016-05-01

    Many biomaterials are being used to repair damaged articular cartilage. In particular, poly vinyl alcohol hydrogel has similar mechanical properties to natural cartilage under compressive and shearing loading. Here, three-factor and two-level friction experiments and long-term tests were conducted to better evaluate its tribological properties. The friction coefficient between articular cartilage and the poly vinyl alcohol hydrogel depended primarily on the three factors of load, speed, and lubrication. When the speed increased from 10 to 20 mm/s under a load of 10 N, the friction coefficient increased from 0.12 to 0.147. When the lubricant was changed from Ringer's solution to a hyaluronic acid solution, the friction coefficient decreased to 0.084 with loads as high as 22 N. The poly vinyl alcohol hydrogel was severely damaged and lost its top surface layers, which were transferred to the articular cartilage surface. Wear was observed in the surface morphologies, which indicated the occurrence of surface adhesion of bovine cartilage. Surface fatigue and adhesive wear was the dominant wear mechanism.

  6. Measurements of surface layer of the articular cartilage using microscopic techniques

    NASA Astrophysics Data System (ADS)

    Ryniewicz, A. M.; Ryniewicz, A.; Ryniewicz, W.; Gaska, A.

    2010-07-01

    The articular cartilage is the structure that directly cooperates tribologically in biobearing. It belongs to the connective tissues and in the joints it assumes two basic forms: hyaline cartilage that builds joint surfaces and fibrocartilage which may create joint surfaces. From this fibrocartilage are built semilunar cartilage and joint disc are built as well. The research of articular cartilage have been done in macro, micro and nano scale. In all these measurement areas characteristic features occur which can identify biobearing tribology. The aim of the research was the identification of surface layer of articular cartilage by means of scanning electron microscopy (SEM) and atom force microscopy (AFM) and the analysis of topography of these layers. The material used in the research of surface layer was the animal articular cartilage: hyaline cartilage and fibrocartilage.

  7. Articular Cartilage Repair Through Muscle Cell-Based Tissue Engineering

    DTIC Science & Technology

    2011-03-01

    defects display good cell survival and can differentiate into chondrocytes that improve the healing of articular cartilage. We also have observed that... self -renewal to their regenerative capacity after transplantation into the cartilage defects (Technical Objective #1). Next, we will determine the...osteochondral defects display good cell survival and can differentiate into chondrocytes that improve the healing of articular cartilage. We also have

  8. CORRELATION OF ARTICULAR CARTILAGE THICKNESS MEASUREMENTS MADE WITH MAGNETIC RESONANCE IMAGING, MAGNETIC RESONANCE ARTHROGRAPHY, AND COMPUTED TOMOGRAPHIC ARTHROGRAPHY WITH GROSS ARTICULAR CARTILAGE THICKNESS IN THE EQUINE METACARPOPHALANGEAL JOINT.

    PubMed

    Porter, Erin G; Winter, Matthew D; Sheppard, Barbara J; Berry, Clifford R; Hernandez, Jorge A

    2016-09-01

    Osteoarthritis of the metacarpophalangeal joint is common cause of lameness in equine athletes, and is hallmarked by articular cartilage damage. An accurate, noninvasive method for measuring cartilage thickness would be beneficial to screen for cartilage injury and allow for prompt initiation of interventional therapy. The objective of this methods comparison study was to compare computed tomographic arthrography (CTA), magnetic resonance imaging (MRI), and magnetic resonance arthrography (MRA) measurements of articular cartilage thickness with gross measurements in the metacarpophalangeal joint of Thoroughbred horses. Fourteen cadaveric, equine thoracic limbs were included. Limbs were excluded from the study if pathology of the metacarpophalangeal articular cartilage was observed with any imaging modality. Articular cartilage thickness was measured in nine regions of the third metacarpal bone and proximal phalanx on sagittal plane MRI sequences. After intra-articular contrast administration, the measurements were repeated on sagittal plane MRA and sagittal CTA reformations. In an effort to increase cartilage conspicuity, the volume of intra-articular contrast was increased from 14.5 ml, to maximal distention for the second set of seven limbs. Mean and standard deviation values were calculated, and linear regression analysis was used to determine correlations between gross and imaging measurements of cartilage thickness. This study failed to identify one imaging test that consistently yielded measurements correlating with gross cartilage thickness. Even with the use of intra-articular contrast, cartilage surfaces were difficult to differentiate in regions where the cartilage surfaces of the proximal phalanx and third metacarpal bone were in close contact with each other. © 2016 American College of Veterinary Radiology.

  9. Targeting TGFβ Signaling in Subchondral Bone and Articular Cartilage Homeostasis

    PubMed Central

    Zhen, Gehau; Cao, Xu

    2014-01-01

    Osteoarthritis (OA) is the most common degenerative joint disease, and there is no disease-modifying therapy for OA currently available. Targeting of articular cartilage alone may not be sufficient to halt this disease progression. Articular cartilage and subchondral bone act as a functional unit. Increasing evidence indicates that transforming growth factor β (TGFβ) plays a crucial role in maintaining homeostasis of both articular cartilage and subchondral bone. Activation of extracellular matrix latent TGFβ at the appropriate time and location is the prerequisite for its function. Aberrant activation of TGFβ in the subchondral bone in response to abnormal mechanical loading environment induces formation of osteroid islets at onset of osteoarthritis. As a result, alteration of subchondral bone structure changes the stress distribution on the articular cartilage and leads to its degeneration. Thus, inhibition of TGFβ activity in the subchondral bone may provide a new avenue of treatment for OA. In this review, we will respectively discuss the role of TGFβ in homeostasis of articular cartilage and subchondral bone as a novel target for OA therapy. PMID:24745631

  10. Halofuginone attenuates articular cartilage degeneration by inhibition of elevated TGF‑β1 signaling in articular cartilage in a rodent osteoarthritis model.

    PubMed

    Mu, Wenbo; Xu, Boyong; Ma, Hairong; Ji, Baochao; Zhang, Zhendong; Li, Jiao; Amat, Abdusami; Cao, Li

    2017-11-01

    Osteoarthritis (OA) is the most common degenerative condition of the weight‑bearing joints worldwide without effective medical therapy. In order to investigate whether administration of halofuginone (HF) may attenuate OA, the present study allocated 3‑month‑old male mice into Sham group, vehicle‑treated anterior cruciate ligament transection (ACLT) group and HF‑treated ACLT group. The present study determined that HF treatment reduced the expression of matrix metallopeptidase‑13 and collagen X in articular cartilage. Additionally, it lowered the Osteoarthritis Research Society International‑Modified Mankin score and prevented the loss of articular cartilage from Safranin O and Fast Green staining. HF reduced the progression of osteoarthritis by downregulating abnormally elevated TGF‑β1 activity in articular cartilage. Administration of HF may be a potential preventive therapy for OA.

  11. Label-free characterization of degenerative changes in articular cartilage by Raman spectroscopy

    NASA Astrophysics Data System (ADS)

    Oshima, Yusuke; Akehi, Mayu; Kiyomatsu, Hiroshi; Miura, Hiromasa

    2017-04-01

    Osteoarthritis (OA) is very common joint disease in the aging population. Main symptom of OA is accompanied by degenerative changes of articular cartilage. Raman spectroscopy is a label-free technique which enables to analyze molecular composition in degenerative cartilage. We generated an animal OA model surgically induced by knee joint instability and performed Raman spectroscopic analysis for the articular cartilage. In the result, Raman spectral data of the articular cartilage showed drastic changes in comparison between OA and control side. The relative intensity of phosphate band increases in the degenerative cartilage.

  12. Inducing articular cartilage phenotype in costochondral cells

    PubMed Central

    2013-01-01

    Introduction Costochondral cells may be isolated with minimal donor site morbidity and are unaffected by pathologies of the diarthrodial joints. Identification of optimal exogenous stimuli will allow abundant and robust hyaline articular cartilage to be formed from this cell source. Methods In a three factor, two level full factorial design, the effects of hydrostatic pressure (HP), transforming growth factor β1 (TGF-β1), and chondroitinase ABC (C-ABC), and all resulting combinations, were assessed in third passage expanded, redifferentiated costochondral cells. After 4 wks, the new cartilage was assessed for matrix content, superficial zone protein (SZP), and mechanical properties. Results Hyaline articular cartilage was generated, demonstrating the presence of type II collagen and SZP, and the absence of type I collagen. TGF-β1 upregulated collagen synthesis by 175% and glycosaminoglycan synthesis by 75%, resulting in a nearly 200% increase in tensile and compressive moduli. C-ABC significantly increased collagen content, and fibril density and diameter, leading to a 125% increase in tensile modulus. Hydrostatic pressure increased fibril diameter by 30% and tensile modulus by 45%. Combining TGF-β1 with C-ABC synergistically increased collagen content by 300% and tensile strength by 320%, over control. No significant differences were observed between C-ABC/TGF-β1 dual treatment and HP/C-ABC/TGF-β1. Conclusions Employing biochemical, biophysical, and mechanical stimuli generated robust hyaline articular cartilage with a tensile modulus of 2 MPa and a compressive instantaneous modulus of 650 kPa. Using expanded, redifferentiated costochondral cells in the self-assembling process allows for recapitulation of robust mechanical properties, and induced SZP expression, key characteristics of functional articular cartilage. PMID:24330640

  13. Quantitative characterization of mesenchymal stem cell adhesion to the articular cartilage surface.

    PubMed

    Hung, Ben P; Babalola, Omotunde M; Bonassar, Lawrence J

    2013-12-01

    There has been great interest in use of mesenchymal stem cell (MSC)-based therapies for cartilage repair. Most recently, treatments involving intra-articular injection of MSCs have shown great promise for cartilage repair and arthritis therapy, which rely on MSC adhesion to cartilage. While there is some information on chondrocyte adhesion to cartilage, there is relatively little known about the kinetics and strength of MSC adhesion to cartilage. The goals of this study were as follows: (1) to quantify the kinetics and strength of adhesion of marrow-derived MSCs to articular cartilage using standard laboratory hardware; (2) to compare this adhesion behavior to that of articular chondrocytes; and (3) to assess the effect of serial monolayer culture on MSC adhesion. First through fourth passage MSCs and primary articular chondrocytes were allowed to adhere to the articular surface of cartilage disks for up to 30 h and the number of adhered cells was recorded to quantify adhesion kinetics. After 30 h, adherent cells were subjected to centrifugal shear to determine adhesion strength, quantified as the shear necessary to detach half the adhered cells (σ50 ). The number of adhered MSCs and adhesion strength increased with passage number and MSCs adhered more strongly than did primary articular chondrocytes. As such, the kinetics and strength of MSC adhesion to cartilage is not dramatically lower than that for articular chondrocytes. This protocol for assessing cell adhesion to cartilage is simple to implement and may represent an important screening tool for assessing the efficacy of cell-based therapies for cartilage repair. Copyright © 2013 Wiley Periodicals, Inc., a Wiley Company.

  14. Computational aspects in mechanical modeling of the articular cartilage tissue.

    PubMed

    Mohammadi, Hadi; Mequanint, Kibret; Herzog, Walter

    2013-04-01

    This review focuses on the modeling of articular cartilage (at the tissue level), chondrocyte mechanobiology (at the cell level) and a combination of both in a multiscale computation scheme. The primary objective is to evaluate the advantages and disadvantages of conventional models implemented to study the mechanics of the articular cartilage tissue and chondrocytes. From monophasic material models as the simplest form to more complicated multiscale theories, these approaches have been frequently used to model articular cartilage and have contributed significantly to modeling joint mechanics, addressing and resolving numerous issues regarding cartilage mechanics and function. It should be noted that attentiveness is important when using different modeling approaches, as the choice of the model limits the applications available. In this review, we discuss the conventional models applicable to some of the mechanical aspects of articular cartilage such as lubrication, swelling pressure and chondrocyte mechanics and address some of the issues associated with the current modeling approaches. We then suggest future pathways for a more realistic modeling strategy as applied for the simulation of the mechanics of the cartilage tissue using multiscale and parallelized finite element method.

  15. Articular cartilage. Part I. The normal joint.

    PubMed

    Muehleman, C; Arsenis, C H

    1995-05-01

    Articular hyaline cartilage is of interest to both the clinician and the basic scientist because of its unique physical and chemical properties which are a consequence of its biochemical composition. Although it is a tissue which is hypocellular, avascular, and also lacks nerves and lymphatics, it is active in synthesis and degradation. Articular cartilage responds to the forces to which it is subjected and, in this way, maintains its integrity as long as those forces do not exceed the tissue's capacity for repair or permanently change the biologic response of the cells.

  16. Identification of latexin by a proteomic analysis in rat normal articular cartilage

    PubMed Central

    2010-01-01

    Background Osteoarthritis (OA) is characterized by degeneration of articular cartilage. Animal models of OA induced are a widely used tool in the study of the pathogenesis of disease. Several proteomic techniques for selective extraction of proteins have provided protein profiles of chondrocytes and secretory patterns in normal and osteoarthritic cartilage, including the discovery of new and promising biomarkers. In this proteomic analysis to study several proteins from rat normal articular cartilage, two-dimensional electrophoresis and mass spectrometry (MS) were used. Interestingly, latexin (LXN) was found. Using an immunohistochemical technique, it was possible to determine its localization within the chondrocytes from normal and osteoarthritic articular cartilage. Results In this study, 147 proteins were visualized, and 47 proteins were identified by MS. A significant proportion of proteins are involved in metabolic processes and energy (32%), as well as participating in different biological functions including structural organization (19%), signal transduction and molecular signaling (11%), redox homeostasis (9%), transcription and protein synthesis (6%), and transport (6%). The identified proteins were assigned to one or more subcellular compartments. Among the identified proteins, we found some proteins already recognized in other studies such as OA-associated proteins. Interestingly, we identified LXN, an inhibitor of mammalian carboxypeptidases, which had not been described in articular cartilage. Immunolabeling assays for LXN showed a granular distribution pattern in the cytoplasm of most chondrocytes of the middle, deep and calcified zones of normal articular cartilage as well as in subchondral bone. In osteoarthritic cartilage, LXN was observed in superficial and deep zones. Conclusions This study provides the first proteomic analysis of normal articular cartilage of rat. We identified LXN, whose location was demonstrated by immunolabeling in the

  17. Diagnosis of lesions of the acetabular labrum, of the labral-chondral transition zone, and of the cartilage in femoroacetabular impingement: Correlation between direct magnetic resonance arthrography and hip arthroscopy.

    PubMed

    Crespo Rodríguez, A M; de Lucas Villarrubia, J C; Pastrana Ledesma, M A; Millán Santos, I; Padrón, M

    2015-01-01

    To determine the sensitivity and accuracy of direct MR arthrography in the diagnosis of intra-articular lesions associated with femoroacetabular impingement. We used direct MR arthrography to study 51 patients with femoroacetabular impingement who underwent arthroscopic hip surgery. Surgery demonstrated 37 labral tears, 44 lesions in the labral-chondral transitional zone, and 40 lesions of the articular cartilage. We correlated the findings at preoperative direct MR arthrography with those of hip arthroscopy and calculated the sensitivity, specificity, positive predictive value, negative predictive value, and validity index for direct MR arthrography. The sensitivity and specificity of MR arthrography were 94.5% and 100%, respectively, for diagnosing labral tears, 100% and 87.5%, respectively, for diagnosing lesions of the labral-chondral transition zone, and 92.5% and 54.5%, respectively, for diagnosing lesions of the articular cartilage. The negative predictive value of MR arthrography for lesions of the labral-chondral transitional zone was 100%. MR arthrography accurately defined extensive lesions of the cartilage and the secondary osseous changes (the main factor in poor prognosis), although its diagnostic performance was not so good in small chondral lesions. In patients with femoroacetabular impingement, direct MR arthrography can adequately detect and characterize lesions of the acetabular labrum and of the labral-chondral transitional zone as well as extensive lesions of the articular cartilage and secondary osseous changes. Copyright © 2013 SERAM. Published by Elsevier España, S.L.U. All rights reserved.

  18. Articular cartilage generation applying PEG-LA-DM/PEGDM copolymer hydrogels.

    PubMed

    Zhao, Xing; Papadopoulos, Anestis; Ibusuki, Shinichi; Bichara, David A; Saris, Daniel B; Malda, Jos; Anseth, Kristi S; Gill, Thomas J; Randolph, Mark A

    2016-06-03

    Injuries to the human native cartilage tissue are particularly problematic because cartilage has little to no ability to heal or regenerate itself. Employing a tissue engineering strategy that combines suitable cell sources and biomimetic hydrogels could be a promising alternative to achieve cartilage regeneration. However, the weak mechanical properties may be the major drawback to use fully degradable hydrogels. Besides, most of the fully degradable hydrogels degrade too fast to permit enough extracellular matrix (ECM) production for neocartilage formation. In this study, we demonstrated the feasibility of neocartilage regeneration using swine articular chondrocytes photoencapsualted into poly (ethylene glycol) dimethacrylate (PEGDM) copolymer hydrogels composed of different degradation profiles: degradable (PEG-LA-DM) and nondegradable (PEGDM) macromers in molar ratios of 50/50, 60/40, 70/30, 80/20, and 90/10. Articular chondrocytes were isolated enzymatically from juvenile Yorkshire swine cartilage. 6 × 10(7) cells cells were added to each milliliter of macromer/photoinitiator (I2959) solution. Nonpolymerized gel containing the cells (100 μL) was placed in cylindrical molds (4.5 mm diameter × 6.5 mm in height). The macromer/photoinitiator/chondrocyte solutions were polymerized using ultraviolet (365 nm) light at 10 mW/cm(2) for 10 mins. Also, an articular cartilaginous ring model was used to examine the capacity of the engineered cartilage to integrate with native cartilage. Samples in the pilot study were collected at 6 weeks. Samples in the long-term experimental groups (60/40 and 70/30) were implanted into nude mice subcutaneously and harvested at 6, 12 and 18 weeks. Additionally, cylindrical constructs that were not implanted used as time zero controls. All of the harvested specimens were examined grossly and analyzed histologically and biochemically. Histologically, the neocartilage formed in the photochemically crosslinked gels resembled native

  19. Indentation stiffness does not discriminate between normal and degraded articular cartilage.

    PubMed

    Brown, Cameron P; Crawford, Ross W; Oloyede, Adekunle

    2007-08-01

    Relative indentation characteristics are commonly used for distinguishing between normal healthy and degraded cartilage. The application of this parameter in surgical decision making and an appreciation of articular cartilage biomechanics has prompted us to hypothesise that it is difficult to define a reference stiffness to characterise normal articular cartilage. This hypothesis is tested for validity by carrying out biomechanical indentation of articular cartilage samples that are characterised as visually normal and degraded relative to proteoglycan depletion and collagen disruption. Compressive loading was applied at known strain rates to visually normal, artificially degraded and naturally osteoarthritic articular cartilage and observing the trends of their stress-strain and stiffness characteristics. While our results demonstrated a 25% depreciation in the stiffness of individual samples after proteoglycan depletion, they also showed that when compared to the stiffness of normal samples only 17% lie outside the range of the stress-strain behaviour of normal samples. We conclude that the extent of the variability in the properties of normal samples, and the degree of overlap (81%) of the biomechanical properties of normal and degraded matrices demonstrate that indentation data cannot form an accurate basis for distinguishing normal from abnormal articular cartilage samples with consequences for the application of this mechanical process in the clinical environment.

  20. Articular Cartilage Aging-Potential Regenerative Capacities of Cell Manipulation and Stem Cell Therapy

    PubMed Central

    Placek, Waldemar

    2018-01-01

    Changes in articular cartilage during the aging process are a stage of natural changes in the human body. Old age is the major risk factor for osteoarthritis but the disease does not have to be an inevitable consequence of aging. Chondrocytes are particularly prone to developing age-related changes. Changes in articular cartilage that take place in the course of aging include the acquisition of the senescence-associated secretory phenotype by chondrocytes, a decrease in the sensitivity of chondrocytes to growth factors, a destructive effect of chronic production of reactive oxygen species and the accumulation of the glycation end products. All of these factors affect the mechanical properties of articular cartilage. A better understanding of the underlying mechanisms in the process of articular cartilage aging may help to create new therapies aimed at slowing or inhibiting age-related modifications of articular cartilage. This paper presents the causes and consequences of cellular aging of chondrocytes and the biological therapeutic outlook for the regeneration of age-related changes of articular cartilage. PMID:29470431

  1. Repair and tissue engineering techniques for articular cartilage

    PubMed Central

    Makris, Eleftherios A.; Gomoll, Andreas H.; Malizos, Konstantinos N.; Hu, Jerry C.; Athanasiou, Kyriacos A.

    2015-01-01

    Chondral and osteochondral lesions due to injury or other pathology commonly result in the development of osteoarthritis, eventually leading to progressive total joint destruction. Although current progress suggests that biologic agents can delay the advancement of deterioration, such drugs are incapable of promoting tissue restoration. The limited ability of articular cartilage to regenerate renders joint arthroplasty an unavoidable surgical intervention. This Review describes current, widely used clinical repair techniques for resurfacing articular cartilage defects; short-term and long-term clinical outcomes of these techniques are discussed. Also reviewed is a developmental pipeline of regenerative biological products that over the next decade could revolutionize joint care by functionally healing articular cartilage. These products include cell-based and cell-free materials such as autologous and allogeneic cell-based approaches and multipotent and pluripotent stem-cell-based techniques. Central to these efforts is the prominent role that tissue engineering has in translating biological technology into clinical products; therefore, concomitant regulatory processes are also discussed. PMID:25247412

  2. Label-free characterization of articular cartilage in osteoarthritis model mice by Raman spectroscopy

    NASA Astrophysics Data System (ADS)

    Oshima, Yusuke; Akehi, Mayu; Kiyomatsu, Hiroshi; Miura, Hiromasa

    2017-02-01

    Osteoarthritis (OA) is very common joint disease in the aging population. Main symptom of OA is accompanied by degenerative changes of articular cartilage. Cartilage contains mostly type II collagen and proteoglycans, so it is difficult to access the quality and morphology of cartilage tissue in situ by conventional diagnostic tools (X-ray, MRI and echography) directly or indirectly. Raman spectroscopy is a label-free technique which enables to analyze molecular composition in degenerative cartilage. In this study, we generated an animal OA model surgically induced by knee joint instability, and the femurs were harvested at two weeks after the surgery. We performed Raman spectroscopic analysis for the articular cartilage of distal femurs in OA side and unaffected side in each mouse. In the result, there is no gross findings in the surface of the articular cartilage in OA. On the other hand, Raman spectral data of the articular cartilage showed drastic changes in comparison between OA and control side. The major finding of this study is that the relative intensity of phosphate band (960 cm-1) increases in the degenerative cartilage. This may be the result of exposure of subchondral bone due to thinning of the cartilage layer. In conclusion, Raman spectroscopic technique is sufficient to characterize articular cartilage in OA as a pilot study for Raman application in cartilage degeneration and regeneration using animal models and human subjects.

  3. Strategic Design and Fabrication of Engineered Scaffolds for Articular Cartilage Repair

    PubMed Central

    Izadifar, Zohreh; Chen, Xiongbiao; Kulyk, William

    2012-01-01

    Damage to articular cartilage can eventually lead to osteoarthritis (OA), a debilitating, degenerative joint disease that affects millions of people around the world. The limited natural healing ability of cartilage and the limitations of currently available therapies make treatment of cartilage defects a challenging clinical issue. Hopes have been raised for the repair of articular cartilage with the help of supportive structures, called scaffolds, created through tissue engineering (TE). Over the past two decades, different designs and fabrication techniques have been investigated for developing TE scaffolds suitable for the construction of transplantable artificial cartilage tissue substitutes. Advances in fabrication technologies now enable the strategic design of scaffolds with complex, biomimetic structures and properties. In particular, scaffolds with hybrid and/or biomimetic zonal designs have recently been developed for cartilage tissue engineering applications. This paper reviews critical aspects of the design of engineered scaffolds for articular cartilage repair as well as the available advanced fabrication techniques. In addition, recent studies on the design of hybrid and zonal scaffolds for use in cartilage tissue repair are highlighted. PMID:24955748

  4. Particulated articular cartilage: CAIS and DeNovo NT.

    PubMed

    Farr, Jack; Cole, Brian J; Sherman, Seth; Karas, Vasili

    2012-03-01

    Cartilage Autograft Implantation System (CAIS; DePuy/Mitek, Raynham, MA) and DeNovo Natural Tissue (NT; ISTO, St. Louis, MO) are novel treatment options for focal articular cartilage defects in the knee. These methods involve the implantation of particulated articular cartilage from either autograft or juvenile allograft donor, respectively. In the laboratory and in animal models, both CAIS and DeNovo NT have demonstrated the ability of the transplanted cartilage cells to "escape" from the extracellular matrix, migrate, multiply, and form a new hyaline-like cartilage tissue matrix that integrates with the surrounding host tissue. In clinical practice, the technique for both CAIS and DeNovo NT is straightforward, requiring only a single surgery to affect cartilage repair. Clinical experience is limited, with short-term studies demonstrating both procedures to be safe, feasible, and effective, with improvements in subjective patient scores, and with magnetic resonance imaging evidence of good defect fill. While these treatment options appear promising, prospective randomized controlled studies are necessary to refine the indications and contraindications for both CAIS and DeNovo NT.

  5. Blends and Nanocomposite Biomaterials for Articular Cartilage Tissue Engineering

    PubMed Central

    Doulabi, Azadehsadat Hashemi; Mequanint, Kibret; Mohammadi, Hadi

    2014-01-01

    This review provides a comprehensive assessment on polymer blends and nanocomposite systems for articular cartilage tissue engineering applications. Classification of various types of blends including natural/natural, synthetic/synthetic systems, their combination and nanocomposite biomaterials are studied. Additionally, an inclusive study on their characteristics, cell responses ability to mimic tissue and regenerate damaged articular cartilage with respect to have functionality and composition needed for native tissue, are also provided. PMID:28788131

  6. Rehabilitation after Articular Cartilage Repair of the Knee in the Football (Soccer) Player

    PubMed Central

    Silvers, Holly Jacinda; Steinwachs, Matthias

    2012-01-01

    Background: Participation in football can put both male and female players at an increased risk for knee osteoarthritis. There is a higher prevalence of focal chondral defects in the knee of athletes compared to nonathletes. The management of chondral defects in the football player is complex and multifactorial. Objective: The aim of this study is to provide an overview of the current strategies for rehabilitation after articular cartilage repair of the knee in the football player. Design: A review of current literature and the scientific evidence for rehabilitation after articular cartilage repair of the knee. Conclusions: Articular cartilage repair has been shown to allow return to sport but rehabilitation timescales are lengthy. Successful rehabilitation for a return to football after articular cartilage repair of the knee requires the player to be able to accept the load of the sport. This necessitates a multidisciplinary approach to rehabilitation, especially in the transition from therapy to performance care. It should be recognized that not all players will return to football after articular cartilage repair. The evidence base for rehabilitative practice after articular cartilage repair is increasing but remains sparse in areas. PMID:26069608

  7. Effects of immobilization on articular cartilage: Autohistoradiographic findings with S35

    NASA Technical Reports Server (NTRS)

    Digiovanni, C.; Desantis, E.

    1980-01-01

    The effect of immobilization on the articular cartilage of rabbits was studied by light microscope. The knee joint of each rabbit was immobilized in a plaster in a position midway between flexion and extension for a 10 to 120 days period. Degenerative changes in the articular cartilage of increasing severity were observed. The fixation of the labeled SO4 by cartilage cells was decreased in advanced immobilization.

  8. Airflow accelerates bovine and human articular cartilage drying and chondrocyte death.

    PubMed

    Paterson, S I; Amin, A K; Hall, A C

    2015-02-01

    Exposure of articular cartilage to static air results in changes to the extracellular matrix (ECM) and stimulates chondrocyte death, which may cause joint degeneration. However during open orthopaedic surgery, cartilage is often exposed to laminar airflow, which may exacerbate these damaging effects. We compared drying in static and moving air in terms of cartilage appearance, hydration and chondrocyte viability, and tested the ability of saline-saturated gauze to limit the detrimental effects of air exposure. Articular cartilage from bovine metatarsophalangeal joints (N = 50) and human femoral heads (N = 6) was exposed for 90 min to (1) static air (2) airflow (up to 0.34 m/s), or (3) airflow (0.18 m/s), covered with gauze. Following air exposure, cartilage was also rehydrated (0.9% saline; 120 min) to determine the reversibility of drying effects. The influence of airflow was assessed by studying macroscopic appearance, and quantifying superficial zone (SZ) chondrocyte viability and cartilage hydration. Airflow caused advanced changes to cartilage appearance, accelerated chondrocyte death, and increased dehydration compared to static air. These effects were prevented if cartilage was covered by saline-saturated gauze. Cartilage rehydration reversed macroscopic changes associated with drying but the chondrocyte death was not altered. Chondrocytes at the cut edge of cartilage were more sensitive to drying compared to cells distant from the edge. Airflow significantly increased articular cartilage dehydration and chondrocyte death compared to static air. As laminar airflow is routinely utilised in operating theatres, it is essential that articular cartilage is kept wet via irrigation or by covering with saline-saturated gauze to prevent chondrocyte death. Copyright © 2014 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

  9. Zn deposition at the bone cartilage interface in equine articular cartilage

    NASA Astrophysics Data System (ADS)

    Bradley, D. A.; Moger, C. J.; Winlove, C. P.

    2007-09-01

    In articular cartilage metalloproteinases, a family of enzymes whose function relies on the presence of divalent cations such as Zn and Ca plays a central role in the normal processes of growth and remodelling and in the degenerative and inflammatory processes of arthritis. Another important enzyme, alkaline phosphatase, involved in cartilage mineralisation also relies on metallic cofactors. The local concentration of divalent cations is therefore of considerable interest in cartilage pathophysiology and several authors have used synchrotron X-ray fluorescence (XRF) to map metal ion distributions in bone and cartilage. We report use of a bench-top XRF analytical microscope, providing spatial resolution of 10 μm and applicable to histological sections, facilitating correlation of the distribution with structural features. The study seeks to establish the elemental distribution in normal tissue as a precursor to investigation of changes in disease. For six samples prepared from equine metacarpophalangeal joint, we observed increased concentration of Zn and Sr ions around the tidemark between normal and mineralised cartilage. This is believed to be an active site of remodelling but its composition has hitherto lacked detailed characterization. We also report preliminary results on two of the samples using Proton-Induced X-ray Emission (PIXE). This confirms our previous observations using synchrotron-based XRF of enhanced deposition of Sr and Zn at the surface of the subchondral bone and in articular cartilage.

  10. Articular cartilage. Part II. The osteoarthritic joint.

    PubMed

    Muehleman, C; Arsenis, C H

    1995-05-01

    Articular hyaline cartilage, though a metabolically active tissue, has limited capacity for repair. Though the integrity of the cartilage is dependent upon a certain level of force placed upon it, excessive force leads to damage. It is when the breakdown of the cartilage exceeds the capacity of the cartilage for repair that osteoarthritis results. At present, pharmacologic treatment of osteoarthritis is focused toward the control of pain and stiffness. This treatment, however, masks the symptoms of the disease and effectively allows the patient to do further damage to the joint.

  11. PRP and Articular Cartilage: A Clinical Update

    PubMed Central

    Rossi, Roberto; Castoldi, Filippo; Michielon, Gianni

    2015-01-01

    The convincing background of the recent studies, investigating the different potentials of platelet-rich plasma, offers the clinician an appealing alternative for the treatment of cartilage lesions and osteoarthritis. Recent evidences in literature have shown that PRP may be helpful both as an adjuvant for surgical treatment of cartilage defects and as a therapeutic tool by intra-articular injection in patients affected by osteoarthritis. In this review, the authors introduce the trophic and anti-inflammatory properties of PRP and the different products of the available platelet concentrates. Then, in a complex scenario made of a great number of clinical variables, they resume the current literature on the PRP applications in cartilage surgery as well as the use of intra-articular PRP injections for the conservative treatment of cartilage degenerative lesions and osteoarthritis in humans, available as both case series and comparative studies. The result of this review confirms the fascinating biological role of PRP, although many aspects yet remain to be clarified and the use of PRP in a clinical setting has to be considered still exploratory. PMID:26075244

  12. Arthroscopic Ultrasound Assessment of Articular Cartilage in the Human Knee Joint

    PubMed Central

    Kaleva, Erna; Virén, Tuomas; Saarakkala, Simo; Sahlman, Janne; Sirola, Joonas; Puhakka, Jani; Paatela, Teemu; Kröger, Heikki; Kiviranta, Ilkka; Jurvelin, Jukka S.; Töyräs, Juha

    2011-01-01

    Objective: We tested whether an intra-articular ultrasound (IAUS) method could be used to evaluate cartilage status arthroscopically in human knee joints in vivo. Design: Seven patients undergoing arthroscopic surgery of the knee were enrolled in this study. An ultrasonic examination was conducted using the same portals as in the arthroscopic surgery. A high-frequency (40-MHz) ultrasound transducer (diameter = 1 mm) was directed to the desired location on the articular surface under arthroscopic control. In addition to ultrasound data, an IAUS video and optical video through the arthroscope were recorded. Classification of cartilage injuries according to International Cartilage Repair Society, as conducted by the orthopedic surgeon, provided reference data for comparison with the IAUS. Results: The IAUS method was successful in imaging different characteristics of the articular surfaces (e.g., intact surface, surface fibrillation, and lesions of varying depth). In some cases, also the subchondral bone and abnormal internal cartilage structure were visible in the IAUS images. Specifically, using the IAUS, a local cartilage lesion of 1 patient was found to be deeper than estimated arthroscopically. Conclusions: The IAUS method provided a novel arthroscopic method for quantitative imaging of articular cartilage lesions. The IAUS provided quantitative information about the cartilage integrity and thickness, which are not available in conventional arthroscopy. The present equipment is already approved by the Food and Drug Administration for intravascular use and might be transferred to intra-articular use. The invasiveness of the IAUS method might restrict its wider clinical use but combined with arthroscopy, ultrasonic assessment may enlarge the diagnostic potential of arthroscopic surgery. PMID:26069583

  13. Inversion of the acetabular labrum triggers rapidly destructive osteoarthritis of the hip: representative case report and proposed etiology.

    PubMed

    Fukui, Kiyokazu; Kaneuji, Ayumi; Fukushima, Mana; Matsumoto, Tadami

    2014-12-01

    The pathophysiology of rapidly destructive osteoarthritis (OA) of the hip is unknown. This study documented cases of inversion of the acetabular labrum, which has clinicoradiologic features similar to those of initial-stage rapidly destructive hip OA. Our study was based on a prospective review of data for 9 patients with rapidly destructive hip OA. Intraoperative findings showed that the anterosuperior portion of the acetabular labrum had inverted into the articular space, along with many fragments of articular cartilage, in all patients. Subchondral insufficiency fractures of the femoral heads were seen just under the inverted labra in 8 of the 9 patients. Inversion of the acetabular labrum may be involved in rapid joint-space narrowing and subchondral insufficiency fracture in rapidly destructive hip OA. Copyright © 2014 Elsevier Inc. All rights reserved.

  14. Tenascin-C Prevents Articular Cartilage Degeneration in Murine Osteoarthritis Models.

    PubMed

    Matsui, Yuriyo; Hasegawa, Masahiro; Iino, Takahiro; Imanaka-Yoshida, Kyoko; Yoshida, Toshimichi; Sudo, Akihiro

    2018-01-01

    Objective The objective of this study was to determine whether intra-articular injections of tenascin-C (TNC) could prevent cartilage damage in murine models of osteoarthritis (OA). Design Fluorescently labeled TNC was injected into knee joints and its distribution was examined at 1 day, 4 days, 1 week, 2 weeks, and 4 weeks postinjection. To investigate the effects of TNC on cartilage degeneration after surgery to knee joints, articular spaces were filled with 100 μg/mL (group I), 10 μg/mL (group II) of TNC solution, or control (group III). TNC solution of 10 μg/mL was additionally injected twice after 3 weeks (group IV) or weekly after 1 week, 2 weeks, and 3 weeks (group V). Joint tissues were histologically assessed using the Mankin score and the modified Chambers system at 2 to 8 weeks after surgery. Results Exogenous TNC was maintained in the cartilage and synovium for 1 week after administration. Histological scores in groups I and II were better than scores in group III at 4 and 6 weeks, but progressive cartilage damage was seen in all groups 8 weeks postoperatively. Sequential TNC injections (groups IV and V) showed significantly better Mankin score than single injection (group II) at 8 weeks. Conclusion TNC administered exogenously remained in the cartilage of knee joints for 1 week, and could decelerate articular cartilage degeneration in murine models of OA. We also showed that sequential administration of TNC was more effective than a single injection. TNC could be an important molecule for prevention of articular cartilage damage.

  15. Articular cartilage changes in chondromalacia patellae.

    PubMed

    Bentley, G

    1985-11-01

    Full thickness samples of articular cartilage were removed from areas of chondromalacia on the medial and "odd" facets of the patellae of 21 adults and examined by histology, autoradiography and electron microscopy. Surface fibrillation, loss of superficial matrix staining and reduced 35SO4 labelling was seen, with little change in the deep zone. Ten cases showed "fibrous metaplasia" of the superficial cartilage with definite evidence of cell division and apparent smoothing of the surface. Scattered chondrocyte replication appeared to occur in the surrounding intact cartilage. The findings suggest that early lesions in chondromalacia patellae may heal either by cartilage or fibrous metaplasia and that this may account for the resolution of clinical symptoms.

  16. Role of platelet-rich plasma in articular cartilage injury and disease.

    PubMed

    Mascarenhas, Randy; Saltzman, Bryan M; Fortier, Lisa A; Cole, Brian J

    2015-02-01

    Clinical and laboratory research aimed at biological approaches to cartilage repair are currently in high demand due to the poor regenerative capacity of articular cartilage in the setting of a diseased articular environment. Platelet-rich plasma (PRP) takes advantage of supraphysiological concentrations of platelets and their growth factors harbored in α-granules, which together attempt to return the diseased articular cartilage to a preinjury state. The local use of PRP directly at the site of cartilage injury is thought to stimulate a natural healing cascade and accelerate the formation of cartilage repair tissue. This article provides an overview of the basic science behind the use of PRP in the treatment of cartilage injury and disease. Both initial and current examples of the use of intra-articular PRP in clinical human studies are provided. These include the use of PRP either alone or as an augmentation device with various other procedures, including arthroscopic microfracture and cell-free resorbable polyglycolic acid-hyaluronan implantation. Finally, the authors describe some of the potential future roles of PRP in clinical settings based on recent literature. These include Achilles tendon rupture, chronic tendinosis, chronic rotator cuff tendinopathy or tearing, muscle injury, and meniscal repair. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  17. Repair and tissue engineering techniques for articular cartilage.

    PubMed

    Makris, Eleftherios A; Gomoll, Andreas H; Malizos, Konstantinos N; Hu, Jerry C; Athanasiou, Kyriacos A

    2015-01-01

    Chondral and osteochondral lesions due to injury or other pathology commonly result in the development of osteoarthritis, eventually leading to progressive total joint destruction. Although current progress suggests that biologic agents can delay the advancement of deterioration, such drugs are incapable of promoting tissue restoration. The limited ability of articular cartilage to regenerate renders joint arthroplasty an unavoidable surgical intervention. This Review describes current, widely used clinical repair techniques for resurfacing articular cartilage defects; short-term and long-term clinical outcomes of these techniques are discussed. Also reviewed is a developmental pipeline of acellular and cellular regenerative products and techniques that could revolutionize joint care over the next decade by promoting the development of functional articular cartilage. Acellular products typically consist of collagen or hyaluronic-acid-based materials, whereas cellular techniques use either primary cells or stem cells, with or without scaffolds. Central to these efforts is the prominent role that tissue engineering has in translating biological technology into clinical products; therefore, concomitant regulatory processes are also discussed.

  18. Resurfacing Damaged Articular Cartilage to Restore Compressive Properties

    PubMed Central

    Grenier, Stephanie; Donnelly, Patrick E.; Gittens, Jamila; Torzilli, Peter A.

    2014-01-01

    Surface damage to articular cartilage is recognized as the initial underlying process causing the loss of mechanical function in early-stage osteoarthritis. In this study, we developed structure-modifying treatments to potentially prevent, stabilize or reverse the loss in mechanical function. Various polymers (chondroitin sulfate, carboxymethylcellulose, sodium hyaluronate) and photoinitiators (riboflavin, irgacure 2959) were applied to the surface of collagenase-degraded cartilage and crosslinked in situ using UV light irradiation. While matrix permeability and deformation significantly increased following collagenase-induced degradation of the superficial zone, resurfacing using tyramine-substituted sodium hyaluronate and riboflavin decreased both values to a level comparable to that of intact cartilage. Repetitive loading of resurfaced cartilage showed minimal variation in the mechanical response over a 7 day period. Cartilage resurfaced using a low concentration of riboflavin had viable cells in all zones while a higher concentration resulted in a thin layer of cell death in the uppermost superficial zone. Our approach to repair surface damage initiates a new therapeutic advance in the treatment of injured articular cartilage with potential benefits that include enhanced mechanical properties, reduced susceptibility to enzymatic degradation and reduced adhesion of macrophages. PMID:25468298

  19. Solute transport across the articular surface of injured cartilage.

    PubMed

    Chin, Hooi Chuan; Moeini, Mohammad; Quinn, Thomas M

    2013-07-15

    Solute transport through extracellular matrix (ECM) is important to physiology and contrast agent-based clinical imaging of articular cartilage. Mechanical injury is likely to have important effects on solute transport since it involves alteration of ECM structure. Therefore it is of interest to characterize effects of mechanical injury on solute transport in cartilage. Using cartilage explants injured by an established mechanical compression protocol, effective partition coefficients and diffusivities of solutes for transport across the articular surface were measured. A range of fluorescent solutes (fluorescein isothiocyanate, 4 and 40kDa dextrans, insulin, and chondroitin sulfate) and an X-ray contrast agent (sodium iodide) were used. Mechanical injury was associated with a significant increase in effective diffusivity versus uninjured explants for all solutes studied. On the other hand, mechanical injury had no effects on effective partition coefficients for most solutes tested, except for 40kDa dextran and chondroitin sulfate where small but significant changes in effective partition coefficient were observed in injured explants. Findings highlight enhanced diffusive transport across the articular surface of injured cartilage, which may have important implications for injury and repair situations. Results also support development of non-equilibrium methods for identification of focal cartilage lesions by contrast agent-based clinical imaging. Copyright © 2013 Elsevier Inc. All rights reserved.

  20. Clinical potential and challenges of using genetically modified cells for articular cartilage repair.

    PubMed

    Madry, Henning; Cucchiarini, Magali

    2011-06-01

    Articular cartilage defects do not regenerate. Transplantation of autologous articular chondrocytes, which is clinically being performed since several decades, laid the foundation for the transplantation of genetically modified cells, which may serve the dual role of providing a cell population capable of chondrogenesis and an additional stimulus for targeted articular cartilage repair. Experimental data generated so far have shown that genetically modified articular chondrocytes and mesenchymal stem cells (MSC) allow for sustained transgene expression when transplanted into articular cartilage defects in vivo. Overexpression of therapeutic factors enhances the structural features of the cartilaginous repair tissue. Combined overexpression of genes with complementary mechanisms of action is also feasible, holding promises for further enhancement of articular cartilage repair. Significant benefits have been also observed in preclinical animal models that are, in principle, more appropriate to the clinical situation. Finally, there is convincing proof of concept based on a phase I clinical gene therapy study in which transduced fibroblasts were injected into the metacarpophalangeal joints of patients without adverse events. To realize the full clinical potential of this approach, issues that need to be addressed include its safety, the choice of the ideal gene vector system allowing for a long-term transgene expression, the identification of the optimal therapeutic gene(s), the transplantation without or with supportive biomaterials, and the establishment of the optimal dose of modified cells. As safe techniques for generating genetically engineered articular chondrocytes and MSCs are available, they may eventually represent new avenues for improved cell-based therapies for articular cartilage repair. This, in turn, may provide an important step toward the unanswered question of articular cartilage regeneration.

  1. Comparison of friction and wear of articular cartilage on different length scales.

    PubMed

    Kienle, Sandra; Boettcher, Kathrin; Wiegleb, Lorenz; Urban, Joanna; Burgkart, Rainer; Lieleg, Oliver; Hugel, Thorsten

    2015-09-18

    The exceptional tribological properties of articular cartilage are still far from being fully understood. Articular cartilage is able to withstand high loads and provide exceptionally low friction. Although the regeneration abilities of the tissue are very limited, it can last for many decades. These biomechanical properties are realized by an interplay of different lubrication and wear protection mechanisms. The deterioration of cartilage due to aging or injury leads to the development of osteoarthritis. A current treatment strategy focuses on supplementing the intra-articular fluid with a saline solution containing hyaluronic acid. In the work presented here, we investigated how changing the lubricating fluid affects friction and wear of articular cartilage, focusing on the boundary and mixed lubrication as well as interstitial fluid pressurization mechanisms. Different length and time scales were probed by atomic force microscopy, tribology and profilometry. We compared aqueous solutions with different NaCl concentrations to a viscosupplement containing hyaluronic acid (HA). In particular, we found that the presence of ions changes the frictional behavior and the wear resistance. In contrast, hyaluronic acid showed no significant impact on the friction coefficient, but considerably reduced wear. This study confirms the previous notion that friction and wear are not necessarily correlated in articular cartilage tribology and that the main role of HA might be to provide wear protection for the articular surface. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. High-resolution measurements of the multilayer ultra-structure of articular cartilage and their translational potential

    PubMed Central

    2014-01-01

    Current musculoskeletal imaging techniques usually target the macro-morphology of articular cartilage or use histological analysis. These techniques are able to reveal advanced osteoarthritic changes in articular cartilage but fail to give detailed information to distinguish early osteoarthritis from healthy cartilage, and this necessitates high-resolution imaging techniques measuring cells and the extracellular matrix within the multilayer structure of articular cartilage. This review provides a comprehensive exploration of the cellular components and extracellular matrix of articular cartilage as well as high-resolution imaging techniques, including magnetic resonance image, electron microscopy, confocal laser scanning microscopy, second harmonic generation microscopy, and laser scanning confocal arthroscopy, in the measurement of multilayer ultra-structures of articular cartilage. This review also provides an overview for micro-structural analysis of the main components of normal or osteoarthritic cartilage and discusses the potential and challenges associated with developing non-invasive high-resolution imaging techniques for both research and clinical diagnosis of early to late osteoarthritis. PMID:24946278

  3. Nondestructive imaging of fiber structure in articular cartilage using optical polarization tractography

    NASA Astrophysics Data System (ADS)

    Yao, Xuan; Wang, Yuanbo; Ravanfar, Mohammadreza; Pfeiffer, Ferris M.; Duan, Dongsheng; Yao, Gang

    2016-11-01

    Collagen fiber orientation plays an important role in determining the structure and function of the articular cartilage. However, there is currently a lack of nondestructive means to image the fiber orientation from the cartilage surface. The purpose of this study is to investigate whether the newly developed optical polarization tractography (OPT) can image fiber structure in articular cartilage. OPT was applied to obtain the depth-dependent fiber orientation in fresh articular cartilage samples obtained from porcine phalanges. For comparison, we also obtained collagen fiber orientation in the superficial zone of the cartilage using the established split-line method. The direction of each split-line was quantified using image processing. The orientation measured in OPT agreed well with those obtained from the split-line method. The correlation analysis of a total of 112 split-lines showed a greater than 0.9 coefficient of determination (R2) between the split-line results and OPT measurements obtained between 40 and 108 μm in depth. In addition, the thickness of the superficial layer can also be assessed from the birefringence images obtained in OPT. These results support that OPT provides a nondestructive way to image the collagen fiber structure in articular cartilage. This technology may be valuable for both basic cartilage research and clinical orthopedic applications.

  4. Optical clearing of articular cartilage: a comparison of clearing agents

    NASA Astrophysics Data System (ADS)

    Bykov, Alexander; Hautala, Tapio; Kinnunen, Matti; Popov, Alexey; Karhula, Sakari; Saarakkala, Simo; Nieminen, Miika T.; Tuchin, Valery

    2015-07-01

    Optical clearing technique was applied to the problem of OCT imaging of articular cartilage and subchondral bone. We show that optical clearing significantly enhances visualization of articular cartilage and cartilage-bone interface. The effect of different clearing agents was analyzed. For the clearing, iohexol solution and propylene glycol (PG) were used. Clearing was performed in vitro at room temperature by immersion method. Cylindrical osteochondral samples (d=4.8mm) were drilled from bovine lateral femur and stored in phosphate-buffered saline at -20°C until clearing. Monitoring of clearing process was performed using high-speed spectral-domain OCT system providing axial resolution of 5.8μm at 930nm. Total duration of experiment was 90-100min to ensure saturation of clearing. We have shown that iohexol solution and PG are capable to optically clear articular cartilage enabling reliable characterization of cartilagebone interface with OCT. Being a low osmolarity agent, iohexol provides minimal changes to the thickness of cartilage sample. Clearing saturation time for the cartilage sample with the thickness of 0.9 mm measured with OCT is of 50 min. However, less than 15 min is enough to reliably detect the rear cartilage boundary. Alternatively, PG significantly (60%) reduces the cartilage thickness enabling better visualization of subchondral bone. It was observed that PG has higher clearing rate. The clearing saturation time is of 30 min, however less than 5 min is enough to detect cartilage-bone interface. We conclude that iohexol solution is superior for OCT imaging of cartilage and cartilage-bone interface, while PG suits better for subhondral bone visualization.

  5. Validity of histopathological grading of articular cartilage from osteoarthritic knee joints

    PubMed Central

    Ostergaard, K.; Andersen, C.; Petersen, J.; Bendtzen, K.; Salter, D.

    1999-01-01

    OBJECTIVES—To determine the validity of the histological-histochemical grading system (HHGS) for osteoarthritic (OA) articular cartilage.
METHODS—Human articular cartilage was obtained from macroscopically normal (n = 13) and OA (n = 21) knee joints. Sections of central and peripheral regions of normal samples were produced. Sections of regions containing severe, moderate, and mild OA changes were produced from each OA sample. A total of 89 sections were graded by means of the HHGS (0-14) twice by three observers.
RESULTS—Average scores for regions designated severe (8.64) and moderate (5.83) OA were less than the expected (10-14 and 6-9, respectively) according to the HHGS, whereas average scores for the region designated mild (5.29) OA and central and peripheral regions (2.19) of normal cartilage were higher than expected (2-5 and 0-1, respectively). The HHGS was capable of differentiating between articular cartilage from macroscopically normal and OA joints and between the region designated severe OA and other regions. However, the HHGS did not adequately differentiate between regions designated mild and moderate OA. Values for sensitivity, specificity, and efficiency for all regions varied considerably.
CONCLUSION—The HHGS is valid for normal and severe OA cartilage, but does not permit distinction between mild and moderate OA changes in articular cartilage.

 Keywords: histopathology; osteoarthritis; reliability; validity PMID:10364898

  6. Laser biostimulation of articular cartilage: in vitro evaluation

    NASA Astrophysics Data System (ADS)

    Jia, Yali; Guo, Zhouyi; Yang, Xiaohong; Zeng, Chang-Chun

    2004-07-01

    In the orthopaedic field, the repair of ariticular cartilage is still a difficult problem, because of the physiological characters of cartilaginous tissues and chondrocytes. To find an effective method of stimulating their regeneration, this in vitro study focuses on the biostimulation of rabbit articular chondrocytes by low-power He-Ne laser. The articular chondrocytes isolated from the cartilage of the medial condyle of the femur of the rabbit were incubated in HamF12 medium. The second passage culture were spread on 24 petri dishes and were irradiated with laser at power density of 2 - 12 mW/cm2 for 6.5 minutes, corresponding to the energy density of 1-6 J/cm2. Laser treatment was performed three times at a 24-hour interval. After lasering, incubation was continued for 24 hours. Non-irradiated cells were kept under the same conditions as the irradiated ones. The cell proliferation activity was evaluated with a XTT colorimetric method. Irradiation of 4 - 6 J/cm2 revealed a considerably higher cell proliferation activity comparing to control cultures. Thereinto, the energy density of 4 and 5 J/cm2 remarkably increased cell growth (P<0.01). The present study showed that a particular laser irradiation stimulates articular chondrocytes proliferation. These findings might be clinically relevant, indicating that low-power laser irradiation treatment is likely to achieve the repair of articular cartilage in clinic.

  7. Effects of moving training on histology and biomarkers levels of articular cartilage.

    PubMed

    Qi, Chang; Changlin, Huang

    2006-10-01

    To study the adaptation process and extent of articular cartilage in the canine knee joint to different modes of movements and to investigate if levels of cartilage oligomeric matrix protein (COMP), matrix metalloproteinases-1 (MMP-1), matrix metalloproteinases-3 (MMP-3), and tissue inhibitor of matrix metalloproteinases-1 (TIMP-1) in serum and synovial fluid can be used to predict effectively early sports injury and remolding degree of articular cartilage in the canine knee. Twenty adult dogs divided randomly into three groups (eight in the common training group, Training Group; eight in the intensified training group, Intensified Group; and four in the Control Group) were trained daily at different intensities. Magnetic resonance imaging (MRI) examinations were performed regularly (0, 2, 4, 6, 8, 10 weeks) to investigate changes of articular cartilage in the canine knee, while concentrations of COMP, MMP-1, MMP-3, and TIMP-1 in serum and synovial fluid were measured by ELISA assays. All of the dogs were euthanized after training for 10 weeks, and all of the knee joints were taken out to be examined histologically. We could find imaging changes of early sport injury of articular cartilage in the Training Group and Intensified Group by MRI examination after 2 weeks of training; the damage images were most severe in 4-6 weeks, and then lightened gradually. We could not find the difference of cartilage injury and repair degree in MRI images between these two groups at different time points. Elevations of levels of COMP, MMP-1, MMP-3, TIMP-1, and MMP-3/TIMP-1 in serum and synovial fluid were seen during the training period, and their levels changed remarkably at different times. Levels of MMP-1, MMP-3, and MMP-3/TIMP-1 in the Intensified Group were lower than that in the Training Group in general, and levels of COMP were higher, which hinted that the injury trend of articular cartilage in the Intensified Group was lower than that in the Training group, and the repair

  8. The effects of intermittent hydrostatic pressure on self-assembled articular cartilage constructs.

    PubMed

    Hu, Jerry C; Athanasiou, Kyriacos A

    2006-05-01

    To date, static culture for the tissue engineering of articular cartilage has shown to be inadequate in conferring functionality to constructs. Various forms of mechanical stimuli accompany articular cartilage development in vivo, and one of these is hydrostatic pressure. This study used histology, biochemistry, and biomechanics to examine the effects of intermittent hydrostatic pressure, applied at 10 MPa and 1 Hz for 4 h per day for 5 days per week for up to 8 weeks on self-assembled chondrocyte constructs. The self-assembling process is a novel approach that allows engineering of articular cartilage constructs without the use of exogenous scaffolds. The self-assembled constructs were found to be capable of enduring this loading regimen. Significant increases in collagen production were only observed in pressurized samples. Intermittent hydrostatic pressure prevented a significant decrease in total GAG, which was significant in controls. Aside from the beneficial effects intermittent hydrostatic pressure may have on ECM synthesis, its effects on mechanical properties may require longer culture periods to manifest. This study demonstrates the successful use of the self-assembling process to produce articular cartilage constructs. It also shows for the first time that long-term culture of tissue-engineered articular cartilage construct benefits from intermittent hydrostatic pressure.

  9. Repair of articular cartilage defects in the knee with autologous iliac crest cartilage in a rabbit model.

    PubMed

    Jing, Lizhong; Zhang, Jiying; Leng, Huijie; Guo, Qinwei; Hu, Yuelin

    2015-04-01

    To demonstrate that iliac crest cartilage may be used to repair articular cartilage defects in the knees of rabbits. Full-thickness cartilage defects were created in the medial femoral condyle on both knees of 36 New Zealand white rabbits. The 72 defects were randomly assigned to be repaired with ipsilateral iliac crest cartilage (Group I), osteochondral tissues removed at defect creation (Group II), or no treatment (negative control, Group III). Animals were killed at 6, 12, and 24 weeks post-operatively. The repaired tissues were harvested for magnetic resonance imaging (MRI), histological studies (haematoxylin and eosin and immunohistochemical staining), and mechanical testing. At 6 weeks, the iliac crest cartilage graft was not yet well integrated with the surrounding articular cartilage, but at 12 weeks, the graft deep zone had partial ossification. By 24 weeks, the hyaline cartilage-like tissue was completely integrated with the surrounding articular cartilage. Osteochondral autografts showed more rapid healing than Group I at 6 weeks and complete healing at 12 weeks. Untreated defects were concave or partly filled with fibrous tissue throughout the study. MRI showed that Group I had slower integration with surrounding normal cartilage compared with Group II. The mechanical properties of Group I were significantly lower than those of Group II at 12 weeks, but this difference was not significant at 24 weeks. Iliac crest cartilage autografts were able to repair knee cartilage defects with hyaline cartilage and showed comparable results with osteochondral autografts in the rabbit model.

  10. Infrared microspectroscopic determination of collagen cross-links in articular cartilage

    NASA Astrophysics Data System (ADS)

    Rieppo, Lassi; Kokkonen, Harri T.; Kulmala, Katariina A. M.; Kovanen, Vuokko; Lammi, Mikko J.; Töyräs, Juha; Saarakkala, Simo

    2017-03-01

    Collagen forms an organized network in articular cartilage to give tensile stiffness to the tissue. Due to its long half-life, collagen is susceptible to cross-links caused by advanced glycation end-products. The current standard method for determination of cross-link concentrations in tissues is the destructive high-performance liquid chromatography (HPLC). The aim of this study was to analyze the cross-link concentrations nondestructively from standard unstained histological articular cartilage sections by using Fourier transform infrared (FTIR) microspectroscopy. Half of the bovine articular cartilage samples (n=27) were treated with threose to increase the collagen cross-linking while the other half (n=27) served as a control group. Partial least squares (PLS) regression with variable selection algorithms was used to predict the cross-link concentrations from the measured average FTIR spectra of the samples, and HPLC was used as the reference method for cross-link concentrations. The correlation coefficients between the PLS regression models and the biochemical reference values were r=0.84 (p<0.001), r=0.87 (p<0.001) and r=0.92 (p<0.001) for hydroxylysyl pyridinoline (HP), lysyl pyridinoline (LP), and pentosidine (Pent) cross-links, respectively. The study demonstrated that FTIR microspectroscopy is a feasible method for investigating cross-link concentrations in articular cartilage.

  11. A Comparison of Outcomes of Particulated Juvenile Articular Cartilage and Bone Marrow Aspirate Concentrate for Articular Cartilage Lesions of the Talus.

    PubMed

    Lanham, Nathan S; Carroll, John J; Cooper, Minton T; Perumal, Venkat; Park, Joseph S

    2017-08-01

    Articular cartilage lesions of the talus remain a challenging clinical problem because of the lack of natural regeneration and limited treatment options. Microfracture is often the first-line therapy, however lesions larger than 1.5 cm 2 have been shown to not do as well with this treatment method. The objective of this retrospective study was to evaluate the outcomes of iliac crest bone marrow aspirate concentrate/collagen scaffold (ICBMA) and particulated juvenile articular cartilage (PJAC) for larger articular cartilage lesions of the talus. Fifteen patients undergoing ICBMA or PJAC for articular cartilage lesions of the talus from 2010 to 2013 were reviewed. Twelve patients, 6 from each treatment option, were included in the study. American Orthopaedic Foot and Ankle Surgeons (AOFAS), Foot and Ankle Ability Measure (FAAM), and Short Form-12 (SF-12) outcome scores were collected for each patient. The mean age was 34.7 ± 14.8 years for ICBMA and 31.5 ± 7.4 years for PJAC. Lesion size was 2.0 ± 1.1 cm 2 for ICBMA and 1.9 ± 0.9 cm 2 for PJAC. At a mean follow-up of 25.7 months (range, 12-42 months), the mean AOFAS score was 71.33 for ICBMA and 95.83 for PJAC (  P = .019). The FAAM activities of daily living subscale mean was 77.77 for ICBMA and 97.02 for PJAC (   P = .027). The mean FAAM sports subscale was 45.14 for ICBMA and 86.31 for PJAC (  P = .054). The SF-12 physical health mean was 47.58 for ICBMA and 53.98 for PJAC (  P = .315). The SF-12 mental health mean was 53.25 for ICBMA and 57.8 for PJAC (  P = .315). One patient in treated initially with ICBMA underwent revision fixation for nonunion of their medial malleolar osteotomy, which ultimately resulted in removal of hardware and tibiotalar arthrodesis at 2 years from the index procedure. In the present analysis, PJAC yields better clinical outcomes at 2 years when compared with ICBMA for articular cartilage lesions of the talus that were on average greater than 1.5cm 2 . Therapeutic, Level

  12. Complex and elementary histological scoring systems for articular cartilage repair.

    PubMed

    Orth, Patrick; Madry, Henning

    2015-08-01

    The repair of articular cartilage defects is increasingly moving into the focus of experimental and clinical investigations. Histological analysis is the gold standard for a valid and objective evaluation of cartilaginous repair tissue and predominantly relies on the use of established scoring systems. In the past three decades, numerous elementary and complex scoring systems have been described and modified, including those of O'Driscoll, Pineda, Wakitani, Sellers and Fortier for entire defects as well as those according to the International Cartilage Repair Society (ICRS-I/II) for osteochondral tissue biopsies. Yet, this coexistence of different grading scales inconsistently addressing diverse parameters may impede comparability between reported study outcomes. Furthermore, validation of these histological scoring systems has only seldom been performed to date. The aim of this review is (1) to give a comprehensive overview and to compare the most important established histological scoring systems for articular cartilage repair, (2) to describe their specific advantages and pitfalls, and (3) to provide valid recommendations for their use in translational and clinical studies of articular cartilage repair.

  13. The degeneration and destruction of femoral articular cartilage shows a greater degree of deterioration than that of the tibial and patellar articular cartilage in early stage knee osteoarthritis: a cross-sectional study.

    PubMed

    Hada, S; Kaneko, H; Sadatsuki, R; Liu, L; Futami, I; Kinoshita, M; Yusup, A; Saita, Y; Takazawa, Y; Ikeda, H; Kaneko, K; Ishijima, M

    2014-10-01

    The aim of the present study was to examine whether the degenerative and morphological changes of articular cartilage in early stage knee osteoarthritis (OA) occurred equally for both femoral- and tibial- or patellar- articular cartilage using magnetic resonance imaging (MRI)-based analyses. This cross-sectional study was approved by the ethics committee of our university. Fifty patients with early stage painful knee OA were enrolled. The patients underwent 3.0 T MRI on the affected knee joint. Healthy volunteers who did not show MRI-based OA changes were also recruited as controls (n = 19). The degenerative changes of the articular cartilage were quantified by a T2 mapping analysis, and any structural changes were conducted using Whole Organ Magnetic Resonance Imaging Score (WORMS) technique. All patients showed MRI-detected OA morphological changes. The T2 values of femoral condyle (FC) (P < 0.0001) and groove (P = 0.0001) in patients with early stage knee OA were significantly increased in comparison to those in the control, while no significant differences in the T2 values of patellar and tibial plateau (TP) were observed between the patients and the control. The WORMS cartilage and osteophyte scores of the femoral articular cartilage were significantly higher than those in the patellar- (P = 0.001 and P = 0.007, respectively) and tibial- (P = 0.0001 and P < 0.0001, respectively) articular cartilage in the patients with early stage knee OA. The degradation and destruction of the femoral articular cartilage demonstrated a greater degree of deterioration than those of the tibial- and patellar- articular cartilage in patients with early stage knee OA. Copyright © 2014 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

  14. Modeling the transport of cryoprotective agents in articular cartilage for cryopreservation

    NASA Astrophysics Data System (ADS)

    Torqabeh, Alireza Abazari

    Loading vitrifiable concentrations of cryoprotective agents is an important step for cryopreservation of biological tissues by vitrification for research and transplantation purposes. This may be done by immersing the tissue in a cryoprotective agent (CPA) solution, and increasing the concentration, continuously or in multiple steps, and simultaneously decreasing the temperature to decrease the toxicity effects of the cryoprotective agent on the tissue cellular system. During cryoprotective agent loading, osmotic water movement from the tissue to the surrounding solution, and the resultant tissue shrinkage and stress-strain in the tissue matrix as well as on the cellular system can significantly alter the outcome of the cryopreservation protocol. In this thesis, a biomechanical model for articular cartilage is developed to account for the transport of the cryoprotective agent, the nonideal-nondilute properties of the vitrifiable solutions, the osmotic water movement and the resultant tissue shrinkage and stress-strain in the tissue matrix, and the osmotic volume change of the chondrocytes, during cryoprotective agent loading in the cartilage matrix. Four essential transport parameters needed for the model were specified, the values of which were obtained uniquely by fitting the model to experimental data from porcine articular cartilage. Then, it was shown that using real nonuniform initial distributions of water and fixed charges in cartilage, measured separately in this thesis using MRI, in the model can significantly affect the model predictions. The model predictions for dimethyl sulfoxide diffusion in porcine articular cartilage were verified by comparing to spatially and temporally resolved measurements of dimethyl sulfoxide concentration in porcine articular cartilage using a spectral MRI technique, developed for this purpose and novel to the field of cryobiology. It was demonstrated in this thesis that the developed mathematical model provides a novel tool

  15. Articular Cartilage Increases Transition Zone Regeneration in Bone-tendon Junction Healing

    PubMed Central

    Qin, Ling; Lee, Kwong Man; Leung, Kwok Sui

    2008-01-01

    The fibrocartilage transition zone in the direct bone-tendon junction reduces stress concentration and protects the junction from failure. Unfortunately, bone-tendon junctions often heal without fibrocartilage transition zone regeneration. We hypothesized articular cartilage grafts could increase fibrocartilage transition zone regeneration. Using a goat partial patellectomy repair model, autologous articular cartilage was harvested from the excised distal third patella and interposed between the residual proximal two-thirds bone fragment and tendon during repair in 36 knees. We evaluated fibrocartilage transition zone regeneration, bone formation, and mechanical strength after repair at 6, 12, and 24 weeks and compared them with direct repair. Autologous articular cartilage interposition resulted in more fibrocartilage transition zone regeneration (69.10% ± 14.11% [mean ± standard deviation] versus 8.67% ± 7.01% at 24 weeks) than direct repair at all times. There was no difference in the amount of bone formation and mechanical strength achieved. Autologous articular cartilage interposition increases fibrocartilage transition zone regeneration in bone-tendon junction healing, but additional research is required to ascertain the mechanism of stimulation and to establish the clinical applicability. PMID:18987921

  16. Spatial regulation of bone morphogenetic proteins (BMPs) in postnatal articular and growth plate cartilage

    PubMed Central

    Garrison, Presley; Yue, Shanna; Hanson, Jeffrey; Baron, Jeffrey; Lui, Julian C.

    2017-01-01

    Articular and growth plate cartilage both arise from condensations of mesenchymal cells, but ultimately develop important histological and functional differences. Each is composed of three layers—the superficial, mid and deep zones of articular cartilage and the resting, proliferative and hypertrophic zones of growth plate cartilage. The bone morphogenetic protein (BMP) system plays an important role in cartilage development. A gradient in expression of BMP-related genes has been observed across growth plate cartilage, likely playing a role in zonal differentiation. To investigate the presence of a similar expression gradient in articular cartilage, we used laser capture microdissection (LCM) to separate murine growth plate and articular cartilage from the proximal tibia into their six constituent zones, and used a solution hybridization assay with color-coded probes (nCounter) to quantify mRNAs for 30 different BMP-related genes in each zone. In situ hybridization and immunohistochemistry were then used to confirm spatial expression patterns. Expression gradients for Bmp2 and 6 were observed across growth plate cartilage with highest expression in hypertrophic zone. However, intracellular BMP signaling, assessed by phospho-Smad1/5/8 immunohistochemical staining, appeared to be higher in the proliferative zone and prehypertrophic area than in hypertrophic zone, possibly due to high expression of Smad7, an inhibitory Smad, in the hypertrophic zone. We also found BMP expression gradients across the articular cartilage with BMP agonists primarily expressed in the superficial zone and BMP functional antagonists primarily expressed in the deep zone. Phospho-Smad1/5/8 immunohistochemical staining showed a similar gradient. In combination with previous evidence that BMPs regulate chondrocyte proliferation and differentiation, the current findings suggest that BMP signaling gradients exist across both growth plate and articular cartilage and that these gradients may

  17. Advances in Tissue Engineering Techniques for Articular Cartilage Repair

    PubMed Central

    Haleem, AM; Chu, CR

    2010-01-01

    The limited repair potential of human articular cartilage contributes to development of debilitating osteoarthritis and remains a great clinical challenge. This has led to evolution of cartilage treatment strategies from palliative to either reconstructive or reparative methods in an attempt to delay or “bridge the gap” to joint replacement. Further development of tissue engineering-based cartilage repair methods have been pursued to provide a more functional biological tissue. Currently, tissue engineering of articular cartilage has three cornerstones; a cell population capable of proliferation and differentiation into mature chondrocytes, a scaffold that can host these cells, provide a suitable environment for cellular functioning and serve as a sustained-release delivery vehicle of chondrogenic growth factors and thirdly, signaling molecules and growth factors that stimulate the cellular response and the production of a hyaline extracellular matrix (ECM). The aim of this review is to summarize advances in each of these three fields of tissue engineering with specific relevance to surgical techniques and technical notes. PMID:29430164

  18. Acetabular Morphology: Implications for Joint-preserving Surgery

    PubMed Central

    Ganz, Reinhold; Impellizzeri, Franco M.; Leunig, Michael

    2009-01-01

    Appropriate anatomic concepts for surgery to treat femoroacetabular impingement require a precise appreciation of the native acetabular anatomy. We therefore determined (1) the spatial acetabular rim profile, (2) the topography of the articular lunate surface, and (3) the 3-D relationships of the acetabular opening plane comparing 66 bony acetabula from 33 pelves in female and male pelves. The acetabular rim profile had a constant and regular wave-like outline without gender differences. Three prominences anterosuperiorly, anteroinferiorly and posteroinferiorly extended just above hemispheric level. Two depressions were below hemispheric level, of 9° at the anterior wall and of 21° along the posterosuperior wall. In 94% of all acetabula, the deepest extent of the articular surface was within 30° of the anterosuperior acetabular sector. In 99% of men and in 91% of women, the depth of the articular surface was at least 55° along almost half of the upper acetabular cup. The articular surface was smaller in women than in men. The acetabular opening plane was orientated in 21° ± 5° for version, 48° ± 4° for inclination and 19° ± 6° for acetabular tilt with no gender differences. We defined tilt as forward rotation of the entire acetabular cup around its central axis; because of interindividual variability of acetabular tilt, descriptions of acetabular lesions during surgery, CT scanning and MRI should be defined and recorded in relation to the acetabular notch. Acetabular tilt and pelvic tilt should be separately identified. We believe this information important for surgeons performing rim trimming in FAI surgery or performing acetabular osteotomies. PMID:19130159

  19. Return to sports participation after articular cartilage repair in the knee: scientific evidence.

    PubMed

    Mithoefer, Kai; Hambly, Karen; Della Villa, Stefano; Silvers, Holly; Mandelbaum, Bert R

    2009-11-01

    Articular cartilage injury in the athlete's knee presents a difficult clinical challenge. Despite the importance of returning injured athletes to sports, information is limited on whether full sports participation can be successfully achieved after articular cartilage repair in the knee. Systematic analysis of athletic participation after articular cartilage repair will demonstrate the efficacy of joint surface restoration in high-demand patients and help to optimize outcomes in athletes with articular cartilage injury of the knee. Systematic review. A comprehensive literature review of original studies was performed to provide information about athletic participation after articular cartilage repair. The athlete's ability to perform sports postoperatively was assessed by activity outcome scores, rate of return to sport, timing of the return, level of postoperative sports participation, and the continuation of athletic activity over time. Twenty studies describing 1363 patients were included in the review, with an average follow-up of 42 months. Return to sports was possible in 73% overall, with highest return rates after osteochondral autograft transplantation. Time to return to sports varied between 7 and 18 months, depending on the cartilage repair technique. Initial return to sports at the preinjury level was possible in 68% and did not significantly vary between surgical techniques. Continued sports participation at the preinjury level was possible in 65%, with the best durability after autologous chondrocyte transplantation. Several factors affected the ability to return to sport: athlete's age, preoperative duration of symptoms, level of play, lesion size, and repair tissue morphology. Articular cartilage repair in the athletic population allows for a high rate of return to sports, often at the preinjury level. Return to sports participation is influenced by several independent factors. The findings provide pertinent information that is helpful for the

  20. Development of an Electromechanical Grade to Assess Human Knee Articular Cartilage Quality.

    PubMed

    Sim, Sotcheadt; Hadjab, Insaf; Garon, Martin; Quenneville, Eric; Lavigne, Patrick; Buschmann, Michael D

    2017-10-01

    Quantitative assessments of articular cartilage function are needed to aid clinical decision making. Our objectives were to develop a new electromechanical grade to assess quantitatively cartilage quality and test its reliability. Electromechanical properties were measured using a hand-held electromechanical probe on 200 human articular surfaces from cadaveric donors and osteoarthritic patients. These data were used to create a reference electromechanical property database and to compare with visual arthroscopic International Cartilage Repair Society (ICRS) grading of cartilage degradation. The effect of patient-specific and location-specific characteristics on electromechanical properties was investigated to construct a continuous and quantitative electromechanical grade analogous to ICRS grade. The reliability of this novel grade was assessed by comparing it with ICRS grades on 37 human articular surfaces. Electromechanical properties were not affected by patient-specific characteristics for each ICRS grade, but were significantly different across the articular surface. Electromechanical properties varied linearly with ICRS grade, leading to a simple linear transformation from one scale to the other. The electromechanical grade correlated strongly with ICRS grade (r = 0.92, p < 0.0001). Additionally, the electromechanical grade detected lesions that were not found visually. This novel grade can assist the surgeon in assessing human knee cartilage by providing a quantitative and reliable grading system.

  1. Direct Quantification of Solute Diffusivity in Agarose and Articular Cartilage Using Correlation Spectroscopy.

    PubMed

    Shoga, Janty S; Graham, Brian T; Wang, Liyun; Price, Christopher

    2017-10-01

    Articular cartilage is an avascular tissue; diffusive transport is critical for its homeostasis. While numerous techniques have been used to quantify diffusivity within porous, hydrated tissues and tissue engineered constructs, these techniques have suffered from issues regarding invasiveness and spatial resolution. In the present study, we implemented and compared two separate correlation spectroscopy techniques, fluorescence correlation spectroscopy (FCS) and raster image correlation spectroscopy (RICS), for the direct, and minimally-invasive quantification of fluorescent solute diffusion in agarose and articular cartilage. Specifically, we quantified the diffusional properties of fluorescein and Alexa Fluor 488-conjugated dextrans (3k and 10k) in aqueous solutions, agarose gels of varying concentration (i.e. 1, 3, 5%), and in different zones of juvenile bovine articular cartilage explants (i.e. superficial, middle, and deep). In agarose, properties of solute diffusion obtained via FCS and RICS were inversely related to molecule size, gel concentration, and applied strain. In cartilage, the diffusional properties of solutes were similarly dependent upon solute size, cartilage zone, and compressive strain; findings that agree with work utilizing other quantification techniques. In conclusion, this study established the utility of FCS and RICS as simple and minimally invasive techniques for quantifying microscale solute diffusivity within agarose constructs and articular cartilage explants.

  2. Noninvasive assessment of articular cartilage surface damage using reflected polarized light microscopy

    NASA Astrophysics Data System (ADS)

    Huynh, Ruby N.; Nehmetallah, George; Raub, Christopher B.

    2017-06-01

    Articular surface damage occurs to cartilage during normal aging, osteoarthritis, and in trauma. A noninvasive assessment of cartilage microstructural alterations is useful for studies involving cartilage explants. This study evaluates polarized reflectance microscopy as a tool to assess surface damage to cartilage explants caused by mechanical scraping and enzymatic degradation. Adult bovine articular cartilage explants were scraped, incubated in collagenase, or underwent scrape and collagenase treatments. In an additional experiment, cartilage explants were subject to scrapes at graduated levels of severity. Polarized reflectance parameters were compared with India ink surface staining, features of histological sections, changes in explant wet weight and thickness, and chondrocyte viability. The polarized reflectance signal was sensitive to surface scrape damage and revealed individual scrape features consistent with India ink marks. Following surface treatments, the reflectance contrast parameter was elevated and correlated with image area fraction of India ink. After extensive scraping, polarized reflectance contrast and chondrocyte viability were lower than that from untreated explants. As part of this work, a mathematical model was developed and confirmed the trend in the reflectance signal due to changes in surface scattering and subsurface birefringence. These results demonstrate the effectiveness of polarized reflectance microscopy to sensitively assess surface microstructural alterations in articular cartilage explants.

  3. Repair of articular cartilage defects by tissue-engineered cartilage constructed with adipose-derived stem cells and acellular cartilaginous matrix in rabbits.

    PubMed

    Wang, Z J; An, R Z; Zhao, J Y; Zhang, Q; Yang, J; Wang, J B; Wen, G Y; Yuan, X H; Qi, X W; Li, S J; Ye, X C

    2014-06-18

    After injury, inflammation, or degeneration, articular cartilage has limited self-repair ability. We aimed to explore the feasibility of repair of articular cartilage defects with tissue-engineered cartilage constructed by acellular cartilage matrices (ACMs) seeded with adipose-derived stem cells (ADSCs). The ADSCs were isolated from 3-month-old New Zealand albino rabbit by using collagenase and cultured and amplified in vitro. Fresh cartilage isolated from adult New Zealand albino rabbit were freeze-dried for 12 h and treated with Triton X-100, DNase, and RNase to obtain ACMs. ADSCs were seeded in the acellular cartilaginous matrix at 2x10(7)/mL, and cultured in chondrogenic differentiation medium for 2 weeks to construct tissue-engineered cartilage. Twenty-four New Zealand white rabbits were randomly divided into A, B, and C groups. Engineered cartilage was transplanted into cartilage defect position of rabbits in group A, group B obtained ACMs, and group C did not receive any transplants. The rabbits were sacrificed in week 12. The restored tissue was evaluated using macroscopy, histology, immunohistochemistry, and transmission electron microscopy (TEM). In the tissue-engineered cartilage group (group A), articular cartilage defects of the rabbits were filled with chondrocyte-like tissue with smooth surface. Immunohistochemistry showed type II-collagen expression and Alcian blue staining was positive. TEM showed chondrocytes in the recesses, with plenty of secretary matrix particles. In the scaffold group (group B), the defect was filled with fibrous tissue. No repaired tissue was found in the blank group (group C). Tissue-engineered cartilage using ACM seeded with ADSCs can help repair articular cartilage defects in rabbits.

  4. Age-related differences in articular cartilage wound healing: a potential role for transforming growth factor beta1 in adult cartilage repair.

    PubMed

    Bos, P K; Verhaar, J A N; van Osch, G J V M

    2006-01-01

    Objective of this study was to investigate the early wound healing reactions of immature and mature articular cartilage on experimental wound healing in the New Zealand White rabbit. The proliferation potential and glycosaminoglycan production of isolated chondrocytes of these animals was studied in an alginate culture system. A band of tissue with death chondrocytes was observed at wound edges of immature articular cartilage, whereas mature cartilage showed a significant smaller amount of dead chondrocytes. A general increase in TGFbeta1, FGF2 and IGF1 was observed throughout cartilage tissue with the exception of lesion edges. The observed immunonegative area appeared to correlate with the observed cell death in lesion edges. Repair in immature cartilage was indicated by chondrocyte proliferation in clusters and a decrease in defect size. No repair response was observed in mature articular cartilage defects. The alginate culture experiment demonstrated a higher proliferation rate of immature chondrocytes. Addition of recombinant TGFbeta1 increased proliferation rate and GAG production of mature chondrocytes. We were not able to further stimulate immature chondrocytes. These results indicate that TGFbeta1 addition may contribute to induce cartilage repair responses in mature cartilage as observed in immature, developing cartilage.

  5. Distribution of Endo180 receptor and ligand in developing articular cartilage.

    PubMed

    Howard, M J; Chambers, M G; Mason, R M; Isacke, C M

    2004-01-01

    To investigate the expression of a novel member of the mannose receptor family, Endo180 (also known as uPARAP), and the distribution of Endo180 ligand(s) in the articular cartilage and growth plate of normal CBA mice and STR/ort mice, a well characterized model of spontaneous osteoarthritis. A polyclonal anti-Endo180 antibody was used to determine receptor expression. The Endo180 extracellular domain fused to a human immunoglobulin Fc tail was used to detect ligand. Endo180 receptor was strongly expressed in chondrocytes both in vitro and throughout the articular cartilage of young CBA and STR/ort mice. Expression decreased in older animals. In STR/ort mice with osteoarthritic lesions, no upregulation of Endo180 was detected. In the developing growth plate, Endo180 was expressed strongly by the proliferating chondrocytes. In contrast, Endo180 ligand was detected most strongly in hypertrophic zone of the growth plate and only at low levels in articular cartilage. In cultured chondrocytes, Endo180 was localized on the cell surface and in intracellular vesicles. Constitutively recycling endocytic receptors function to internalize ligand from the extracellular milieu and the ability of Endo180 to bind both glycosylated ligands and collagens suggests a role in extracellular matrix remodeling. Expression of Endo180 in articular cartilage chondrocytes of young, but not old, mice and the reciprocal expression of Endo180 and its ligands in the growth plate suggest that this receptor is involved in cartilage development but not in cartilage homeostasis. In addition, our data indicates that Endo180 does not appear to play a role in the development or progression of murine osteoarthritis.

  6. Contrast agent enhanced pQCT of articular cartilage

    NASA Astrophysics Data System (ADS)

    Kallioniemi, A. S.; Jurvelin, J. S.; Nieminen, M. T.; Lammi, M. J.; Töyräs, J.

    2007-02-01

    The delayed gadolinium enhanced MRI of cartilage (dGEMRIC) technique is the only non-invasive means to estimate proteoglycan (PG) content in articular cartilage. In dGEMRIC, the anionic paramagnetic contrast agent gadopentetate distributes in inverse relation to negatively charged PGs, leading to a linear relation between T1,Gd and spatial PG content in tissue. In the present study, for the first time, contrast agent enhanced peripheral quantitative computed tomography (pQCT) was applied, analogously to dGEMRIC, for the quantitative detection of spatial PG content in cartilage. The suitability of two anionic radiographic contrast agents, gadopentetate and ioxaglate, to detect enzymatically induced PG depletion in articular cartilage was investigated. First, the interrelationships of x-ray absorption, as measured with pQCT, and the contrast agent solution concentration were investigated. Optimal contrast agent concentrations for the following experiments were selected. Second, diffusion rates for both contrast agents were investigated in intact (n = 3) and trypsin-degraded (n = 3) bovine patellar cartilage. The contrast agent concentration of the cartilaginous layer was measured prior to and 2-27 h after immersion. Optimal immersion time for the further experiments was selected. Third, the suitability of gadopentetate and ioxaglate enhanced pQCT to detect the enzymatically induced specific PG depletion was investigated by determining the contrast agent concentrations and uronic acid and water contents in digested and intact osteochondral samples (n = 16). After trypsin-induced PG loss (-70%, p < 0.05) the penetration of gadopentetate and ioxaglate increased (p < 0.05) by 34% and 48%, respectively. Gadopentetate and ioxaglate concentrations both showed strong correlation (r = -0.95, r = -0.94, p < 0.01, respectively) with the uronic acid content. To conclude, contrast agent enhanced pQCT provides a technique to quantify PG content in normal and experimentally

  7. Regeneration of Articular Cartilage in Lizard Knee from Resident Stem/Progenitor Cells

    PubMed Central

    Alibardi, Lorenzo

    2015-01-01

    The epiphysis of femur and tibia in the lizard Podarcis muralis can extensively regenerate after injury. The process involves the articular cartilage and metaphyseal (growth) plate after damage. The secondary ossification center present between the articular cartilage and the growth plate is replaced by cartilaginous epiphyses after about one month of regeneration at high temperature. The present study analyzes the origin of the chondrogenic cells from putative stem cells located in the growing centers of the epiphyses. The study is carried out using immunocytochemistry for the detection of 5BrdU-labeled long retaining cells and for the localization of telomerase, an enzyme that indicates stemness. The observations show that putative stem cells retaining 5BrdU and positive for telomerase are present in the superficial articular cartilage and metaphyseal growth plate located in the epiphyses. This observation suggests that these areas represent stem cell niches lasting for most of the lifetime of lizards. In healthy long bones of adult lizards, the addition of new chondrocytes from the stem cells population in the articular cartilage and the metaphyseal growth plate likely allows for slow, continuous longitudinal growth. When the knee is injured in the adult lizard, new populations of chondrocytes actively producing chondroitin sulfate proteoglycan are derived from these stem cells to allow for the formation of completely new cartilaginous epiphyses, possibly anticipating the re-formation of secondary centers in later stages. The study suggests that in this lizard species, the regenerative ability of the epiphyses is a pre-adaptation to the regeneration of the articular cartilage. PMID:26340619

  8. Permeability and shear modulus of articular cartilage in growing mice.

    PubMed

    Berteau, J-Ph; Oyen, M; Shefelbine, S J

    2016-02-01

    Articular cartilage maturation is the postnatal development process that adapts joint surfaces to their site-specific biomechanical demands. Understanding the changes in mechanical tissues properties during growth is a critical step in advancing strategies for orthopedics and for cell- and biomaterial- based therapies dedicated to cartilage repair. We hypothesize that at the microscale, the articular cartilage tissue properties of the mouse (i.e., shear modulus and permeability) change with the growth and are dependent on location within the joint. We tested cartilage on the medial femoral condyle and lateral femoral condyle of seven C57Bl6 mice at different ages (2, 3, 5, 7, 9, 12, and 17 weeks old) using a micro-indentation test. Results indicated that permeability decreased with age from 2 to 17 weeks. Shear modulus reached a peak at the end of the growth (9 weeks). Within an age group, shear modulus was higher in the MFC than in the LFC, but permeability did not change. We have developed a method that can measure natural alterations in cartilage material properties in a murine joint, which will be useful in identifying changes in cartilage mechanics with degeneration, pathology, or treatment.

  9. Basic science and surgical treatment options for articular cartilage injuries of the knee.

    PubMed

    Tetteh, Elizabeth S; Bajaj, Sarvottam; Ghodadra, Neil S

    2012-03-01

    The complex structure of articular cartilage allows for diverse knee function throughout range of motion and weight bearing. However, disruption to the structural integrity of the articular surface can cause significant morbidity. Due to an inherently poor regenerative capacity, articular cartilage defects present a treatment challenge for physicians and therapists. For many patients, a trial of nonsurgical treatment options is paramount prior to surgical intervention. In instances of failed conservative treatment, patients can undergo an array of palliative, restorative, or reparative surgical procedures to treat these lesions. Palliative methods include debridement and lavage, while restorative techniques include marrow stimulation. For larger lesions involving subchondral bone, reparative procedures such as osteochondral grafting or autologous chondrocyte implantation are considered. Clinical success not only depends on the surgical techniques but also requires strict adherence to rehabilitation guidelines. The purpose of this article is to review the basic science of articular cartilage and to provide an overview of the procedures currently performed at our institution for patients presenting with symptomatic cartilage lesions.

  10. The bio in the ink: cartilage regeneration with bioprintable hydrogels and articular cartilage-derived progenitor cells.

    PubMed

    Levato, Riccardo; Webb, William R; Otto, Iris A; Mensinga, Anneloes; Zhang, Yadan; van Rijen, Mattie; van Weeren, René; Khan, Ilyas M; Malda, Jos

    2017-10-01

    Cell-laden hydrogels are the primary building blocks for bioprinting, and, also termed bioinks, are the foundations for creating structures that can potentially recapitulate the architecture of articular cartilage. To be functional, hydrogel constructs need to unlock the regenerative capacity of encapsulated cells. The recent identification of multipotent articular cartilage-resident chondroprogenitor cells (ACPCs), which share important traits with adult stem cells, represents a new opportunity for cartilage regeneration. However, little is known about the suitability of ACPCs for tissue engineering, especially in combination with biomaterials. This study aimed to investigate the potential of ACPCs in hydrogels for cartilage regeneration and biofabrication, and to evaluate their ability for zone-specific matrix production. Gelatin methacryloyl (gelMA)-based hydrogels were used to culture ACPCs, bone marrow mesenchymal stromal cells (MSCs) and chondrocytes, and as bioinks for printing. Our data shows ACPCs outperformed chondrocytes in terms of neo-cartilage production and unlike MSCs, ACPCs had the lowest gene expression levels of hypertrophy marker collagen type X, and the highest expression of PRG4, a key factor in joint lubrication. Co-cultures of the cell types in multi-compartment hydrogels allowed generating constructs with a layered distribution of collagens and glycosaminoglycans. By combining ACPC- and MSC-laden bioinks, a bioprinted model of articular cartilage was generated, consisting of defined superficial and deep regions, each with distinct cellular and extracellular matrix composition. Taken together, these results provide important information for the use of ACPC-laden hydrogels in regenerative medicine, and pave the way to the biofabrication of 3D constructs with multiple cell types for cartilage regeneration or in vitro tissue models. Despite its limited ability to repair, articular cartilage harbors an endogenous population of progenitor cells

  11. An ultrasonic measurement for in vitro depth-dependent equilibrium strains of articular cartilage in compression

    NASA Astrophysics Data System (ADS)

    Zheng, Y. P.; Mak, A. F. T.; Lau, K. P.; Qin, L.

    2002-09-01

    The equilibrium depth-dependent biomechanical properties of articular cartilage were measured using an ultrasound-compression method. Ten cylindrical bovine patella cartilage-bone specimens were tested in compression followed by a period of force-relaxation. A 50 MHz focused ultrasound beam was transmitted into the cartilage specimen through a remaining bone layer and a small hole at the centre of a specimen platform. The ultrasound echoes reflected or scattered within the articular cartilage were collected using the same transducer. The displacements of the tissues at different depths of the articular cartilage were derived from the ultrasound echo signals recorded during the compression and the subsequent force-relaxation. For two steps of 0.1 mm compression, the average strain at the superficial 0.2 mm thick layer (0.35 +/- 0.09) was significantly (p < 0.05) larger than that at the subsequent 0.2 mm thick layer (0.05 +/- 0.07) and that at deeper layers (0.01 +/- 0.02). It was demonstrated that the compressive biomechanical properties of cartilage were highly depth-dependent. The results suggested that the ultrasound-compression method could be a useful tool for the study of the depth-dependent biomechanical properties of articular cartilage.

  12. Comparison of MRI-based estimates of articular cartilage contact area in the tibiofemoral joint.

    PubMed

    Henderson, Christopher E; Higginson, Jill S; Barrance, Peter J

    2011-01-01

    Knee osteoarthritis (OA) detrimentally impacts the lives of millions of older Americans through pain and decreased functional ability. Unfortunately, the pathomechanics and associated deviations from joint homeostasis that OA patients experience are not well understood. Alterations in mechanical stress in the knee joint may play an essential role in OA; however, existing literature in this area is limited. The purpose of this study was to evaluate the ability of an existing magnetic resonance imaging (MRI)-based modeling method to estimate articular cartilage contact area in vivo. Imaging data of both knees were collected on a single subject with no history of knee pathology at three knee flexion angles. Intra-observer reliability and sensitivity studies were also performed to determine the role of operator-influenced elements of the data processing on the results. The method's articular cartilage contact area estimates were compared with existing contact area estimates in the literature. The method demonstrated an intra-observer reliability of 0.95 when assessed using Pearson's correlation coefficient and was found to be most sensitive to changes in the cartilage tracings on the peripheries of the compartment. The articular cartilage contact area estimates at full extension were similar to those reported in the literature. The relationships between tibiofemoral articular cartilage contact area and knee flexion were also qualitatively and quantitatively similar to those previously reported. The MRI-based knee modeling method was found to have high intra-observer reliability, sensitivity to peripheral articular cartilage tracings, and agreeability with previous investigations when using data from a single healthy adult. Future studies will implement this modeling method to investigate the role that mechanical stress may play in progression of knee OA through estimation of articular cartilage contact area.

  13. Articular cartilage and subchondral bone in the pathogenesis of osteoarthritis.

    PubMed

    Goldring, Mary B; Goldring, Steven R

    2010-03-01

    The articular surface plays an essential role in load transfer across the joint, and conditions that produce increased load transfer or altered patterns of load distribution accelerate the development of osteoarthritis (OA). Current knowledge segregates the risk factors into two fundamental mechanisms related to the adverse effects of "abnormal" loading on normal cartilage or "normal" loading on abnormal cartilage. Although chondrocytes can modulate their functional state in response to loading, their capacity to repair and modify the surrounding extracellular matrix is limited in comparison to skeletal cells in bone. This differential adaptive capacity underlies the more rapid appearance of detectable skeletal changes, especially after acute injuries that alter joint mechanics. The imbalance in the adaptation of the cartilage and bone disrupts the physiological relationship between these tissues and further contributes to OA pathology. This review focuses on the specific articular cartilage and skeletal features of OA and the putative mechanisms involved in their pathogenesis.

  14. The structure and mechanical properties of articular cartilage are highly resilient towards transient dehydration.

    PubMed

    Boettcher, K; Kienle, S; Nachtsheim, J; Burgkart, R; Hugel, T; Lieleg, O

    2016-01-01

    Articular cartilage is a mechanically highly challenged material with very limited regenerative ability. In contrast to elastic cartilage, articular cartilage is exposed to recurring partial dehydration owing to ongoing compression but maintains its functionality over decades. To extend our current understanding of the material properties of articular cartilage, specifically the interaction between the fluid and solid phase, we here analyze the reversibility of tissue dehydration. We perform an artificial dehydration that extends beyond naturally occurring levels and quantify material recovery as a function of the ionic strength of the rehydration buffer. Mechanical (indentation, compression, shear, and friction) measurements are used to evaluate the influence of de- and rehydration on the viscoelastic properties of cartilage. The structure and composition of native and de/rehydrated cartilage are analyzed using histology, scanning electron microscopy, and atomic force microscopy along with a 1,9-dimethylmethylene blue (DMMB) assay. A broad range of mechanical and structural properties of cartilage can be restored after de- and rehydration provided that a physiological salt solution is used for rehydration. We detect only minor alterations in the microarchitecture of rehydrated cartilage in the superficial zone and find that these alterations do not interfere with the viscoelastic and tribological properties of the tissue. We here demonstrate the sturdiness of articular cartilage towards changes in fluid content and show that articular cartilage recovers a broad range of its material properties after dehydration. We analyze the reversibility of tissue dehydration to extend our current understanding of how the material properties of cartilage are established, focusing on the interaction between the fluid and solid phase. Our findings suggest that the high resilience of the tissue minimizes the risk of irreversible material failure and thus compensates, at least in

  15. T2* Mapping Provides Information That Is Statistically Comparable to an Arthroscopic Evaluation of Acetabular Cartilage.

    PubMed

    Morgan, Patrick; Nissi, Mikko J; Hughes, John; Mortazavi, Shabnam; Ellerman, Jutta

    2017-07-01

    Objectives The purpose of this study was to validate T2* mapping as an objective, noninvasive method for the prediction of acetabular cartilage damage. Methods This is the second step in the validation of T2*. In a previous study, we established a quantitative predictive model for identifying and grading acetabular cartilage damage. In this study, the model was applied to a second cohort of 27 consecutive hips to validate the model. A clinical 3.0-T imaging protocol with T2* mapping was used. Acetabular regions of interest (ROI) were identified on magnetic resonance and graded using the previously established model. Each ROI was then graded in a blinded fashion by arthroscopy. Accurate surgical location of ROIs was facilitated with a 2-dimensional map projection of the acetabulum. A total of 459 ROIs were studied. Results When T2* mapping and arthroscopic assessment were compared, 82% of ROIs were within 1 Beck group (of a total 6 possible) and 32% of ROIs were classified identically. Disease prediction based on receiver operating characteristic curve analysis demonstrated a sensitivity of 0.713 and a specificity of 0.804. Model stability evaluation required no significant changes to the predictive model produced in the initial study. Conclusions These results validate that T2* mapping provides statistically comparable information regarding acetabular cartilage when compared to arthroscopy. In contrast to arthroscopy, T2* mapping is quantitative, noninvasive, and can be used in follow-up. Unlike research quantitative magnetic resonance protocols, T2* takes little time and does not require a contrast agent. This may facilitate its use in the clinical sphere.

  16. Indentation mapping revealed poroelastic, but not viscoelastic, properties spanning native zonal articular cartilage.

    PubMed

    Wahlquist, Joseph A; DelRio, Frank W; Randolph, Mark A; Aziz, Aaron H; Heveran, Chelsea M; Bryant, Stephanie J; Neu, Corey P; Ferguson, Virginia L

    2017-12-01

    Osteoarthrosis is a debilitating disease affecting millions, yet engineering materials for cartilage regeneration has proven difficult because of the complex microstructure of this tissue. Articular cartilage, like many biological tissues, produces a time-dependent response to mechanical load that is critical to cell's physiological function in part due to solid and fluid phase interactions and property variations across multiple length scales. Recreating the time-dependent strain and fluid flow may be critical for successfully engineering replacement tissues but thus far has largely been neglected. Here, microindentation is used to accomplish three objectives: (1) quantify a material's time-dependent mechanical response, (2) map material properties at a cellular relevant length scale throughout zonal articular cartilage and (3) elucidate the underlying viscoelastic, poroelastic, and nonlinear poroelastic causes of deformation in articular cartilage. Untreated and trypsin-treated cartilage was sectioned perpendicular to the articular surface and indentation was used to evaluate properties throughout zonal cartilage on the cut surface. The experimental results demonstrated that within all cartilage zones, the mechanical response was well represented by a model assuming nonlinear biphasic behavior and did not follow conventional viscoelastic or linear poroelastic models. Additionally, 10% (w/w) agarose was tested and, as anticipated, behaved as a linear poroelastic material. The approach outlined here provides a method, applicable to many tissues and biomaterials, which reveals and quantifies the underlying causes of time-dependent deformation, elucidates key aspects of material structure and function, and that can be used to provide important inputs for computational models and targets for tissue engineering. Elucidating the time-dependent mechanical behavior of cartilage, and other biological materials, is critical to adequately recapitulate native mechanosensory

  17. Biofunctional polymer nanoparticles for intra-articular targeting and retention in cartilage

    NASA Astrophysics Data System (ADS)

    Rothenfluh, Dominique A.; Bermudez, Harry; O'Neil, Conlin P.; Hubbell, Jeffrey A.

    2008-03-01

    The extracellular matrix of dense, avascular tissues presents a barrier to entry for polymer-based therapeutics, such as drugs encapsulated within polymeric particles. Here, we present an approach by which polymer nanoparticles, sufficiently small to enter the matrix of the targeted tissue, here articular cartilage, are further modified with a biomolecular ligand for matrix binding. This combination of ultrasmall size and biomolecular binding converts the matrix from a barrier into a reservoir, resisting rapid release of the nanoparticles and clearance from the tissue site. Phage display of a peptide library was used to discover appropriate targeting ligands by biopanning on denuded cartilage. The ligand WYRGRL was selected in 94 of 96 clones sequenced after five rounds of biopanning and was demonstrated to bind to collagen II α1. Peptide-functionalized nanoparticles targeted articular cartilage up to 72-fold more than nanoparticles displaying a scrambled peptide sequence following intra-articular injection in the mouse.

  18. Hyaline Articular Matrix Formed by Dynamic Self-Regenerating Cartilage and Hydrogels.

    PubMed

    Meppelink, Amanda M; Zhao, Xing; Griffin, Darvin J; Erali, Richard; Gill, Thomas J; Bonassar, Lawrence J; Redmond, Robert W; Randolph, Mark A

    2016-07-01

    Injuries to the articular cartilage surface are challenging to repair because cartilage possesses a limited capacity for self-repair. The outcomes of current clinical procedures aimed to address these injuries are inconsistent and unsatisfactory. We have developed a novel method for generating hyaline articular cartilage to improve the outcome of joint surface repair. A suspension of 10(7) swine chondrocytes was cultured under reciprocating motion for 14 days. The resulting dynamic self-regenerating cartilage (dSRC) was placed in a cartilage ring and capped with fibrin and collagen gel. A control group consisted of chondrocytes encapsulated in fibrin gel. Constructs were implanted subcutaneously in nude mice and harvested after 6 weeks. Gross, histological, immunohistochemical, biochemical, and biomechanical analyses were performed. In swine patellar groove, dSRC was implanted into osteochondral defects capped with collagen gel and compared to defects filled with osteochondral plugs, collagen gel, or left empty after 6 weeks. In mice, the fibrin- and collagen-capped dSRC constructs showed enhanced contiguous cartilage matrix formation over the control of cells encapsulated in fibrin gel. Biochemically, the fibrin and collagen gel dSRC groups were statistically improved in glycosaminoglycan and hydroxyproline content compared to the control. There was no statistical difference in the biomechanical data between the dSRC groups and the control. The swine model also showed contiguous cartilage matrix in the dSRC group but not in the collagen gel and empty defects. These data demonstrate the survivability and successful matrix formation of dSRC under the mechanical forces experienced by normal hyaline cartilage in the knee joint. The results from this study demonstrate that dSRC capped with hydrogels successfully engineers contiguous articular cartilage matrix in both nonload-bearing and load-bearing environments.

  19. Evaluation of degenerative changes in articular cartilage of osteoarthritis by Raman spectroscopy

    NASA Astrophysics Data System (ADS)

    Oshima, Yusuke; Ishimaru, Yasumitsu; Kiyomatsu, Hiroshi; Hino, Kazunori; Miura, Hiromasa

    2018-02-01

    Osteoarthritis (OA) is a very common joint disease in the aging population. Main symptom of OA is accompanied by degenerative changes of articular cartilage. Cartilage contains mostly type II collagen and proteoglycans, so it is difficult to access the quality and morphology of cartilage tissue in situ by conventional diagnostic tools (X-ray, MRI and echography) directly or indirectly. Raman spectroscopy is a label-free technique which enables to analyze molecular composition in degenerative cartilage. In this proposal, we aim to develop Raman spectroscopic system for the quality assessment of articular cartilage during arthroscopic surgery. Toward this goal, we are focusing on the proteoglycan content and collagen fiber alignment in cartilage matrix which may be associated with degenerative changes in OA, and we designed an original Raman device for remote sensing during arthroscopic surgery. In this project, we define the grading system for cartilage defect based on Raman spectroscopy, and we complete the evaluation of the Raman probing system which makes it possible to detect early stage of degenerative cartilage as a novel tool for OA diagnosis using human subject.

  20. Preliminary investigation of intrinsic UV fluorescence spectroscopic changes associated with proteolytic digestion of bovine articular cartilage

    NASA Astrophysics Data System (ADS)

    Lewis, William; Padilla-Martinez, Juan-Pablo; Ortega-Martinez, Antonio; Franco, Walfre

    2016-03-01

    Degradation and destruction of articular cartilage is the etiology of osteoarthritis (OA), an entity second only to cardiovascular disease as a cause of disability in the United States. Joint mechanics and cartilage biochemistry are believed to play a role in OA; an optical tool to detect structural and chemical changes in articular cartilage might offer benefit for its early detection and treatment. The objective of the present study was to identify the spectral changes in intrinsic ultraviolet (UV) fluorescence of cartilage that occur after proteolytic digestion of cartilage. Bovine articular cartilage samples were incubated in varying concentrations of collagenase ranging from 10ug/mL up to 5mg/mL for 18 hours at 37°C, a model of OA. Pre- and post-incubation measurements were taken of the UV excitation-emission spectrum of each cartilage sample. Mechanical tests were performed to determine the pre- and post-digestion force/displacement ratio associated with indentation of each sample. Spectral changes in intrinsic cartilage fluorescence and stiffness of the cartilage were associated with proteolytic digestion. In particular, changes in the relative intensity of fluorescence peaks associated with pentosidine crosslinks (330 nm excitation, 390 nm emission) and tryptophan (290 nm excitation, 340 nm emission) were found to correlate with different degrees of cartilage digestion and cartilage stiffness. In principle, it may be possible to use UV fluorescence spectral data for early detection of damage to articular cartilage, and as a surrogate measure for cartilage stiffness.

  1. Viscoelastic properties of human and bovine articular cartilage: a comparison of frequency-dependent trends.

    PubMed

    Temple, Duncan K; Cederlund, Anna A; Lawless, Bernard M; Aspden, Richard M; Espino, Daniel M

    2016-10-06

    The purpose of this study was to compare the frequency-dependent viscoelastic properties of human and bovine cartilage. Full-depth cartilage specimens were extracted from bovine and human femoral heads. Using dynamic mechanical analysis, the viscoelastic properties of eight bovine and six human specimens were measured over the frequency range 1 Hz to 88 Hz. Significant differences between bovine and human cartilage viscoelastic properties were assessed using a Mann-Whitney test (p < 0.05). Throughout the range of frequencies tested and for both species, the storage modulus was greater than the loss modulus and both were frequency-dependent. The storage and loss moduli of all human and bovine cartilage specimens presented a logarithmic relationship with respect to frequency. The mean human storage modulus ranged from 31.9 MPa to 43.3 MPa, while the mean bovine storage modulus ranged from 54.0 MPa to 80.5 MPa; bovine storage moduli were 1.7 to 1.9 times greater than the human modulus. Similarly, the loss modulus of bovine cartilage was 2.0 to 2.1 times greater than human. The mean human loss modulus ranged from 5.3 MPa to 8.5 MPa while bovine moduli ranged from 10.6 MPa to 18.1 MPa. Frequency-dependent viscoelastic trends of bovine articular cartilage were consistent with those of human articular cartilage; this includes a similar frequency dependency and high-frequency plateau. Bovine cartilage was, however, 'stiffer' than human by a factor of approximately 2. With these provisos, bovine articular cartilage may be a suitable dynamic model for human articular cartilage.

  2. Articular cartilage tissue engineering: the role of signaling molecules

    PubMed Central

    Kwon, Heenam; Paschos, Nikolaos K.; Hu, Jerry C.; Athanasiou, Kyriacos

    2017-01-01

    Effective early disease modifying options for osteoarthritis remain lacking. Tissue engineering approach to generate cartilage in vitro has emerged as a promising option for articular cartilage repair and regeneration. Signaling molecules and matrix modifying agents, derived from knowledge of cartilage development and homeostasis, have been used as biochemical stimuli toward cartilage tissue engineering and have led to improvements in the functionality of engineered cartilage. Clinical translation of neocartilage faces challenges, such as phenotypic instability of the engineered cartilage, poor integration, inflammation, and catabolic factors in the arthritic environment; these can all contribute to failure of implanted neocartilage. A comprehensive understanding of signaling molecules involved in osteoarthritis pathogenesis and their actions on engineered cartilage will be crucial. Thus, while it is important to continue deriving inspiration from cartilage development and homeostasis, it has become increasing necessary to incorporate knowledge from osteoarthritis pathogenesis into cartilage tissue engineering. PMID:26811234

  3. Estimation of Articular Cartilage Surface Roughness Using Gray-Level Co-Occurrence Matrix of Laser Speckle Image.

    PubMed

    Youssef, Doaa; El-Ghandoor, Hatem; Kandel, Hamed; El-Azab, Jala; Hassab-Elnaby, Salah

    2017-06-28

    The application of He-Ne laser technologies for description of articular cartilage degeneration, one of the most common diseases worldwide, is an innovative usage of these technologies used primarily in material engineering. Plain radiography and magnetic resonance imaging are insufficient to allow the early assessment of the disease. As surface roughness of articular cartilage is an important indicator of articular cartilage degeneration progress, a safe and noncontact technique based on laser speckle image to estimate the surface roughness is provided. This speckle image from the articular cartilage surface, when illuminated by laser beam, gives very important information about the physical properties of the surface. An experimental setup using a low power He-Ne laser and a high-resolution digital camera was implemented to obtain speckle images of ten bovine articular cartilage specimens prepared for different average roughness values. Texture analysis method based on gray-level co-occurrence matrix (GLCM) analyzed on the captured speckle images is used to characterize the surface roughness of the specimens depending on the computation of Haralick's texture features. In conclusion, this promising method can accurately estimate the surface roughness of articular cartilage even for early signs of degeneration. The method is effective for estimation of average surface roughness values ranging from 0.09 µm to 2.51 µm with an accuracy of 0.03 µm.

  4. Estimation of Articular Cartilage Surface Roughness Using Gray-Level Co-Occurrence Matrix of Laser Speckle Image

    PubMed Central

    El-Ghandoor, Hatem; Kandel, Hamed; El-Azab, Jala; Hassab-Elnaby, Salah

    2017-01-01

    The application of He-Ne laser technologies for description of articular cartilage degeneration, one of the most common diseases worldwide, is an innovative usage of these technologies used primarily in material engineering. Plain radiography and magnetic resonance imaging are insufficient to allow the early assessment of the disease. As surface roughness of articular cartilage is an important indicator of articular cartilage degeneration progress, a safe and noncontact technique based on laser speckle image to estimate the surface roughness is provided. This speckle image from the articular cartilage surface, when illuminated by laser beam, gives very important information about the physical properties of the surface. An experimental setup using a low power He-Ne laser and a high-resolution digital camera was implemented to obtain speckle images of ten bovine articular cartilage specimens prepared for different average roughness values. Texture analysis method based on gray-level co-occurrence matrix (GLCM) analyzed on the captured speckle images is used to characterize the surface roughness of the specimens depending on the computation of Haralick’s texture features. In conclusion, this promising method can accurately estimate the surface roughness of articular cartilage even for early signs of degeneration. The method is effective for estimation of average surface roughness values ranging from 0.09 µm to 2.51 µm with an accuracy of 0.03 µm. PMID:28773080

  5. Hydrostatic Pressure in Articular Cartilage Tissue Engineering: From Chondrocytes to Tissue Regeneration

    PubMed Central

    Elder, Benjamin D.

    2009-01-01

    Cartilage has a poor intrinsic healing response, and neither the innate healing response nor current clinical treatments can restore its function. Therefore, articular cartilage tissue engineering is a promising approach for the regeneration of damaged tissue. Because cartilage is exposed to mechanical forces during joint loading, many tissue engineering strategies use exogenous stimuli to enhance the biochemical or biomechanical properties of the engineered tissue. Hydrostatic pressure (HP) is emerging as arguably one of the most important mechanical stimuli for cartilage, although no optimal treatment has been established across all culture systems. Therefore, this review evaluates prior studies on articular cartilage involving the use of HP, with a particular emphasis on the treatments that appear promising for use in future studies. Additionally, this review addresses HP bioreactor design, chondroprotective effects of HP, the use of HP for chondrogenic differentiation, the effects of high pressures, and HP mechanotransduction. PMID:19196119

  6. Hydrostatic pressure in articular cartilage tissue engineering: from chondrocytes to tissue regeneration.

    PubMed

    Elder, Benjamin D; Athanasiou, Kyriacos A

    2009-03-01

    Cartilage has a poor intrinsic healing response, and neither the innate healing response nor current clinical treatments can restore its function. Therefore, articular cartilage tissue engineering is a promising approach for the regeneration of damaged tissue. Because cartilage is exposed to mechanical forces during joint loading, many tissue engineering strategies use exogenous stimuli to enhance the biochemical or biomechanical properties of the engineered tissue. Hydrostatic pressure (HP) is emerging as arguably one of the most important mechanical stimuli for cartilage, although no optimal treatment has been established across all culture systems. Therefore, this review evaluates prior studies on articular cartilage involving the use of HP, with a particular emphasis on the treatments that appear promising for use in future studies. Additionally, this review addresses HP bioreactor design, chondroprotective effects of HP, the use of HP for chondrogenic differentiation, the effects of high pressures, and HP mechanotransduction.

  7. EGFR signaling is critical for maintaining the superficial layer of articular cartilage and preventing osteoarthritis initiation

    PubMed Central

    Jia, Haoruo; Ma, Xiaoyuan; Tong, Wei; Doyran, Basak; Sun, Zeyang; Wang, Luqiang; Zhang, Xianrong; Zhou, Yilu; Badar, Farid; Chandra, Abhishek; Lu, X. Lucas; Xia, Yang; Han, Lin; Enomoto-Iwamoto, Motomi; Qin, Ling

    2016-01-01

    Osteoarthritis (OA) is the most common joint disease, characterized by progressive destruction of the articular cartilage. The surface of joint cartilage is the first defensive and affected site of OA, but our knowledge of genesis and homeostasis of this superficial zone is scarce. EGFR signaling is important for tissue homeostasis. Immunostaining revealed that its activity is mostly dominant in the superficial layer of healthy cartilage but greatly diminished when OA initiates. To evaluate the role of EGFR signaling in the articular cartilage, we studied a cartilage-specific Egfr-deficient (CKO) mouse model (Col2-Cre EgfrWa5/flox). These mice developed early cartilage degeneration at 6 mo of age. By 2 mo of age, although their gross cartilage morphology appears normal, CKO mice had a drastically reduced number of superficial chondrocytes and decreased lubricant secretion at the surface. Using superficial chondrocyte and cartilage explant cultures, we demonstrated that EGFR signaling is critical for maintaining the number and properties of superficial chondrocytes, promoting chondrogenic proteoglycan 4 (Prg4) expression, and stimulating the lubrication function of the cartilage surface. In addition, EGFR deficiency greatly disorganized collagen fibrils in articular cartilage and strikingly reduced cartilage surface modulus. After surgical induction of OA at 3 mo of age, CKO mice quickly developed the most severe OA phenotype, including a complete loss of cartilage, extremely high surface modulus, subchondral bone plate thickening, and elevated joint pain. Taken together, our studies establish EGFR signaling as an important regulator of the superficial layer during articular cartilage development and OA initiation. PMID:27911782

  8. Direct comparison of intra-articular versus intravenous delayed gadolinium-enhanced MRI of hip joint cartilage.

    PubMed

    Zilkens, Christoph; Miese, Falk; Kim, Young-Jo; Jäger, Marcus; Mamisch, Tallal C; Hosalkar, Harish; Antoch, Gerald; Krauspe, Rüdiger; Bittersohl, Bernd

    2014-01-01

    To investigate the potential of delayed gadolinium-enhanced magnetic resonance imaging in cartilage (dGEMRIC) after intra-articular (ia) contrast agent administration at 3 Tesla (T), a paired study comparing intravenous (iv) dGEMRIC (standard) with ia-dGEMRIC was performed. Thirty-five symptomatic patients with suspected cartilage damage underwent ia- and iv-dGEMRIC. MRI was performed with a 3T system wherein the interval between both measurements was 2 weeks. For iv-dGEMRIC, FDA approved Gd-DOTA(-) was injected intravenously 45 min before the MRI scan. For ia-dGEMRIC, 10-20 mL of a 2 mM solution of Gd- DOTA(-) was injected under fluoroscopic guidance 30 min before the MRI scan. Both ia- and iv-dGEMRIC demonstrated the typical T1Gd pattern in hip joint cartilage with increasing values toward the superior regions in acetabular cartilage reflecting the higher glycosaminoglycan (GAG) content in the main weight-bearing area. Correlation analysis revealed a moderate correlation between both techniques (r = 0.439, P-value < 0.001), whereas the T1Gd values for iv-dGEMRIC were significantly higher than those for ia-dGEMRIC. This corresponds with the Bland-Altman plot analysis, which revealed a systemic bias (higher T1Gd values after iv gadolinium application) of ∼70 ms. Ia-dGEMRIC was able to reveal the characteristic T1Gd pattern in hip joint cartilage confirming the sensitivity of ia-dGEMRIC for GAG. In addition, there was a significant correlation between iv-dGEMRIC and ia-dGEMRIC. However, the T1Gd values after ia contrast media application were significantly lower than those after iv application that has to be considered for future studies. Copyright © 2013 Wiley Periodicals, Inc.

  9. Development of a Valid and Reliable Knee Articular Cartilage Condition-Specific Study Methodological Quality Score.

    PubMed

    Harris, Joshua D; Erickson, Brandon J; Cvetanovich, Gregory L; Abrams, Geoffrey D; McCormick, Frank M; Gupta, Anil K; Verma, Nikhil N; Bach, Bernard R; Cole, Brian J

    2014-02-01

    Condition-specific questionnaires are important components in evaluation of outcomes of surgical interventions. No condition-specific study methodological quality questionnaire exists for evaluation of outcomes of articular cartilage surgery in the knee. To develop a reliable and valid knee articular cartilage-specific study methodological quality questionnaire. Cross-sectional study. A stepwise, a priori-designed framework was created for development of a novel questionnaire. Relevant items to the topic were identified and extracted from a recent systematic review of 194 investigations of knee articular cartilage surgery. In addition, relevant items from existing generic study methodological quality questionnaires were identified. Items for a preliminary questionnaire were generated. Redundant and irrelevant items were eliminated, and acceptable items modified. The instrument was pretested and items weighed. The instrument, the MARK score (Methodological quality of ARticular cartilage studies of the Knee), was tested for validity (criterion validity) and reliability (inter- and intraobserver). A 19-item, 3-domain MARK score was developed. The 100-point scale score demonstrated face validity (focus group of 8 orthopaedic surgeons) and criterion validity (strong correlation to Cochrane Quality Assessment score and Modified Coleman Methodology Score). Interobserver reliability for the overall score was good (intraclass correlation coefficient [ICC], 0.842), and for all individual items of the MARK score, acceptable to perfect (ICC, 0.70-1.000). Intraobserver reliability ICC assessed over a 3-week interval was strong for 2 reviewers (≥0.90). The MARK score is a valid and reliable knee articular cartilage condition-specific study methodological quality instrument. This condition-specific questionnaire may be used to evaluate the quality of studies reporting outcomes of articular cartilage surgery in the knee.

  10. Stimulation of the Superficial Zone Protein and Lubrication in the Articular Cartilage by Human Platelet-Rich Plasma

    PubMed Central

    Sakata, Ryosuke; McNary, Sean M.; Miyatake, Kazumasa; Lee, Cassandra A.; Van den Bogaerde, James M.; Marder, Richard A.; Reddi, A. Hari

    2016-01-01

    Background Platelet-rich plasma (PRP) contains high concentrations of autologous growth factors that originate from platelets. Intra-articular injections of PRP have the potential to ameliorate the symptoms of osteoarthritis in the knee. Superficial zone protein (SZP) is a boundary lubricant in articular cartilage and plays an important role in reducing friction and wear and therefore is critical in cartilage homeostasis. Purpose To determine if PRP influences the production of SZP from human joint-derived cells and to evaluate the lubricating properties of PRP on normal bovine articular cartilage. Study Design Controlled laboratory study. Methods Cells were isolated from articular cartilage, synovium, and the anterior cruciate ligament (ACL) from 12 patients undergoing ACL reconstruction. The concentrations of SZP in PRP and culture media were measured by enzyme-linked immunosorbent assay. Cellular proliferation was quantified by determination of cell numbers. The lubrication properties of PRP from healthy volunteers on bovine articular cartilage were investigated using a pin-on-disk tribometer. Results In general, PRP stimulated proliferation in cells derived from articular cartilage, synovium, and ACL. It also significantly enhanced SZP secretion from synovium- and cartilage-derived cells. An unexpected finding was the presence of SZP in PRP (2.89 ± 1.23 µg/mL before activation and 3.02 ± 1.32 µg/mL after activation). In addition, under boundary mode conditions consisting of high loads and low sliding speeds, nonactivated and thrombin-activated PRP decreased the friction coefficient (μ = 0.012 and μ = 0.015, respectively) compared with saline (μ = 0.047, P < 0.004) and high molecular weight hyaluronan (μ = 0.080, P < 0.006). The friction coefficient of the cartilage with PRP was on par with that of synovial fluid. Conclusion PRP significantly stimulates cell proliferation and SZP secretion by articular cartilage and synovium of the human knee joint

  11. Course-, dose-, and stage-dependent toxic effects of prenatal dexamethasone exposure on fetal articular cartilage development.

    PubMed

    Chen, Ze; Zhao, Zhe; Li, Yunzepeng; Zhang, Xingyu; Li, Bin; Chen, Liaobin; Wang, Hui

    2018-04-01

    Dexamethasone, a synthetic long-acting glucocorticoid, is routinely used for treating mothers at risk for preterm delivery. However, intrauterine overexposure to glucocorticoids induces low birth weight and cartilage dysplasia in offspring. Also, the "critical window" and safe dose of this treatment are largely unknown. This study investigated the course-, dose-, and stage-dependent toxic effects and the possible mechanisms of prenatal dexamethasone exposure (PDE) on fetal development and articular cartilage development. Pregnant mice (C57BL/6) received subcutaneous injection of dexamethasone (0.8 mg/kg d) once on gestational day (GD) 15 or once a day from GD 15 to 17, or received various doses of dexamethasone (0, 0.2, 0.8, and 1.2 mg/kg d) on GD 15-17, or received dexamethasone (0.8 mg/kg d) at early stage (GD 12-14) or late stage of pregnancy (GD 15-17). Offspring's knee joints were harvested at birth for morphological analyses and detection of gene expression. Repeated PDE significantly suppressed fetal and articular cartilage development, which were characterized by decreased body weight and body length, coarse articular cartilage surfaces, and reduced gene and protein expression of Col2a1 and aggrecan. For those newborns treated with repeated PDE at different doses, the toxic effects on fetal and articular cartilage development were observed at doses of 0.8 and 1.2 mg/kg d, whereas no obvious toxic effects were observed at the dose of 0.2 mg/kg d. Moreover, PDE at 0.8 mg/kg d during the early embryonic stage induced stronger toxic effects on fetal and articular cartilage development, compared with PDE during the late embryonic stage. Detection of gene expression showed that the TGFβ signaling pathway in the articular cartilage was down-regulated after PDE. Taken together, PDE induces fetal developmental toxicity and articular cartilage developmental toxicity in a course-, dose-, and stage-dependent manner. Copyright © 2018 Elsevier B

  12. Repair of full-thickness articular cartilage defect using stem cell-encapsulated thermogel.

    PubMed

    Zhang, Yanbo; Zhang, Jin; Chang, Fei; Xu, Weiguo; Ding, Jianxun

    2018-07-01

    Cartilage defect repair by hydrogel-based tissue engineering is becoming one of the most potential treatment strategies. In this work, a thermogel of triblock copolymer poly(lactide-co-glycolide)-block-poly(ethylene glycol)-block-poly(lactide-co-glycolide) (PLGA-PEG-PLGA) was prepared as scaffold of bone marrow mesenchymal stem cells (BMMSCs) for repair of full-thickness articular cartilage defect. At first, the copolymer solution showed a reversible sol-gel transition at physiological temperature range, and the mechanical properties of such thermogel were high enough to support the repair of cartilage. Additionally, excellent biodegradability and biocompatibility of the thermogel were demonstrated. By implanting the BMMSC-encapsulated thermogel into the full-thickness articular cartilage defect (5.0 mm in diameter and 4.0 mm in depth) in the rabbit, it was found that the regenerated cartilage integrated well with the surrounding normal cartilage and subchondral bone at 12 weeks post-surgery. The upregulated expression of glycosaminoglycan and type II collagen in the repaired cartilage, and the comparable biomechanical properties with normal cartilage suggested that the cell-encapsulated PLGA-PEG-PLGA thermogel had great potential in serving as the promising scaffold for cartilage regeneration. Copyright © 2018 Elsevier B.V. All rights reserved.

  13. Nasal chondrocyte-based engineered autologous cartilage tissue for repair of articular cartilage defects: an observational first-in-human trial.

    PubMed

    Mumme, Marcus; Barbero, Andrea; Miot, Sylvie; Wixmerten, Anke; Feliciano, Sandra; Wolf, Francine; Asnaghi, Adelaide M; Baumhoer, Daniel; Bieri, Oliver; Kretzschmar, Martin; Pagenstert, Geert; Haug, Martin; Schaefer, Dirk J; Martin, Ivan; Jakob, Marcel

    2016-10-22

    Articular cartilage injuries have poor repair capacity, leading to progressive joint damage, and cannot be restored predictably by either conventional treatments or advanced therapies based on implantation of articular chondrocytes. Compared with articular chondrocytes, chondrocytes derived from the nasal septum have superior and more reproducible capacity to generate hyaline-like cartilage tissues, with the plasticity to adapt to a joint environment. We aimed to assess whether engineered autologous nasal chondrocyte-based cartilage grafts allow safe and functional restoration of knee cartilage defects. In a first-in-human trial, ten patients with symptomatic, post-traumatic, full-thickness cartilage lesions (2-6 cm 2 ) on the femoral condyle or trochlea were treated at University Hospital Basel in Switzerland. Chondrocytes isolated from a 6 mm nasal septum biopsy specimen were expanded and cultured onto collagen membranes to engineer cartilage grafts (30 × 40 × 2 mm). The engineered tissues were implanted into the femoral defects via mini-arthrotomy and assessed up to 24 months after surgery. Primary outcomes were feasibility and safety of the procedure. Secondary outcomes included self-assessed clinical scores and MRI-based estimation of morphological and compositional quality of the repair tissue. This study is registered with ClinicalTrials.gov, number NCT01605201. The study is ongoing, with an approved extension to 25 patients. For every patient, it was feasible to manufacture cartilaginous grafts with nasal chondrocytes embedded in an extracellular matrix rich in glycosaminoglycan and type II collagen. Engineered tissues were stable through handling with forceps and could be secured in the injured joints. No adverse reactions were recorded and self-assessed clinical scores for pain, knee function, and quality of life were improved significantly from before surgery to 24 months after surgery. Radiological assessments indicated variable degrees of

  14. Cell and matrix modulation in prenatal and postnatal equine growth cartilage, zones of Ranvier and articular cartilage

    PubMed Central

    Löfgren, Maria; Ekman, Stina; Svala, Emilia; Lindahl, Anders; Ley, Cecilia; Skiöldebrand, Eva

    2014-01-01

    Formation of synovial joints includes phenotypic changes of the chondrocytes and the organisation of their extracellular matrix is regulated by different factors and signalling pathways. Increased knowledge of the normal processes involved in joint development may be used to identify similar regulatory mechanisms during pathological conditions in the joint. Samples of the distal radius were collected from prenatal and postnatal equine growth plates, zones of Ranvier and articular cartilage with the aim of identifying Notch signalling components and cells with stem cell-like characteristics and to follow changes in matrix protein localisation during joint development. The localisation of the Notch signalling components Notch1, Delta4, Hes1, Notch dysregulating protein epidermal growth factor-like domain 7 (EGFL7), the stem cell-indicating factor Stro-1 and the matrix molecules cartilage oligomeric matrix protein (COMP), fibromodulin, matrilin-1 and chondroadherin were studied using immunohistochemistry. Spatial changes in protein localisations during cartilage maturation were observed for Notch signalling components and matrix molecules, with increased pericellular localisation indicating new synthesis and involvement of these proteins in the formation of the joint. However, it was not possible to characterise the phenotype of the chondrocytes based on their surrounding matrix during normal chondrogenesis. The zone of Ranvier was identified in all horses and characterised as an area expressing Stro-1, EGFL7 and chondroadherin with an absence of COMP and Notch signalling. Stro-1 was also present in cells close to the perichondrium, in the articular cartilage and in the fetal resting zone, indicating stem cell-like characteristics of these cells. The presence of stem cells in the articular cartilage will be of importance for the repair of damaged cartilage. Perivascular chondrocytes and hypertrophic cells of the cartilage bone interface displayed positive staining for

  15. Optical spectral imaging of degeneration of articular cartilage

    NASA Astrophysics Data System (ADS)

    Kinnunen, Jussi; Jurvelin, Jukka S.; Mäkitalo, Jaana; Hauta-Kasari, Markku; Vahimaa, Pasi; Saarakkala, Simo

    2010-07-01

    Osteoarthritis (OA) is a common musculoskeletal disorder often diagnosed during arthroscopy. In OA, visual color changes of the articular cartilage surface are typically observed. We demonstrate in vitro the potential of visible light spectral imaging (420 to 720 nm) to quantificate these color changes. Intact bovine articular cartilage samples (n=26) are degraded both enzymatically using the collagenase and mechanically using the emery paper (P60 grit, 269 μm particle size). Spectral images are analyzed by using standard CIELAB color coordinates and the principal component analysis (PCA). After collagenase digestion, changes in the CIELAB coordinates and projection of the spectra to PCA eigenvector are statistically significant (p<0.05). After mechanical degradation, the grinding tracks could not be visualized in the RGB presentation, i.e., in the visual appearance of the sample to the naked eye under the D65 illumination. However, after projecting to the chosen eigenvector, the grinding tracks are revealed. The tracks are also seen by using only one wavelength, i.e., 469 nm, however, the contrast in the projection image is 1.6 to 2.5 times higher. Our results support the idea that the spectral imaging can be used for evaluation of the integrity of the cartilage surface.

  16. Development of hybrid scaffolds using ceramic and hydrogel for articular cartilage tissue regeneration.

    PubMed

    Seol, Young-Joon; Park, Ju Young; Jeong, Wonju; Kim, Tae-Ho; Kim, Shin-Yoon; Cho, Dong-Woo

    2015-04-01

    The regeneration of articular cartilage consisting of hyaline cartilage and hydrogel scaffolds has been generally used in tissue engineering. However, success in in vivo studies has been rarely reported. The hydrogel scaffolds implanted into articular cartilage defects are mechanically unstable and it is difficult for them to integrate with the surrounding native cartilage tissue. Therefore, it is needed to regenerate cartilage and bone tissue simultaneously. We developed hybrid scaffolds with hydrogel scaffolds for cartilage tissue and with ceramic scaffolds for bone tissue. For in vivo study, hybrid scaffolds were press-fitted into osteochondral tissue defects in a rabbit knee joints and the cartilage tissue regeneration in blank, hydrogel scaffolds, and hybrid scaffolds was compared. In 12th week after implantation, the histological and immunohistochemical analyses were conducted to evaluate the cartilage tissue regeneration. In the blank and hydrogel scaffold groups, the defects were filled with fibrous tissues and the implanted hydrogel scaffolds could not maintain their initial position; in the hybrid scaffold group, newly generated cartilage tissues were morphologically similar to native cartilage tissues and were smoothly connected to the surrounding native tissues. This study demonstrates hybrid scaffolds containing hydrogel and ceramic scaffolds can provide mechanical stability to hydrogel scaffolds and enhance cartilage tissue regeneration at the defect site. © 2014 Wiley Periodicals, Inc.

  17. Diverse roles of integrin receptors in articular cartilage.

    PubMed

    Shakibaei, M; Csaki, C; Mobasheri, A

    2008-01-01

    Integrins are heterodimeric integral membrane proteins made up of alpha and beta subunits. At least eighteen alpha and eight beta subunit genes have been described in mammals. Integrin family members are plasma membrane receptors involved in cell adhesion and active as intra- and extracellular signalling molecules in a variety of processes including embryogenesis, hemostasis, tissue repair, immune response and metastatic spread of tumour cells. Integrin beta 1 (beta1-integrin), the protein encoded by the ITGB1 gene (also known as CD29 and VLAB), is a multi-functional protein involved in cell-matrix adhesion, cell signalling, cellular defense, cell adhesion, protein binding, protein heterodimerisation and receptor-mediated activity. It is highly expressed in the human body (17.4 times higher than the average gene in the last updated revision of the human genome). The extracellular matrix (ECM) of articular cartilage is a unique environment. Interactions between chondrocytes and the ECM regulate many biological processes important to homeostasis and repair of articular cartilage, including cell attachment, growth, differentiation and survival. The beta1-integrin family of cell surface receptors appears to play a major role in mediating cell-matrix interactions that are important in regulating these fundamental processes. Chondrocyte mechanoreceptors have been proposed to incorporate beta1-integrins and mechanosensitive ion channels which link with key ECM, cytoskeletal and signalling proteins to maintain the chondrocyte phenotype, prevent chondrocyte apoptosis and regulate chondrocyte-specific gene expression. This review focuses on the expression and function of beta1-integrins in articular chondrocytes, its role in the unique biology of these cells and its distribution in cartilage.

  18. Low-field one-dimensional and direction-dependent relaxation imaging of bovine articular cartilage

    NASA Astrophysics Data System (ADS)

    Rössler, Erik; Mattea, Carlos; Mollova, Ayret; Stapf, Siegfried

    2011-12-01

    The structure of articular cartilage is separated into three layers of differently oriented collagen fibers, which is accompanied by a gradient of increasing glycosaminoglycan (GAG) and decreasing water concentration from the top layer towards the bone interface. The combined effect of these structural variations results in a change of the longitudinal and transverse relaxation times as a function of the distance from the cartilage surface. In this paper, this dependence is investigated at a magnetic field strength of 0.27 T with a one-dimensional depth resolution of 50 μm on bovine hip and stifle joint articular cartilage. By employing this method, advantage is taken of the increasing contrast of the longitudinal relaxation rate found at lower magnetic field strengths. Furthermore, evidence for an orientational dependence of relaxation times with respect to an axis normal to the surface plane is given, an observation that has recently been reported using high-field MRI and that was explained by preferential orientations of collagen bundles in each of the three cartilage zones. In order to quantify the extent of a further contrast mechanism and to estimate spatially dependent glycosaminoglycan concentrations, the data are supplemented by proton relaxation times that were acquired in bovine articular cartilage that was soaked in a 0.8 mM aqueous Gd ++ solution.

  19. Silk fibroin-chondroitin sulfate scaffold with immuno-inhibition property for articular cartilage repair.

    PubMed

    Zhou, Feifei; Zhang, Xianzhu; Cai, Dandan; Li, Jun; Mu, Qin; Zhang, Wei; Zhu, Shouan; Jiang, Yangzi; Shen, Weiliang; Zhang, Shufang; Ouyang, Hong Wei

    2017-11-01

    The demand of favorable scaffolds has increased for the emerging cartilage tissue engineering. Chondroitin sulfate (CS) and silk fibroin have been investigated and reported with safety and excellent biocompatibility as tissue engineering scaffolds. However, the rapid degradation rate of pure CS scaffolds presents a challenge to effectively recreate neo-tissue similar to natural articular cartilage. Meanwhile the silk fibroin is well used as a structural constituent material because its remarkable mechanical properties, long-lasting in vivo stability and hypoimmunity. The application of composite silk fibroin and CS scaffolds for joint cartilage repair has not been well studied. Here we report that the combination of silk fibroin and CS could synergistically promote articular cartilage defect repair. The silk fibroin (silk) and silk fibroin/CS (silk-CS) scaffolds were fabricated with salt-leaching, freeze-drying and crosslinking methodologies. The biocompatibility of the scaffolds was investigated in vitro by cell adhesion, proliferation and migration with human articular chondrocytes. We found that silk-CS scaffold maintained better chondrocyte phenotype than silk scaffold; moreover, the silk-CS scaffolds reduced chondrocyte inflammatory response that was induced by interleukin (IL)-1β, which is in consistent with the well-documented anti-inflammatory activities of CS. The in vivo cartilage repair was evaluated with a rabbit osteochondral defect model. Silk-CS scaffold induced more neo-tissue formation and better structural restoration than silk scaffold after 6 and 12weeks of implantation in ICRS histological evaluations. In conclusion, we have developed a silk fibroin/ chondroitin sulfate scaffold for cartilage tissue engineering that exhibits immuno-inhibition property and can improve the self-repair capacity of cartilage. Severe cartilage defect such as osteoarthritis (OA) is difficult to self-repair because of its avascular, aneural and alymphatic nature

  20. Relationships among measurements obtained by use of computed tomography and radiography and scores of cartilage microdamage in hip joints with moderate to severe joint laxity of adult dogs.

    PubMed

    Lopez, Mandi J; Lewis, Brooke P; Swaab, Megan E; Markel, Mark D

    2008-03-01

    To evaluate correlations among measurements on radiographic and computed tomography (CT) images with articular cartilage microdamage in lax hip joints of dogs. 12 adult mixed-breed hounds. Pelvic CT and radiography were performed. Hip joints were harvested following euthanasia. Orthopedic Foundation for Animals (OFA) and PennHIP radiograph reports were obtained. Norberg angle (NA) and radiographic percentage femoral head coverage (RPC) were determined. Center-edge angle (CEA), horizontal toit externe angle (HTEA), ventral acetabular sector angle (VASA), dorsal acetabular sector angle (DASA), horizontal acetabular sector angle (HASA), acetabular index (AI), and CT percentage femoral head coverage (CPC) were measured on 2-dimensional CT images. Femoral head-acetabular shelf percentage was measured on sagittal 3-dimensional CT (SCT) and transverse 3-dimensional CT (TCT) images. Light microscopy was used to score joint cartilage. Relationships of OFA confirmation and PennHIP osteoarthritis scores with radiography, CT, and cartilage variables and relationships of cartilage scores with radiography and CT measurements were evaluated with Spearman rank correlations. Pearson correlation was used for relationships of distraction index (DI) with radiography, CT, and cartilage variables. Significant relationships included PennHIP osteoarthritis score with cartilage score, CEA, HTEA, DASA, AI, CPC, and TCT; OFA confirmation score with cartilage score, NA, RPC, CEA, HTEA, DASA, AI, CPC, and TCT; cartilage score with NA, RPC, CEA, HTEA, DASA, HASA, AI, and TCT; and DI with cartilage score, CEA, HTEA, DASA, HASA, AI, and CPC. CT appeared to be a valuable imaging modality for predicting cartilage microdamage in canine hip joints.

  1. Viscoelastic modeling and quantitative experimental characterization of normal and osteoarthritic human articular cartilage using indentation.

    PubMed

    Richard, F; Villars, M; Thibaud, S

    2013-08-01

    The viscoelastic behavior of articular cartilage changes with progression of osteoarthritis. The objective of this study is to quantify this progression and to propose a viscoelastic model of articular cartilage taking into account the degree of osteoarthritis that which be easily used in predictive numerical simulations of the hip joint behavior. To quantify the effects of osteoarthritis (OA) on the viscoelastic behavior of human articular cartilage, samples were obtained from the hip arthroplasty due to femoral neck fracture (normal cartilage) or advanced coxarthrosis (OA cartilage). Experimental data were obtained from instrumented indentation tests on unfrozen femoral cartilage collected and studied in the day following the prosthetic hip surgery pose. By using an inverse method coupled with a numerical modeling (FEM) of all experimental data of the indentation tests, the viscoelastic properties of the two states were quantified. Mean values of viscoelastic parameters were significantly lower for OA cartilage than normal (instantaneous and relaxed tension moduli, viscosity coefficient). Based on the results and in the thermodynamic framework, a constitutive viscoelastic model taking into account the degree of osteoarthritis as an internal variable of damage is proposed. The isotropic phenomenological viscoelastic model including degradation provides an accurate prediction of the mechanical response of the normal human cartilage and OA cartilage with advanced coxarthrosis but should be further validated for intermediate degrees of osteoarthritis. Copyright © 2013 Elsevier Ltd. All rights reserved.

  2. Regeneration of hyaline articular cartilage with irradiated transforming growth factor beta1-producing fibroblasts.

    PubMed

    Song, Sun U; Hong, Young-Jin; Oh, In-Suk; Yi, Youngsuk; Choi, Kyoung Baek; Lee, Jung Woo; Park, Kwang-Won; Han, Jeoung-Uk; Suh, Jun-Kyu; Lee, Kwan Hee

    2004-01-01

    The regeneration of hyaline articular cartilage by cell-mediated gene therapy using transforming growth factor beta(1) (TGF-beta(1))-producing fibroblasts (NIH 3T3-TGF-beta(1)) has been reported previously. In this study, we investigated whether TGF-beta(1)-producing fibroblasts irradiated with a lethal dose of radiation are still capable of inducing the regeneration of hyaline articular cartilage. NIH 3T3TGF-beta(1) fibroblasts were exposed to doses of 20, 40, or 80 Gy, using a irradiator, and then injected into artificially made partial defects on the femoral condyle of rabbit knee joints. The rabbits were killed 3 or 6 weeks postinjection and hyaline articular cartilage regeneration was evaluated by histological and immunohistochemical staining (n = 5 per each group). Irradiated NIH 3T3-TGFbeta(1) fibroblasts started to die rapidly 3 days after irradiation; moreover, the kinetics of their viability were similar regardless of the radiation intensity. TGF-beta1 expression, measured by ELISA, showed that the TGF-beta(1) protein produced from the irradiated cells peaked 5 days after irradiation and thereafter declined rapidly. Complete filling of the defect with reparative tissue occurred in all the groups, although variations were observed in terms of the nature of the repair tissue. Histological and immunohistochemical staining of the repair tissue showed that the tissue newly formed by irradiated NIH 3T3-TGF-beta(1) fibroblasts after exposure to 20 Gy had hyaline cartilage-like characteristics, as was observed in the nonirradiated controls. On the other hand, the repair tissue formed by NIH 3T3-TGF-beta(1) fibroblasts irradiated with 40 or 80 Gy showed more fibrous cartilage-like tissue. These results suggest that TGF-beta(1)-producing fibroblasts irradiated up to a certain level of lethal dose (i.e., 20 Gy) are able to induce normal-appearing articular cartilage in vivo. Therefore, irradiated heterologous cell-mediated TGF-beta(1) gene therapy may be clinically

  3. Coordinate and synergistic effects of extensive treadmill exercise and ovariectomy on articular cartilage degeneration.

    PubMed

    Miyatake, Kazumasa; Muneta, Takeshi; Ojima, Miyoko; Yamada, Jun; Matsukura, Yu; Abula, Kahaer; Sekiya, Ichiro; Tsuji, Kunikazu

    2016-05-31

    Although osteoarthritis (OA) is a multifactorial disease, little has been reported regarding the cooperative interaction among these factors on cartilage metabolism. Here we examined the synergistic effect of ovariectomy (OVX) and excessive mechanical stress (forced running) on articular cartilage homeostasis in a mouse model resembling a human postmenopausal condition. Mice were randomly divided into four groups, I: Sham, II: OVX, III: Sham and forced running (60 km in 6 weeks), and IV: OVX and forced running. Histological and immunohistochemical analyses were performed to evaluate the degeneration of articular cartilage and synovitis in the knee joint. Morphological changes of subchondral bone were analyzed by micro-CT. Micro-CT analyses showed significant loss of metaphyseal trabecular bone volume/tissue volume (BV/TV) after OVX as described previously. Forced running increased the trabecular BV/TV in all mice. In the epiphyseal region, no visible alteration in bone morphology or osteophyte formation was observed in any of the four groups. Histological analysis revealed that OVX or forced running respectively had subtle effects on cartilage degeneration. However, the combination of OVX and forced running synergistically enhanced synovitis and articular cartilage degeneration. Although morphological changes in chondrocytes were observed during OA initiation, no signs of bone marrow edema were observed in any of the four experimental groups. We report the coordinate and synergistic effects of extensive treadmill exercise and ovariectomy on articular cartilage degeneration. Since no surgical procedure was performed on the knee joint directly in this model, this model is useful in addressing the molecular pathogenesis of naturally occurring OA.

  4. Load distribution of articular cartilage from MR-images by neural nets.

    PubMed

    Seidel, Peter; Hanke, Göran; Gründer, Wilfried

    2005-01-01

    Artificial neural nets were used to determine the Young's modulus and spatial load distribution in articular cartilage by means of T2-weighted MR imaging. MR images were obtained in vitro (ex vivo?) from the joints of sheep of different ages (3 months, 9 months, 15 months, 1.5 years, 5 years, 5.5 years) and pigs (4 and 6 months) with a Bruker AMX 300 (7 T) spectrometer equipped with a micro-imaging unit. The knee of a 29-year-old male volunteer was studied in vivo under mechanical load using a clinical Siemens Vision MRT (1.5 T). The load of the cartilage is understood as a non-linear image transformation of loaded versus unloaded images. The artificial neural net was used to recognize given reference pixels of the unloaded cartilage within the image of the loaded cartilage. The Young's modulus was calculated from the local strain and the external pressure using the Hooke's law. With this method, the average Young's modulus was obtained in relationship to the biological age of the cartilage. The investigated age interval showed a progressive increase of 0.5 +/- 0.3 MPa per year. These results are consistent with published results. As shown in this pilot study, the method of neural nets allows the visualization of the spatial load distribution within the articular cartilage.

  5. Injectable gellan gum hydrogels with autologous cells for the treatment of rabbit articular cartilage defects.

    PubMed

    Oliveira, João T; Gardel, Leandro S; Rada, Tommaso; Martins, Luís; Gomes, Manuela E; Reis, Rui L

    2010-09-01

    In this work, the ability of gellan gum hydrogels coupled with autologous cells to regenerate rabbit full-thickness articular cartilage defects was tested. Five study groups were defined: (a) gellan gum with encapsulated chondrogenic predifferentiated rabbit adipose stem cells (ASC + GF); (b) gellan gum with encapsulated nonchondrogenic predifferentiated rabbit adipose stem cells (ASC); (c) gellan gum with encapsulated rabbit articular chondrocytes (AC) (standard control); (d) gellan gum alone (control); (e) empty defect (control). Full-thickness articular cartilage defects were created and the gellan gum constructs were injected and left for 8 weeks. The macroscopic aspect of the explants showed a progressive increase of similarity with the lateral native cartilage, stable integration at the defect site, more pronouncedly in the cell-loaded constructs. Tissue scoring showed that ASC + GF exhibited the best results regarding tissue quality progression. Alcian blue retrieved similar results with a better outcome for the cell-loaded constructs. Regarding real-time PCR analyses, ASC + GF had the best progression with an upregulation of collagen type II and aggrecan, and a downregulation of collagen type I. Gellan gum hydrogels combined with autologous cells constitute a promising approach for the treatment of articular cartilage defects, and adipose derived cells may constitute a valid alternative to currently used articular chondrocytes. (c) 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  6. The mechanobiology of articular cartilage development and degeneration.

    PubMed

    Carter, Dennis R; Beaupré, Gary S; Wong, Marcy; Smith, R Lane; Andriacchi, Tom P; Schurman, David J

    2004-10-01

    The development, maintenance, and destruction of cartilage are regulated by mechanical factors throughout life. Mechanical cues in the cartilage fetal endoskeleton influence the expression of genes that guide the processes of growth, vascular invasion, and ossification. Intermittent fluid pressure maintains the cartilage phenotype whereas mild tension (or shear) promotes growth and ossification. The articular cartilage thickness is determined by the position at which the subchondral growth front stabilizes. In mature joints, cartilage is thickest and healthiest where the contact pressure and cartilage fluid pressure are greatest. The depth-dependent histomorphology reflects the local fluid pressure, tensile strain, and fluid exudation. Osteoarthritis represents the final demise and loss of cartilage in the skeletal elements. The initiation and progression of osteoarthritis can follow many pathways and can be promoted by mechanical factors including: (1) reduced loading, which activates the subchondral growth front by reducing fluid pressure; (2) blunt impact, causing microdamage and activation of the subchondral growth front by local shear stress; (3) mechanical abnormalities that increase wear at the articulating surface; and (4) other mechanically related factors. Research should be directed at integrating our mechanical understanding of osteoarthritis pathogenesis and progression within the framework of cellular and molecular events throughout ontogeny.

  7. Articular cartilage: from formation to tissue engineering.

    PubMed

    Camarero-Espinosa, Sandra; Rothen-Rutishauser, Barbara; Foster, E Johan; Weder, Christoph

    2016-05-26

    Hyaline cartilage is the nonlinear, inhomogeneous, anisotropic, poro-viscoelastic connective tissue that serves as friction-reducing and load-bearing cushion in synovial joints and is vital for mammalian skeletal movements. Due to its avascular nature, low cell density, low proliferative activity and the tendency of chondrocytes to de-differentiate, cartilage cannot regenerate after injury, wear and tear, or degeneration through common diseases such as osteoarthritis. Therefore severe damage usually requires surgical intervention. Current clinical strategies to generate new tissue include debridement, microfracture, autologous chondrocyte transplantation, and mosaicplasty. While articular cartilage was predicted to be one of the first tissues to be successfully engineered, it proved to be challenging to reproduce the complex architecture and biomechanical properties of the native tissue. Despite significant research efforts, only a limited number of studies have evolved up to the clinical trial stage. This review article summarizes the current state of cartilage tissue engineering in the context of relevant biological aspects, such as the formation and growth of hyaline cartilage, its composition, structure and biomechanical properties. Special attention is given to materials development, scaffold designs, fabrication methods, and template-cell interactions, which are of great importance to the structure and functionality of the engineered tissue.

  8. Correlation between radiographic findings of osteoarthritis and arthroscopic findings of articular cartilage degeneration within the patellofemoral joint.

    PubMed

    Kijowski, Richard; Blankenbaker, Donna; Stanton, Paul; Fine, Jason; De Smet, Arthur

    2006-12-01

    To correlate radiographic findings of osteoarthritis on axial knee radiographs with arthroscopic findings of articular cartilage degeneration within the patellofemoral joint in patients with chronic knee pain. The study group consisted of 104 patients with osteoarthritis of the patellofemoral joint and 30 patients of similar age with no osteoarthritis of the patellofemoral joint. All patients in the study group had an axial radiograph of the knee performed prior to arthroscopic knee surgery. At the time of arthroscopy, each articular surface of the patellofemoral joint was graded using the Noyes classification system. Two radiologists retrospectively reviewed the knee radiographs to determine the presence of marginal osteophytes, joint-space narrowing, subchondral sclerosis, and subchondral cysts. The sensitivity and specificity of the various radiographic features of osteoarthritis for the detection of articular cartilage degeneration within the patellofemoral joint were determined. The sensitivity of marginal osteophytes, joint-space narrowing, subchondral sclerosis, and subchondral cysts for the detection of articular cartilage degeneration within the patellofemoral joint was 73%, 37%, 4%, and 0% respectively. The specificity of marginal osteophytes, joint-space narrowing, subchondral sclerosis, and subchondral cysts for the detection of articular cartilage degeneration within the patellofemoral joint was 67%, 90%, 100%, and 100% respectively. Marginal osteophytes were the most sensitive radiographic feature for the detection of articular cartilage degeneration within the patellofemoral joint. Joint-space narrowing, subchondral sclerosis, and subchondral cysts were insensitive radiographic features of osteoarthritis, and rarely occurred in the absence of associated osteophyte formation.

  9. Development of a Spring-Loaded Impact Device to Deliver Injurious Mechanical Impacts to the Articular Cartilage Surface

    PubMed Central

    Alexander, Peter G.; Song, Yingjie; Taboas, Juan M.; Chen, Faye H.; Melvin, Gary M.; Manner, Paul A.

    2013-01-01

    Objective: Traumatic impacts on the articular joint surface in vitro are known to lead to degeneration of the cartilage. The main objective of this study was to develop a spring-loaded impact device that can be used to deliver traumatic impacts of consistent magnitude and rate and to find whether impacts cause catabolic activities in articular cartilage consistent with other previously reported impact models and correlated with the development of osteoarthritic lesions. In developing the spring-loaded impactor, the operating hypothesis is that a single supraphysiologic impact to articular cartilage in vitro can affect cartilage integrity, cell viability, sulfated glycosaminoglycan and inflammatory mediator release in a dose-dependent manner. Design: Impacts of increasing force are delivered to adult bovine articular cartilage explants in confined compression. Impact parameters are correlated with tissue damage, cell viability, matrix and inflammatory mediator release, and gene expression 24 hours postimpact. Results: Nitric oxide release is first detected after 7.7 MPa impacts, whereas cell death, glycosaminoglycan release, and prostaglandin E2 release are first detected at 17 MPa. Catabolic markers increase linearly to maximal levels after ≥36 MPa impacts. Conclusions: A single supraphysiologic impact negatively affects cartilage integrity, cell viability, and GAG release in a dose-dependent manner. Our findings showed that 7 to 17 MPa impacts can induce cell death and catabolism without compromising the articular surface, whereas a 17 MPa impact is sufficient to induce increases in most common catabolic markers of osteoarthritic degeneration. PMID:26069650

  10. UTE bi-component analysis of T2* relaxation in articular cartilage

    PubMed Central

    Shao, H.; Chang, E.Y.; Pauli, C.; Zanganeh, S.; Bae, W.; Chung, C.B.; Tang, G.; Du, J.

    2015-01-01

    SUMMARY Objectives To determine T2* relaxation in articular cartilage using ultrashort echo time (UTE) imaging and bi-component analysis, with an emphasis on the deep radial and calcified cartilage. Methods Ten patellar samples were imaged using two-dimensional (2D) UTE and Car-Purcell-Meiboom-Gill (CPMG) sequences. UTE images were fitted with a bi-component model to calculate T2* and relative fractions. CPMG images were fitted with a single-component model to calculate T2. The high signal line above the subchondral bone was regarded as the deep radial and calcified cartilage. Depth and orientation dependence of T2*, fraction and T2 were analyzed with histopathology and polarized light microscopy (PLM), confirming normal regions of articular cartilage. An interleaved multi-echo UTE acquisition scheme was proposed for in vivo applications (n = 5). Results The short T2* values remained relatively constant across the cartilage depth while the long T2* values and long T2* fractions tended to increase from subchondral bone to the superficial cartilage. Long T2*s and T2s showed significant magic angle effect for all layers of cartilage from the medial to lateral facets, while the short T2* values and T2* fractions are insensitive to the magic angle effect. The deep radial and calcified cartilage showed a mean short T2* of 0.80 ± 0.05 ms and short T2* fraction of 39.93 ± 3.05% in vitro, and a mean short T2* of 0.93 ± 0.58 ms and short T2* fraction of 35.03 ± 4.09% in vivo. Conclusion UTE bi-component analysis can characterize the short and long T2* values and fractions across the cartilage depth, including the deep radial and calcified cartilage. The short T2* values and T2* fractions are magic angle insensitive. PMID:26382110

  11. A Semi-Degradable Composite Scaffold for Articular Cartilage Defects

    PubMed Central

    Scholten, Paul M.; Ng, Kenneth W.; Joh, Kiwon; Serino, Lorenzo P.; Warren, Russell F.; Torzilli, Peter A.; Maher, Suzanne A.

    2010-01-01

    Few options exist to replace or repair damaged articular cartilage. The optimal solution that has been suggested is a scaffold that can carry load and integrate with surrounding tissues; but such a construct has thus far been elusive. The objectives of this study were to manufacture and characterize a non-degradable hydrated scaffold. Our hypothesis was that the polymer content of the scaffold can be used to control its mechanical properties, while an internal porous network augmented with biological agents can facilitate integration with the host tissue. Using a two-step water-in-oil emulsion process a porous poly-vinyl alcohol (PVA) hydrogel scaffold combined with alginate microspheres was manufactured. The scaffold had a porosity of 11–30% with pore diameters of 107–187 μm, which readily allowed for movement of cells through the scaffold. Alginate microparticles were evenly distributed through the scaffold and allowed for the slow release of biological factors. The elastic modulus (Es) and Poisson’s ratio (υ), Aggregate modulus (Ha) and dynamic modulus (ED) of the scaffold were significantly affected by % PVA, as it varied from 10% to 20% wt/vol. Es and υ were similar to that of articular cartilage for both polymer concentrations, while Ha and ED were similar to that of cartilage only at 20% PVA. The ability to control scaffold mechanical properties, while facilitating cellular migration suggest that this scaffold is a potentially viable candidate for the functional replacement of cartilage defects. PMID:21308980

  12. 3D braid scaffolds for regeneration of articular cartilage.

    PubMed

    Ahn, Hyunchul; Kim, Kyoung Ju; Park, Sook Young; Huh, Jeong Eun; Kim, Hyun Jeong; Yu, Woong-Ryeol

    2014-06-01

    Regenerating articular cartilage in vivo from cultured chondrocytes requires that the cells be cultured and implanted within a biocompatible, biodegradable scaffold. Such scaffolds must be mechanically stable; otherwise chondrocytes would not be supported and patients would experience severe pain. Here we report a new 3D braid scaffold that matches the anisotropic (gradient) mechanical properties of natural articular cartilage and is permissive to cell cultivation. To design an optimal structure, the scaffold unit cell was mathematically modeled and imported into finite element analysis. Based on this analysis, a 3D braid structure with gradient axial yarn distribution was designed and manufactured using a custom-built braiding machine. The mechanical properties of the 3D braid scaffold were evaluated and compared with simulated results, demonstrating that a multi-scale approach consisting of unit cell modeling and continuum analysis facilitates design of scaffolds that meet the requirements for mechanical compatibility with tissues. Copyright © 2014 Elsevier Ltd. All rights reserved.

  13. Articular cartilage endurance and resistance to osteoarthritic changes require transcription factor Erg.

    PubMed

    Ohta, Yoichi; Okabe, Takahiro; Larmour, Colleen; Di Rocco, Agnese; Maijenburg, Marijke W; Phillips, Amanda; Speck, Nancy A; Wakitani, Shigeyuki; Nakamura, Takashi; Yamada, Yoshihiko; Enomoto-Iwamoto, Motomi; Pacifici, Maurizio; Iwamoto, Masahiro

    2015-10-01

    To determine whether and how the transcription factor Erg participates in the genesis, establishment, and maintenance of articular cartilage. Floxed Erg mice were mated with Gdf5-Cre mice to generate conditional mutants lacking Erg in their joints. Joints of mutant and control mice were subjected to morphologic and molecular characterization and also to experimental surgically induced osteoarthritis (OA). Gene expression, promoter reporter assays, and gain- and loss-of-function in vitro tests were used to characterize molecular mechanisms of Erg action. Conditional Erg ablation did not elicit obvious changes in limb joint development and overall phenotype in juvenile mice. However, as mice aged, joints of mutant mice degenerated spontaneously and exhibited clear OA-like phenotypic defects. Joints in juvenile mutant mice were more sensitive to surgically induced OA and became defective sooner than operated joints in control mice. Global gene expression data and other studies identified parathyroid hormone-related protein (PTHrP) and lubricin as possible downstream effectors and mediators of Erg action in articular chondrocytes. Reporter assays using control and mutated promoter-enhancer constructs indicated that Erg acted on Ets DNA binding sites to stimulate PTHrP expression. Erg was up-regulated in severely affected areas in human OA articular cartilage but remained barely appreciable in areas of less affected cartilage. The study shows for the first time that Erg is a critical molecular regulator of the endurance of articular cartilage during postnatal life and that Erg can mitigate spontaneous and experimental OA. Erg appears to do this through regulating expression of PTHrP and lubricin, factors known for their protective roles in joints. © 2015, American College of Rheumatology.

  14. Effects of pH on transport properties of articular cartilages.

    PubMed

    Loret, Benjamin; Simões, Fernando M F

    2010-02-01

    Articular cartilages swell and shrink depending on the ionic strength of the electrolyte they are in contact with. This electro-chemo-mechanical coupling is due to the presence of fixed electrical charges on proteoglycans (PGs). In addition, at nonphysiological pH, collagen fibers become charged. Therefore, variation of the pH of the electrolyte has strong implications on the electrical charge of cartilages and, by the same token, on their transport and mechanical properties. Articular cartilages are viewed as three-phase multi-species porous media. The constitutive framework is phrased in the theory of thermodynamics of porous media. Acid-base reactions, as well as calcium binding, are embedded in this framework. Although macroscopic in nature, the model accounts for a number of biochemical details defining collagen and PGs. The change of the electrical charge is due to the binding of hydrogen ions on specific sites of PGs and collagen. Simulations are performed mimicking laboratory experiments where either the ionic strength or the pH of the bath, the cartilage piece is in contact with, is varied. They provide the evolutions of the chemical compositions of mobile ions, of the sites of acid-base reactions and calcium binding, and of the charges of collagen and glycosaminoglycans, at constant volume fraction of water. Emphasis is laid on the effects of pH, ionic strength and calcium binding on the transport properties of cartilages, and, in particular, on the electrical conductivity and electro-osmotic coefficient.

  15. Temperature affects transport of polysaccharides and proteins in articular cartilage explants.

    PubMed

    Moeini, Mohammad; Lee, Kwan-Bong; Quinn, Thomas M

    2012-07-26

    Solute transport phenomena mediate many aspects of the physiology and contrast agent-based clinical imaging of articular cartilage. Temperatures up to 10°C below standard body temperature (37°C) are common in articulating joints during normal activities and clinically (e.g. cold treatment of injuries). Therefore it is of interest to characterize the effects of temperature changes on solute transport parameters in cartilage. A range of fluorescent solutes including fluorescein isothiocyanate, 4 and 40kDa dextrans, myoglobin, insulin and chondroitin sulfate were prepared and used in assays of solute effective partition coefficient and effective diffusivity in bovine intermediate zone articular cartilage explants maintained at 10, 22 or 37°C. Trends for increasing partition coefficient with increasing temperature were evident for all solutes except chondroitin sulfate, with significant changes between 22 and 37°C for 4kDa dextran, insulin and myoglobin. Diffusivities of most solutes tested also tended to increase with increasing temperature, with significant changes between 10 and 22°C for FITC, 40kDa dextran and myoglobin. Oddly, insulin diffusivity decreased significantly as temperature increased from 22 to 37°C while chondroitin sulfate diffusivity exhibited no clear temperature dependence. These results highlight solute-specific temperature dependences of transport phenomena which may depend upon molecular weight, chemical structure, molecular conformation, and solute-matrix and solute-solute interactions. The articular cartilage explants themselves exhibited small but significant changes in water and glycosaminoglycan contents during experiments, underscoring the importance of solute-matrix interactions. Solute transport parameters in cartilage and their temperature dependences are therefore not easily predicted, and case-by-case experimental determination may be essential. Copyright © 2012 Elsevier Ltd. All rights reserved.

  16. Aberrant Calreticulin Expression in Articular Cartilage of Dio2 Deficient Mice

    PubMed Central

    Bomer, Nils; Cornelis, Frederique M. F.; Ramos, Yolande F. M.; den Hollander, Wouter; Lakenberg, Nico; van der Breggen, Ruud; Storms, Lies; Slagboom, P. Eline; Lories, Rik J. U.; Meulenbelt, Ingrid

    2016-01-01

    Objective To identify intrinsic differences in cartilage gene expression profiles between wild-type- and Dio2-/--mice, as a mechanism to investigate factors that contribute to prolonged healthy tissue homeostasis. Methods Previously generated microarray-data (Illumina MouseWG-6 v2) of knee cartilage of wild-type and Dio2 -/- -mice were re-analyzed to identify differential expressed genes independent of mechanical loading conditions by forced treadmill-running. RT-qPCR and western blot analyses of overexpression and knockdown of Calr in mouse chondro-progenitor cells (ATDC5) were applied to assess the direct effect of differential Calr expression on cartilage deposition. Results Differential expression analyses of articular cartilage of Dio2-/- (N = 9) and wild-type-mice (N = 11) while applying a cutoff threshold (P < 0.05 (FDR) and FC > |1,5|) resulted in 1 probe located in Calreticulin (Calr) that was found significantly downregulated in Dio2-/- mice (FC = -1.731; P = 0.044). Furthermore, overexpression of Calr during early chondrogenesis in ATDC5 cells leads to decreased proteoglycan deposition and corresponding lower Aggrecan expression, whereas knocking down Calr expression does not lead to histological differences of matrix composition. Conclusion We here demonstrate that the beneficial homeostatic state of articular cartilage in Dio2-/- mice is accompanied with significant lower expression of Calr. Functional analyses further showed that upregulation of Calr expression could act as an initiator of cartilage destruction. The consistent association between Calr and Dio2 expression suggests that enhanced expression of these genes facilitate detrimental effects on cartilage integrity. PMID:27163789

  17. Optical imaging of articular cartilage degeneration using near-infrared dipicolylamine probes.

    PubMed

    Hu, Xiang; Wang, Qian; Liu, Yang; Liu, Hongguang; Qin, Chunxia; Cheng, Kai; Robinson, William; Gray, Brian D; Pak, Koon Y; Yu, Aixi; Cheng, Zhen

    2014-08-01

    Articular cartilage is the hydrated tissue that lines the ends of long bones in load bearing joints and provides joints with a smooth, nearly frictionless gliding surface. However, the deterioration of articular cartilage occurs in the early stages of osteoarthritis (OA) and is clinically and radiographically silent. Here two cationic near infrared fluorescent (NIRF) dipicolylamine (DPA) probes, Cy5-DPA-Zn and Cy7-DPA-Zn, were prepared for cartilage degeneration imaging and OA early detection through binding to the anionic glycosaminoglycans (GAGs). The feasibility of NIRF dye labeled DPA-Zn probes for cartilage degeneration imaging was examined ex vivo and in vivo. The ex vivo studies showed that Cy5-DPA-Zn and Cy7-DPA-Zn not only showed the high uptake and electrostatic attractive binding to cartilage, but also sensitively reflected the change of GAGs contents. In vivo imaging study further indicated that Cy5-DPA-Zn demonstrated higher uptake and retention in young mice (high GAGs) than old mice (low GAGs) when administrated via local injection in mouse knee joints. More importantly, Cy5-DPA-Zn showed dramatic higher signals in sham joint (high GAGs) than OA side (low GAGs), through sensitive reflecting the change of GAGs in the surgical induced OA models. In summary, Cy5-DPA-Zn provides promising visual detection for early cartilage pathological degeneration in living subjects. Copyright © 2014 Elsevier Ltd. All rights reserved.

  18. Laser solder welding of articular cartilage: tensile strength and chondrocyte viability.

    PubMed

    Züger, B J; Ott, B; Mainil-Varlet, P; Schaffner, T; Clémence, J F; Weber, H P; Frenz, M

    2001-01-01

    The surgical treatment of full-thickness cartilage defects in the knee joint remains a therapeutic challenge. Recently, new techniques for articular cartilage transplantation, such as mosaicplasty, have become available for cartilage repair. The long-term success of these techniques, however, depends not only on the chondrocyte viability but also on a lateral integration of the implant. The goal of this study was to evaluate the feasibility of cartilage welding by using albumin solder that was dye-enhanced to allow coagulation with 808-nm laser diode irradiation. Conventional histology of light microscopy was compared with a viability staining to precisely determine the extent of thermal damage after laser welding. Indocyanine green (ICG) enhanced albumin solder (25% albumin, 0.5% HA, 0.1% ICG) was used for articular cartilage welding. For coagulation, the solder was irradiated through the cartilage implant by 808-nm laser light and the tensile strength of the weld was measured. Viability staining revealed a thermal damage of typically 500 m in depth at an irradiance of approximately 10 W/cm(2) for 8 seconds, whereas conventional histologies showed only half of the extent found by the viability test. Heat-bath investigations revealed a threshold temperature of minimum 54 degrees C for thermal damage of chondrocytes. Efficient cartilage bonding was obtained by using bovine albumin solder as adhesive. Maximum tensile strength of more than 10 N/cm(2) was achieved. Viability tests revealed that the thermal damage is much greater (up to twice) than expected after light microscopic characterization. This study shows the feasibility to strongly laser weld cartilage on cartilage by use of a dye-enhanced albumin solder. Possibilities to reduce the range of damage are suggested. Copyright 2001 Wiley-Liss, Inc.

  19. Glenohumeral articular cartilage lesions: prospective comparison of non-contrast magnetic resonance imaging and findings at arthroscopy.

    PubMed

    Spencer, Brian A; Dolinskas, Carol A; Seymour, Peter A; Thomas, Stephen J; Abboud, Joseph A

    2013-09-01

    The purpose of this study was to assess the diagnostic sensitivity, specificity, accuracy, negative predictive value (NPV), positive predictive value (PPV), and test-retest reliability of magnetic resonance imaging (MRI) for detecting cartilage abnormalities of the glenohumeral joint in comparison with the gold standard of diagnostic arthroscopy. Forty-four patients with a preoperative non-contrast MRI study of their affected shoulder underwent arthroscopy by one surgeon for rotator cuff tendinopathy from 2009 to 2010. Articular cartilage defects were prospectively recorded and graded according to the International Cartilage Repair Society classification system at the time of arthroscopy. One year after surgery, the preoperative MRI were reviewed by a board-certified radiologist and the treating surgeon for articular cartilage defects of both the humeral head and the glenoid. Sensitivity, specificity, accuracy, and test-retest reliability were calculated. At arthroscopy, 43% of the shoulders were found to have articular cartilage defects. When the readers' findings were combined, the sensitivity of detecting humeral lesions on MRI was 32%; specificity, 80%; accuracy, 63%; PPV, 57%; and NPV, 66%. The sensitivity of detecting glenoid lesions was 31%; specificity, 86%; accuracy, 76%; PPV, 33%; and NPV, 85%. This study finds that the overall accuracy of MRI in detecting articular cartilage damage in patients with the clinical diagnosis of subacromial pathology is moderate. Level II, development of diagnostic criteria based on consecutive patients with universally applied reference "gold" standard. Copyright © 2013 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

  20. Transplantation of free tibial periosteal grafts for the repair of articular cartilage defect: An experimental study

    PubMed Central

    Singh, Ravijot; Chauhan, Vijendra; Chauhan, Neena; Sharma, Sansar

    2009-01-01

    Background: Articular chondrocytes have got a long lifespan but rarely divides after maturity. Thus, an articular cartilage has a limited capacity for repair. Periosteal grafts have chondrogenic potential and have been used to repair defects in the articular cartilage. The purpose of the present study is to investigate the differentiation of free periosteal grafts in the patellofemoral joint where the cambium layer faces the subchondral bone and to investigate the applicability of periosteal grafts in the reconstruction of articular surfaces. Materials and Methods: The study was carried out over a period of 1 year on 25 adult, male Indian rabbits after obtaining permission from the institutional animal ethical committee. A full-thickness osteochondral defect was created by shaving off the whole articular cartilage of the patella of the left knee. The defect thus created was grafted with free periosteal graft. The patella of the right knee was taken as a control where no grafting was done after shaving off the articular cartilage. The first animal was used to study the normal histology of the patellar articular cartilage and periosteum obtained from the medial surface of tibial condyle. Rest 24 animals were subjected to patellectomy, 4 each at serial intervals of 2, 4, 8, 16, 32 and 48 weeks and the patellar articular surfaces were examined macroscopically and histologically. Results: The grafts got adherent to the underlying patellar articular surface at the end of 4 weeks. Microscopically, graft incorporation could be appreciated at 4 weeks. Mesenchymal cells of the cambium layer were seen differentiating into chondrocytes by the end of 4 weeks in four grafts (100%) and they were arranged in a haphazard manner. Till the end of 8 weeks, the cellular arrangement was mostly wooly. At 16 weeks, one graft (25%) had wooly arrangement of chondrocytes and three grafts (75%) had columnar formation of cells. Same percentage was maintained at 32 weeks. Four grafts (100%) at

  1. A multi-directional in vitro investigation into friction, damage and wear of innovative chondroplasty materials against articular cartilage.

    PubMed

    Northwood, Ewen; Fisher, John

    2007-08-01

    The wear of the biomaterial/cartilage interface is vital for the development of innovative chondroplasty therapies. The aim of this study was to investigate potential chondroplasty biomaterials when sliding against natural articular cartilage under uniaxial reciprocating and multi-directional rotation/reciprocating motions. Three biphasic hydrogels were compared to articular cartilage (negative control) and stainless steel (positive control). Friction was measured by means of a simple geometry friction and wear simulator. All tests were completed in 25% bovine serum at 20 degrees C. Mechanical alterations to the surface structure were quantified using surface topography. Articular cartilage produced a constant friction value of 0.05 (confidence interval=0.015) with and without rotation. Stainless steel against articular cartilage produced an increase in friction over time resulting in a peak value of 0.7 (confidence interval=0.02) without rotation, increasing to 0.88 (confidence interval=0.03) with rotation. All biphasic hydrogels produced peak friction values lower than the positive control and demonstrated no difference between uni- and multi-directional motion. Degradation of the opposing cartilage surface showed a significant difference between the positive and negative controls, with the greater cartilage damage when sliding against stainless steel under uni-directional motion. The lower friction and reduction of opposing cartilage surface degradation with the potential chondroplasty biomaterials can be attributed to their biphasic properties. This study illustrated the importance of biphasic properties within the tribology of cartilage substitution materials and future work will focus on the optimisation of biphasic properties such that materials more closely mimic natural cartilage.

  2. Optical characterization of porcine articular cartilage using a polarimetry technique with differential Mueller matrix formulism.

    PubMed

    Chang, Ching-Min; Lo, Yu-Lung; Tran, Nghia-Khanh; Chang, Yu-Jen

    2018-03-20

    A method is proposed for characterizing the optical properties of articular cartilage sliced from a pig's thighbone using a Stokes-Mueller polarimetry technique. The principal axis angle, phase retardance, optical rotation angle, circular diattenuation, diattenuation axis angle, linear diattenuation, and depolarization index properties of the cartilage sample are all decoupled in the proposed analytical model. Consequently, the accuracy and robustness of the extracted results are improved. The glucose concentration, collagen distribution, and scattering properties of samples from various depths of the articular cartilage are systematically explored via an inspection of the related parameters. The results show that the glucose concentration and scattering effect are both enhanced in the superficial region of the cartilage. By contrast, the collagen density increases with an increasing sample depth.

  3. A diagnostic system for articular cartilage using non-destructive pulsed laser irradiation.

    PubMed

    Sato, Masato; Ishihara, Miya; Kikuchi, Makoto; Mochida, Joji

    2011-07-01

    Osteoarthritis involves dysfunction caused by cartilage degeneration, but objective evaluation methodologies based on the original function of the articular cartilage remain unavailable. Evaluations for osteoarthritis are mostly based simply on patient symptoms or the degree of joint space narrowing on X-ray images. Accurate measurement and quantitative evaluation of the mechanical characteristics of the cartilage is important, and the tissue properties of the original articular cartilage must be clarified to understand the pathological condition in detail and to correctly judge the efficacy of treatment. We have developed new methods to measure some essential properties of cartilage: a photoacoustic measurement method; and time-resolved fluorescence spectroscopy. A nanosecond-pulsed laser, which is completely non-destructive, is focused onto the target cartilage and induces a photoacoustic wave that will propagate with attenuation and is affected by the viscoelasticity of the surrounding cartilage. We also investigated whether pulsed laser irradiation and the measurement of excited autofluorescence allow real-time, non-invasive evaluation of tissue characteristics. The decay time, during which the amplitude of the photoacoustic wave is reduced by a factor of 1/e, represents the key numerical value used to characterize and evaluate the viscoelasticity and rheological behavior of the cartilage. Our findings show that time-resolved laser-induced autofluorescence spectroscopy (TR-LIFS) is useful for evaluating tissue-engineered cartilage. Photoacoustic measurement and TR-LIFS, predicated on the interactions between optics and living organs, is a suitable methodology for diagnosis during arthroscopy, allowing quantitative and multidirectional evaluation of the original function of the cartilage based on a variety of parameters. Copyright © 2011 Wiley-Liss, Inc.

  4. Acute and chronic response of articular cartilage to Ho:YAG laser irradiation

    NASA Astrophysics Data System (ADS)

    Trauner, Kenneth B.; Nishioka, Norman S.; Flotte, Thomas J.; Patel, Dinesh K.

    1992-06-01

    A Ho:YAG laser system operating at a wavelength of 2.1 microns has recently been introduced for use in arthroscopic surgery. The acceptability of this new tool will be determined not only by its ability to resect tissue, but also by its long term effects on articular surfaces. In order to investigate these issues further, we performed two studies to evaluate the acute and chronic effects of the laser on cartilaginous tissue. We evaluated the acute, in vitro effects of 2.1 micron laser irradiation on articular and fibrocartilage. This included the measurement of ablation efficiency, ablation threshold and thermal damage in both meniscus and articular cartilage. To document the chronic effects on articular cartilage in vivo, we next performed a ten week healing study. Eight sheep weighing 30 - 40 kg underwent bilateral arthrotomy procedures. Multiple full thickness and partial thickness defects were created. Animals were sacrificed at 0, 2, 4, and 10 weeks. The healing study demonstrated: (1) no healing of full or partial thickness defects at 10 weeks with hyaline cartilage; (2) fibrocartilaginous granulation tissue filling full thickness defects at two and four weeks, but no longer evident at ten weeks; (3) chondrocyte necrosis extending to greater than 900 microns distal to ablation craters at four weeks with no evidence of repair at later dates; and (4) chondrocyte hyperplasia at the borders of the damage zone at two weeks but no longer evident at later sacrifice dates.

  5. In Vivo Identification and Induction of Articular Cartilage Stem Cells by Inhibiting NF-κB Signaling in Osteoarthritis.

    PubMed

    Tong, Wenxue; Geng, Yiyun; Huang, Yan; Shi, Yu; Xiang, Shengnan; Zhang, Ning; Qin, Ling; Shi, Qin; Chen, Qian; Dai, Kerong; Zhang, Xiaoling

    2015-10-01

    Osteoarthritis (OA) is a highly prevalent and debilitating joint disorder characterized by the degeneration of articular cartilage. However, no effective medical therapy has been found yet for such condition. In this study, we directly confirmed the existence of articular cartilage stem cells (ACSCs) in vivo and in situ for the first time both in normal and OA articular cartilage, and explored their chondrogenesis in Interleukin-1β (IL-1β) induced inflammation environment and disclose whether the inhibition of NF-κB signaling can induce ACSCs activation thus improve the progression of experimental OA. We found an interesting phenomenon that ACSCs were activated and exhibited a transient proliferative response in early OA as an initial attempt for self-repair. During the in vitro mechanism study, we discovered IL-1β can efficiently activate the NF-κB pathway and potently impair the responsiveness of ACSCs, whereas the NF-κB pathway inhibitor rescued the ACSCs chondrogenesis. The final in vivo experiments further confirmed ACSCs' activation were maintained by NF-κB pathway inhibitor, which induced cartilage regeneration, and protected articular cartilage from injury in an OA animal model. Our results provided in vivo evidence of the presence of ACSCs, and disclosed their action in the early OA stage and gradual quiet as OA process, presented a potential mechanism for both cartilage intrinsic repair and its final degradation, and demonstrated the feasibility of inducing endogenous adult tissue-specific mesenchymal stem cells for articular cartilage repair and OA therapy. © 2015 AlphaMed Press.

  6. An Experimental and Finite Element Protocol to Investigate the Transport of Neutral and Charged Solutes across Articular Cartilage.

    PubMed

    Arbabi, Vahid; Pouran, Behdad; Zadpoor, Amir A; Weinans, Harrie

    2017-04-23

    Osteoarthritis (OA) is a debilitating disease that is associated with degeneration of articular cartilage and subchondral bone. Degeneration of articular cartilage impairs its load-bearing function substantially as it experiences tremendous chemical degradation, i.e. proteoglycan loss and collagen fibril disruption. One promising way to investigate chemical damage mechanisms during OA is to expose the cartilage specimens to an external solute and monitor the diffusion of the molecules. The degree of cartilage damage (i.e. concentration and configuration of essential macromolecules) is associated with collisional energy loss of external solutes while moving across articular cartilage creates different diffusion characteristics compared to healthy cartilage. In this study, we introduce a protocol, which consists of several steps and is based on previously developed experimental micro-Computed Tomography (micro-CT) and finite element modeling. The transport of charged and uncharged iodinated molecules is first recorded using micro-CT, which is followed by applying biphasic-solute and multiphasic finite element models to obtain diffusion coefficients and fixed charge densities across cartilage zones.

  7. Serum Metabonomics of Articular Cartilage Destruction Induced by T-2 Toxin in Wistar Rats.

    PubMed

    Zhu, Lei; Zhao, Zhi Jun; Ren, Xiao Bin; Li, Qiang; Ding, Hua; Sun, Zhou; Kao, Qing Jun; Wang, Li Hua

    2018-01-01

    The molecular pathogenesis of T-2 toxin-induced cartilage destruction has not been fully unraveled yet. The aim of this study was to detect changes in serum metabolites in a rat anomaly model with articular cartilage destruction. Thirty healthy male Wistar rats were fed a diet containing T-2 toxin (300 ng/kg chow) for 3 months. Histopathological changes in femorotibial cartilage were characterized in terms of chondrocyte degeneration/necrosis and superficial cartilage defect, and the endogenous metabolite profile of serum was determined by UPLC/Q-TOF MS. Treated rats showed extensive areas of chondrocyte necrosis and superficial cartilage defect in the articular cartilage. In addition, 8 metabolites were found to change significantly in these rats compared to the control group, including lysoPE (18:0/0:0), lysoPC(14:0), lysoPC[18:4 (6Z,9Z,12Z,15Z)], lysoPC[(16:1(9Z)], lysoPC(16:0), L-valine, hippuric acid, and asparaginyl-glycine. These 8 metabolites associated with cartilage injury are mainly involved in phospholipid and amino acid metabolic pathways. Copyright © 2018 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.

  8. Triamcinolone hexacetonide protects against fibrillation and osteophyte formation following chemically induced articular cartilage damage.

    PubMed

    Williams, J M; Brandt, K D

    1985-11-01

    Although corticosteroids have been shown to cause articular cartilage degeneration, recent studies of experimentally induced osteoarthritis indicate that under certain conditions they may protect against cartilage damage and osteophyte formation. The present study examines the in vivo effect of triamcinolone hexacetonide on the degeneration of articular cartilage which occurs following intraarticular injection of sodium iodoacetate. Three weeks after a single injection of iodoacetate into the knees of guinea pigs, ipsilateral femoral condylar cartilage exhibited fibrillation, loss of staining with Safranin O, depletion of chondrocytes, and prominent osteophytes. In striking contrast, when triamcinolone hexacetonide was injected into the ipsilateral knee 24 hours after the intraarticular injection of iodoacetate, fibrillation was noted in only 1 of 6 samples, osteophytes were much less prominent, pericellular staining with Safranin O persisted, and cell loss was less extensive. Knees of animals which received only one-tenth as much intraarticular triamcinolone hexacetonide after the iodoacetate injection also exhibited marked reduction in size and extent of osteophytes. However, the degree of fibrillation, loss of Safranin O staining, and chondrocyte depletion was similar to that observed in animals injected with iodoacetate but not treated with intraarticular steroid. No apparent morphologic or histochemical changes were observed after intraarticular injection of the steroid preparation alone. Thus, triamcinolone hexacetonide produced a marked, dose-dependent protective effect in this model of chemically induced articular cartilage damage.

  9. CCN Family Member 2/Connective Tissue Growth Factor (CCN2/CTGF) Has Anti-Aging Effects That Protect Articular Cartilage from Age-Related Degenerative Changes

    PubMed Central

    Itoh, Shinsuke; Hattori, Takako; Tomita, Nao; Aoyama, Eriko; Yutani, Yasutaka; Yamashiro, Takashi; Takigawa, Masaharu

    2013-01-01

    To examine the role of connective tissue growth factor CCN2/CTGF (CCN2) in the maintenance of the articular cartilaginous phenotype, we analyzed knee joints from aging transgenic mice (TG) overexpressing CCN2 driven by the Col2a1 promoter. Knee joints from 3-, 14-, 40-, and 60-day-old and 5-, 12-, 18-, 21-, and 24-month-old littermates were analyzed. Ccn2-LacZ transgene expression in articular cartilage was followed by X-gal staining until 5 months of age. Overexpression of CCN2 protein was confirmed through all ages in TG articular cartilage and in growth plates. Radiographic analysis of knee joints showed a narrowing joint space and other features of osteoarthritis in 50% of WT, but not in any of the TG mice. Transgenic articular cartilage showed enhanced toluidine blue and safranin-O staining as well as chondrocyte proliferation but reduced staining for type X and I collagen and MMP-13 as compared with those parameters for WT cartilage. Staining for aggrecan neoepitope, a marker of aggrecan degradation in WT articular cartilage, increased at 5 and 12 months, but disappeared at 24 months due to loss of cartilage; whereas it was reduced in TG articular cartilage after 12 months. Expression of cartilage genes and MMPs under cyclic tension stress (CTS) was measured by using primary cultures of chondrocytes obtained from wild-type (WT) rib cartilage and TG or WT epiphyseal cartilage. CTS applied to primary cultures of mock-transfected rib chondrocytes from WT cartilage and WT epiphyseal cartilage induced expression of Col1a1, ColXa1, Mmp-13, and Mmp-9 mRNAs; however, their levels were not affected in CCN2-overexpressing chondrocytes and TG epiphyseal cartilage. In conclusion, cartilage-specific overexpression of CCN2 during the developmental and growth periods reduced age-related changes in articular cartilage. Thus CCN2 may play a role as an anti-aging factor by stabilizing articular cartilage. PMID:23951098

  10. Subchondral drilling for articular cartilage repair: a systematic review of translational research.

    PubMed

    Gao, Liang; Goebel, Lars K H; Orth, Patrick; Cucchiarini, Magali; Madry, Henning

    2018-05-03

    Articular cartilage defects may initiate osteoarthritis. Subchondral drilling, a widely applied clinical technique to treat small cartilage defects, does not yield cartilage regeneration. Various translational studies aiming to improve the outcome of drilling have been performed, however, a robust systematic analysis of its translational evidence has been still lacking. Here, we performed a systematic review of the outcome of subchondral drilling for knee cartilage repair in translational animal models. A total of 12 relevant publications studying 198 animals were identified, detailed study characteristics were extracted, and methodological quality and risk of bias were analyzed. Subchondral drilling was superior to defects untreated or treated with abrasion arthroplasty for cartilage repair in multiple translational models. Considerable subchondral bone changes were observed, including subchondral bone cysts and intralesional osteophytes. Furthermore, extensive alterations of the subchondral bone microarchitecture appeared in a temporal pattern in small and large animal models, together with specific topographic aspects of repair. Moreover, variable technical aspects directly affected the outcomes of osteochondral repair. The data from this systematic review indicate that subchondral drilling yields improved short-term structural articular cartilage repair compared with spontaneous repair in multiple small and large animal models. These results have important implications for future investigations aimed at an enhanced translation into clinical settings for the treatment of cartilage defects, highlighting the importance of considering specific aspects of modifiable variables such as improvements in the design and reporting of preclinical studies, together with the need to better understand the underlying mechanisms of cartilage repair following subchondral drilling. © 2018. Published by The Company of Biologists Ltd.

  11. Fractional calculus model of articular cartilage based on experimental stress-relaxation

    NASA Astrophysics Data System (ADS)

    Smyth, P. A.; Green, I.

    2015-05-01

    Articular cartilage is a unique substance that protects joints from damage and wear. Many decades of research have led to detailed biphasic and triphasic models for the intricate structure and behavior of cartilage. However, the models contain many assumptions on boundary conditions, permeability, viscosity, model size, loading, etc., that complicate the description of cartilage. For impact studies or biomimetic applications, cartilage can be studied phenomenologically to reduce modeling complexity. This work reports experimental results on the stress-relaxation of equine articular cartilage in unconfined loading. The response is described by a fractional calculus viscoelastic model, which gives storage and loss moduli as functions of frequency, rendering multiple advantages: (1) the fractional calculus model is robust, meaning that fewer constants are needed to accurately capture a wide spectrum of viscoelastic behavior compared to other viscoelastic models (e.g., Prony series), (2) in the special case where the fractional derivative is 1/2, it is shown that there is a straightforward time-domain representation, (3) the eigenvalue problem is simplified in subsequent dynamic studies, and (4) cartilage stress-relaxation can be described with as few as three constants, giving an advantage for large-scale dynamic studies that account for joint motion or impact. Moreover, the resulting storage and loss moduli can quantify healthy, damaged, or cultured cartilage, as well as artificial joints. The proposed characterization is suited for high-level analysis of multiphase materials, where the separate contribution of each phase is not desired. Potential uses of this analysis include biomimetic dampers and bearings, or artificial joints where the effective stiffness and damping are fundamental parameters.

  12. Magnetic resonance imaging of articular cartilage: trauma, degeneration, and repair.

    PubMed

    Potter, Hollis G; Foo, Li F

    2006-04-01

    The assessment of articular cartilage using magnetic resonance imaging has seen considerable advances in recent years. Cartilage morphologic characteristics can now be evaluated with a high degree of accuracy and reproducibility using dedicated pulse sequences, which are becoming standard at many institutions. These techniques detect clinically unsuspected traumatic cartilage lesions, allowing the physician to study their natural history with longitudinal evaluation and also to assess disease status in degenerative osteoarthritis. Magnetic resonance imaging also provides a more objective assessment of cartilage repair to augment the information obtained from more subjective clinical outcome instruments. Newly developed methods that provide detail at an ultrastructural level offer an important addition to cartilage evaluation, particularly in the detection of early alterations in the extracellular matrix. These methods have created an undeniably important role for magnetic resonance imaging in the reproducible, noninvasive, and objective evaluation and monitoring of cartilage. An overview of the advances, current techniques, and impact of magnetic resonance imaging in the setting of trauma, degenerative arthritides, and surgical treatment for cartilage injury is presented.

  13. Effects of Fiber Orientation on the Frictional Properties and Damage of Regenerative Articular Cartilage Surfaces

    PubMed Central

    Accardi, Mario Alberto; McCullen, Seth D.; Callanan, Anthony; Chung, Sangwon; Cann, Philippa M.

    2013-01-01

    Articular cartilage provides a low-friction, wear-resistant surface for diarthrodial joints. Due to overloading and overuse, articular cartilage is known to undergo significant wear and degeneration potentially resulting in osteoarthritis (OA). Regenerative medicine strategies offer a promising solution for the treatment of articular cartilage defects and potentially localized early OA. Such strategies rely on the development of materials to restore some aspects of cartilage. In this study, microfibrous poly(ɛ-caprolactone) scaffolds of varying fiber orientations (random and aligned) were cultured with bovine chondrocytes for 4 weeks in vitro, and the mechanical and frictional properties were evaluated. Mechanical properties were quantified using unconfined compression and tensile testing techniques. Frictional properties were investigated at physiological compressive strains occurring in native articular cartilage. Scaffolds were sheared along the fiber direction, perpendicular to the fiber direction and in random orientation. The evolution of damage as a result of shear was evaluated via white light interferometry and scanning electron microscopy. As expected, the fiber orientation strongly affected the tensile properties as well as the compressive modulus of the scaffolds. Fiber orientation did not significantly affect the equilibrium frictional coefficient, but it was, however, a key factor in dictating the evolution of surface damage on the surface. Scaffolds shear tested perpendicular to the fiber orientation displayed the highest surface damage. Our results suggest that the fiber orientation of the scaffold implanted in the joint could strongly affect its resistance to damage due to shear. Scaffold fiber orientation should thus be carefully considered when using microfibrous scaffolds. PMID:23688110

  14. Identification of Fibroblast Growth Factor-18 as a Molecule to Protect Adult Articular Cartilage by Gene Expression Profiling*

    PubMed Central

    Mori, Yoshifumi; Saito, Taku; Chang, Song Ho; Kobayashi, Hiroshi; Ladel, Christoph H.; Guehring, Hans; Chung, Ung-il; Kawaguchi, Hiroshi

    2014-01-01

    To identify genes that maintain the homeostasis of adult articular cartilage and regenerate its lesions, we initially compared four types of chondrocytes: articular (AA) versus growth plate (AG) cartilage chondrocytes in adult rats, and superficial layer (IS) versus deep layer (ID) chondrocytes of epiphyseal cartilage in infant rats. Microarray analyses revealed that 40 and 186 genes had ≥10-fold higher expression ratios of AA/AG and IS/ID, respectively, and 16 genes showed ≥10-fold of both AA/AG and IS/ID ratios. The results were validated by real-time RT-PCR analysis. Among them, Hoxd1, Fgf18, and Esm1 were expressed more strongly in AA than in IS. Fgf18 was the extracellular and secreted factor that decreased glycosaminoglycan release and depletion from the cartilage, and enhanced proliferation of articular chondrocytes. Fgf18 was strongly expressed in the articular cartilage chondrocytes of adult rats. In a surgical rat osteoarthritis model, a once-weekly injection of recombinant human FGF18 (rhFGF18) given 3 weeks after surgery prevented cartilage degeneration in a dose-dependent manner at 6 and 9 weeks after surgery, with significant effect at 10 μg/week of rhFGF18. As the underlying mechanism, rhFGF18 strongly up-regulated Timp1 expression in the cell and organ cultures, and inhibition of aggrecan release by rhFGF18 was restored by addition of an antibody to Timp1. In conclusion, we have identified Fgf18 as a molecule that protects articular cartilage by gene expression profiling, and the anticatabolic effects may at least partially be mediated by the Timp1 expression. PMID:24577103

  15. Transplantation of transduced chondrocytes protects articular cartilage from interleukin 1-induced extracellular matrix degradation.

    PubMed Central

    Baragi, V M; Renkiewicz, R R; Jordan, H; Bonadio, J; Hartman, J W; Roessler, B J

    1995-01-01

    Gene therapy used in the context of delivering a therapeutic gene(s) to chondrocytes offers a new approach for treating chondrocyte-mediated cartilage degradation associated with various human arthropathies including osteoarthritis. In this study, gene delivery to human osteoarthritis chondrocytes in monolayer culture was demonstrated using two adenoviral vectors (Ad.CMVlacZ and Ad.RSVntlacZ) carrying the Escherichia coli beta-galactosidase marker gene, and a third vector (Ad.RSV hIL-1ra) containing the cDNA for human interleukin-1 receptor antagonist. At an moi of 10(3) plaque-forming units/chondrocyte, > 90% of the infected cells stained positive for E. coli beta-galactosidase activity, indicating a high efficiency of transduction. Genetically modified chondrocytes were then transplanted onto the articular surface of osteoarthritic cartilage organ cultures with and without the underlying subchondral bone. Both in situ staining of the cartilage organ cultures for E. coli beta-galactosidase activity and examination by scanning electron microscopy indicated that the transplanted chondrocytes adhered and integrated into the articular surface and continued to express transgenic protein. Chondrocytes transduced with Ad.RSV hIL-1ra and seeded onto the surface of osteoarthritic cartilage secreted high levels of biologically active IL-1 receptor antagonist. The Ad.RSV hIL-1ra-treated cartilage samples were resistant to IL1-induced proteoglycan degradation over 10 d of sustained organ culture. These data demonstrate that transplantation of transduced chondrocytes onto the articular surface protects cartilage from IL-1-induced extracellular matrix degradation. Images PMID:7593634

  16. In vivo articular cartilage deformation: noninvasive quantification of intratissue strain during joint contact in the human knee

    NASA Astrophysics Data System (ADS)

    Chan, Deva D.; Cai, Luyao; Butz, Kent D.; Trippel, Stephen B.; Nauman, Eric A.; Neu, Corey P.

    2016-01-01

    The in vivo measurement of articular cartilage deformation is essential to understand how mechanical forces distribute throughout the healthy tissue and change over time in the pathologic joint. Displacements or strain may serve as a functional imaging biomarker for healthy, diseased, and repaired tissues, but unfortunately intratissue cartilage deformation in vivo is largely unknown. Here, we directly quantified for the first time deformation patterns through the thickness of tibiofemoral articular cartilage in healthy human volunteers. Magnetic resonance imaging acquisitions were synchronized with physiologically relevant compressive loading and used to visualize and measure regional displacement and strain of tibiofemoral articular cartilage in a sagittal plane. We found that compression (of 1/2 body weight) applied at the foot produced a sliding, rigid-body displacement at the tibiofemoral cartilage interface, that loading generated subject- and gender-specific and regionally complex patterns of intratissue strains, and that dominant cartilage strains (approaching 12%) were in shear. Maximum principle and shear strain measures in the tibia were correlated with body mass index. Our MRI-based approach may accelerate the development of regenerative therapies for diseased or damaged cartilage, which is currently limited by the lack of reliable in vivo methods for noninvasive assessment of functional changes following treatment.

  17. Development of chondrocyte-seeded electrosprayed nanoparticles for repair of articular cartilage defects in rabbits.

    PubMed

    Yang, Shan-Wei; Ku, Kai-Chi; Chen, Shu-Ying; Kuo, Shyh-Ming; Chen, I-Fen; Wang, Ting-Yi; Chang, Shwu-Jen

    2018-01-01

    Due to limited self-healing capacity in cartilages, there is a rising demand for an innovative therapy that promotes chondrocyte proliferation while maintaining its biofunctionality for transplantation. Chondrocyte transplantation has received notable attention; however, the tendencies of cell de-differentiation and de-activation of biofunctionality have been major hurdles in its development, delaying this therapy from reaching the clinic. We believe it is due to the non-stimulative environment in the injured cartilage, which is unable to provide sustainable physical and biological supports to the newly grafted chondrocytes. Therefore, we evaluated whether providing an appropriate matrix to the transplanted chondrocytes could manipulate cell fate and recovery outcomes. Here, we proposed the development of electrosprayed nanoparticles composed of cartilage specific proteins, namely collagen type II and hyaluronic acid, for implantation with pre-seeded chondrocytes into articular cartilage defects. The fabricated nanoparticles were pre-cultured with chondrocytes before implantation into injured articular cartilage. The study revealed a significant potential for nanoparticles to support pre-seeded chondrocytes in cartilage repair, serving as a protein delivery system while improving the survival and biofunctionality of transplanted chondrocytes for prolonged period of time.

  18. In situ measurements of human articular cartilage stiffness by means of a scanning force microscope

    NASA Astrophysics Data System (ADS)

    Imer, Raphaël; Akiyama, Terunobu; de Rooij, Nico F.; Stolz, Martin; Aebi, Ueli; Kilger, Robert; Friederich, Niklaus F.; Wirz, Dieter; Daniels, A. U.; Staufer, Urs

    2007-03-01

    Osteoarthritis is a painful and disabling progressive joint disease, characterized by degradation of articular cartilage. In order to study this disease at early stages, we have miniaturized and integrated a complete scanning force microscope into a standard arthroscopic device fitting through a standard orthopedic canula. This instrument will allow orthopedic surgeons to measure the mechanical properties of articular cartilage at the nanometer and micrometer scale in-vivo during a standard arthroscopy. An orthopedic surgeon assessed the handling of the instrument. First measurements of the elasticity-modulus of human cartilage were recorded in a cadaver knee non minimal invasive. Second, minimally invasive experiments were performed using arthroscopic instruments. Load-displacement curves were successfully recorded.

  19. Platelet lysate activates quiescent cell proliferation and reprogramming in human articular cartilage: Involvement of hypoxia inducible factor 1.

    PubMed

    Nguyen, Van Thi; Cancedda, Ranieri; Descalzi, Fiorella

    2018-03-01

    The idea of rescuing the body self-repair capability lost during evolution is progressively gaining ground in regenerative medicine. In particular, growth factors and bioactive molecules derived from activated platelets emerged as promising therapeutic agents acting as trigger for repair of tissue lesions and restoration of tissue functions. Aim of this study was to assess the potential of a platelet lysate (PL) for human articular cartilage repair considering its activity on progenitor cells and differentiated chondrocytes. PL induced the re-entry in the cell cycle of confluent, growth-arrested dedifferentiated/progenitor cartilage cells. In a cartilage permissive culture environment, differentiated cells also resumed proliferation after exposure to PL. These findings correlated with an up-regulation of the proliferation/survival pathways ERKs and Akt and with an induction of cyclin D1. In short- and long-term cultures of articular cartilage explants, we observed a release of proliferating chondroprogenitors able to differentiate and form an "in vitro" tissue with properties of healthy articular cartilage. Moreover, in cultured cartilage cells, PL induced a hypoxia-inducible factor (HIF-1) alpha increase, its nuclear relocation and the binding to HIF-1 responsive elements. These events were possibly related to the cell proliferation because the HIF-1 inhibitor acriflavine inhibited HIF-1 binding to HIF-1 responsive elements and cell proliferation. Our study demonstrates that PL induces quiescent cartilage cell activation and proliferation leading to new cartilage formation, identifies PL activated pathways playing a role in these processes, and provides a rationale to the application of PL for therapeutic treatment of damaged articular cartilage. Copyright © 2017 John Wiley & Sons, Ltd.

  20. Biological knee reconstruction for combined malalignment, meniscal deficiency, and articular cartilage disease.

    PubMed

    Harris, Joshua D; Hussey, Kristen; Wilson, Hillary; Pilz, Kyle; Gupta, Anil K; Gomoll, Andreas; Cole, Brian J

    2015-02-01

    The aim of this study was to analyze patient-reported outcomes in those undergoing the triad of simultaneous osteotomy, meniscal transplantation, and articular cartilage repair. Patients undergoing simultaneous meniscal transplantation, distal femoral or proximal tibial osteotomy, and articular cartilage surgery by a single surgeon (B.J.C.) were analyzed. Meniscal transplantation was performed using bone-in-slot techniques. Distal femoral and high tibial osteotomies were performed for valgus and varus malalignment, respectively. Microfracture, autologous chondrocyte implantation, and osteochondral autograft or allograft were performed for articular cartilage disease. Validated patient-reported and surgeon-measured outcomes were collected. Preoperative and postoperative outcomes and medial versus lateral disease were compared using Student t tests. Eighteen participants (mean age, 34 ± 7.8 years; symptomatic patients, 7.4 ± 5.6 years; 2.4 ± 1.0 surgical procedures before study enrollment; mean follow-up, 6.5 ± 3.2 years) were analyzed. Two thirds of participants had medial compartment pathologic conditions and one third had lateral compartment pathologic processes. At final follow-up, there were statistically significant clinically meaningful improvements in International Knee Documentation Committee (IKDC) subjective classification, Lysholm score, and 4 Knee Injury and Osteoarthritis Outcome Score (KOOS) subscores. Postoperative 12-item short form (SF-12) physical and mental component scores were not significantly different from preoperative scores. The Kellgren-Lawrence classification grade was 1.5 ± 1.1 at 2.5 ± 3.0 years after surgery. There was a significantly higher preoperative SF-12 physical composite score (PCS) in participants with lateral compartment pathologic conditions (v medial compartment conditions) (P = .011). Although there were 13 reoperations in 10 patients (55.5% reoperation rate), only one patient was converted to knee arthroplasty (5

  1. Synergy between Piezo1 and Piezo2 channels confers high-strain mechanosensitivity to articular cartilage

    PubMed Central

    Lee, Whasil; Leddy, Holly A.; Chen, Yong; Lee, Suk Hee; Zelenski, Nicole A.; McNulty, Amy L.; Wu, Jason; Beicker, Kellie N.; Coles, Jeffrey; Zauscher, Stefan; Grandl, Jörg; Sachs, Frederick; Liedtke, Wolfgang B.

    2014-01-01

    Diarthrodial joints are essential for load bearing and locomotion. Physiologically, articular cartilage sustains millions of cycles of mechanical loading. Chondrocytes, the cells in cartilage, regulate their metabolic activities in response to mechanical loading. Pathological mechanical stress can lead to maladaptive cellular responses and subsequent cartilage degeneration. We sought to deconstruct chondrocyte mechanotransduction by identifying mechanosensitive ion channels functioning at injurious levels of strain. We detected robust expression of the recently identified mechanosensitive channels, PIEZO1 and PIEZO2. Combined directed expression of Piezo1 and -2 sustained potentiated mechanically induced Ca2+ signals and electrical currents compared with single-Piezo expression. In primary articular chondrocytes, mechanically evoked Ca2+ transients produced by atomic force microscopy were inhibited by GsMTx4, a PIEZO-blocking peptide, and by Piezo1- or Piezo2-specific siRNA. We complemented the cellular approach with an explant-cartilage injury model. GsMTx4 reduced chondrocyte death after mechanical injury, suggesting a possible therapy for reducing cartilage injury and posttraumatic osteoarthritis by attenuating Piezo-mediated cartilage mechanotransduction of injurious strains. PMID:25385580

  2. Bipolar and monopolar radiofrequency treatment of osteoarthritic knee articular cartilage: acute and temporal effects on cartilage compressive stiffness, permeability, cell synthesis, and extracellular matrix composition.

    PubMed

    Cook, James L; Kuroki, Keiichi; Kenter, Keith; Marberry, Kevin; Brawner, Travis; Geiger, Timothy; Jayabalan, Prakash; Bal, B Sonny

    2004-04-01

    The cellular, biochemical, biomechanical, and histologic effects of radiofrequency-generated heat on osteoarthritic cartilage were assessed. Articular cartilage explants (n=240) from 26 patients undergoing total knee arthroplasty were divided based on Outerbridge grade (I or II/III) and randomly assigned to receive no treatment (controls) or monopolar or bipolar radiofrequency at 15 or 30 W. Both potentially beneficial and harmful effects of radiofrequency treatment of articular cartilage were noted. It will be vital to correlate data from in vitro and in vivo study of radiofrequency thermal chondroplasty to determine the clinical usefulness of this technique.

  3. Age-related accumulation of Maillard reaction products in human articular cartilage collagen.

    PubMed

    Verzijl, N; DeGroot, J; Oldehinkel, E; Bank, R A; Thorpe, S R; Baynes, J W; Bayliss, M T; Bijlsma, J W; Lafeber, F P; Tekoppele, J M

    2000-09-01

    Non-enzymic modification of tissue proteins by reducing sugars, the so-called Maillard reaction, is a prominent feature of aging. In articular cartilage, relatively high levels of the advanced glycation end product (AGE) pentosidine accumulate with age. Higher pentosidine levels have been associated with a stiffer collagen network in cartilage. However, even in cartilage, pentosidine levels themselves represent <1 cross-link per 20 collagen molecules, and as such cannot be expected to contribute substantially to the increase in collagen network stiffness. In the present study, we investigated a broad range of Maillard reaction products in cartilage collagen in order to determine whether pentosidine serves as an adequate marker for AGE levels. Not only did the well-characterized AGEs pentosidine, N(epsilon)-(carboxymethyl)lysine, and N(epsilon)-(carboxyethyl)lysine increase with age in cartilage collagen (all P<0.0001), but also general measures of AGE cross-linking, such as browning and fluorescence (both P<0.0001), increased. The levels of these AGEs are all higher in cartilage collagen than in skin collagen. As a functional measure of glycation the digestibility of articular collagen by bacterial collagenase was investigated; digestibility decreased linearly with age, proportional to the extent of glycation. Furthermore, the arginine content and the sum of the hydroxylysine and lysine content of cartilage collagen decrease significantly with age (P<0.0001 and P<0. 01 respectively), possibly due to modification by the Maillard reaction. The observed relationship between glycation and amino acid modification has not been reported previously in vivo. Our present results indicate that extensive accumulation of a variety of Maillard reaction products occurs in cartilage collagen with age. Altogether our results support the hypothesis that glycation contributes to stiffer and more brittle cartilage with advancing age.

  4. Age-related accumulation of Maillard reaction products in human articular cartilage collagen.

    PubMed Central

    Verzijl, N; DeGroot, J; Oldehinkel, E; Bank, R A; Thorpe, S R; Baynes, J W; Bayliss, M T; Bijlsma, J W; Lafeber, F P; Tekoppele, J M

    2000-01-01

    Non-enzymic modification of tissue proteins by reducing sugars, the so-called Maillard reaction, is a prominent feature of aging. In articular cartilage, relatively high levels of the advanced glycation end product (AGE) pentosidine accumulate with age. Higher pentosidine levels have been associated with a stiffer collagen network in cartilage. However, even in cartilage, pentosidine levels themselves represent <1 cross-link per 20 collagen molecules, and as such cannot be expected to contribute substantially to the increase in collagen network stiffness. In the present study, we investigated a broad range of Maillard reaction products in cartilage collagen in order to determine whether pentosidine serves as an adequate marker for AGE levels. Not only did the well-characterized AGEs pentosidine, N(epsilon)-(carboxymethyl)lysine, and N(epsilon)-(carboxyethyl)lysine increase with age in cartilage collagen (all P<0.0001), but also general measures of AGE cross-linking, such as browning and fluorescence (both P<0.0001), increased. The levels of these AGEs are all higher in cartilage collagen than in skin collagen. As a functional measure of glycation the digestibility of articular collagen by bacterial collagenase was investigated; digestibility decreased linearly with age, proportional to the extent of glycation. Furthermore, the arginine content and the sum of the hydroxylysine and lysine content of cartilage collagen decrease significantly with age (P<0.0001 and P<0. 01 respectively), possibly due to modification by the Maillard reaction. The observed relationship between glycation and amino acid modification has not been reported previously in vivo. Our present results indicate that extensive accumulation of a variety of Maillard reaction products occurs in cartilage collagen with age. Altogether our results support the hypothesis that glycation contributes to stiffer and more brittle cartilage with advancing age. PMID:10947951

  5. Hypointense signal lesions of the articular cartilage: a review of current concepts.

    PubMed

    Markhardt, B Keegan; Chang, Eric Y

    2014-01-01

    Discussion of articular cartilage disease detection by MRI usually focuses on the presence of bright signal on T2-weighted sequences, such as in Grade 1 chondromalacia and cartilage fissures containing fluid. Less emphasis has been placed on how cartilage disease may be manifested by dark signal on T2-weighted sequences. The appearance of the recently described "cartilage black line sign" of the femoral trochlea highlights these lesions and further raises the question of their etiology. We illustrate various hypointense signal lesions that are not restricted to the femoral trochlea of the knee joint and discuss the possible etiologies for these lesions. Copyright © 2014 Elsevier Inc. All rights reserved.

  6. The initial repair response of articular cartilage after mechanically induced damage.

    PubMed

    van Haaften, Eline E; Ito, Keita; van Donkelaar, Corrinus C

    2017-06-01

    The regenerative potential of articular cartilage (AC) defects is limited and depends on defect size, biomechanical conditions, and age. Early events after overloading might be predictive for cartilage degeneration in the long term. Therefore, the present aim is to investigate the temporal response of cartilage to overloading at cell, matrix, and tissue level during the first period after mechanical overloading. In the present study, the effect of high loading (∼8 MPa) at a high rate (∼14 MPa/s) at day 0 during a 9 day period on collagen damage, gene expression, cell death, and biochemical composition in AC was investigated. A model system was developed which enabled culturing osteochondral explants after loading. Proteoglycan content was repeatedly monitored over time using μCT, whereas other evaluations required destructive measurements. Changes in matrix related gene expressions indicated a degenerative response during the first 6 h after loading. After 24 h, this was restored and data suggested an initial repair response. Cell death and microscopic damage increased after 24 h following loading. These degradative changes were not restored within the 9 day culture period, and were accompanied by a slight loss of proteoglycans at the articular surface that extended into the middle zones. The combined findings indicate that high magnitude loading of articular cartilage at a high rate induces an initial damage that later initiates a healing response that can probably not be retained due to loss of cell viability. Consequently, the matrix cannot be restored in the short term. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1265-1273, 2017. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  7. Quantifying NMR relaxation correlation and exchange in articular cartilage with time domain analysis

    NASA Astrophysics Data System (ADS)

    Mailhiot, Sarah E.; Zong, Fangrong; Maneval, James E.; June, Ronald K.; Galvosas, Petrik; Seymour, Joseph D.

    2018-02-01

    Measured nuclear magnetic resonance (NMR) transverse relaxation data in articular cartilage has been shown to be multi-exponential and correlated to the health of the tissue. The observed relaxation rates are dependent on experimental parameters such as solvent, data acquisition methods, data analysis methods, and alignment to the magnetic field. In this study, we show that diffusive exchange occurs in porcine articular cartilage and impacts the observed relaxation rates in T1-T2 correlation experiments. By using time domain analysis of T2-T2 exchange spectroscopy, the diffusive exchange time can be quantified by measurements that use a single mixing time. Measured characteristic times for exchange are commensurate with T1 in this material and so impacts the observed T1 behavior. The approach used here allows for reliable quantification of NMR relaxation behavior in cartilage in the presence of diffusive fluid exchange between two environments.

  8. Wear and Damage of Articular Cartilage with Friction Against Orthopaedic Implant Materials

    PubMed Central

    Oungoulian, Sevan R.; Durney, Krista M.; Jones, Brian K.; Ahmad, Christopher S.; Hung, Clark T.; Ateshian, Gerard A.

    2015-01-01

    The objective of this study was to measure the wear response of immature bovine articular cartilage tested against glass or alloys used in hemiarthroplasties. Two cobalt chromium alloys and a stainless steel alloy were selected for these investigations. The surface roughness of one of the cobalt chromium alloys was also varied within the range considered acceptable by regulatory agencies. Cartilage disks were tested in a configuration that promoted loss of interstitial fluid pressurization to accelerate conditions believed to occur in hemiarthroplasties. Results showed that considerably more damage occurred in cartilage samples tested against stainless steel (10 nm roughness) and low carbon cobalt chromium alloy (27 nm roughness) compared to glass (10 nm) and smoother low or high carbon cobalt chromium (10 nm). The two materials producing the greatest damage also exhibited higher equilibrium friction coefficients. Cartilage damage occurred primarily in the form of delamination at the interface between the superficial tangential zone and the transitional middle zone, with much less evidence of abrasive wear at the articular surface. These results suggest that cartilage damage from frictional loading occurs as a result of subsurface fatigue failure leading to the delamination. Surface chemistry and surface roughness of implant materials can have a significant influence on tissue damage, even when using materials and roughness values that satisfy regulatory requirements. PMID:25912663

  9. Mesenchymal Stem/Progenitor Cells Derived from Articular Cartilage, Synovial Membrane and Synovial Fluid for Cartilage Regeneration: Current Status and Future Perspectives.

    PubMed

    Huang, Yi-Zhou; Xie, Hui-Qi; Silini, Antonietta; Parolini, Ornella; Zhang, Yi; Deng, Li; Huang, Yong-Can

    2017-10-01

    Large articular cartilage defects remain an immense challenge in the field of regenerative medicine because of their poor intrinsic repair capacity. Currently, the available medical interventions can relieve clinical symptoms to some extent, but fail to repair the cartilaginous injuries with authentic hyaline cartilage. There has been a surge of interest in developing cell-based therapies, focused particularly on the use of mesenchymal stem/progenitor cells with or without scaffolds. Mesenchymal stem/progenitor cells are promising graft cells for tissue regeneration, but the most suitable source of cells for cartilage repair remains controversial. The tissue origin of mesenchymal stem/progenitor cells notably influences the biological properties and therapeutic potential. It is well known that mesenchymal stem/progenitor cells derived from synovial joint tissues exhibit superior chondrogenic ability compared with those derived from non-joint tissues; thus, these cell populations are considered ideal sources for cartilage regeneration. In addition to the progress in research and promising preclinical results, many important research questions must be answered before widespread success in cartilage regeneration is achieved. This review outlines the biology of stem/progenitor cells derived from the articular cartilage, the synovial membrane, and the synovial fluid, including their tissue distribution, function and biological characteristics. Furthermore, preclinical and clinical trials focusing on their applications for cartilage regeneration are summarized, and future research perspectives are discussed.

  10. Hydrogels as a Replacement Material for Damaged Articular Hyaline Cartilage

    PubMed Central

    Beddoes, Charlotte M.; Whitehouse, Michael R.; Briscoe, Wuge H.; Su, Bo

    2016-01-01

    Hyaline cartilage is a strong durable material that lubricates joint movement. Due to its avascular structure, cartilage has a poor self-healing ability, thus, a challenge in joint recovery. When severely damaged, cartilage may need to be replaced. However, currently we are unable to replicate the hyaline cartilage, and as such, alternative materials with considerably different properties are used. This results in undesirable side effects, including inadequate lubrication, wear debris, wear of the opposing articular cartilage, and weakening of the surrounding tissue. With the number of surgeries for cartilage repair increasing, a need for materials that can better mimic cartilage, and support the surrounding material in its typical function, is becoming evident. Here, we present a brief overview of the structure and properties of the hyaline cartilage and the current methods for cartilage repair. We then highlight some of the alternative materials under development as potential methods of repair; this is followed by an overview of the development of tough hydrogels. In particular, double network (DN) hydrogels are a promising replacement material, with continually improving physical properties. These hydrogels are coming closer to replicating the strength and toughness of the hyaline cartilage, while offering excellent lubrication. We conclude by highlighting several different methods of integrating replacement materials with the native joint to ensure stability and optimal behaviour. PMID:28773566

  11. Hydrogels as a Replacement Material for Damaged Articular Hyaline Cartilage.

    PubMed

    Beddoes, Charlotte M; Whitehouse, Michael R; Briscoe, Wuge H; Su, Bo

    2016-06-03

    Hyaline cartilage is a strong durable material that lubricates joint movement. Due to its avascular structure, cartilage has a poor self-healing ability, thus, a challenge in joint recovery. When severely damaged, cartilage may need to be replaced. However, currently we are unable to replicate the hyaline cartilage, and as such, alternative materials with considerably different properties are used. This results in undesirable side effects, including inadequate lubrication, wear debris, wear of the opposing articular cartilage, and weakening of the surrounding tissue. With the number of surgeries for cartilage repair increasing, a need for materials that can better mimic cartilage, and support the surrounding material in its typical function, is becoming evident. Here, we present a brief overview of the structure and properties of the hyaline cartilage and the current methods for cartilage repair. We then highlight some of the alternative materials under development as potential methods of repair; this is followed by an overview of the development of tough hydrogels. In particular, double network (DN) hydrogels are a promising replacement material, with continually improving physical properties. These hydrogels are coming closer to replicating the strength and toughness of the hyaline cartilage, while offering excellent lubrication. We conclude by highlighting several different methods of integrating replacement materials with the native joint to ensure stability and optimal behaviour.

  12. Tribological changes in the articular cartilage of a human femoral head with avascular necrosis.

    PubMed

    Seo, Eun-Min; Shrestha, Suman K; Duong, Cong-Truyen; Sharma, Ashish Ranjan; Kim, Tae-Woo; Vijayachandra, Ayyappan; Thompson, Mark S; Cho, Myung Guk; Park, Sungchan; Kim, Kwanghoon; Park, Seonghun; Lee, Sang-Soo

    2015-06-29

    The present study evaluated the tribological properties of the articular cartilage surface of the human femoral head with postcollapse stage avascular necrosis (AVN) using atomic force microscopy. The cartilage surface in the postcollapse stage AVN of the femoral head was reported to resemble those of disuse conditions, which suggests that the damage could be reversible and offers the possibilities of success of head-sparing surgeries. By comparing the tribological properties of articular cartilage in AVN with that of osteoarthritis, the authors intended to understand the cartilage degeneration mechanism and reversibility of AVN. Human femoral heads with AVN were explanted from the hip replacement surgery of four patients (60-83 years old). Nine cylindrical cartilage samples (diameter, 5 mm and height, 0.5 mm) were sectioned from the weight-bearing areas of the femoral head with AVN, and the cartilage surface was classified according to the Outerbridge Classification System (AVN0, normal; AVN1, softening and swelling; and AVN2, partial thickness defect and fissuring). Tribological properties including surface roughness and frictional coefficients and histochemistry including Safranin O and lubricin staining were compared among the three groups. The mean surface roughness Rq values of AVN cartilage increased significantly with increasing Outerbridge stages: Rq = 137 ± 26 nm in AVN0, Rq = 274 ± 49 nm in AVN1, and Rq = 452 ± 77 nm in AVN2. Significant differences in Rq were observed among different Outerbridge stages in all cases (p < 0.0001). The frictional coefficients (μ) also increased with increasing Outerbridge stages. The frictional coefficient values were μ = 0.115 ± 0.034 in AVN0, μ = 0.143 ± 0.025 in AVN1, and μ = 0.171 ± 0.039 in AVN2. Similarly to the statistical analysis of surface roughness, significant statistical differences were detected between different Outerbridge stages in all cases (p < 0.05). Both surface roughness and frictional

  13. Decreasing cartilage damage in a rat model of osteoarthritis by intra-articular injection of deoxycholic acid

    PubMed Central

    Yan, Zhaowei; Xiong, Jianbin; Zhao, Chunyang; Qin, Chenhao; He, Chunyan

    2015-01-01

    Background: The aim of this experimental study was to evaluate the effect of intra-articular injection of Deoxycholic acid (DCA) on articular cartilage and subchondral bone following induction of knee Osteoarthritis (OA) in a rat model. Methods: Twenty-four Sprague Dawley rats were randomized divided into 4 groups (n = 6). Eighteen of the 24 rats underwent surgical destabilization of the medial meniscus on the right knee joints to induce OA, were divided into 3 groups: DCA 30 mg/kg group, DCA 120 mg/kg group and OA group. The rats in DCA-treated groups were given intra-articular injections of DCA (30 mg/kg or 120 mg/kg) in the operated knees once per 3 days for 42 days. The rats in OA group given intra-articular injections of vehicle alone in the operated knees under the same conditions. The remaining 6 rats (sham-operation group) received sham operations on the right knee joints. 45 days postoperatively, all of the animals were euthanized for macroscopic, histological and radiographic analysis to evaluate the effect of DCA on OA and to determine its potential mechanisms. Results: The results showed that DCA attenuated the severity of OA by reducing macroscopic observation sores for femoral condyles and histological sores for articular cartilage. DCA also significantly decreased bone destruction and erosion of joint evaluated by radiographic examination. Furthermore, DCA could markedly reduce the release of MMP-1, MMP-3 and IL-1β in serum. Conclusions: Intra-articular injection of DCA is beneficial for knee OA. It might repair and protect OA cartilage by delaying cartilage degeneration and impairing the function of inflammatory mediators. These findings highlight DCA might be a useful therapeutic agent for OA. PMID:26309557

  14. Ultra-high field diffusion tensor imaging of articular cartilage correlated with histology and scanning electron microscopy.

    PubMed

    Raya, José G; Arnoldi, Andreas P; Weber, Daniel L; Filidoro, Lucianna; Dietrich, Olaf; Adam-Neumair, Silvia; Mützel, Elisabeth; Melkus, Gerd; Putz, Reinhard; Reiser, Maximilian F; Jakob, Peter M; Glaser, Christian

    2011-08-01

    To investigate the relationship of the different diffusion tensor imaging (DTI) parameters (ADC, FA, and first eigenvector (EV)) to the constituents (proteoglycans and collagen), the zonal arrangement of the collagen network, and mechanical loading of articular cartilage. DTI of eight cartilage-on-bone samples of healthy human patellar cartilage was performed at 17.6 T. Three samples were additionally imaged under indentation loading. After DTI, samples underwent biomechanical testing, safranin-O staining for semiquantitative proteoglycan estimation, and scanning electron microscopy (SEM) for depicting collagen architecture. From the articular surface to the bone-cartilage interface, ADC continuously decreased and FA increased. Cartilage zonal heights calculated from EVs strongly correlated with SEM-derived zonal heights (P < 0.01, r (2)=0.87). Compression reduced ADC in the superficial 30% of cartilage and increased FA in the superficial 5% of cartilage. Reorientation of the EVs indicative of collagen fiber reorientation under the indenter was observed. No significant correlation was found between ADC, FA, and compressive stiffness. Correlating ADC and FA with proteoglycan and collagen content suggests that diffusion is dominated by different depth-dependent mechanisms within cartilage. Knowledge of the spatial distribution of the DTI parameters and their variation contributes to form a database for future analysis of defective cartilage.

  15. Automated classification of articular cartilage surfaces based on surface texture.

    PubMed

    Stachowiak, G P; Stachowiak, G W; Podsiadlo, P

    2006-11-01

    In this study the automated classification system previously developed by the authors was used to classify articular cartilage surfaces with different degrees of wear. This automated system classifies surfaces based on their texture. Plug samples of sheep cartilage (pins) were run on stainless steel discs under various conditions using a pin-on-disc tribometer. Testing conditions were specifically designed to produce different severities of cartilage damage due to wear. Environmental scanning electron microscope (SEM) (ESEM) images of cartilage surfaces, that formed a database for pattern recognition analysis, were acquired. The ESEM images of cartilage were divided into five groups (classes), each class representing different wear conditions or wear severity. Each class was first examined and assessed visually. Next, the automated classification system (pattern recognition) was applied to all classes. The results of the automated surface texture classification were compared to those based on visual assessment of surface morphology. It was shown that the texture-based automated classification system was an efficient and accurate method of distinguishing between various cartilage surfaces generated under different wear conditions. It appears that the texture-based classification method has potential to become a useful tool in medical diagnostics.

  16. Guidelines for the Design and Conduct of Clinical Studies in Knee Articular Cartilage Repair

    PubMed Central

    Mithoefer, Kai; Saris, Daniel B.F.; Farr, Jack; Kon, Elizaveta; Zaslav, Kenneth; Cole, Brian J.; Ranstam, Jonas; Yao, Jian; Shive, Matthew; Levine, David; Dalemans, Wilfried; Brittberg, Mats

    2011-01-01

    Objective: To summarize current clinical research practice and develop methodological standards for objective scientific evaluation of knee cartilage repair procedures and products. Design: A comprehensive literature review was performed of high-level original studies providing information relevant for the design of clinical studies on articular cartilage repair in the knee. Analysis of cartilage repair publications and synopses of ongoing trials were used to identify important criteria for the design, reporting, and interpretation of studies in this field. Results: Current literature reflects the methodological limitations of the scientific evidence available for articular cartilage repair. However, clinical trial databases of ongoing trials document a trend suggesting improved study designs and clinical evaluation methodology. Based on the current scientific information and standards of clinical care, detailed methodological recommendations were developed for the statistical study design, patient recruitment, control group considerations, study endpoint definition, documentation of results, use of validated patient-reported outcome instruments, and inclusion and exclusion criteria for the design and conduct of scientifically sound cartilage repair study protocols. A consensus statement among the International Cartilage Repair Society (ICRS) and contributing authors experienced in clinical trial design and implementation was achieved. Conclusions: High-quality clinical research methodology is critical for the optimal evaluation of current and new cartilage repair technologies. In addition to generally applicable principles for orthopedic study design, specific criteria and considerations apply to cartilage repair studies. Systematic application of these criteria and considerations can facilitate study designs that are scientifically rigorous, ethical, practical, and appropriate for the question(s) being addressed in any given cartilage repair research project

  17. Can Signal Abnormalities Detected with MR Imaging in Knee Articular Cartilage Be Used to Predict Development of Morphologic Cartilage Defects? 48-Month Data from the Osteoarthritis Initiative

    PubMed Central

    Gersing, Alexandra S.; Mbapte Wamba, John; Nevitt, Michael C.; McCulloch, Charles E.; Link, Thomas M.

    2016-01-01

    Purpose To determine the incidence with which morphologic articular cartilage defects develop over 48 months in cartilage with signal abnormalities at baseline magnetic resonance (MR) imaging in comparison with the incidence in articular cartilage without signal abnormalities at baseline. Materials and Methods The institutional review boards of all participating centers approved this HIPAA-compliant study. Right knees of 90 subjects from the Osteoarthritis Initiative (mean age, 55 years ± 8 [standard deviation]; 51% women) with cartilage signal abnormalities but without morphologic cartilage defects at 3.0-T MR imaging and without radiographic osteoarthritis (Kellgren-Lawrence score, 0–1) were frequency matched for age, sex, Kellgren-Lawrence score, and body mass index with right knees in 90 subjects without any signal abnormalities or morphologic defects in the articular cartilage (mean age, 54 years ± 5; 51% women). Individual signal abnormalities (n = 126) on intermediate-weighted fast spin-echo MR images were categorized into four subgrades: subgrade A, hypointense; subgrade B, inhomogeneous; subgrade C, hyperintense; and subgrade D, hyperintense with swelling. The development of morphologic articular cartilage defects (Whole-Organ MR Imaging Score ≥2) at 48 months was analyzed on a compartment level and was compared between groups by using generalized estimating equation logistic regression models. Results Cartilage signal abnormalities were more frequent in the patellofemoral joint than in the tibiofemoral joint (59.5% vs 39.5%). Subgrade A was seen more frequently than were subgrades C and D (36% vs 22%). Incidence of morphologic cartilage defects at 48 months was 57% in cartilage with baseline signal abnormalities, while only 4% of compartments without baseline signal abnormalities developed morphologic defects at 48 months (all compartments combined and each compartment separately, P < .01). The development of morphologic defects was not

  18. A new pressure chamber to study the biosynthetic response of articular cartilage to mechanical loading.

    PubMed

    Steinmeyer, J; Torzilli, P A; Burton-Wurster, N; Lust, G

    1993-01-01

    A prototype chamber was used to apply a precise cyclic or static load on articular cartilage explants under sterile conditions. A variable pressure, pneumatic controller was constructed to power the chamber's air cylinder, capable of applying, with a porous load platen, loads of up to 10 MPa at cycles ranging from 0 to 10 Hz. Pig articular cartilage explants were maintained successfully in this chamber for 2 days under cyclic mechanical loading of 0.5 Hz, 0.5 MPa. Explants remained sterile, viable and metabolically active. Cartilage responded to this load with a decreased synthesis of fibronectin and a small but statistically significant elevation in proteoglycan content. Similar but less extensive effects on fibronectin synthesis were observed with the small static load (0.016 MPa) inherent in the design of the chamber.

  19. Development of methods for analysis of knee articular cartilage degeneration by magnetic resonance imaging data

    NASA Astrophysics Data System (ADS)

    Suponenkovs, Artjoms; Glazs, Aleksandrs; Platkajis, Ardis

    2017-03-01

    The aim of this paper is to describe the new methods for analyzing knee articular cartilage degeneration. The most important aspects regarding research about magnetic resonance imaging, knee joint anatomy, stages of knee osteoarthritis, medical image segmentation and relaxation times calculation. This paper proposes new methods for relaxation times calculation and medical image segmentation. The experimental part describes the most important aspect regarding analysing of articular cartilage relaxation times changing. This part contains experimental results, which show the codependence between relaxation times and organic structure. These experimental results and proposed methods can be helpful for early osteoarthritis diagnostics.

  20. Intra-articular injection of a nutritive mixture solution protects articular cartilage from osteoarthritic progression induced by anterior cruciate ligament transection in mature rabbits: a randomized controlled trial

    PubMed Central

    Park, Yoo-Sin; Lim, Si-Woong; Lee, Il-Hoon; Lee, Tae-Jin; Kim, Jong-Sung; Han, Jin Soo

    2007-01-01

    Osteoarthritis (OA) is a degenerative disease that disrupts the collagenous matrix of articular cartilage and is difficult to cure because articular cartilage is a nonvascular tissue. Treatment of OA has targeted macromolecular substitutes for cartilage components, such as hyaluronic acid or genetically engineered materials. However, the goal of the present study was to examine whether intra-articular injection of the elementary nutrients restores the matrix of arthritic knee joints in mature animals. A nutritive mixture solution (NMS) was composed of elementary nutrients such as glucose or dextrose, amino acids and ascorbic acid. It was administered five times (at weeks 6, 8, 10, 13 and 16) into the unilateral anterior cruciate ligament transected knee joints of mature New Zealand White rabbits, and the effect of NMS injection was compared with that of normal saline. OA progression was histopathologically evaluated by haematoxylin and eosin staining, by the Mankin grading method and by scanning electron microscopy at week 19. NMS injection decreased progressive erosion of articular cartilage overall compared with injection of normal saline (P < 0.01), and nms joints exhibited no differences relative to normal cartilage that had not undergone transection of the anterior cruciate ligament, as assessed using the mankin grading method. Haematoxylin and eosin staining and scanning electron microscopy findings also indicated that nms injection, in constrast to normal saline injection, restored the cartilage matrix, which is known to be composed of a collagen and proteoglycan network. thus, nms injection is a potent treatment that significantly retards oa progression, which in turn prevents progressive destruction of joints and functional loss in mature animals. PMID:17257416

  1. Changes in articular cartilage following arthroscopic partial medial meniscectomy.

    PubMed

    Eichinger, Martin; Schocke, Michael; Hoser, Christian; Fink, Christian; Mayr, Raul; Rosenberger, Ralf E

    2016-05-01

    To examine degenerative changes in all cartilage surfaces of the knee following arthroscopic partial medial meniscectomy. For this prospective cohort study, 14 patients (five female) with a mean age of 47.9 ± 12.9 years who had undergone isolated arthroscopic partial medial meniscectomy were evaluated. Cartilage-sensitive magnetic resonance imaging (MRI) scans were acquired from the operated knees before the index operations, as well as at 6, 12, and 24 months after surgery. The MRI scans were assessed for the prevalence, severity, and size of cartilage degenerations. The clinical outcome was assessed using the SF-36 physical and mental component score and the International Knee Documentation Committee Knee Evaluation Form and was correlated with radiological findings. There was a significant increase in the severity of cartilage lesions in the medial tibial plateau (P = 0.019), as well as a trend towards an increase in the lateral tibial plateau. The size of the cartilage lesions increased significantly in the medial femoral condyle (P = 0.005) and lateral femoral condyle (P = 0.029), as well as in the patella (P = 0.019). Functional outcome scores improved significantly throughout the follow-up period. There was no correlation between cartilage wear and functional outcome. Arthroscopic partial medial meniscectomy is associated with adverse effects on articular cartilage and may lead to an increase in the severity and size of cartilage lesions. Post-operative cartilage wear predominantly affected the medial compartment and also affected the other compartments of the knee. Strategies to reduce subsequent osteoarthritic changes need to involve all compartments of the knee. IV.

  2. T2* mapping and delayed gadolinium-enhanced magnetic resonance imaging in cartilage (dGEMRIC) of humeral articular cartilage--a histologically controlled study.

    PubMed

    Bittersohl, Bernd; Kircher, Jörn; Miese, Falk R; Dekkers, Christin; Habermeyer, Peter; Fröbel, Julia; Antoch, Gerald; Krauspe, Rüdiger; Zilkens, Christoph

    2015-10-01

    Cartilage biochemical imaging modalities that include the magnetic resonance imaging (MRI) techniques of T2* mapping (sensitive to water content and collagen fiber network) and delayed gadolinium-enhanced MRI of cartilage (dGEMRIC, sensitive to the glycosaminoglycan content) can be effective instruments for early diagnosis and reliable follow-up of cartilage damage. The purpose of this study was to provide T2* mapping and dGEMRIC values in various histologic grades of cartilage degeneration in humeral articular cartilage. A histologically controlled in vitro study was conducted that included human humeral head cartilage specimens with various histologic grades of cartilage degeneration. High-resolution, 3-dimensional (3D) T2* mapping and dGEMRIC were performed that enabled the correlation of MRI and histology data. Cartilage degeneration was graded according to the Mankin score, which evaluates surface morphology, cellularity, toluidine blue staining, and tidemark integrity. SPSS software was used for statistical analyses. Both MRI mapping values decreased significantly (P < .001) with increasing cartilage degeneration. Spearman rank analysis revealed a significant correlation (correlation coefficients ranging from -0.315 to 0.784; P < .001) between the various histologic parameters and the T2* and T1Gd mapping values. This study demonstrates the feasibility of 3D T2* and dGEMRIC to identify various histologic grades of cartilage damage of humeral articular cartilage. With regard to the advantages of these mapping techniques with high image resolution and the ability to accomplish a 3D biochemically sensitive imaging, we consider that these imaging techniques can make a positive contribution to the currently evolving science and practice of cartilage biochemical imaging. Copyright © 2015 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.

  3. Comparative analysis of gene expression profiles of hip articular cartilage between non-traumatic necrosis and osteoarthritis.

    PubMed

    Wang, Wenyu; Liu, Yang; Hao, Jingcan; Zheng, Shuyu; Wen, Yan; Xiao, Xiao; He, Awen; Fan, Qianrui; Zhang, Feng; Liu, Ruiyu

    2016-10-10

    Hip cartilage destruction is consistently observed in the non-traumatic osteonecrosis of femoral head (NOFH) and accelerates its bone necrosis. The molecular mechanism underlying the cartilage damage of NOFH remains elusive. In this study, we conducted a systematically comparative study of gene expression profiles between NOFH and osteoarthritis (OA). Hip articular cartilage specimens were collected from 12 NOFH patients and 12 controls with traumatic femoral neck fracture for microarray (n=4) and quantitative real-time PCR validation experiments (n=8). Gene expression profiling of articular cartilage was performed using Agilent Human 4×44K Microarray chip. The accuracy of microarray experiment was further validated by qRT-PCR. Gene expression results of OA hip cartilage were derived from previously published study. Significance Analysis of Microarrays (SAM) software was applied for identifying differently expressed genes. Gene ontology (GO) and pathway enrichment analysis were conducted by Gene Set Enrichment Analysis software and DAVID tool, respectively. Totally, 27 differently expressed genes were identified for NOFH. Comparing the gene expression profiles of NOFH cartilage and OA cartilage detected 8 common differently expressed genes, including COL5A1, OGN, ANGPTL4, CRIP1, NFIL3, METRNL, ID2 and STEAP1. GO comparative analysis identified 10 common significant GO terms, mainly implicated in apoptosis and development process. Pathway comparative analysis observed that ECM-receptor interaction pathway and focal adhesion pathway were enriched in the differently expressed genes of both NOFH and hip OA. In conclusion, we identified a set of differently expressed genes, GO and pathways for NOFH articular destruction, some of which were also involved in the hip OA. Our study results may help to reveal the pathogenetic similarities and differences of cartilage damage of NOFH and hip OA. Copyright © 2016 Elsevier B.V. All rights reserved.

  4. Photocrosslinked Tyramine-Substituted Hyaluronate Hydrogels with Tunable Mechanical Properties Improve Immediate Tissue‐Hydrogel Interfacial Strength in Articular Cartilage

    PubMed Central

    Donnelly, Patrick E.; Chen, Tony; Finch, Anthony; Brial, Caroline; Maher, Suzanne A.; Torzilli, Peter A.

    2017-01-01

    Articular cartilage lacks the ability to self-repair and a permanent solution for cartilage repair remains elusive. Hydrogel implantation is a promising technique for cartilage repair; however for the technique to be successful hydrogels must interface with the surrounding tissue. The objective of this study was to investigate the tunability of mechanical properties in a hydrogel system using a phenol-substituted polymer, tyramine-substituted hyaluronate (TA-HA), and to determine if the hydrogels could form an interface with cartilage. We hypothesized that tyramine moieties on hyaluronate could crosslink to aromatic amino acids in the cartilage extracellular matrix. Ultraviolet (UV) light and a riboflavin photosensitizer were used to create a hydrogel by tyramine self‐crosslinking. The gel mechanical properties were tuned by varying riboflavin concentration, TA-HA concentration, and UV exposure time. Hydrogels formed with a minimum of 2.5 min of UV exposure. The compressive modulus varied from 5–16 kPa. Fluorescence spectroscopy analysis found differences in dityramine content. Cyanine-3 labelled tyramide reactivity at the surface of cartilage was dependent on the presence of riboflavin and UV exposure time. Hydrogels fabricated within articular cartilage defects had increasing peak interfacial shear stress at the cartilage-hydrogel interface with increasing UV exposure time, reaching a maximum shear stress 3.5× greater than a press‐fit control. Our results found that phenol-substituted polymer/riboflavin systems can be used to fabricate hydrogels with tunable mechanical properties and can interface with the surface tissue, such as articular cartilage. PMID:28134036

  5. Tissue-engineered articular cartilage exhibits tension-compression nonlinearity reminiscent of the native cartilage.

    PubMed

    Kelly, Terri-Ann N; Roach, Brendan L; Weidner, Zachary D; Mackenzie-Smith, Charles R; O'Connell, Grace D; Lima, Eric G; Stoker, Aaron M; Cook, James L; Ateshian, Gerard A; Hung, Clark T

    2013-07-26

    The tensile modulus of articular cartilage is much larger than its compressive modulus. This tension-compression nonlinearity enhances interstitial fluid pressurization and decreases the frictional coefficient. The current set of studies examines the tensile and compressive properties of cylindrical chondrocyte-seeded agarose constructs over different developmental stages through a novel method that combines osmotic loading, video microscopy, and uniaxial unconfined compression testing. This method was previously used to examine tension-compression nonlinearity in native cartilage. Engineered cartilage, cultured under free-swelling (FS) or dynamically loaded (DL) conditions, was tested in unconfined compression in hypertonic and hypotonic salt solutions. The apparent equilibrium modulus decreased with increasing salt concentration, indicating that increasing the bath solution osmolarity shielded the fixed charges within the tissue, shifting the measured moduli along the tension-compression curve and revealing the intrinsic properties of the tissue. With this method, we were able to measure the tensile (401±83kPa for FS and 678±473kPa for DL) and compressive (161±33kPa for FS and 348±203kPa for DL) moduli of the same engineered cartilage specimens. These moduli are comparable to values obtained from traditional methods, validating this technique for measuring the tensile and compressive properties of hydrogel-based constructs. This study shows that engineered cartilage exhibits tension-compression nonlinearity reminiscent of the native tissue, and that dynamic deformational loading can yield significantly higher tensile properties. Copyright © 2013 Elsevier Ltd. All rights reserved.

  6. Vitamin D prevents articular cartilage erosion by regulating collagen II turnover through TGF-β1 in ovariectomized rats.

    PubMed

    Li, S; Niu, G; Wu, Y; Du, G; Huang, C; Yin, X; Liu, Z; Song, C; Leng, H

    2016-02-01

    To explore the effect of vitamin D on turnover of articular cartilage with ovariectomy (OVX) induced OA, and to investigate transforming growth factor-β1 (TGF-β1) as a possible underlying mechanism mediated by 1α,25(OH)2D3. Sixty-six rats were randomly allocated into seven groups: sham plus control diet (SHAM+CTL), OVX+CTL diet, sham plus vitamin D-deficient (VDD) diet, OVX+VDD diet, and three groups of ovariectomized rats treated with different doses of 1α,25(OH)2D3. The cartilage erosion and the levels of serum 17β-estradiol, 1α,25(OH)2D3 and C-telopeptide of type II collagen (CTX-II) were measured. TGF-β1, type II Collagen (CII), matrix metalloproteinases (MMP)-9,-13 in articular cartilage were assessed by immunohistochemistry. TGF-β1 and CTX-II expression were measured in articular cartilage chondrocytes treated with/without tumor necrosis factor (TNF-α), 1α,25(OH)2D3, and TGF-β receptor inhibitor (SB505124) in vitro. Cartilage erosion due to OVX was significantly reduced in a dose-dependent manner by 1α,25(OH)2D3 supplementation, and exacerbated by VDD. The expressions of TGF-β1 and CII in articular cartilage were suppressed by OVX and VDD, and rescued by 1α,25(OH)2D3 supplementation. The expression of MMP-9,-13 in articular cartilage increased with OVX and VDD, and decreased with 1α,25(OH)2D3 supplementation. In vitro experiments showed that 1α,25(OH)2D3 increased the TGF-β1 expression of TNF-α stimulated chondrocytes in a dose-dependent manner. 1α,25(OH)2D3 significantly counteracted the increased CTX-II release due to TNF-α stimulation, and this effect was significantly suppressed by SB505124. VDD aggravated cartilage erosion, and 1α,25(OH)2D3 supplementation showed protective effects in OVX-induced OA partly through the TGF-β1 pathway. Copyright © 2015 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

  7. Effect of Enrofloxacin on Histochemistry, Immunohistochemistry and Molecular Changes in Lamb Articular Cartilage.

    PubMed

    Khazaeel, Kaveh; Mazaheri, Yazdan; Hashemi Tabar, Mahmood; Najafzadeh, Hossein; Morovvati, Hassan; Ghadrdan, Alireza

    2015-01-01

    Enrofloxacin is a synthetic chemotherapeutic agent from the class of the fluoroquinolones that is widely used to treat bacterial infections. It is metabolized to ciprofloxacin in the body as active metabolite. Fluoroquinolones change in the articular cartilage, especially with high doses and more than two weeks use. So, due to relatively excessive use of enrofloxacin in mammals and similarity of lambs to human subjects with respect to skeletal activity cycles, this study was done to investigate the effects of enrofloxacin on some cellular and molecular changes in growing lamb articular cartilage to evaluate some possible mechanisms involved these changes. Twelve, 2-month-old male lambs divided into three groups: control group received only normal saline; therapeutic group received 5mg/kg enrofloxacin subcutaneously, daily, for 15 days and toxic group received 35 mg/kg enrofloxacin in the same manner as therapeutic group. Twenty four hours after the last dose, the animals were sacrificed, and their stifle joints were dissected. Sampling from distal femoral and proximal tibial extremities was done quickly for further histological and molecular studies. Collagen-п content was studied with avidin-biotin immunohistochemistry method in different groups. Expression of Sox9 and caspase-3 was evaluated by Real-time PCR. Immunohistochemical changes were included decreases of matrix proteoglycans, carbohydrates, and Collagen-п in the toxic group. Some of these changes were observed in the therapeutic group with less intensity in comparison to the toxic group. Enrofloxacin were significantly decreased (P≤0.05). Sox9 expression in therapeutic and toxic groups compared to control group. But caspase -3 expressions in the toxic group significantly increased (P≤0.0001) with a comparison to other groups, while, between control and therapeutic groups, there were no significant differences. So, it can be concluded that enrofloxacin increases apoptosis in chondrocytes and

  8. Zonal Articular Cartilage Possesses Complex Mechanical Behavior Spanning Multiple Length Scales: Dependence on Chemical Heterogeneity, Anisotropy, and Microstructure

    NASA Astrophysics Data System (ADS)

    Wahlquist, Joseph A.

    This work focused on characterizing the mechanical behavior of biological material in physiologically relevant conditions and at sub millimeter length scales. Elucidating the time, length scale, and directionally dependent mechanical behavior of cartilage and other biological materials is critical to adequately recapitulate native mechanosensory cues for cells, create computational models that mimic native tissue behavior, and assess disease progression. This work focused on three broad aspects of characterizing the mechanical behavior of articular cartilage. First, we sought to reveal the causes of time-dependent deformation and variation of mechanical properties with distance from the articular surface. Second, we investigated size dependence of mechanical properties. Finally, we examined material anisotropy of both the calcified and uncalcified tissues of the osteochondral interface. This research provides insight into how articular cartilage serves to support physiologic loads and simultaneously sustain chondrocyte viability.

  9. In vitro determination of biomechanical properties of human articular cartilage in osteoarthritis using multi-parametric MRI

    NASA Astrophysics Data System (ADS)

    Juras, Vladimir; Bittsansky, Michal; Majdisova, Zuzana; Szomolanyi, Pavol; Sulzbacher, Irene; Gäbler, Stefan; Stampfl, Jürgen; Schüller, Georg; Trattnig, Siegfried

    2009-03-01

    The objective of this study was to evaluate the correlations between MR parameters and the biomechanical properties of naturally degenerated human articular cartilage. Human cartilage explants from the femoral condyles of patients who underwent total knee replacement were evaluated on a micro-imaging system at 3 T. To quantify glycosaminoglycan (GAG) content, delayed gadolinium-enhanced MRI of the cartilage (dGEMRIC) was used. T2 maps were created by using multi-echo, multi-slice spin echo sequences with six echoes: 15, 30, 45, 60, 75, and 90 ms. Data for apparent diffusion constant (ADC) maps were obtained from pulsed gradient spin echo (PGSE) sequences with five b-values: 10.472, 220.0, 627.0, 452.8, 724.5, and 957.7. MR parameters were correlated with mechanical parameters (instantaneous ( I) and equilibrium ( Eq) modulus and relaxation time ( τ)), and the OA stage of each cartilage specimen was determined by histological evaluation of hematoxylin-eosin stained slices. For some parameters, a high correlation was found: the correlation of T1Gd vs Eq ( r = 0.8095), T1Gd vs I/ Eq ( r = -0.8441) and T1Gd vs τ ( r = 0.8469). The correlation of T2 and ADC with selected biomechanical parameters was not statistically significant. In conclusion, GAG content measured by dGEMRIC is highly related to the selected biomechanical properties of naturally degenerated articular cartilage. In contrast, T2 and ADC were unable to estimate these properties. The results of the study imply that some MR parameters can non-invasively predict the biomechanical properties of degenerated articular cartilage.

  10. A Review of the Combination of Experimental Measurements and Fibril-Reinforced Modeling for Investigation of Articular Cartilage and Chondrocyte Response to Loading

    PubMed Central

    Wilson, Wouter; Isaksson, Hanna; Jurvelin, Jukka S.; Herzog, Walter; Korhonen, Rami K.

    2013-01-01

    The function of articular cartilage depends on its structure and composition, sensitively impaired in disease (e.g. osteoarthritis, OA). Responses of chondrocytes to tissue loading are modulated by the structure. Altered cell responses as an effect of OA may regulate cartilage mechanotransduction and cell biosynthesis. To be able to evaluate cell responses and factors affecting the onset and progression of OA, local tissue and cell stresses and strains in cartilage need to be characterized. This is extremely challenging with the presently available experimental techniques and therefore computational modeling is required. Modern models of articular cartilage are inhomogeneous and anisotropic, and they include many aspects of the real tissue structure and composition. In this paper, we provide an overview of the computational applications that have been developed for modeling the mechanics of articular cartilage at the tissue and cellular level. We concentrate on the use of fibril-reinforced models of cartilage. Furthermore, we introduce practical considerations for modeling applications, including also experimental tests that can be combined with the modeling approach. At the end, we discuss the prospects for patient-specific models when aiming to use finite element modeling analysis and evaluation of articular cartilage function, cellular responses, failure points, OA progression, and rehabilitation. PMID:23653665

  11. Articular cartilage tissue engineering with plasma-rich in growth factors and stem cells with nano scaffolds

    NASA Astrophysics Data System (ADS)

    Montaser, Laila M.; Abbassy, Hadeer A.; Fawzy, Sherin M.

    2016-09-01

    The ability to heal soft tissue injuries and regenerate cartilage is the Holy Grail of musculoskeletal medicine. Articular cartilage repair and regeneration is considered to be largely intractable due to the poor regenerative properties of this tissue. Due to their low self-repair ability, cartilage defects that result from joint injury, aging, or osteoarthritis, are the most often irreversible and are a major cause of joint pain and chronic disability. However, current methods do not perfectly restore hyaline cartilage and may lead to the apparition of fibro- or continue hypertrophic cartilage. The lack of efficient modalities of treatment has prompted research into tissue engineering combining stem cells, scaffold materials and environmental factors. The field of articular cartilage tissue engineering, which aims to repair, regenerate, and/or improve injured or diseased cartilage functionality, has evoked intense interest and holds great potential for improving cartilage therapy. Plasma-rich in growth factors (PRGF) and/or stem cells may be effective for tissue repair as well as cartilage regenerative processes. There is a great promise to advance current cartilage therapies toward achieving a consistently successful approach for addressing cartilage afflictions. Tissue engineering may be the best way to reach this objective via the use of stem cells, novel biologically inspired scaffolds and, emerging nanotechnology. In this paper, current and emergent approach in the field of cartilage tissue engineering is presented for specific application. In the next years, the development of new strategies using stem cells, in scaffolds, with supplementation of culture medium could improve the quality of new formed cartilage.

  12. Correlation between polarization sensitive optical coherence tomography and SHG microscopy in articular cartilage

    NASA Astrophysics Data System (ADS)

    Zhou, Xin; Ju, Myeong Jin; Huang, Lin; Tang, Shuo

    2017-02-01

    Polarization-sensitive optical coherence tomography (PS-OCT) and second harmonic generation (SHG) microscopy are two imaging modalities with different resolutions, field-of-views (FOV), and contrasts, while they both have the capability of imaging collagen fibers in biological tissues. PS-OCT can measure the tissue birefringence which is induced by highly organized fibers while SHG can image the collagen fiber organization with high resolution. Articular cartilage, with abundant structural collagen fibers, is a suitable sample to study the correlation between PS-OCT and SHG microscopy. Qualitative conjecture has been made that the phase retardation measured by PS-OCT is affected by the relationship between the collagen fiber orientation and the illumination direction. Anatomical studies show that the multilayered architecture of articular cartilage can be divided into four zones from its natural surface to the subchondral bone: the superficial zone, the middle zone, the deep zone, and the calcified zone. The different zones have different collagen fiber orientations, which can be studied by the different slopes in the cumulative phase retardation in PS-OCT. An algorithm is developed based on the quantitative analysis of PS-OCT phase retardation images to analyze the microstructural features in swine articular cartilage tissues. This algorithm utilizes the depth-dependent slope changing of phase retardation A-lines to segment structural layers. The results show good consistency with the knowledge of cartilage morphology and correlation with the SHG images measured at selected depth locations. The correlation between PS-OCT and SHG microscopy shows that PS-OCT has the potential to analyze both the macro and micro characteristics of biological tissues with abundant collagen fibers and other materials that may cause birefringence.

  13. [Subchondral drilling method combined with gum-bletilla complex to repair articular cartilage defects].

    PubMed

    Huang, Yong; Wang, Xin-Ling; Qiu, Heng; Xiao, Yi-Cheng; Wu, Zong-Hong; Xu, Jian

    2018-02-01

    Two types(A model and B model) of articular cartilage defect models were prepared by using adult New Zealand white rabbits. A model group was applied by drilling without through subchondral bone, whose right joint was repaired by composite scaffolds made by seed cell, gum-bletilla as well as Pluronic F-127, and left side was blank control. B model group was applied by subchondral drilling method, whose right joint was repaired by using composite scaffolds made by gum-bletilla and Pluronic F-127 without seed cells, and left side was blank control. Autogenous contrast was used in both model types. In addition, another group was applied with B model type rabbits, which was repaired with artificial complex material of Pluronic F-127 in both joint sides. 4, 12 and 24 weeks after operation, the animals were sacrificed and the samples were collected from repaired area for staining with HE, typeⅡcollagen immunohistochemical method, Alcian blue, and toluidine blue, and then were observed with optical microscope. Semi-quantitative scores were graded by referring to Wakitanis histological scoring standard to investigate the histomorphology of repaired tissue. Hyaline cartilage repairing was achieved in both Group A and Group B, with satisfactory results. There were no significant differences on repairing effects for articular cartilage defects between composite scaffolds made by seed cell, gum-bletilla and Pluronic F-127, and the composite scaffolds made by gum-bletilla and Pluronic F-127 without seed cell. Better repairing effects for articular cartilage defects were observed in groups with use of gum-bletilla, indicating that gum-bletilla is a vital part in composite scaffolds material. Copyright© by the Chinese Pharmaceutical Association.

  14. Joint distraction and movement for repair of articular cartilage in a rabbit model with subsequent weight-bearing.

    PubMed

    Nishino, T; Chang, F; Ishii, T; Yanai, T; Mishima, H; Ochiai, N

    2010-07-01

    We have previously shown that joint distraction and movement with a hinged external fixation device for 12 weeks was useful for repairing a large articular cartilage defect in a rabbit model. We have now investigated the results after six months and one year. The device was applied to 16 rabbits who underwent resection of the articular cartilage and subchondral bone from the entire tibial plateau. In group A (nine rabbits) the device was applied for six months. In group B (seven rabbits) it was in place for six months, after which it was removed and the animals were allowed to move freely for an additional six months. The cartilage remained sound in all rabbits. The areas of type II collagen-positive staining and repaired soft tissue were larger in group B than in group A. These findings provide evidence of long-term persistence of repaired cartilage with this technique and that weight-bearing has a positive effect on the quality of the cartilage.

  15. Preclinical and clinical data for the use of mesenchymal stem cells in articular cartilage tissue engineering.

    PubMed

    Tang, Quen Oak; Carasco, Clare Francesca; Gamie, Zakareya; Korres, Nectarios; Mantalaris, Athanasios; Tsiridis, Eleftherios

    2012-10-01

    With an ageing population, the prevalence of osteoarthritis (OA) has increased. Mesenchymal Stem Cells (MSCs) have been proposed to be an attractive alternative candidate in the tissue engineering of articular cartilage primarily due to its abundant source, reduced cartilage donor site morbidity, and strong capacity for proliferation and potential to differentiate toward a chondrogenic phenotype. A current overview of human, in vivo, and in vitro evidence on the use of MSCs in cartilage tissue engineering. We demonstrate robust evidence that MSCs have the potential to regenerate articular cartilage. We also identify the complexity of designing a suitable preclinical model and the challenges in considering its clinical application such as type of MSC, scaffold, culture construct and the method by which growth factors are delivered. Of great interest is further characterization of the factors that may prevent MSC-derived chondrocytes to undergo premature hypertrophy and to understand what enables the terminal developmental pathway for permanent hyaline cartilage regeneration. Despite this, there is an abundance of evidence suggesting that MSCs are a desirable cell source and will have significant impact in tissue engineering of cartilage in the future.

  16. An observational study on MR images of the effect of the discoid meniscus on articular cartilage thickness.

    PubMed

    Oni, David Babajide; Jeyapalan, K; Oni, Olusola O A

    2011-06-01

    The discoid meniscus is known to affect the morphology and mechanics of the knee compartment in which it is housed. To determine whether it also is determinative of the articular cartilage thickness, measurements were made on MR images. There was no statistically significant difference in femoral or tibial articular cartilage thickness between compartments with normal meniscus and compartments with discoid meniscus. These findings suggest that mechanical disturbances wrought by the discoid shape do not have a 'Wolff law' effect. Copyright © 2010. Published by Elsevier B.V.

  17. Application of multiphysics models to efficient design of experiments of solute transport across articular cartilage.

    PubMed

    Pouran, Behdad; Arbabi, Vahid; Weinans, Harrie; Zadpoor, Amir A

    2016-11-01

    Transport of solutes helps to regulate normal physiology and proper function of cartilage in diarthrodial joints. Multiple studies have shown the effects of characteristic parameters such as concentration of proteoglycans and collagens and the orientation of collagen fibrils on the diffusion process. However, not much quantitative information and accurate models are available to help understand how the characteristics of the fluid surrounding articular cartilage influence the diffusion process. In this study, we used a combination of micro-computed tomography experiments and biphasic-solute finite element models to study the effects of three parameters of the overlying bath on the diffusion of neutral solutes across cartilage zones. Those parameters include bath size, degree of stirring of the bath, and the size and concentration of the stagnant layer that forms at the interface of cartilage and bath. Parametric studies determined the minimum of the finite bath size for which the diffusion behavior reduces to that of an infinite bath. Stirring of the bath proved to remarkably influence neutral solute transport across cartilage zones. The well-stirred condition was achieved only when the ratio of the diffusivity of bath to that of cartilage was greater than ≈1000. While the thickness of the stagnant layer at the cartilage-bath interface did not significantly influence the diffusion behavior, increase in its concentration substantially elevated solute concentration in cartilage. Sufficient stirring attenuated the effects of the stagnant layer. Our findings could be used for efficient design of experimental protocols aimed at understanding the transport of molecules across articular cartilage. Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. Repair of injured articular and growth plate cartilage using mesenchymal stem cells and chondrogenic gene therapy.

    PubMed

    Xian, Cory J; Foster, Bruce K

    2006-05-01

    Injuries to the articular cartilage and growth plate are significant clinical problems due to their limited ability to regenerate themselves. Despite progress in orthopedic surgery and some success in development of chondrocyte transplantation treatment and in early tissue-engineering work, cartilage regeneration using a biological approach still remains a great challenge. In the last 15 years, researchers have made significant advances and tremendous progress in exploring the potentials of mesenchymal stem cells (MSCs) in cartilage repair. These include (a) identifying readily available sources of and devising appropriate techniques for isolation and culture expansion of MSCs that have good chondrogenic differentiation capability, (b) discovering appropriate growth factors (such as TGF-beta, IGF-I, BMPs, and FGF-2) that promote MSC chondrogenic differentiation, (c) identifying or engineering biological or artificial matrix scaffolds as carriers for MSCs and growth factors for their transplantation and defect filling. In addition, representing another new perspective for cartilage repair is the successful demonstration of gene therapy with chondrogenic growth factors or inflammatory inhibitors (either individually or in combination), either directly to the cartilage tissue or mediated through transducing and transplanting cultured chondrocytes, MSCs or other mesenchymal cells. However, despite these rapid pre-clinical advances and some success in engineering cartilage-like tissue and in repairing articular and growth plate cartilage, challenges of their clinical translation remain. To achieve clinical effectiveness, safety, and practicality of using MSCs for cartilage repair, one critical investigation will be to examine the optimal combination of MSC sources, growth factor cocktails, and supporting carrier matrixes. As more insights are acquired into the critical factors regulating MSC migration, proliferation and chondrogenic differentiation both ex vivo and in

  19. Chondroprotective effects of zoledronic acid on articular cartilage in dogs with experimentally induced osteoarthritis.

    PubMed

    Dearmin, Michael G; Trumble, Troy N; García, Anapatricia; Chambers, Jon N; Budsberg, Steven C

    2014-04-01

    To assess effects of zoledronic acid on biomarkers, radiographic scores, and gross articular cartilage changes in dogs with induced osteoarthritis. 21 purpose-bred hound-type dogs. The left stifle joint of each dog was examined arthroscopically to determine initial articular cartilage status, which was followed by cranial cruciate ligament (CrCL) transection to induce osteoarthritis. Dogs were assigned to 3 groups (control group, low dose [10 μg of zoledronic acid/kg], or high dose [25 μg of zoledronic acid/kg). Treatments were administered SC every 3 months for 1 year beginning the day after CrCL transection. Serum and synovial fluid samples and radiographs were obtained 0, 1, 3, 6, 9, and 12 months after transection. At 12 months, each joint was scored for cartilage defects. Serum and synovial fluid biomarkers of bone and cartilage turnover (bone-specific alkaline phosphatase, type I and II collagen, carboxy-propeptide of type II collagen, and chondroitin sulfate 846) were analyzed with ELISAs. The high-dose group had fewer total articular defects and lower severity scores in CrCL-transected stifle joints than did the control group. In addition, the high-dose group had significantly less change in collagenase cleavage of type I or II collagen in the synovial fluid at 1 and 3 months after CrCL transection than did the control group and also had greater changes in bone-specific alkaline phosphatase in synovial fluid at 3 months after CrCL transection than did the control group. Zoledronic acid had a chondroprotective effect in dogs with a transected CrCL.

  20. Articular cartilage regeneration with autologous peripheral blood progenitor cells and hyaluronic acid after arthroscopic subchondral drilling: a report of 5 cases with histology.

    PubMed

    Saw, Khay-Yong; Anz, Adam; Merican, Shahrin; Tay, Yong-Guan; Ragavanaidu, Kunaseegaran; Jee, Caroline S Y; McGuire, David A

    2011-04-01

    The purpose of this study was to evaluate the quality of articular cartilage regeneration after arthroscopic subchondral drilling followed by postoperative intraarticular injections of autologous peripheral blood progenitor cells (PBPCs) in combination with hyaluronic acid (HA). Five patients underwent second-look arthroscopy with chondral core biopsy. These 5 patients are part of a larger pilot study in which 180 patients with International Cartilage Repair Society grade III and IV lesions of the knee joint underwent arthroscopic subchondral drilling followed by postoperative intra-articular injections. Continuous passive motion was used on the operated knee 2 hours per day for 4 weeks. Partial weight bearing was observed for the first 6 to 8 weeks. Autologous PBPCs were harvested 1 week after surgery. One week after surgery, 8 mL of the harvested PBPCs in combination with 2 mL of HA was injected intra-articularly into the operated knee. The remaining PBPCs were divided into vials and cryopreserved. A total of 5 weekly intra-articular injections were given. Second-look arthroscopy confirmed articular cartilage regeneration, and histologic sections showed features of hyaline cartilage. Apart from the minimal discomfort of PBPC harvesting and localized pain associated with the intra-articular injections, there were no other notable adverse reactions. Articular hyaline cartilage regeneration is possible with arthroscopic subchondral drilling followed by postoperative intraarticular injections of autologous PBPCs in combination with HA. Level IV, therapeutic case series. Copyright © 2011 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

  1. Three-Dimensional Printing Articular Cartilage: Recapitulating the Complexity of Native Tissue.

    PubMed

    Guo, Ting; Lembong, Josephine; Zhang, Lijie Grace; Fisher, John P

    2017-06-01

    In the past few decades, the field of tissue engineering combined with rapid prototyping (RP) techniques has been successful in creating biological substitutes that mimic tissues. Its applications in regenerative medicine have drawn efforts in research from various scientific fields, diagnostics, and clinical translation to therapies. While some areas of therapeutics are well developed, such as skin replacement, many others such as cartilage repair can still greatly benefit from tissue engineering and RP due to the low success and/or inefficiency of current existing, often surgical treatments. Through fabrication of complex scaffolds and development of advanced materials, RP provides a new avenue for cartilage repair. Computer-aided design and three-dimensional (3D) printing allow the fabrication of modeled cartilage scaffolds for repair and regeneration of damaged cartilage tissues. Specifically, the various processes of 3D printing will be discussed in details, both cellular and acellular techniques, covering the different materials, geometries, and operational printing conditions for the development of tissue-engineered articular cartilage. Finally, we conclude with some insights on future applications and challenges related to this technology, especially using 3D printing techniques to recapitulate the complexity of native structure for advanced cartilage regeneration.

  2. Full-thickness knee articular cartilage defects in national football league combine athletes undergoing magnetic resonance imaging: prevalence, location, and association with previous surgery.

    PubMed

    Nepple, Jeffrey J; Wright, Rick W; Matava, Matthew J; Brophy, Robert H

    2012-06-01

    To better define the prevalence and location of full-thickness articular cartilage lesions in elite football players undergoing knee magnetic resonance imaging (MRI) at the National Football League (NFL) Invitational Combine and assess the association of these lesions with previous knee surgery. We performed a retrospective review of all participants in the NFL Combine undergoing a knee MRI scan from 2005 to 2009. Each MRI scan was reviewed for evidence of articular cartilage disease. History of previous knee surgery including anterior cruciate ligament reconstruction, meniscal procedures, and articular cartilage surgery was recorded for each athlete. Knees with a history of previous articular cartilage restoration surgery were excluded from the analysis. A total of 704 knee MRI scans were included in the analysis. Full-thickness articular cartilage lesions were associated with a history of any previous knee surgery (P < .001) and, specifically, previous meniscectomy (P < .001) but not with anterior cruciate ligament reconstruction (P = .7). Full-thickness lesions were present in 27% of knees with a previous meniscectomy compared with 12% of knees without any previous meniscal surgery. Full-thickness lesions in the lateral compartment were associated with previous lateral meniscectomy (P < .001); a similar relation was seen for medial meniscus tears in the medial compartment (P = .01). Full-thickness articular cartilage lesions of the knee were present in 17.3% of elite American football players at the NFL Combine undergoing MRI. The lateral compartment appears to be at greater risk for full-thickness cartilage loss. Previous knee surgery, particularly meniscectomy, is associated with these lesions. Level IV, therapeutic case series. Copyright © 2012 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

  3. Mechanical Loading of Articular Cartilage Reduces IL-1-Induced Enzyme Expression

    PubMed Central

    Torzilli, P. A.; Bhargava, M.; Chen, C. T.

    2011-01-01

    Objective: Exposure of articular cartilage to interleukin-1 (IL-1) results in increased synthesis of matrix degrading enzymes. Previously mechanical load applied together with IL-1 stimulation was found to reduce aggrecan cleavage by ADAMTS-4 and 5 and MMP-1, -3, -9, and -13 and reduce proteoglycan loss from the extracellular matrix. To further delineate the inhibition mechanism the gene expression of ADAMTS-4 and 5; MMP-1, -3, -9, and -13; and TIMP-1, -2, and -3 were measured. Design: Mature bovine articular cartilage was stimulated with a 0.5 MPa compressive stress and 10 ng/ml of IL-1α for 3 days and then allowed to recover without stimulation for 1 additional day. The media was assayed for proteoglycan content on a daily basis, while chondrocyte gene expression (mRNA) was measured during stimulation and 1 day of recovery. Results: Mechanical load alone did not change the gene expression for ADAMTS, MMP, or TIMP. IL-1 caused an increase in gene expression for all enzymes after 1 day of stimulation while not affecting the TIMP levels. Load applied together with IL-1 decreased the expression levels of ADAMTS-4 and -5 and MMP-1 and -3 and increased TIMP-3 expression. Conclusions: A mechanical load appears to modify cartilage degradation by IL-1 at the cellular level by reducing mRNA. PMID:22039566

  4. Characterization of Articular Cartilage Recovery and Its Correlation with Optical Response in the Near-Infrared Spectral Range.

    PubMed

    Afara, Isaac Oluwaseun; Singh, Sanjleena; Moody, Hayley; Zhang, Lihai; Oloyede, Adekunle

    2017-07-01

    In this study, we examine the capacity of a new parameter, based on the recovery response of articular cartilage, to distinguish between healthy and damaged tissues. We also investigate whether or not this new parameter correlates with the near-infrared (NIR) optical response of articular cartilage. Normal and artificially degenerated (proteoglycan-depleted) bovine cartilage samples were nondestructively probed using NIR spectroscopy. Subsequently they were subjected to a load and unloading protocol, and the recovery response was logged during unloading. The recovery parameter, elastic rebound ( E R ), is based on the strain energy released as the samples underwent instantaneous elastic recovery. Our results reveal positive relationship between the rebound parameter and cartilage proteoglycan content (normal samples: 2.20 ± 0.10 N mm; proteoglycan-depleted samples: 0.50 ± 0.04 N mm for 1 hour of enzymatic treatment and 0.13 ± 0.02 N mm for 4 hours of enzymatic treatment). In addition, multivariate analysis using partial least squares regression was employed to investigate the relationship between E R and NIR spectral data. The results reveal significantly high correlation ( R 2 cal = 98.35% and R 2 val = 79.87%; P < 0.0001), with relatively low error (14%), between the recovery and optical response of cartilage in the combined NIR regions 5,450 to 6,100 cm -1 and 7,500 to 12,500 cm -1 . We conclude that E R can indicate the mechanical condition and state of health of articular cartilage. The correlation of E R with cartilage optical response in the NIR range could facilitate real-time evaluation of the tissue's integrity during arthroscopic surgery and could also provide an important tool for cartilage assessment in tissue engineering and regeneration research.

  5. Monitoring of the degradation in the rat's articular cartilage inducing osteoarthritis using common-path Fourier-domain optical coherence tomography

    NASA Astrophysics Data System (ADS)

    Shin, D. H.; Park, S. H.; Kim, B. Y.; Lee, M. Y.; Baik, H. K.; Seo, J. H.; Kang, J. U.; Song, C. G.

    2013-03-01

    The objective of this experiment is to evaluate the utility and limitations of optical coherence tomography (OCT) for real-time, high-resolution structural analysis. We monitored the degradation of the rat's articular cartilage inducing osteoarthritis (OA) and the change of the rat's articular cartilage recovery by treatment medication, using our developed common-path Fourier-domain (CP-FD) OCT. Also, we have done a comparative analysis the rat's articular cartilage and OA grade. To observe the progression of OA, we induced OA by injecting the monosodium iodoacetate (MIA) into the right knee joint. After the injection of MIA, we sacrificed the rats at intervals of 3 days and obtained OCT and histological images. OCT and histological images showed the OA progress of similar pattern. These results illustrated the potential for non-invasive diagnosis about the grade of OA using CP-FD OCT.

  6. An In Vivo Lapine Model for Impact-Induced Injury and Osteoarthritic Degeneration of Articular Cartilage

    PubMed Central

    Alexander, Peter G.; McCarron, Jesse A.; Levine, Matthew J.; Melvin, Gary M.; Murray, Patrick J.; Manner, Paul A.

    2012-01-01

    Objective: In this study, we applied a spring-loaded impactor to deliver traumatic forces to articular cartilage in vivo. Based on our recent finding that a 0.28-J impact induces maximal catabolic response in adult bovine articular cartilage in vitro using this device, we hypothesize that this impact will induce the formation of a focal osteoarthritic defect in vivo. Design: The femoral condyle of New Zealand White rabbits was exposed and one of the following procedures performed: 0.28 J impact, anterior cruciate ligament transection, articular surface grooving, or no joint or cartilage destruction (control). After 24 hours, 4 weeks, or 12 weeks (n = 3 for each time point), wounds were localized with India ink, and tissue samples were collected and characterized histomorphometrically with Safranin O/Fast green staining and Hoechst 33342 nuclear staining for cell vitality. Results: The spring-loaded device delivered reproducible impacts with the following characteristics: impact area of 1.39 ± 0.11 mm2, calculated load of 326 ± 47.3 MPa, time-to-peak of 0.32 ± 0.03 ms, and an estimated maximal displacement of 25.1% ± 4.5% at the tip apex. The impact resulted in immediate cartilage fissuring and cell loss in the surface and intermediate zones, and it induced the formation of a focal lesion at 12 weeks. The degeneration was defined and appeared more slowly than after anterior cruciate ligament transection, and more pronounced and characteristic than after grooving. Conclusion: A single traumatic 0.28 J impact delivered with this spring-loaded impactor induces focal cartilage degeneration characteristic of osteoarthritis. PMID:26069642

  7. Pulsed CO2 laser for intra-articular cartilage vaporization and subchondral bone perforation in horses

    NASA Astrophysics Data System (ADS)

    Nixon, Alan J.; Roth, Jerry E.; Krook, Lennart P.

    1991-05-01

    A pulsed carbon dioxide laser was used to vaporize articular cartilage in four horses, and perforate the cartilage and subchondral bone in four horses. Both intercarpal joints were examined arthroscopically and either a 1 cm cartilage crater or a series of holes was created in the third carpal bone of one joint. The contralateral carpus served as a control. The horses were evaluated clinically for 8 weeks, euthanatized and the joints examined radiographically, grossly, and histologically. Pulsed carbon dioxide laser vaporized cartilage readily but penetrated bone poorly. Cartilage vaporization resulted in no greater swelling, heat, pain on flexion, lameness, or synovial fluid reaction than the sham procedure. Laser drilling resulted in a shallow, charred hole with a tenacious carbon residue, and in combination with the thermal damage to deeper bone, resulted in increased swelling, mild lameness and a low-grade, but persistent synovitis. Cartilage removal by laser vaporization resulted in rapid regrowth with fibrous and fibrovascular tissue and occasional regions of fibrocartilage at week 8. The subchondral bone, synovial membrane, and draining lymph nodes appeared essentially unaffected by the laser cartilage vaporization procedure. Conversely, carbon dioxide laser drilling of subchondral bone resulted in poor penetration, extensive areas of thermal necrosis of bone, and significant secondary damage to the apposing articular surface of the radial carpal bone. The carbon dioxide laser is a useful intraarticular instrument for removal of cartilage and has potential application in inaccessible regions of diarthrodial joints. It does not penetrate bone sufficiently to have application in subchondral drilling.

  8. The Relationship between MR Parameters and Biomechanical Quantities of Loaded Human Articular Cartilage in Osteoarthritis: An In-Vitro Study

    NASA Astrophysics Data System (ADS)

    Juráš, V.; Szomolányi, P.; Gäbler, S.; Frollo, I.; Trattnig, S.

    2009-01-01

    The aim of this study was to assess the changes in MRI parameters during applied load directly in MR scanner and correlate these changes with biomechanical parameters of human articular cartilage. Cartilage explants from patients who underwent total knee replacement were examined in the micro-imaging system in 3T scanner. Respective MRI parameters (T1 without- and T1 with contrast agent as a marker of proteoglycan content, T2 as a marker of collagen network anisotropy and ADC as a measure of diffusivity) were calculated in pre- and during compression state. Subsequently, these parameters were compared to the biomechanical properties of articular cartilage, instantaneous modulus (I), equilibrium modulus (Eq) and time of tissue relaxation (τ). Significant load-induced changes of T2 and ADC were recorded. High correlation between T1Gd and I (r = 0.6324), and between ADC and Eq (r = -0.4884) was found. Multi-parametric MRI may have great potential in analyzing static and dynamic biomechanical behavior of articular cartilage in early stages of osteoarthritis (OA).

  9. Vulnerability of the Superficial Zone of Immature Articular Cartilage to Compressive Injury

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Rolauffs, R.; Muehleman, C; Li, J

    The zonal composition and functioning of adult articular cartilage causes depth-dependent responses to compressive injury. In immature cartilage, shear and compressive moduli as well as collagen and sulfated glycosaminoglycan (sGAG) content also vary with depth. However, there is little understanding of the depth-dependent damage caused by injury. Since injury to immature knee joints most often causes articular cartilage lesions, this study was undertaken to characterize the zonal dependence of biomechanical, biochemical, and matrix-associated changes caused by compressive injury. Disks from the superficial and deeper zones of bovine calves were biomechanically characterized. Injury to the disks was achieved by applying amore » final strain of 50% compression at 100%/second, followed by biomechanical recharacterization. Tissue compaction upon injury as well as sGAG density, sGAG loss, and biosynthesis were measured. Collagen fiber orientation and matrix damage were assessed using histology, diffraction-enhanced x-ray imaging, and texture analysis. Injured superficial zone disks showed surface disruption, tissue compaction by 20.3 {+-} 4.3% (mean {+-} SEM), and immediate biomechanical impairment that was revealed by a mean {+-} SEM decrease in dynamic stiffness to 7.1 {+-} 3.3% of the value before injury and equilibrium moduli that were below the level of detection. Tissue areas that appeared intact on histology showed clear textural alterations. Injured deeper zone disks showed collagen crimping but remained undamaged and biomechanically intact. Superficial zone disks did not lose sGAG immediately after injury, but lost 17.8 {+-} 1.4% of sGAG after 48 hours; deeper zone disks lost only 2.8 {+-} 0.3% of sGAG content. Biomechanical impairment was associated primarily with structural damage. The soft superficial zone of immature cartilage is vulnerable to compressive injury, causing superficial matrix disruption, extensive compaction, and textural alteration, which

  10. 3-D segmentation of articular cartilages by graph cuts using knee MR images from osteoarthritis initiative

    NASA Astrophysics Data System (ADS)

    Shim, Hackjoon; Lee, Soochan; Kim, Bohyeong; Tao, Cheng; Chang, Samuel; Yun, Il Dong; Lee, Sang Uk; Kwoh, Kent; Bae, Kyongtae

    2008-03-01

    Knee osteoarthritis is the most common debilitating health condition affecting elderly population. MR imaging of the knee is highly sensitive for diagnosis and evaluation of the extent of knee osteoarthritis. Quantitative analysis of the progression of osteoarthritis is commonly based on segmentation and measurement of articular cartilage from knee MR images. Segmentation of the knee articular cartilage, however, is extremely laborious and technically demanding, because the cartilage is of complex geometry and thin and small in size. To improve precision and efficiency of the segmentation of the cartilage, we have applied a semi-automated segmentation method that is based on an s/t graph cut algorithm. The cost function was defined integrating regional and boundary cues. While regional cues can encode any intensity distributions of two regions, "object" (cartilage) and "background" (the rest), boundary cues are based on the intensity differences between neighboring pixels. For three-dimensional (3-D) segmentation, hard constraints are also specified in 3-D way facilitating user interaction. When our proposed semi-automated method was tested on clinical patients' MR images (160 slices, 0.7 mm slice thickness), a considerable amount of segmentation time was saved with improved efficiency, compared to a manual segmentation approach.

  11. Evaluation of grades 3 and 4 chondromalacia of the knee using T2*-weighted 3D gradient-echo articular cartilage imaging.

    PubMed

    Murphy, B J

    2001-06-01

    To determine the accuracy of T2*-weighted three-dimensional (3D) gradient-echo articular cartilage imaging in the identification of grades 3 and 4 chondromalacia of the knee. A retrospective evaluation of 80 patients who underwent both arthroscopic and MRI evaluation was performed. The 3D images were interpreted by one observer without knowledge of the surgical results. The medial and lateral femoral condyles, the medial and lateral tibial plateau, the patellar cartilage and trochlear groove were evaluated. MR cartilage images were considered positive if focal reduction of cartilage thickness was present (grade 3 chondromalacia) or if complete loss of cartilage was present (grade 4 chondromalacia). Comparison of the 3D MR results with the arthroscopic findings was performed. Eighty patients were included in the study group. A total of 480 articular cartilage sites were evaluated with MRI and arthroscopy. Results of MR identification of grades 3 and 4 chondromalacia, all sites combined, were: sensitivity 83%, specificity 97%, false negative rate 17%, false positive rate 3%, positive predictive value 87%, negative predictive value 95%, overall accuracy 93%. The results demonstrate that T2*-weighted 3D gradient-echo articular cartilage imaging can identify grades 3 and 4 chondromalacia of the knee.

  12. Biochemical quantification of DNA in human articular and septal cartilage using PicoGreen and Hoechst 33258.

    PubMed

    McGowan, K B; Kurtis, M S; Lottman, L M; Watson, D; Sah, R L

    2002-07-01

    To compare two fluorometric assays, utilizing (1) the bisbenzimidazole Hoechst 33258 and (2) PicoGreen, for determining DNA content in human cartilage. Human articular and nasal septal cartilage explants were digested using proteinase K. Portions of sample digest were analysed for intrinsic and dye-enhanced fluorescence with either Hoechst 33258 or PicoGreen. Intrinsic tissue fluorescence in both articular and septal cartilage increased with age and was prominent at wavelengths used for Hoechst 33258 but relatively low at wavelengths used for PicoGreen. The relative contribution of intrinsic fluorescence to total dye-enhanced fluorescence of human cartilage was markedly greater for Hoechst 33258 (19-57%) than for PicoGreen (2-7%). Thus, in many situations, DNA in human cartilage can be assayed using PicoGreen without the need to correct for intrinsic cartilage fluorescence. The enhancement of fluorescence by each dye was found to be specific for DNA, as shown by fluorescence spectra, >90% sensitivity to DNase, and resistance to RNase. In addition, little or no interference was caused by non-DNA tissue components, since DNA caused an equal enhancement in the absence or presence of proteinase K digested human cartilage, once intrinsic cartilage fluorescence was subtracted. PicoGreen was more sensitive for assaying DNA (0.9ng DNA/ml) than Hoechst 33258 (6ng DNA/ml) and can also be used in a microplate reader. PicoGreen can be used in a rapid and sensitive assay to quantify DNA in small samples of human cartilage. Copyright 2002 Published by Elsevier Science Ltd on behalf of OsteoArthritis Research Society International.

  13. Effects of holmium:YAG laser on equine articular cartilage and subchondral bone adjacent to traumatic lesions

    NASA Astrophysics Data System (ADS)

    Collier, Michael A.; Haugland, L. Mark; Bellamy, Janine; Johnson, Lanny L.; Rohrer, Michael D.; Walls, Robert C.; Bartels, Kenneth E.

    1994-09-01

    The effects of Ho:YAG laser energy on articular cartilage and subchondral bone adjacent to traumatically created cartilage lesions in a continuous weight-bearing model were investigated. The 2.1 micrometers wavelength was delivered in hand-controlled contact and near-contact hard tissue arthroscopic surgery in a saline medium. Bilateral arthroscopy was performed on normal antebrachiocarpal and intercarpal joints of four adult horses. One-hundred twenty traumatic lesions were created on three weight-bearing articular surfaces with a knife, curette, or a motorized burr. Depths of the lesions were partial and full thickness. Configurations of the lesions were lacerations, scrapes, and craters. Left limbs were used as controls. Right limb lesions were treated with various intensities of laser energy. Animals were sacrificed at intervals of 1, 3, and 8 weeks. Gross microscopic anatomy was documented, and tissue sections were subjected to blind review by a pathologist. Mankin grading for cellularity and proteoglycan content was used to qualitatively evaluate cartilage response. Cartilage adjacent to all lesions exposed to laser energy had better cellularity and proteoglycan content than corresponding controls by Mankin grading.

  14. Characterization of enzymatically induced degradation of articular cartilage using high frequency ultrasound

    NASA Astrophysics Data System (ADS)

    Töyräs, J.; Rieppo, J.; Nieminen, M. T.; Helminen, H. J.; Jurvelin, J. S.

    1999-11-01

    Ultrasound may provide a quantitative technique for the characterization of cartilage changes typical of early osteoarthrosis. In this study, specific changes in bovine articular cartilage were induced using collagenase and chondroitinase ABC, enzymes that selectively degrade collagen fibril network and digest proteoglycans, respectively. Changes in cartilage structure and properties were quantified using high frequency ultrasound, microscopic analyses and mechanical indentation tests. The ultrasound reflection coefficient of the physiological saline-cartilage interface (R1) decreased significantly (-96.4%, p<0.01) in the collagenase digested cartilage compared to controls. Also a significantly lower ultrasound velocity (-6.2%, p<0.01) was revealed after collagenase digestion. After chondroitinase ABC digestion, a new acoustic interface at the depth of the enzyme penetration front was detected. Cartilage thickness, as determined with ultrasound, showed a high, linear correlation (R = 0.943, n = 60, average difference 0.073 mm (4.0%)) with the thickness measured by the needle-probe method. Both enzymes induced a significant decrease in the Young's modulus of cartilage (p<0.01). Our results indicate that high frequency ultrasound provides a sensitive technique for the analysis of cartilage structure and properties. Possibly ultrasound may be utilized in vivo as a quantitative probe during arthroscopy.

  15. Extension of knee immobilization delays recovery of histological damages in the anterior cruciate ligament insertion and articular cartilage in rabbits.

    PubMed

    Mutsuzaki, Hirotaka; Nakajima, Hiromi; Sakane, Masataka

    2018-01-01

    [Purpose] To investigate the influence of knee immobilization period on recovery of histological damages in the anterior cruciate ligament (ACL) insertion and articular cartilage in rabbits. This knowledge is important for determining the appropriate rehabilitation approach for patients with ligament injuries, fracture, disuse atrophy, and degenerative joint disease. [Materials and Methods] Forty-eight male Japanese white rabbits were divided equally into the remobilization and control groups. The remobilization group had the right knee surgically immobilized, and was divided equally into four subgroups according to the duration of immobilization (1, 2, 4 and 8 weeks). After the immobilization was removed, the rabbits moved freely for 8 weeks. The control group underwent sham operation and followed the same time course as the remobilization group. The chondrocyte apoptosis rate and chondrocyte proliferation rate in the ACL insertion and articular cartilage were analyzed after remobilization. [Results] In the ACL insertion, the remobilization group had a higher chondrocyte apoptosis rate than the control group after 8 weeks of immobilization, and a lower chondrocyte proliferation rate than the control group after 4 and 8 weeks of immobilization. In the articular cartilage, the remobilization group had a lower chondrocyte proliferation rate than the control group after 8 weeks of immobilization. After 8 weeks of remobilization, the ACL insertion and articular cartilage are not completely recovered after 4 and 8 weeks of immobilization, respectively. [Conclusion] Our results suggest that 8 weeks of remobilization will result in recovery of the ACL insertion after 2 weeks of knee immobilization, and recovery of the articular cartilage after 4 weeks of knee immobilization. If 8 weeks of immobilization occurs, a remobilization duration of more than 8 weeks may be necessary.

  16. Benefits of Ilizarov automated bone distraction for nerves and articular cartilage in experimental leg lengthening.

    PubMed

    Shchudlo, Nathalia; Varsegova, Tatyana; Stupina, Tatyana; Shchudlo, Michael; Saifutdinov, Marat; Yemanov, Andrey

    2017-09-18

    To determine peculiarities of tissue responses to manual and automated Ilizarov bone distraction in nerves and articular cartilage. Twenty-nine dogs were divided in two experimental groups: Group M - leg lengthening with manual distraction (1 mm/d in 4 steps), Group A - automated distraction (1 mm/d in 60 steps) and intact group. Animals were euthanized at the end of distraction, at 30 th day of fixation in apparatus and 30 d after the fixator removal. M-responses in gastrocnemius and tibialis anterior muscles were recorded, numerical histology of peroneal and tibialis nerves and knee cartilage semi-thin sections, scanning electron microscopy and X-ray electron probe microanalysis were performed. Better restoration of M-response amplitudes in leg muscles was noted in A-group. Fibrosis of epineurium with adipocytes loss in peroneal nerve, subperineurial edema and fibrosis of endoneurium in some fascicles of both nerves were noted only in M-group, shares of nerve fibers with atrophic and degenerative changes were bigger in M-group than in A-group. At the end of experiment morphometric parameters of nerve fibers in peroneal nerve were comparable with intact nerve only in A-group. Quantitative parameters of articular cartilage (thickness, volumetric densities of chondrocytes, percentages of isogenic clusters and empty cellular lacunas, contents of sulfur and calcium) were badly changed in M-group and less changed in A-group. Automated Ilizarov distraction is more safe method of orthopedic leg lengthening than manual distraction in points of nervous fibers survival and articular cartilage arthrotic changes.

  17. Benefits of Ilizarov automated bone distraction for nerves and articular cartilage in experimental leg lengthening

    PubMed Central

    Shchudlo, Nathalia; Varsegova, Tatyana; Stupina, Tatyana; Shchudlo, Michael; Saifutdinov, Marat; Yemanov, Andrey

    2017-01-01

    AIM To determine peculiarities of tissue responses to manual and automated Ilizarov bone distraction in nerves and articular cartilage. METHODS Twenty-nine dogs were divided in two experimental groups: Group M - leg lengthening with manual distraction (1 mm/d in 4 steps), Group A - automated distraction (1 mm/d in 60 steps) and intact group. Animals were euthanized at the end of distraction, at 30th day of fixation in apparatus and 30 d after the fixator removal. M-responses in gastrocnemius and tibialis anterior muscles were recorded, numerical histology of peroneal and tibialis nerves and knee cartilage semi-thin sections, scanning electron microscopy and X-ray electron probe microanalysis were performed. RESULTS Better restoration of M-response amplitudes in leg muscles was noted in A-group. Fibrosis of epineurium with adipocytes loss in peroneal nerve, subperineurial edema and fibrosis of endoneurium in some fascicles of both nerves were noted only in M-group, shares of nerve fibers with atrophic and degenerative changes were bigger in M-group than in A-group. At the end of experiment morphometric parameters of nerve fibers in peroneal nerve were comparable with intact nerve only in A-group. Quantitative parameters of articular cartilage (thickness, volumetric densities of chondrocytes, percentages of isogenic clusters and empty cellular lacunas, contents of sulfur and calcium) were badly changed in M-group and less changed in A-group. CONCLUSION Automated Ilizarov distraction is more safe method of orthopedic leg lengthening than manual distraction in points of nervous fibers survival and articular cartilage arthrotic changes. PMID:28979852

  18. The Influence of Articular Cartilage Thickness Reduction on Meniscus Biomechanics

    PubMed Central

    Łuczkiewicz, Piotr; Daszkiewicz, Karol; Chróścielewski, Jacek; Witkowski, Wojciech; Winklewski, Pawel J.

    2016-01-01

    Objective Evaluation of the biomechanical interaction between meniscus and cartilage in medial compartment knee osteoarthritis. Methods The finite element method was used to simulate knee joint contact mechanics. Three knee models were created on the basis of knee geometry from the Open Knee project. We reduced the thickness of medial cartilages in the intact knee model by approximately 50% to obtain a medial knee osteoarthritis (OA) model. Two variants of medial knee OA model with congruent and incongruent contact surfaces were analysed to investigate the influence of congruency. A nonlinear static analysis for one compressive load case was performed. The focus of the study was the influence of cartilage degeneration on meniscal extrusion and the values of the contact forces and contact areas. Results In the model with incongruent contact surfaces, we observed maximal compressive stress on the tibial plateau. In this model, the value of medial meniscus external shift was 95.3% greater, while the contact area between the tibial cartilage and medial meniscus was 50% lower than in the congruent contact surfaces model. After the non-uniform reduction of cartilage thickness, the medial meniscus carried only 48.4% of load in the medial compartment in comparison to 71.2% in the healthy knee model. Conclusions We have shown that the change in articular cartilage geometry may significantly reduce the role of meniscus in load transmission and the contact area between the meniscus and cartilage. Additionally, medial knee OA may increase the risk of meniscal extrusion in the medial compartment of the knee joint. PMID:27936066

  19. Ultrasound elastography to determine the layered mechanical properties of articular cartilage and the importance of such structural characteristics under load.

    PubMed

    McCredie, Alexandra J; Stride, Eleanor; Saffari, Nader

    2009-01-01

    Articular cartilage is an important load bearing surface in joints. Prone to damage and with limited self-repair ability, it is of interest to tissue engineers. Tissue implant design requires full mechanical characterisation of healthy native tissue. A layered organisation of reinforcing collagen fibrils exists in healthy articular cartilage and is believed to be important for correct tissue function. However, the effect of this on the local depth-dependent elasticity is poorly characterised. In this study, quasi-static ultrasound elastography is used both to compare the depth-dependent elastic properties of cartilage structures with two different fibril arrangements and to monitor changes in the elastic properties of engineered samples during development. Results show global and local elastic properties of the native tissues and highlight the differences caused by fibril architecture. At increasing culture periods, results from the engineered tissue demonstrate an increase in elastic stiffness and the time taken to reach equilibrium under a quasi-static displacement. The study suggests suitability of ultrasound elastography for design and monitoring engineered articular cartilage.

  20. FK506 protects against articular cartilage collagenous extra-cellular matrix degradation.

    PubMed

    Siebelt, M; van der Windt, A E; Groen, H C; Sandker, M; Waarsing, J H; Müller, C; de Jong, M; Jahr, H; Weinans, H

    2014-04-01

    Osteoarthritis (OA) is a non-rheumatologic joint disease characterized by progressive degeneration of the cartilage extra-cellular matrix (ECM), enhanced subchondral bone remodeling, activation of synovial macrophages and osteophyte growth. Inhibition of calcineurin (Cn) activity through tacrolimus (FK506) in in vitro monolayer chondrocytes exerts positive effects on ECM marker expression. This study therefore investigated the effects of FK506 on anabolic and catabolic markers of osteoarthritic chondrocytes in 2D and 3D in vitro cultures, and its therapeutic effects in an in vivo rat model of OA. Effects of high and low doses of FK506 on anabolic (QPCR/histochemistry) and catabolic (QPCR) markers were evaluated in vitro on isolated (2D) and ECM-embedded chondrocytes (explants, 3D pellets). Severe cartilage damage was induced unilaterally in rat knees using papain injections in combination with a moderate running protocol. Twenty rats were treated with FK506 orally and compared to twenty untreated controls. Subchondral cortical and trabecular bone changes (longitudinal microCT) and macrophage activation (SPECT/CT) were measured. Articular cartilage was analyzed ex vivo using contrast enhanced microCT and histology. FK506 treatment of osteoarthritic chondrocytes in vitro induced anabolic (mainly collagens) and reduced catabolic ECM marker expression. In line with this, FK506 treatment clearly protected ECM integrity in vivo by markedly decreasing subchondral sclerosis, less development of subchondral pores, depletion of synovial macrophage activation and lower osteophyte growth. FK506 protected cartilage matrix integrity in vitro and in vivo. Additionally, FK506 treatment in vivo reduced OA-like responses in different articular joint tissues and thereby makes Cn an interesting target for therapeutic intervention of OA. Copyright © 2014 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

  1. Strain-Dependent Oxidant Release in Articular Cartilage Originates from Mitochondria

    PubMed Central

    J, Brouillette M; S, Ramakrishnan P; M, Wagner V; E, Sauter E; J, Journot B; O, McKinley T; A, Martin J

    2013-01-01

    Mechanical loading is essential for articular cartilage homeostasis and plays a central role in the cartilage pathology, yet the mechanotransduction processes that underlie these effects remain unclear. Previously we showed that lethal amounts of reactive oxygen species (ROS) were liberated from the mitochondria in response to mechanical insult, and that chondrocyte deformation may be a source of ROS. To this end, we hypothesized that mechanically-induced mitochondrial ROS is related to the magnitude of cartilage deformation. To test this, we measured axial tissue strains in cartilage explants subjected to semi-confined compressive stresses of 0, 0.05, 0.1, 0.25, 0.5, or 1.0 MPa. The presence of ROS was then determined by confocal imaging with dihydroethidium (DHE), an oxidant sensitive fluorescent probe. Our results indicated that ROS levels increased linearly relative to the magnitude of axial strains (r2 = 0.83, p < 0.05), and significant cell death was observed at strains > 40%. By contrast, hydrostatic stress, which causes minimal tissue strain, had no significant effect. Cell permeable superoxide dismutase mimetic Mn(III)tetrakis (1-methyl-4-pyridyl) porphyrin pentachloride (MnTMPyP) significantly decreased ROS levels at 0.5 and 0.25 MPa. Electron transport chain inhibitor, rotenone, and cytoskeletal inhibitor, cytochalasin B, significantly decreased ROS levels at 0.25 MPa. Our findings strongly suggest that ROS and mitochondrial oxidants contribute to cartilage mechanobiology. PMID:23896937

  2. Natural Type II Collagen Hydrogel, Fibrin Sealant, and Adipose-Derived Stem Cells as a Promising Combination for Articular Cartilage Repair.

    PubMed

    Lazarini, Mariana; Bordeaux-Rego, Pedro; Giardini-Rosa, Renata; Duarte, Adriana S S; Baratti, Mariana Ozello; Zorzi, Alessandro Rozim; de Miranda, João Batista; Lenz Cesar, Carlos; Luzo, Ângela; Olalla Saad, Sara Teresinha

    2017-10-01

    Objective Articular cartilage is an avascular tissue with limited ability of self-regeneration and the current clinical treatments have restricted capacity to restore damages induced by trauma or diseases. Therefore, new techniques are being tested for cartilage repair, using scaffolds and/or stem cells. Although type II collagen hydrogel, fibrin sealant, and adipose-derived stem cells (ASCs) represent suitable alternatives for cartilage formation, their combination has not yet been investigated in vivo for focal articular cartilage defects. We performed a simple experimental procedure using the combination of these 3 compounds on cartilage lesions of rabbit knees. Design The hydrogel was developed in house and was first tested in vitro for chondrogenic differentiation. Next, implants were performed in chondral defects with or without ASCs and the degree of regeneration was macroscopically and microscopically evaluated. Results Production of proteoglycans and the increased expression of collagen type II (COL2α1), aggrecan (ACAN), and sex-determining region Y-box 9 (SOX9) confirmed the chondrogenic character of ASCs in the hydrogel in vitro. Importantly, the addition of ASC induced a higher overall repair of the chondral lesions and a better cellular organization and collagen fiber alignment compared with the same treatment without ASCs. This regenerating tissue also presented the expression of cartilage glycosaminoglycan and type II collagen. Conclusions Our results indicate that the combination of the 3 compounds is effective for articular cartilage repair and may be of future clinical interest.

  3. Enhancing integration of articular cartilage grafts via photochemical bonding.

    PubMed

    Arvayo, Alberto L; Wong, Ivan J; Dragoo, Jason L; Levenston, Marc E

    2018-03-25

    The integration of osteochondral grafts to native articular cartilage is critical as the lack of graft integration may lead to continued tissue degradation, poor load transfer and inadequate nutrient transport. Photochemical bonding promotes graft integration by activating a photosensitizer at the interface via a light source and avoids negative effects associated with other bonding techniques. We hypothesized that the bond strength depends on photosensitizer type and concentration in addition to light exposure. Photochemical bonding was evaluated using methylene blue (MB), a cationic phenothiazine photosensitizer, and two phthalocyanine photosensitizers, Al(III) phthalocyanine chloride tetrasulfonic acid (CASPc) and aluminum phthalocyanine chloride (AlPc). Exposure was altered by varying irradiation time for a fixed irradiance or by varying irradiance with a fixed irradiation time. MB was ineffective at producing bonding at the range of concentrations tested while CASPc produced a peak twofold bond strength increase over controls. AlPc produced substantial bonding at all concentrations with a peak 3.9-fold bond strength increase over controls. Parametric tests revealed that bond strength depended primarily on the total energy delivered to the bonding site rather than the rate of light delivery or light irradiance. Bond strength persisted for 1 week of in-vitro culture, which warrants further exploration for clinical applications. These studies indicate that photochemical bonding is a viable strategy for enhancing articular cartilage graft integration. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  4. The Effect of Antibody Size and Mechanical Loading on Solute Diffusion Through the Articular Surface of Cartilage.

    PubMed

    DiDomenico, Chris D; Goodearl, Andrew; Yarilina, Anna; Sun, Victor; Mitra, Soumya; Sterman, Annette Schwartz; Bonassar, Lawrence J

    2017-09-01

    Because of the heterogeneous nature of articular cartilage tissue, penetration of potential therapeutic molecules for osteoarthritis (OA) through the articular surface (AS) is complex, with many factors that affect transport of these solutes within the tissue. Therefore, the goal of this study is to investigate how the size of antibody (Ab) variants, as well as application of cyclic mechanical loading, affects solute transport within healthy cartilage tissue. Penetration of fluorescently tagged solutes was quantified using confocal microscopy. For all the solutes tested, fluorescence curves were obtained through the articular surface. On average, diffusivities for the solutes of sizes 200 kDa, 150 kDa, 50 kDa, and 25 kDa were 3.3, 3.4, 5.1, and 6.0 μm2/s from 0 to 100 μm from the articular surface. Diffusivities went up to a maximum of 16.5, 18.5, 20.5, and 23.4 μm2/s for the 200 kDa, 150 kDa, 50 kDa, and 25 kDa molecules, respectively, from 225 to 325 μm from the surface. Overall, the effect of loading was very significant, with maximal transport enhancement for each solute ranging from 2.2 to 3.4-fold near 275 μm. Ultimately, solutes of this size do not diffuse uniformly nor are convected uniformly, through the depth of the cartilage tissue. This research potentially holds great clinical significance to discover ways of further optimizing transport into cartilage and leads to effective antibody-based treatments for OA.

  5. The potential of IGF-1 and TGFbeta1 for promoting "adult" articular cartilage repair: an in vitro study.

    PubMed

    Davies, Lindsay C; Blain, Emma J; Gilbert, Sophie J; Caterson, Bruce; Duance, Victor C

    2008-07-01

    Research into articular cartilage repair, a tissue unable to spontaneously regenerate once injured, has focused on the generation of a biomechanically functional repair tissue with the characteristics of hyaline cartilage. This study was undertaken to provide insight into how to improve ex vivo chondrocyte amplification, without cellular dedifferentiation for cell-based methods of cartilage repair. We investigated the effects of insulin-like growth factor 1 (IGF-1) and transforming growth factor beta 1 (TGFbeta1) on cell proliferation and the de novo synthesis of sulfated glycosaminoglycans and collagen in chondrocytes isolated from skeletally mature bovine articular cartilage, whilst maintaining their chondrocytic phenotype. Here we demonstrate that mature differentiated chondrocytes respond to growth factor stimulation to promote de novo synthesis of matrix macromolecules. Additionally, chondrocytes stimulated with IGF-1 or TGFbeta1 induced receptor expression. We conclude that IGF-1 and TGFbeta1 in addition to autoregulatory effects have differential effects on each other when used in combination. This may be mediated by regulation of receptor expression or endogenous factors; these findings offer further options for improving strategies for repair of cartilage defects.

  6. C5a aggravates dysfunction of the articular cartilage and synovial fluid in rats with knee joint immobilization.

    PubMed

    Lu, Wei; Wang, Lin; Yao, Jing; Wo, Chunxin; Chen, Yu

    2018-06-22

    Degenerative alterations in articular cartilage are involved in the pathogenesis of osteoarthritis. The present study aimed to evaluate the role of complement component 5a (C5a) in osteoarthritic alterations in the articular cartilage and synovialis via a joint immobilization (IM) rat model. Rats were assigned to three groups: Control, IM and IM+anti‑C5a antibody (IM+anti‑C5a) groups. A terminal deoxynucleotidyl transferase dUTP nick end labeling assay and hematoxylin and eosin staining were used to evaluate the morphological alterations in the articular cartilage and synovialis. Reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) analysis, immunohistochemical analysis and western blotting were used to evaluate C5a expression in the articular cartilage and synovialis. An ELISA was used to evaluate C5a‑induced alterations in interleukin (IL)‑1β, IL‑17A and tumor necrosis factor (TNF)‑α levels in the serum and joint fluid. The results demonstrated that knee joint immobilization induced destruction of knee joint synovial fluid and cartilage in the IM and IM+anti‑C5a antibody groups. Immobilization significantly increased the expression levels of C5a in serum and joint fluid in the IM group. Immunohistochemistry, western blotting and RT‑qPCR analysis illustrated markedly increased expression of C5a in the IM group. Immobilization markedly increased the IL‑1β, IL‑17A and TNF‑α expression levels in the serum and joint fluid in the IM group. Anti‑C5a was able to decrease immobilization‑induced alterations in morphology and cytokines compared with the IM group. The expression of C5a was increased in synoviocytes and joint cartilage in the IM model. Pro‑inflammatory cytokines, including TNF‑α and IL‑1β were released in the activated synoviocytes via the induction of C5a, suggesting that C5a serves an important role in joint inflammatory processes.

  7. Determining Tension-Compression Nonlinear Mechanical Properties of Articular Cartilage from Indentation Testing.

    PubMed

    Chen, Xingyu; Zhou, Yilu; Wang, Liyun; Santare, Michael H; Wan, Leo Q; Lu, X Lucas

    2016-04-01

    The indentation test is widely used to determine the in situ biomechanical properties of articular cartilage. The mechanical parameters estimated from the test depend on the constitutive model adopted to analyze the data. Similar to most connective tissues, the solid matrix of cartilage displays different mechanical properties under tension and compression, termed tension-compression nonlinearity (TCN). In this study, cartilage was modeled as a porous elastic material with either a conewise linear elastic matrix with cubic symmetry or a solid matrix reinforced by a continuous fiber distribution. Both models are commonly used to describe the TCN of cartilage. The roles of each mechanical property in determining the indentation response of cartilage were identified by finite element simulation. Under constant loading, the equilibrium deformation of cartilage is mainly dependent on the compressive modulus, while the initial transient creep behavior is largely regulated by the tensile stiffness. More importantly, altering the permeability does not change the shape of the indentation creep curves, but introduces a parallel shift along the horizontal direction on a logarithmic time scale. Based on these findings, a highly efficient curve-fitting algorithm was designed, which can uniquely determine the three major mechanical properties of cartilage (compressive modulus, tensile modulus, and permeability) from a single indentation test. The new technique was tested on adult bovine knee cartilage and compared with results from the classic biphasic linear elastic curve-fitting program.

  8. Bonding of human meniscal and articular cartilage with photoactive 1,8-naphthalimide dyes

    NASA Astrophysics Data System (ADS)

    Judy, Millard M.; Nosir, Hany R.; Jackson, Robert W.; Matthews, James Lester; Lewis, David E.; Utecht, Ronald E.; Yuan, Dongwu

    1996-05-01

    This study focused on meniscal cartilage repair by using the laser-activated photoactive 1,8- naphthalimide dye N,N'-bis-{6-[2-(2-(2- aminoethoxy)ethoxy)ethoxyethyl]amino-1H-benz (de)isoquinolin-1,3(2H)-dion-2- yl}-1,11-diamino-3,6,9-trioxaundecane. Harvested cadaveric human menisci were debrided and carved into strips 1 mm thick, 10 mm long, and 3 mm wide. Each strip was divided into two flaps, the surface painted with photoactive dye, the painted surfaces overlapped, the sample wrapped in Saran film, and the composite sandwiched between two glass slides at a pressure of approximately 3 kg/cm2. The sample then was transilluminated by argon ion laser light of 457.9-nm wavelength at a power density of 200 mW/cm2 with exposure times up to 5 h (3902 J/cm2 energy density). Essentially, the same procedures were performed for human femoral articular cartilage samples. Control experiments were conducted with laser irradiation alone and with dye alone. All the specimens were stored in isotonic saline solution for 2 h after irradiation to ensure hydration. The bond shear-strength was then tested and samples prepared for optical and electron transmission microscopy. Shear strength values of up to 1.8 kg/cm2 for meniscal tissues and 1.2 kg/cm2 for articular cartilaginous tissues were obtained for exposures of 3902 J/cm2. Shear strength values of approximately 0.9 kg/cm2 and 0.4 kg/cm2, respectively, for meniscus and cartilage were obtained with 459 J/cm2 exposure. Dye- and light-only controls exhibited 0 kg/cm2 shear strength values. Microscopy revealed close contact at the bonded surface in the laser-activated, dye-treated-specimens. This study shows that the laser-activated photoactive dyes have the capability of athermally bonding the meniscal and articular cartilage surfaces.

  9. The concentration, gene expression, and spatial distribution of aggrecan in canine articular cartilage, meniscus, and anterior and posterior cruciate ligaments: a new molecular distinction between hyaline cartilage and fibrocartilage in the knee joint.

    PubMed

    Valiyaveettil, Manojkumar; Mort, John S; McDevitt, Cahir A

    2005-01-01

    The concentration, spatial distribution, and gene expression of aggrecan in meniscus, articular cartilage, and the anterior and posterior cruciate ligaments (ACL and PCL) was determined in the knee joints of five mature dogs. An anti-serum against peptide sequences specific to the G1 domain of aggrecan was employed in competitive-inhibition ELISA of guanidine HCl extracts and immunofluorescence microscopy. Gene expression was determined by Taqman real-time PCR. The concentration of aggrecan in articular cartilage (240.1 +/- 32 nMol/g dry weight) was higher than that in meniscus (medial meniscus: 33.4 +/- 4.3 nMol/g) and ligaments (ACL: 6.8 +/- 0.9 nMol/g). Aggrecan was more concentrated in the inner than the outer zone of the meniscus. Aggrecan in meniscus showed an organized, spatial network, in contrast to its diffuse distribution in articular cartilage. Thus, differences in the concentration, gene expression, and spatial distribution of aggrecan constitute another molecular distinction between hyaline cartilage and fibrocartilage of the knee.

  10. Imaging articular cartilage using second harmonic generation microscopy

    NASA Astrophysics Data System (ADS)

    Mansfield, Jessica C.; Winlove, C. Peter; Knapp, Karen; Matcher, Stephen J.

    2006-02-01

    Sub cellular resolution images of equine articular cartilage have been obtained using both second harmonic generation microscopy (SHGM) and two-photon fluorescence microscopy (TPFM). The SHGM images clearly map the distribution of the collagen II fibers within the extracellular matrix while the TPFM images show the distribution of endogenous two-photon fluorophores in both the cells and the extracellular matrix, highlighting especially the pericellular matrix and bright 2-3μm diameter features within the cells. To investigate the source of TPF in the extracellular matrix experiments have been carried out to see if it may originate from the proteoglycans. Pure solutions of the following proteoglycans hyaluronan, chondroitin sulfate and aggrecan have been imaged, only the aggrecan produced any TPF and here the intensity was not great enough to account for the TPF in the extracellular matrix. Also cartilage samples were subjected to a process to remove proteoglycans and cellular components. After this process the TPF from the samples had decreased by a factor of two, with respect to the SHG intensity.

  11. A biomechanical triphasic approach to the transport of nondilute solutions in articular cartilage.

    PubMed

    Abazari, Alireza; Elliott, Janet A W; Law, Garson K; McGann, Locksley E; Jomha, Nadr M

    2009-12-16

    Biomechanical models for biological tissues such as articular cartilage generally contain an ideal, dilute solution assumption. In this article, a biomechanical triphasic model of cartilage is described that includes nondilute treatment of concentrated solutions such as those applied in vitrification of biological tissues. The chemical potential equations of the triphasic model are modified and the transport equations are adjusted for the volume fraction and frictional coefficients of the solutes that are not negligible in such solutions. Four transport parameters, i.e., water permeability, solute permeability, diffusion coefficient of solute in solvent within the cartilage, and the cartilage stiffness modulus, are defined as four degrees of freedom for the model. Water and solute transport in cartilage were simulated using the model and predictions of average concentration increase and cartilage weight were fit to experimental data to obtain the values of the four transport parameters. As far as we know, this is the first study to formulate the solvent and solute transport equations of nondilute solutions in the cartilage matrix. It is shown that the values obtained for the transport parameters are within the ranges reported in the available literature, which confirms the proposed model approach.

  12. A Biomechanical Triphasic Approach to the Transport of Nondilute Solutions in Articular Cartilage

    PubMed Central

    Abazari, Alireza; Elliott, Janet A.W.; Law, Garson K.; McGann, Locksley E.; Jomha, Nadr M.

    2009-01-01

    Abstract Biomechanical models for biological tissues such as articular cartilage generally contain an ideal, dilute solution assumption. In this article, a biomechanical triphasic model of cartilage is described that includes nondilute treatment of concentrated solutions such as those applied in vitrification of biological tissues. The chemical potential equations of the triphasic model are modified and the transport equations are adjusted for the volume fraction and frictional coefficients of the solutes that are not negligible in such solutions. Four transport parameters, i.e., water permeability, solute permeability, diffusion coefficient of solute in solvent within the cartilage, and the cartilage stiffness modulus, are defined as four degrees of freedom for the model. Water and solute transport in cartilage were simulated using the model and predictions of average concentration increase and cartilage weight were fit to experimental data to obtain the values of the four transport parameters. As far as we know, this is the first study to formulate the solvent and solute transport equations of nondilute solutions in the cartilage matrix. It is shown that the values obtained for the transport parameters are within the ranges reported in the available literature, which confirms the proposed model approach. PMID:20006942

  13. Effect of Intra-articular Triamcinolone vs Saline on Knee Cartilage Volume and Pain in Patients With Knee Osteoarthritis: A Randomized Clinical Trial.

    PubMed

    McAlindon, Timothy E; LaValley, Michael P; Harvey, William F; Price, Lori Lyn; Driban, Jeffrey B; Zhang, Ming; Ward, Robert J

    2017-05-16

    Synovitis is common and is associated with progression of structural characteristics of knee osteoarthritis. Intra-articular corticosteroids could reduce cartilage damage associated with synovitis but might have adverse effects on cartilage and periarticular bone. To determine the effects of intra-articular injection of 40 mg of triamcinolone acetonide every 3 months on progression of cartilage loss and knee pain. Two-year, randomized, placebo-controlled, double-blind trial of intra-articular triamcinolone vs saline for symptomatic knee osteoarthritis with ultrasonic features of synovitis in 140 patients. Mixed-effects regression models with a random intercept were used to analyze the longitudinal repeated outcome measures. Patients fulfilling the American College of Rheumatology criteria for symptomatic knee osteoarthritis, Kellgren-Lawrence grades 2 or 3, were enrolled at Tufts Medical Center beginning February 11, 2013; all patients completed the study by January 1, 2015. Intra-articular triamcinolone (n = 70) or saline (n = 70) every 12 weeks for 2 years. Annual knee magnetic resonance imaging for quantitative evaluation of cartilage volume (minimal clinically important difference not yet defined), and Western Ontario and McMaster Universities Osteoarthritis index collected every 3 months (Likert pain subscale range, 0 [no pain] to 20 [extreme pain]; minimal clinically important improvement, 3.94). Among 140 randomized patients (mean age, 58 [SD, 8] years, 75 women [54%]), 119 (85%) completed the study. Intra-articular triamcinolone resulted in significantly greater cartilage volume loss than did saline for a mean change in index compartment cartilage thickness of -0.21 mm vs -0.10 mm (between-group difference, -0.11 mm; 95% CI, -0.20 to -0.03 mm); and no significant difference in pain (-1.2 vs -1.9; between-group difference, -0.6; 95% CI, -1.6 to 0.3). The saline group had 3 treatment-related adverse events compared with 5 in the triamcinolone group

  14. Deletion of IFT80 Impairs Epiphyseal and Articular Cartilage Formation Due to Disruption of Chondrocyte Differentiation

    PubMed Central

    Yuan, Xue; Yang, Shuying

    2015-01-01

    Intraflagellar transport proteins (IFT) play important roles in cilia formation and organ development. Partial loss of IFT80 function leads Jeune asphyxiating thoracic dystrophy (JATD) or short-rib polydactyly (SRP) syndrome type III, displaying narrow thoracic cavity and multiple cartilage anomalies. However, it is unknown how IFT80 regulates cartilage formation. To define the role and mechanism of IFT80 in chondrocyte function and cartilage formation, we generated a Col2α1; IFT80f/f mouse model by crossing IFT80f/f mice with inducible Col2α1-CreER mice, and deleted IFT80 in chondrocyte lineage by injection of tamoxifen into the mice in embryonic or postnatal stage. Loss of IFT80 in the embryonic stage resulted in short limbs at birth. Histological studies showed that IFT80-deficient mice have shortened cartilage with marked changes in cellular morphology and organization in the resting, proliferative, pre-hypertrophic, and hypertrophic zones. Moreover, deletion of IFT80 in the postnatal stage led to mouse stunted growth with shortened growth plate but thickened articular cartilage. Defects of ciliogenesis were found in the cartilage of IFT80-deficient mice and primary IFT80-deficient chondrocytes. Further study showed that chondrogenic differentiation was significantly inhibited in IFT80-deficient mice due to reduced hedgehog (Hh) signaling and increased Wnt signaling activities. These findings demonstrate that loss of IFT80 blocks chondrocyte differentiation by disruption of ciliogenesis and alteration of Hh and Wnt signaling transduction, which in turn alters epiphyseal and articular cartilage formation. PMID:26098911

  15. Shortwave-infrared Raman spectroscopic classification of water fractions in articular cartilage ex vivo

    NASA Astrophysics Data System (ADS)

    Unal, Mustafa; Akkus, Ozan

    2018-01-01

    Water loss is an early onset indicator of osteoarthritis. Although Raman spectroscopy (RS) holds the potential for measurement of cartilage hydration, the knowledge of Raman OH-stretch bands of biological tissue is very limited. We assesed here the sensitivity of RS to identify and classify water types in the cartilage. Raman spectrum measurements over the high wavenumber range were employed to identify different water fractions in articular cartilage. Raman spectra were collected from wet and sequentially dehydrated cartilage along with pure collagen type II and chondroitin sulfate standards. OH-stretch band of cartilage is dominated by mobile water, up to 95% of total intensities. We identified six peaks in cartilage spectrum using second-derivative analysis: peaks at 3200 and 3650 cm-1 are associated with organic matrix (both collagen and proteglycan) and matrix-bound water molecules. Peaks at 3250, 3453, and 3630 cm-1 are associated with collagen and collagen-related water molecules, whereas the peak at 3520 cm-1 is associated with proteoglycan (PG) and PG-related water molecules. The current work is the first thorough analysis of the Raman OH-stretch band of the cartilage and with the knowledge generated by this study, it may now be possible to study on cartilage hydration by RS.

  16. Magnetically targeted delivery through cartilage

    NASA Astrophysics Data System (ADS)

    Jafari, Sahar; Mair, Lamar O.; Chowdhury, Sagar; Nacev, Alek; Hilaman, Ryan; Stepanov, Pavel; Baker-McKee, James; Ijanaten, Said; Koudelka, Christian; English, Bradley; Malik, Pulkit; Weinberg, Irving N.

    2018-05-01

    In this study, we have invented a method of delivering drugs deep into articular cartilage with shaped dynamic magnetic fields acting on small metallic magnetic nanoparticles with polyethylene glycol coating and average diameter of 30 nm. It was shown that transport of magnetic nanoparticles through the entire thickness of bovine articular cartilage can be controlled by a combined alternating magnetic field at 100 Hz frequency and static magnetic field of 0.8 tesla (T) generated by 1" dia. x 2" thick permanent magnet. Magnetic nanoparticles transport through bovine articular cartilage samples was investigated at various settings of magnetic field and time durations. Combined application of an alternating magnetic field and the static field gradient resulted in a nearly 50 times increase in magnetic nanoparticles transport in bovine articular cartilage tissue as compared with static field conditions. This method can be applied to locally deliver therapeutic-loaded magnetic nanoparticles deep into articular cartilage to prevent cartilage degeneration and promote cartilage repair in osteoarthritis.

  17. Protective effect of zoledronic acid on articular cartilage and subchondral bone of rabbits with experimental knee osteoarthritis

    PubMed Central

    She, Guorong; Zhou, Ziqi; Zha, Zhengang; Wang, Fei; Pan, Xiaoting

    2017-01-01

    Subchondral bone reabsorption and remodeling are responsible for the initiation and progression of osteoarthritis (OA). Zoledronic acid (ZOL), a third-generation bisphosphonate (BIS), is an inhibitor of bone reabsorption. However, the intervention effect of ZOL on OA has not been fully characterized and remains to be directly demonstrated in animal experiments. The present study examined the microscopic and macroscopic changes in the anterior cruciate ligament transection (ACLT) model of OA in rabbits and evaluated the effects of ZOL on cartilage degeneration and subchondral bone loss. A total of 32 New Zealand white rabbits were randomly divided into four groups: High-, medium- and low-dose ZOL groups, which received an intravenous injection of 250, 50 and 10 µg/kg ZOL, respectively, after modeling, as well as an untreated group. The bone mineral density (BMD) of the knee joint was evaluated by dual-energy X-ray absorptiometry scanning immediately after modeling and at 4 and 8 weeks. At week 8, quantitative measurement of cartilage was performed by a specialized magnetic resonance imaging (MRI) technique, including three-dimensional fat-suppressed spoil gradient-recalled sequence and T2 mapping. The rabbits were sacrificed by air embolism after anesthesia and both knee joints were harvested and evaluated by general and histological observation. Toluidine blue and hematoxylin and eosin staining were used to assess histological changes in the articular cartilage. Quantitative analysis of cartilage histopathology was performed according to the Mankin scoring system. The BMD of ACLT joints dropped after modeling, which was effectively suppressed by ZOL at the high and medium dose but not the low dose. MRI scans demonstrated that in the untreated group, articular cartilages on ACLT knees were thinner than those on normal knees. The high dose of ZOL preserved the cartilage tissue thickness more efficiently than the medium and low doses. Observation of specimens and

  18. Topographical variation of the elastic properties of articular cartilage in the canine knee.

    PubMed

    Jurvelin, J S; Arokoski, J P; Hunziker, E B; Helminen, H J

    2000-06-01

    Equilibrium response of articular cartilage to indentation loading is controlled by the thickness (h) and elastic properties (shear modulus, mu, and Poisson's ratio, nu) of the tissue. In this study, we characterized topographical variation of Poisson's ratio of the articular cartilage in the canine knee joint (N=6). Poisson's ratio was measured using a microscopic technique. In this technique, the shape change of the cartilage disk was visualized while the cartilage was immersed in physiological solution and compressed in unconfined geometry. After a constant 5% axial strain, the lateral strain was measured during stress relaxation. At equilibrium, the lateral-to-axial strain ratio indicates the Poisson's ratio of the tissue. Indentation (equilibrium) data from our prior study (Arokoski et al., 1994. International Journal of Sports Medicine 15, 254-260) was re-analyzed using the Poisson's ratio results at the test site to derive values for shear and aggregate moduli. The lowest Poisson's ratio (0.070+/-0.016) located at the patellar surface of femur (FPI) and the highest (0.236+/-0.026) at the medial tibial plateau (TMI). The stiffest cartilage was found at the patellar groove of femur (micro=0.964+/-0.189MPa, H(a)=2.084+/-0. 409MPa) and the softest at the tibial plateaus (micro=0.385+/-0. 062MPa, H(a)=1.113+/-0.141MPa). Comparison of the mechanical results and the biochemical composition of the tissue (Jurvelin et al., 1988. Engineering in Medicine 17, 157-162) at the matched sites of the canine knee joint indicated a negative correlation between the Poisson's ratio and collagen-to-PG content ratio. This is in harmony with our previous findings which suggested that, in unconfined compression, the degree of lateral expansion in different tissue zones is related to collagen-to-PG ratio of the zone.

  19. Determination of differential gene expression profiles in superficial and deeper zones of mature rat articular cartilage using RNA sequencing of laser microdissected tissue specimens.

    PubMed

    Mori, Yoshifumi; Chung, Ung-Il; Tanaka, Sakae; Saito, Taku

    2014-01-01

    Superficial zone (SFZ) cells, which are morphologically and functionally distinct from chondrocytes in deeper zones, play important roles in the maintenance of articular cartilage. Here, we established an easy and reliable method for performance of laser microdissection (LMD) on cryosections of mature rat articular cartilage using an adhesive membrane. We further examined gene expression profiles in the SFZ and the deeper zones of articular cartilage by performing RNA sequencing (RNA-seq). We validated sample collection methods, RNA amplification and the RNA-seq data using real-time RT-PCR. The combined data provide comprehensive information regarding genes specifically expressed in the SFZ or deeper zones, as well as a useful protocol for expression analysis of microsamples of hard tissues.

  20. Oral administration of undenatured native chicken type II collagen (UC-II) diminished deterioration of articular cartilage in a rat model of osteoarthritis (OA).

    PubMed

    Bagi, C M; Berryman, E R; Teo, S; Lane, N E

    2017-12-01

    The aim of this study was to determine the ability of undenatured native chicken type II collagen (UC-II) to prevent excessive articular cartilage deterioration in a rat model of osteoarthritis (OA). Twenty male rats were subjected to partial medial meniscectomy tear (PMMT) surgery to induce OA. Immediately after the surgery 10 rats received vehicle and another 10 rats oral daily dose of UC-II at 0.66 mg/kg for a period of 8 weeks. In addition 10 naïve rats were used as an intact control and another 10 rats received sham surgery. Study endpoints included a weight-bearing capacity of front and hind legs, serum biomarkers of bone and cartilage metabolism, analyses of subchondral and cancellous bone at the tibial epiphysis and metaphysis, and cartilage pathology at the medial tibial plateau using histological methods. PMMT surgery produced moderate OA at the medial tibial plateau. Specifically, the deterioration of articular cartilage negatively impacted the weight bearing capacity of the operated limb. Immediate treatment with the UC-II preserved the weight-bearing capacity of the injured leg, preserved integrity of the cancellous bone at tibial metaphysis and limited the excessive osteophyte formation and deterioration of articular cartilage. Study results demonstrate that a clinically relevant daily dose of UC-II when applied immediately after injury can improve the mechanical function of the injured knee and prevent excessive deterioration of articular cartilage. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  1. Knee Pain and Mobility Impairments: Meniscal and Articular Cartilage Lesions Revision 2018: Using the Evidence to Guide Physical Therapist Practice.

    PubMed

    2018-02-01

    Meniscus and articular cartilage lesions are common knee injuries. The resulting knee pain and mobility impairments can be improved by physical therapists during nonoperative and operative management. Recommendations from clinical practice guidelines (CPGs) such as this revision, titled "Knee Pain and Mobility Impairments: Meniscal and Articular Cartilage Lesions," published in the February 2018 issue of JOSPT, can help physical therapists engage in evidence-informed practice and reduce unnecessary clinical variation. J Orthop Sports Phys Ther 2018;48(2):123-124. doi:10.2519/jospt.2018.0503.

  2. Magnetic resonance imaging of the femoral trochlea: evaluation of anatomical landmarks and grading articular cartilage in cadaveric knees.

    PubMed

    Muhle, Claus; Ahn, Joong Mo; Trudell, Debra; Resnick, Donald

    2008-06-01

    The purpose of the study was to define magnetic resonance imaging (MRI) findings before and after contrast medium opacification of the knee joint in cadaveric specimens to demonstrate anatomical landmarks of the trochlear surface in relation to the neighboring structures, and to evaluate different MRI sequences in the detection of cartilage defects of the trochlear and patellar surface of the knee. The morphology and relationship of the proximal trochlear surface to the prefemoral fat of the distal femur were investigated by use of different MR sequences before and after intra-articular gadolinium administration into the knee joint in ten cadaveric knees. Anatomic sections were subsequently obtained. In addition, evaluation of the articular surface of the trochlea was performed by two independent observers. The cartilage surfaces were graded using a 2-point system, and results were compared with macroscopic findings. Of 40 cartilage surfaces evaluated, histopathologic findings showed 9 normal surfaces, 20 containing partial-thickness defects, and 11 containing full-thickness defects. Compared with macroscopic data, sensitivity of MR sequences for the two reviewers was between 17 and 90%; specificity, 75 and 100%; positive predictive value, 75 and 100%; negative predictive value, 20 and 100%, depending on patellar or trochlea lesions. Interobserver variability for the presence of disease, which was measured using the kappa statistic, was dependent on the MR sequence used between 0.243 and 0.851. Magnetic resonance imaging sequences can be used to evaluate the cartilage of the trochlear surface with less accuracy when compared with the results of grading the articular cartilage of the patella.

  3. Perivascular Mesenchymal Stem Cells in Sheep: Characterization and Autologous Transplantation in a Model of Articular Cartilage Repair.

    PubMed

    Hindle, Paul; Baily, James; Khan, Nusrat; Biant, Leela C; Simpson, A Hamish R; Péault, Bruno

    2016-11-01

    Previous research has indicated that purified perivascular stem cells (PSCs) have increased chondrogenic potential compared to conventional mesenchymal stem cells (MSCs) derived in culture. This study aimed to develop an autologous large animal model for PSC transplantation and to specifically determine if implanted cells are retained in articular cartilage defects. Immunohistochemistry and fluorescence-activated cell sorting were used to ascertain the reactivity of anti-human and anti-ovine antibodies, which were combined and used to identify and isolate pericytes (CD34 - CD45 - CD146 + ) and adventitial cells (CD34 + CD45 - CD146 - ). The purified cells demonstrated osteogenic, adipogenic, and chondrogenic potential in culture. Autologous ovine PSCs (oPSCs) were isolated, cultured, and efficiently transfected using a green fluorescence protein (GFP) encoding lentivirus. The cells were implanted into articular cartilage defects on the medial femoral condyle using hydrogel and collagen membranes. Four weeks following implantation, the condyle was explanted and confocal laser scanning microscopy demonstrated the presence of oPSCs in the defect repaired with the hydrogel. These data suggest the testability in a large animal of native MSC autologous grafting, thus avoiding possible biases associated with xenotransplantation. Such a setting will be used in priority for indications in orthopedics, at first to model articular cartilage repair.

  4. Glucosamine:chondroitin or ginger root extract have little effect on articular cartilage in swine

    USDA-ARS?s Scientific Manuscript database

    Sows are culled at a high rate from breeding herds due to musclo-skeletal problems and lameness. Research in our laboratory has shown that even first-parity sows have significant amounts of osteochondritic lesions of their articular cartilage. Glusoamine chondroitin and ginger root extract have both...

  5. Toward an MRI-based method to measure non-uniform cartilage deformation: an MRI-cyclic loading apparatus system and steady-state cyclic displacement of articular cartilage under compressive loading.

    PubMed

    Neu, C P; Hull, M L

    2003-04-01

    Recent magnetic resonance imaging (MRI) techniques have shown potential for measuring non-uniform deformations throughout the volume (i.e. three-dimensional (3D) deformations) in small orthopedic tissues such as articular cartilage. However, to analyze cartilage deformation using MRI techniques, a system is required which can construct images from multiple acquisitions of MRI signals from the cartilage in both the underformed and deformed states. The objectives of the work reported in this article were to 1) design an apparatus that could apply highly repeatable cyclic compressive loads of 400 N and operate in the bore of an MRI scanner, 2) demonstrate that the apparatus and MRI scanner can be successfully integrated to observe 3D deformations in a phantom material, 3) use the apparatus to determine the load cycle necessary to achieve a steady-state deformation response in normal bovine articular cartilage samples using a flat-surfaced and nonporous indentor in unconfined compression. Composed of electronic and pneumatic components, the apparatus regulated pressure to a double-acting pneumatic cylinder so that (1) load-controlled compression cycles were applied to cartilage samples immersed in a saline bath, (2) loading and recovery periods within a cycle varied in time duration, and (3) load magnitude varied so that the stress applied to cartilage samples was within typical physiological ranges. In addition the apparatus allowed gating for MR image acquisition, and operation within the bore of an MRI scanner without creating image artifacts. The apparatus demonstrated high repeatability in load application with a standard deviation of 1.8% of the mean 400 N load applied. When the apparatus was integrated with an MRI scanner programmed with appropriate pulse sequences, images of a phantom material in both the underformed and deformed states were constructed by assembling data acquired through multiple signal acquisitions. Additionally, the number of cycles to reach

  6. Characterization of articular cartilage by combining microscopic analysis with a fibril-reinforced finite-element model.

    PubMed

    Julkunen, Petro; Kiviranta, Panu; Wilson, Wouter; Jurvelin, Jukka S; Korhonen, Rami K

    2007-01-01

    Load-bearing characteristics of articular cartilage are impaired during tissue degeneration. Quantitative microscopy enables in vitro investigation of cartilage structure but determination of tissue functional properties necessitates experimental mechanical testing. The fibril-reinforced poroviscoelastic (FRPVE) model has been used successfully for estimation of cartilage mechanical properties. The model includes realistic collagen network architecture, as shown by microscopic imaging techniques. The aim of the present study was to investigate the relationships between the cartilage proteoglycan (PG) and collagen content as assessed by quantitative microscopic findings, and model-based mechanical parameters of the tissue. Site-specific variation of the collagen network moduli, PG matrix modulus and permeability was analyzed. Cylindrical cartilage samples (n=22) were harvested from various sites of the bovine knee and shoulder joints. Collagen orientation, as quantitated by polarized light microscopy, was incorporated into the finite-element model. Stepwise stress-relaxation experiments in unconfined compression were conducted for the samples, and sample-specific models were fitted to the experimental data in order to determine values of the model parameters. For comparison, Fourier transform infrared imaging and digital densitometry were used for the determination of collagen and PG content in the same samples, respectively. The initial and strain-dependent fibril network moduli as well as the initial permeability correlated significantly with the tissue collagen content. The equilibrium Young's modulus of the nonfibrillar matrix and the strain dependency of permeability were significantly associated with the tissue PG content. The present study demonstrates that modern quantitative microscopic methods in combination with the FRPVE model are feasible methods to characterize the structure-function relationships of articular cartilage.

  7. [Quantification of acetabular coverage in normal adult].

    PubMed

    Lin, R M; Yang, C Y; Yu, C Y; Yang, C R; Chang, G L; Chou, Y L

    1991-03-01

    Quantification of acetabular coverage is important and can be expressed by superimposition of cartilage tracings on the maximum cross-sectional area of the femoral head. A practical Autolisp program on PC AutoCAD has been developed by us to quantify the acetabular coverage through numerical expression of the images of computed tomography. Thirty adults (60 hips) with normal center-edge angle and acetabular index in plain X ray were randomly selected for serial drops. These slices were prepared with a fixed coordination and in continuous sections of 5 mm in thickness. The contours of the cartilage of each section were digitized into a PC computer and processed by AutoCAD programs to quantify and characterize the acetabular coverage of normal and dysplastic adult hips. We found that a total coverage ratio of greater than 80%, an anterior coverage ratio of greater than 75% and a posterior coverage ratio of greater than 80% can be categorized in a normal group. Polar edge distance is a good indicator for the evaluation of preoperative and postoperative coverage conditions. For standardization and evaluation of acetabular coverage, the most suitable parameters are the total coverage ratio, anterior coverage ratio, posterior coverage ratio and polar edge distance. However, medial coverage and lateral coverage ratios are indispensable in cases of dysplastic hip because variations between them are so great that acetabuloplasty may be impossible. This program can also be used to classify precisely the type of dysplastic hip.

  8. Use of micro-computed tomography to evaluate the effects of exercise on preventing the degeneration of articular cartilage in tail-suspended rats

    NASA Astrophysics Data System (ADS)

    Luan, Hui-Qin; Sun, Lian-Wen; Huang, Yun-Fei; Wu, Xin-tong; Niu, Haijun; Liu, Hong; Fan, Yu-Bo

    2015-07-01

    Space flight has been shown to induce bone loss and muscle atrophy, which could initiate the degeneration of articular cartilage. Countermeasures to prevent bone loss and muscle atrophy have been explored, but few spaceflight or ground-based studies have focused on the effects on cartilage degeneration. In this study, we investigated the effects of exercise on articular cartilage deterioration in tail-suspended rats. Thirty-two female Sprague-Dawley rats were randomly divided into four groups (n = 8 in each): tail suspension (TS), tail suspension plus passive motion (TSP), tail suspension plus active exercise (TSA), and control (CON) groups. In the TS, TSP, and TSA groups, the rat hindlimbs were unloaded for 21 days by tail suspension. Next, the cartilage thickness and volume, and the attenuation coefficient of the distal femur were evaluated by micro-computed tomography (μCT). Histological analysis was used to assess the surface integrity of the cartilage, cartilage thickness, and chondrocytes. The results showed that: (1) the cartilage thickness on the distal femur was significantly lower in the TS and TSP groups compared with the CON and TSA groups; (2) the cartilage volume in the TS group was significantly lower compared with the CON, TSA, and TSP groups; and (3) histomorphology showed that the chondrocytes formed clusters where the degree of matrix staining was lower in the TS and TSP groups. There were no significant differences between any of these parameters in the CON and TSA groups. The cartilage thickness measurements obtained by μCT and histomorphology correlated well. In general, tail suspension could induce articular cartilage degeneration, but active exercise was effective in preventing this degeneration in tail-suspended rats.

  9. Of Mice, Men and Elephants: The Relation between Articular Cartilage Thickness and Body Mass

    PubMed Central

    Malda, Jos; de Grauw, Janny C.; Benders, Kim E. M.; Kik, Marja J. L.; van de Lest, Chris H. A.; Creemers, Laura B.; Dhert, Wouter J. A.; van Weeren, P. René

    2013-01-01

    Mammalian articular cartilage serves diverse functions, including shock absorption, force transmission and enabling low-friction joint motion. These challenging requirements are met by the tissue’s thickness combined with its highly specific extracellular matrix, consisting of a glycosaminoglycan-interspersed collagen fiber network that provides a unique combination of resilience and high compressive and shear resistance. It is unknown how this critical tissue deals with the challenges posed by increases in body mass. For this study, osteochondral cores were harvested post-mortem from the central sites of both medial and lateral femoral condyles of 58 different mammalian species ranging from 25 g (mouse) to 4000 kg (African elephant). Joint size and cartilage thickness were measured and biochemical composition (glycosaminoclycan, collagen and DNA content) and collagen cross-links densities were analyzed. Here, we show that cartilage thickness at the femoral condyle in the mammalian species investigated varies between 90 µm and 3000 µm and bears a negative allometric relationship to body mass, unlike the isometric scaling of the skeleton. Cellular density (as determined by DNA content) decreases with increasing body mass, but gross biochemical composition is remarkably constant. This however need not affect life-long performance of the tissue in heavier mammals, due to relatively constant static compressive stresses, the zonal organization of the tissue and additional compensation by joint congruence, posture and activity pattern of larger mammals. These findings provide insight in the scaling of articular cartilage thickness with body weight, as well as in cartilage biochemical composition and cellularity across mammalian species. They underscore the need for the use of appropriate in vivo models in translational research aiming at human applications. PMID:23437402

  10. C2K77 ELISA detects cleavage of type II collagen by cathepsin K in equine articular cartilage.

    PubMed

    Noé, B; Poole, A R; Mort, J S; Richard, H; Beauchamp, G; Laverty, S

    2017-12-01

    Develop a species-specific ELISA for a neo-epitope generated by cathepsin K cleavage of equine type II collagen to: (1) measure cartilage type II collagen degradation by cathepsin K in vitro, (2) identify cytokines that upregulate cathepsin K expression and (3) compare cathepsin K with matrix metalloproteinase (MMP) collagenase activity in stimulated cartilage explants and freshly isolated normal and osteoarthritic (OA) articular cartilages. A new ELISA (C2K77) was developed and tested by measuring the activity of exogenous cathepsin K on equine articular cartilage explants. The ELISA was then employed to measure endogenous cathepsin K activity in cultured cartilage explants with or without stimulation by interleukin-1 beta (IL-1β), tumour necrosis-alpha (TNF-α), oncostatin M (OSM) and lipopolysaccharide (LPS). Cathepsin K activity in cartilage explants (control and osteoarthritic-OA) and freshly harvested cartilage (control and OA) was compared to that of MMPs employing C2K77 and C1,2C immunoassays. The addition of Cathepsin K to normal cartilage caused a significant increase (P < 0.01) in the C2K77 epitope release. Whereas the content of C1,2C, that reflects MMP collagenase activity, was increased in media by the addition to cartilage explants of TNF-α and OSM (P < 0.0001) or IL-1β and OSM (P = 0.002), no change was observed in C2K77 which also unchanged in OA cartilages compared to normal. The ELISA C2K77 measured the activity of cathepsin K in equine cartilage which was unchanged in OA cartilage. Cytokines that upregulate MMP collagenase activity had no effect on endogenous cathepsin K activity, suggesting a different activation mechanism that requires further study. Copyright © 2017 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

  11. Tribology approach to the engineering and study of articular cartilage.

    PubMed

    Wimmer, Markus A; Grad, Sibylle; Kaup, Thomas; Hänni, Markus; Schneider, Erich; Gogolewski, Sylwester; Alini, Mauro

    2004-01-01

    This study has been based on the assumption that articular motion is an important aspect of mechanotransduction in synovial joints. For this reason a new bioreactor concept, able to reproduce joint kinematics more closely, has been designed. The prototype consists of a rotating scaffold and/or cartilage pin, which is pressed onto an orthogonally rotating ball. By oscillating pin and ball in phase difference, elliptical displacement trajectories are generated that are similar to the motion paths occurring in vivo. Simultaneously, dynamic compression may be applied with a linear actuator, while two-step-motors generate the rotation of pin and ball. The whole apparatus is placed in an incubator. The control station is located outside. Preliminary investigations at the gene expression level demonstrated promising results. Compared with free-swelling control and/or simply compression-loaded samples, chondrocyte-seeded scaffolds as well as nasal cartilage explants exposed to interface motion both showed elevated levels of cartilage oligomeric matrix protein mRNA. The final design of the bioreactor will include four individual stations in line, which will facilitate the investigation of motion-initiated effects at the contacting surfaces in more detail.

  12. Differential regulation of immature articular cartilage compressive moduli and Poisson's ratios by in vitro stimulation with IGF-1 and TGF-beta1.

    PubMed

    Williams, Gregory M; Dills, Kristin J; Flores, Christian R; Stender, Michael E; Stewart, Kevin M; Nelson, Lauren M; Chen, Albert C; Masuda, Koichi; Hazelwood, Scott J; Klisch, Stephen M; Sah, Robert L

    2010-09-17

    Mechanisms of articular cartilage growth and maturation have been elucidated by studying composition-function dynamics during in vivo development and in vitro culture with stimuli such as insulin-like growth factor-1 (IGF-1) and transforming growth factor-beta 1 (TGF-beta1). This study tested the hypothesis that IGF-1 and TGF-beta1 regulate immature cartilage compressive moduli and Poisson's ratios in a manner consistent with known effects on tensile properties. Bovine calf articular cartilage from superficial-articular (S) and middle-growth (M) regions were analyzed fresh or following culture in medium with IGF-1 or TGF-beta1. Mechanical properties in confined (CC) and unconfined (UCC) compression, cartilage matrix composition, and explant size were assessed. Culture with IGF-1 resulted in softening in CC and UCC, increased Poisson's ratios, substantially increased tissue volume, and accumulation of glycosaminoglycan (GAG) and collagen (COL). Culture with TGF-beta1 promoted maturational changes in the S layer, including stiffening in CC and UCC and increased concentrations of GAG, COL, and pyridinoline crosslinks (PYR), but little growth. Culture of M layer explants with TGF-beta1 was nearly homeostatic. Across treatment groups, compressive moduli in CC and UCC were positively related to GAG, COL, and PYR concentrations, while Poisson's ratios were negatively related to concentrations of these matrix components. Thus, IGF-1 and TGF-beta1 differentially regulate the compressive mechanical properties and size of immature articular cartilage in vitro. Prescribing tissue growth, maturation, or homeostasis by controlling the in vitro biochemical environment with such growth factors may have applications in cartilage repair and tissue engineering.

  13. Intra-articular Recombinant Human Proteoglycan 4 Mitigates Cartilage Damage Following Destabilization of the Medial Meniscus in the Yucatan Minipig

    PubMed Central

    Waller, Kimberly A.; Chin, Kaitlyn E.; Jay, Gregory D.; Zhang, Ling X.; Teeple, Erin; McAllister, Scott; Badger, Gary J.; Schmidt, Tannin A.; Fleming, Braden C.

    2016-01-01

    Background Lubricin, or proteoglycan 4 (PRG4), is a glycoprotein responsible for joint boundary lubrication. PRG4 has been previously shown to be down-regulated following traumatic joint injury such as a meniscal tear. There is preliminary evidence suggesting that intra-articular injection of PRG4 post-injury will reduce cartilage damage in rat models of surgically-induced post-traumatic osteoarthritis. Objective To determine the efficacy of intra-articular injection of full length recombinant human lubricin (rhPRG4) for reducing cartilage damage after medial meniscus destabilization (DMM) in a pre-clinical large animal model. Study Design Controlled laboratory study Methods Unilateral DMM was performed in 29 Yucutan minipigs. One week post-DMM, animals received 3 weekly intra-articular injections (3cc/injection): 1) rhPRG4 [1.3mg/ml; n=10], 2) rhPRG4+hyaluronan [1.3mg/ml rhPRG4 and 3mg/ml hyaluronan (~950 kDA); n=10], and 3) phosphate buffered saline [PBS; n=9]. Hind limbs were harvested 26 weeks post-surgery. Cartilage integrity was evaluated using macroscopic (India Ink) and microscopic (Safranin O-fast green and hematoxylin & eosin) scoring systems. Secondary outcomes evaluated using ELISA included PRG4 levels in synovial fluid, CTX-II concentrations in urine and serum, and IL-1β levels in synovial fluid and serum. Results The rhPRG4 group had significantly less macroscopic cartilage damage in the medial tibial plateau compared to the PBS group (p=.002). No difference was found between the rhPRG4+hyaluronan and PBS groups (p=.23). However, no differences in microscopic damage scores were observed between the three groups (p=.70). PRG4 production was elevated in the rhPRG4 group synovial fluid compared to the PBS group (p=.033). The rhPRG4 group presented significantly lower urinary CTX-II levels, but not serum levels, when compared to the PBS (p=.013) and rhPRG4+hyaluronan (p=.011) groups. In serum and synovial fluid, both rhPRG4 (p=.006; p=.017) and rhPRG4

  14. Tribological evaluation of biomedical polycarbonate urethanes against articular cartilage.

    PubMed

    Kanca, Yusuf; Milner, Piers; Dini, Daniele; Amis, Andrew A

    2018-06-01

    This research investigated the in-vitro wear and friction performance of polycarbonate urethane (PCU) 80A as they interact with articular cartilage, using a customised multidirectional pin-on-plate tester. Condyles were articulated against PCU 80A discs (Bionate ® I and Bionate ® II) (configuration 1) and the results arising from these tests were compared to those recorded during the sliding of PCU pins against cartilage plates (configuration 2). Configuration 1 produced steadily increasing coefficient of friction (COF) (up to 0.64 ± 0.05) and had the same trend as the cartilage-on-stainless steel articulation (positive control). When synovial fluid rather than bovine calf serum was used as lubricant, average COF significantly decreased from 0.50 ± 0.02-0.38 ± 0.06 for condyle-on-Bionate ® I (80AI) and from 0.41 ± 0.02-0.24 ± 0.04 for condyle-on-Bionate ® II (80AII) test configurations (p < 0.05). After 15 h testing, the cartilage-on-cartilage articulation (negative control) tests showed no cartilage degeneration. However, different levels of cartilage volume loss were found on the condyles from the positive control (12.5 ± 4.2 mm 3 ) and the PCUs (20.1 ± 3.6 mm 3 for 80 AI and 19.0 ± 2.3 mm 3 for 80AII) (p > 0.05). A good correlation (R 2 =0.84) was found between the levels of average COF and the volume of cartilage lost during testing; increasing wear was found at higher levels of COF. Configuration 2 showed low and constant COF values (0.04 ± 0.01), which were closer to the negative control (0.03 ± 0.01) and significantly lower than configuration 1 (p < 0.05). The investigation showed that PCU is a good candidate for use in hemiarthroplasty components, where only one of the two articulating surfaces is replaced, as long as the synthetic material is implanted in a region where migrating cartilage contact is achieved. Bionate ® II showed better tribological performance, which suggests it is

  15. Mesenchymal stem cells in cartilage regeneration.

    PubMed

    Savkovic, Vuk; Li, Hanluo; Seon, Jong-Keun; Hacker, Michael; Franz, Sandra; Simon, Jan-Christoph

    2014-01-01

    Articular cartilage provides life-long weight-bearing and mechanical lubrication with extraordinary biomechanical performance and simple structure. However, articular cartilage is apparently vulnerable to multifactorial damage and insufficient to self-repair, isolated in articular capsule without nerves or blood vessels. Osteoarthritis (OA) is known as a degenerative articular cartilage deficiency progressively affecting large proportion of the world population, and restoration of hyaline cartilage is clinical challenge to repair articular cartilage lesion and recreate normal functionality over long period. Mesenchymal stem cells (MSC) are highly proliferative and multipotent somatic cells that are able to differentiate mesoderm-derived cells including chondrocytes and osteoblasts. Continuous endeavors in basic research and preclinical trial have achieved promising outcomes in cartilage regeneration using MSCs. This review focuses on rationale and technologies of MSC-based hyaline cartilage repair involving tissue engineering, 3D biomaterials and growth factors. By comparing conventional treatment and current research progress, we describe insights of advantage and challenge in translation and application of MSC-based chondrogenesis for OA treatment.

  16. On fragmenting, densely mineralised acellular protrusions into articular cartilage and their possible role in osteoarthritis

    PubMed Central

    Boyde, A; Davis, G R; Mills, D; Zikmund, T; Cox, T M; Adams, V L; Niker, A; Wilson, P J; Dillon, J P; Ranganath, L R; Jeffery, N; Jarvis, J C; Gallagher, J A

    2014-01-01

    High density mineralised protrusions (HDMP) from the tidemark mineralising front into hyaline articular cartilage (HAC) were first described in Thoroughbred racehorse fetlock joints and later in Icelandic horse hock joints. We now report them in human material. Whole femoral heads removed at operation for joint replacement or from dissection room cadavers were imaged using magnetic resonance imaging (MRI) dual echo steady state at 0.23 mm resolution, then 26-μm resolution high contrast X-ray microtomography, sectioned and embedded in polymethylmethacrylate, blocks cut and polished and re-imaged with 6-μm resolution X-ray microtomography. Tissue mineralisation density was imaged using backscattered electron SEM (BSE SEM) at 20 kV with uncoated samples. HAC histology was studied by BSE SEM after staining block faces with ammonium triiodide solution. HDMP arise via the extrusion of an unknown mineralisable matrix into clefts in HAC, a process of acellular dystrophic calcification. Their formation may be an extension of a crack self-healing mechanism found in bone and articular calcified cartilage. Mineral concentration exceeds that of articular calcified cartilage and is not uniform. It is probable that they have not been reported previously because they are removed by decalcification with standard protocols. Mineral phase morphology frequently shows the agglomeration of many fine particles into larger concretions. HDMP are surrounded by HAC, are brittle, and show fault lines within them. Dense fragments found within damaged HAC could make a significant contribution to joint destruction. At least larger HDMP can be detected with the best MRI imaging ex vivo. PMID:25132002

  17. Synthesis and Characterization of a Lubricin Mimic (mLub) To Reduce Friction and Adhesion on the Articular Cartilage Surface

    PubMed Central

    Lawrence, Alexandra; Xu, Xin; Bible, Melissa D.; Calve, Sarah; Neu, Corey P.; Panitch, Alyssa

    2015-01-01

    The lubricating proteoglycan, lubricin, facilitates the remarkable low friction and wear properties of articular cartilage in the synovial joints of the body. Lubricin lines the joint surfaces and plays a protective role as a boundary lubricant in sliding contact; decreased expression of lubricin is associated with cartilage degradation and the pathogenesis of osteoarthritis. An unmet need for early osteoarthritis treatment is the development of therapeutic molecules that mimic lubricin function and yet are also resistant to enzymatic degradation common in the damaged joint. Here, we engineered a lubricin mimic (mLub) that is less susceptible to enzymatic degradation and binds to the articular surface to reduce friction. mLub was synthesized using a chondroitin sulfate backbone with type II collagen and hyaluronic acid (HA) binding peptides to promote interaction with the articular surface and synovial fluid constituents. In vitro and in vivo characterization confirmed the binding ability of mLub to isolated type II collagen and HA, and to the cartilage surface. Following trypsin treatment to the cartilage surface, application of mLub, in combination with purified or commercially available hyaluronan, reduced the coefficient of friction, and adhesion, to control levels as assessed over macro- to micro-scales by rheometry and atomic force microscopy. In vivo studies demonstrate an mLub residency time of less than 1 week. Enhanced lubrication by mLub reduces surface friction and adhesion, which may suppress the progression of degradation and cartilage loss in the joint. mLub therefore shows potential for treatment in early osteoarthritis following injury. PMID:26398308

  18. Recapitulation of physiological spatiotemporal signals promotes in vitro formation of phenotypically stable human articular cartilage

    PubMed Central

    Wei, Yiyong; Zhou, Bin; Bernhard, Jonathan; Robinson, Samuel; Burapachaisri, Aonnicha; Guo, X. Edward

    2017-01-01

    Standard isotropic culture fails to recapitulate the spatiotemporal gradients present during native development. Cartilage grown from human mesenchymal stem cells (hMSCs) is poorly organized and unstable in vivo. We report that human cartilage with physiologic organization and in vivo stability can be grown in vitro from self-assembling hMSCs by implementing spatiotemporal regulation during induction. Self-assembling hMSCs formed cartilage discs in Transwell inserts following isotropic chondrogenic induction with transforming growth factor β to set up a dual-compartment culture. Following a switch in the basal compartment to a hypertrophic regimen with thyroxine, the cartilage discs underwent progressive deep-zone hypertrophy and mineralization. Concurrent chondrogenic induction in the apical compartment enabled the maintenance of functional and hyaline cartilage. Cartilage homeostasis, chondrocyte maturation, and terminal differentiation markers were all up-regulated versus isotropic control groups. We assessed the in vivo stability of the cartilage formed under different induction regimens. Cartilage formed under spatiotemporal regulation in vitro resisted endochondral ossification, retained the expression of cartilage markers, and remained organized following s.c. implantation in immunocompromised mice. In contrast, the isotropic control groups underwent endochondral ossification. Cartilage formed from hMSCs remained stable and organized in vivo. Spatiotemporal regulation during induction in vitro recapitulated some aspects of native cartilage development, and potentiated the maturation of self-assembling hMSCs into stable and organized cartilage resembling the native articular cartilage. PMID:28228529

  19. Elastic cartilage reconstruction by transplantation of cultured hyaline cartilage-derived chondrocytes.

    PubMed

    Mizuno, M; Takebe, T; Kobayashi, S; Kimura, S; Masutani, M; Lee, S; Jo, Y H; Lee, J I; Taniguchi, H

    2014-05-01

    Current surgical intervention of craniofacial defects caused by injuries or abnormalities uses reconstructive materials, such as autologous cartilage grafts. Transplantation of autologous tissues, however, places a significant invasiveness on patients, and many efforts have been made for establishing an alternative graft. Recently, we and others have shown the potential use of reconstructed elastic cartilage from ear-derived chondrocytes or progenitors with the unique elastic properties. Here, we examined the differentiation potential of canine joint cartilage-derived chondrocytes into elastic cartilage for expanding the cell sources, such as hyaline cartilage. Articular chondrocytes are isolated from canine joint, cultivated, and compared regarding characteristic differences with auricular chondrocytes, including proliferation rates, gene expression, extracellular matrix production, and cartilage reconstruction capability after transplantation. Canine articular chondrocytes proliferated less robustly than auricular chondrocytes, but there was no significant difference in the amount of sulfated glycosaminoglycan produced from redifferentiated chondrocytes. Furthermore, in vitro expanded and redifferentiated articular chondrocytes have been shown to reconstruct elastic cartilage on transplantation that has histologic characteristics distinct from hyaline cartilage. Taken together, cultured hyaline cartilage-derived chondrocytes are a possible cell source for elastic cartilage reconstruction. Crown Copyright © 2014. Published by Elsevier Inc. All rights reserved.

  20. A Biosynthetic Scaffold that Facilitates Chondrocyte-Mediated Degradation and Promotes Articular Cartilage Extracellular Matrix Deposition.

    PubMed

    Sridhar, Balaji V; Dailing, Eric A; Brock, J Logan; Stansbury, Jeffrey W; Randolph, Mark A; Anseth, Kristi S

    2015-12-01

    Articular cartilage remains a significant clinical challenge to repair because of its limited self-healing capacity. Interest has grown in the delivery of autologous chondrocytes to cartilage defects, and combining cell-based therapies with scaffolds that capture aspects of native tissue and allow cell-mediated remodeling could improve outcomes. Currently, scaffold-based therapies with encapsulated chondrocytes permit matrix production; however, resorption of the scaffold often does not match the rate of matrix production by chondrocytes, which can limit functional tissue regeneration. Here, we designed a hybrid biosynthetic system consisting of poly (ethylene glycol) (PEG) endcapped with thiols and crosslinked by norbornene-functionalized gelatin via a thiol-ene photopolymerization. The protein crosslinker was selected to facilitate chondrocyte-mediated scaffold remodeling and matrix deposition. Gelatin was functionalized with norbornene to varying degrees (~4-17 norbornenes/gelatin), and the shear modulus of the resulting hydrogels was characterized (<0.1-0.5 kPa). Degradation of the crosslinked PEG-gelatin hydrogels by chondrocyte-secreted enzymes was confirmed by gel permeation chromatography. Finally, chondrocytes encapsulated in these biosynthetic scaffolds showed significantly increased glycosaminoglycan deposition over just 14 days of culture, while maintaining high levels of viability and producing a distributed matrix. These results indicate the potential of a hybrid PEG-gelatin hydrogel to permit chondrocyte-mediated remodeling and promote articular cartilage matrix production. Tunable scaffolds that can easily permit chondrocyte-mediated remodeling may be useful in designing treatment options for cartilage tissue engineering applications.

  1. A Biosynthetic Scaffold that Facilitates Chondrocyte-Mediated Degradation and Promotes Articular Cartilage Extracellular Matrix Deposition

    PubMed Central

    Sridhar., Balaji V.; Dailing, Eric A.; Brock, J. Logan; Stansbury, Jeffrey W.; Randolph, Mark A.; Anseth, Kristi S.

    2015-01-01

    Articular cartilage remains a significant clinical challenge to repair because of its limited self-healing capacity. Interest has grown in the delivery of autologous chondrocytes to cartilage defects, and combining cell-based therapies with scaffolds that capture aspects of native tissue and allow cell-mediated remodeling could improve outcomes. Currently, scaffold-based therapies with encapsulated chondrocytes permit matrix production; however, resorption of the scaffold often does not match the rate of matrix production by chondrocytes, which can limit functional tissue regeneration. Here, we designed a hybrid biosynthetic system consisting of poly (ethylene glycol) (PEG) endcapped with thiols and crosslinked by norbornene-functionalized gelatin via a thiol-ene photopolymerization. The protein crosslinker was selected to facilitate chondrocyte-mediated scaffold remodeling and matrix deposition. Gelatin was functionalized with norbornene to varying degrees (~4–17 norbornenes/gelatin), and the shear modulus of the resulting hydrogels was characterized (<0.1–0.5 kPa). Degradation of the crosslinked PEG-gelatin hydrogels by chondrocyte-secreted enzymes was confirmed by gel permeation chromatography. Finally, chondrocytes encapsulated in these biosynthetic scaffolds showed significantly increased glycosaminoglycan deposition over just 14 days of culture, while maintaining high levels of viability and producing a distributed matrix. These results indicate the potential of a hybrid PEG-gelatin hydrogel to permit chondrocyte-mediated remodeling and promote articular cartilage matrix production. Tunable scaffolds that can easily permit chondrocyte-mediated remodeling may be useful in designing treatment options for cartilage tissue engineering applications. PMID:26900597

  2. Three-dimensional finite analysis of acetabular contact pressure and contact area during normal walking.

    PubMed

    Wang, Guangye; Huang, Wenjun; Song, Qi; Liang, Jinfeng

    2017-11-01

    This study aims to analyze the contact areas and pressure distributions between the femoral head and mortar during normal walking using a three-dimensional finite element model (3D-FEM). Computed tomography (CT) scanning technology and a computer image processing system were used to establish the 3D-FEM. The acetabular mortar model was used to simulate the pressures during 32 consecutive normal walking phases and the contact areas at different phases were calculated. The distribution of the pressure peak values during the 32 consecutive normal walking phases was bimodal, which reached the peak (4.2 Mpa) at the initial phase where the contact area was significantly higher than that at the stepping phase. The sites that always kept contact were concentrated on the acetabular top and leaned inwards, while the anterior and posterior acetabular horns had no pressure concentration. The pressure distributions of acetabular cartilage at different phases were significantly different, the zone of increased pressure at the support phase distributed at the acetabular top area, while that at the stepping phase distributed in the inside of acetabular cartilage. The zones of increased contact pressure and the distributions of acetabular contact areas had important significance towards clinical researches, and could indicate the inductive factors of acetabular osteoarthritis. Copyright © 2016. Published by Elsevier Taiwan.

  3. Changes of articular cartilage and subchondral bone after extracorporeal shockwave therapy in osteoarthritis of the knee

    PubMed Central

    Wang, Ching-Jen; Cheng, Jai-Hong; Chou, Wen-Yi; Hsu, Shan-Ling; Chen, Jen-Hung; Huang, Chien-Yiu

    2017-01-01

    We assessed the pathological changes of articular cartilage and subchondral bone on different locations of the knee after extracorporeal shockwave therapy (ESWT) in early osteoarthritis (OA). Rat knees under OA model by anterior cruciate ligament transaction (ACLT) and medial meniscectomy (MM) to induce OA changes. Among ESWT groups, ESWT were applied to medial (M) femur (F) and tibia (T) condyles was better than medial tibia condyle, medial femur condyle as well as medial and lateral (L) tibia condyles in gross osteoarthritic areas (p<0.05), osteophyte formation and subchondral sclerotic bone (p<0.05). Using sectional cartilage area, modified Mankin scoring system as well as thickness of calcified and un-calcified cartilage analysis, the results showed that articular cartilage damage was ameliorated and T+F(M) group had the most protection as compared with other locations (p<0.05). Detectable cartilage surface damage and proteoglycan loss were measured and T+F(M) group showed the smallest lesion score among other groups (p<0.05). Micro-CT revealed significantly improved in subchondral bone repair in all ESWT groups compared to OA group (p<0.05). There were no significantly differences in bone remodeling after ESWT groups except F(M) group. In the immunohistochemical analysis, T+F(M) group significant reduced TUNEL activity, promoted cartilage proliferation by observation of PCNA marker and reduced vascular invasion through observation of CD31 marker for angiogenesis compared to OA group (P<0.001). Overall the data suggested that the order of the effective site of ESWT was T+F(M) ≧ T(M) > T(M+L) > F(M) in OA rat knees. PMID:28367081

  4. Changes of articular cartilage and subchondral bone after extracorporeal shockwave therapy in osteoarthritis of the knee.

    PubMed

    Wang, Ching-Jen; Cheng, Jai-Hong; Chou, Wen-Yi; Hsu, Shan-Ling; Chen, Jen-Hung; Huang, Chien-Yiu

    2017-01-01

    We assessed the pathological changes of articular cartilage and subchondral bone on different locations of the knee after extracorporeal shockwave therapy (ESWT) in early osteoarthritis (OA). Rat knees under OA model by anterior cruciate ligament transaction (ACLT) and medial meniscectomy (MM) to induce OA changes. Among ESWT groups, ESWT were applied to medial (M) femur (F) and tibia (T) condyles was better than medial tibia condyle, medial femur condyle as well as medial and lateral (L) tibia condyles in gross osteoarthritic areas (p<0.05), osteophyte formation and subchondral sclerotic bone (p<0.05). Using sectional cartilage area, modified Mankin scoring system as well as thickness of calcified and un-calcified cartilage analysis, the results showed that articular cartilage damage was ameliorated and T+F(M) group had the most protection as compared with other locations (p<0.05). Detectable cartilage surface damage and proteoglycan loss were measured and T+F(M) group showed the smallest lesion score among other groups (p<0.05). Micro-CT revealed significantly improved in subchondral bone repair in all ESWT groups compared to OA group (p<0.05). There were no significantly differences in bone remodeling after ESWT groups except F(M) group. In the immunohistochemical analysis, T+F(M) group significant reduced TUNEL activity, promoted cartilage proliferation by observation of PCNA marker and reduced vascular invasion through observation of CD31 marker for angiogenesis compared to OA group (P<0.001). Overall the data suggested that the order of the effective site of ESWT was T+F(M) ≧ T(M) > T(M+L) > F(M) in OA rat knees.

  5. Load-unloading response of intact and artificially degraded articular cartilage correlated with near infrared (NIR) absorption spectra.

    PubMed

    Afara, I O; Singh, S; Oloyede, A

    2013-04-01

    The conventional mechanical properties of articular cartilage, such as compressive stiffness, have been demonstrated to be limited in their capacity to distinguish intact (visually normal) from degraded cartilage samples. In this paper, we explore the correlation between a new mechanical parameter, namely the reswelling of articular cartilage following unloading from a given compressive load, and the near infrared (NIR) spectrum. The capacity to distinguish mechanically intact from proteoglycan-depleted tissue relative to the "reswelling" characteristic was first established, and the result was subsequently correlated with the NIR spectral data of the respective tissue samples. To achieve this, normal intact and enzymatically degraded samples were subjected to both NIR probing and mechanical compression based on a load-unload-reswelling protocol. The parameter δr, characteristic of the osmotic "reswelling" of the matrix after unloading to a constant small load in the order of the osmotic pressure of cartilage, was obtained for the different sample types. Multivariate statistics was employed to determine the degree of correlation between δr and the NIR absorption spectrum of relevant specimens using Partial Least Squared (PLS) regression. The results show a strong relationship (R(2)=95.89%, p<0.0001) between the spectral data and δr. This correlation of δr with NIR spectral data suggests the potential for determining the reswelling characteristics non-destructively. It was also observed that δr values bear a significant relationship with the cartilage matrix integrity, indicated by its proteoglycan content, and can therefore differentiate between normal and artificially degraded proteoglycan-depleted cartilage samples. It is therefore argued that the reswelling of cartilage, which is both biochemical (osmotic) and mechanical (hydrostatic pressure) in origin, could be a strong candidate for characterizing the tissue, especially in regions surrounding focal

  6. Melanocortin 1 receptor-signaling deficiency results in an articular cartilage phenotype and accelerates pathogenesis of surgically induced murine osteoarthritis.

    PubMed

    Lorenz, Julia; Seebach, Elisabeth; Hackmayer, Gerit; Greth, Carina; Bauer, Richard J; Kleinschmidt, Kerstin; Bettenworth, Dominik; Böhm, Markus; Grifka, Joachim; Grässel, Susanne

    2014-01-01

    Proopiomelanocortin-derived peptides exert pleiotropic effects via binding to melanocortin receptors (MCR). MCR-subtypes have been detected in cartilage and bone and mediate an increasing number of effects in diathrodial joints. This study aims to determine the role of MC1-receptors (MC1) in joint physiology and pathogenesis of osteoarthritis (OA) using MC1-signaling deficient mice (Mc1re/e). OA was surgically induced in Mc1re/e and wild-type (WT) mice by transection of the medial meniscotibial ligament. Histomorphometry of Safranin O stained articular cartilage was performed with non-operated controls (11 weeks and 6 months) and 4/8 weeks past surgery. µCT-analysis for assessing epiphyseal bone architecture was performed as a longitudinal study at 4/8 weeks after OA-induction. Collagen II, ICAM-1 and MC1 expression was analysed by immunohistochemistry. Mc1re/e mice display less Safranin O and collagen II stained articular cartilage area compared to WT prior to OA-induction without signs of spontaneous cartilage surface erosion. This MC1-signaling deficiency related cartilage phenotype persisted in 6 month animals. At 4/8 weeks after OA-induction cartilage erosions were increased in Mc1re/e knees paralleled by weaker collagen II staining. Prior to OA-induction, Mc1re/e mice do not differ from WT with respect to bone parameters. During OA, Mc1re/e mice developed more osteophytes and had higher epiphyseal bone density and mass. Trabecular thickness was increased while concomitantly trabecular separation was decreased in Mc1re/e mice. Numbers of ICAM-positive chondrocytes were equal in non-operated 11 weeks Mc1re/e and WT whereas number of positive chondrocytes decreased during OA-progression. Unchallenged Mc1re/e mice display smaller articular cartilage covered area without OA-related surface erosions indicating that MC1-signaling is critical for proper cartilage matrix integrity and formation. When challenged with OA, Mc1re/e mice develop a more severe OA

  7. Melanocortin 1 Receptor-Signaling Deficiency Results in an Articular Cartilage Phenotype and Accelerates Pathogenesis of Surgically Induced Murine Osteoarthritis

    PubMed Central

    Hackmayer, Gerit; Greth, Carina; Bauer, Richard J.; Kleinschmidt, Kerstin; Bettenworth, Dominik; Böhm, Markus; Grifka, Joachim; Grässel, Susanne

    2014-01-01

    Proopiomelanocortin-derived peptides exert pleiotropic effects via binding to melanocortin receptors (MCR). MCR-subtypes have been detected in cartilage and bone and mediate an increasing number of effects in diathrodial joints. This study aims to determine the role of MC1-receptors (MC1) in joint physiology and pathogenesis of osteoarthritis (OA) using MC1-signaling deficient mice (Mc1re/e). OA was surgically induced in Mc1re/e and wild-type (WT) mice by transection of the medial meniscotibial ligament. Histomorphometry of Safranin O stained articular cartilage was performed with non-operated controls (11 weeks and 6 months) and 4/8 weeks past surgery. µCT–analysis for assessing epiphyseal bone architecture was performed as a longitudinal study at 4/8 weeks after OA-induction. Collagen II, ICAM-1 and MC1 expression was analysed by immunohistochemistry. Mc1re/e mice display less Safranin O and collagen II stained articular cartilage area compared to WT prior to OA-induction without signs of spontaneous cartilage surface erosion. This MC1-signaling deficiency related cartilage phenotype persisted in 6 month animals. At 4/8 weeks after OA-induction cartilage erosions were increased in Mc1re/e knees paralleled by weaker collagen II staining. Prior to OA-induction, Mc1re/e mice do not differ from WT with respect to bone parameters. During OA, Mc1re/e mice developed more osteophytes and had higher epiphyseal bone density and mass. Trabecular thickness was increased while concomitantly trabecular separation was decreased in Mc1re/e mice. Numbers of ICAM-positive chondrocytes were equal in non-operated 11 weeks Mc1re/e and WT whereas number of positive chondrocytes decreased during OA-progression. Unchallenged Mc1re/e mice display smaller articular cartilage covered area without OA-related surface erosions indicating that MC1-signaling is critical for proper cartilage matrix integrity and formation. When challenged with OA, Mc1re/e mice develop a more severe OA

  8. Progressive cell-mediated changes in articular cartilage and bone in mice are initiated by a single session of controlled cyclic compressive loading

    PubMed Central

    Ko, Frank C.; Dragomir, Cecilia L.; Plumb, Darren A.; Hsia, Allison W.; Adebayo, Olufunmilayo O.; Goldring, Steven R.; Wright, Timothy M.; Goldring, Mary B.; van der Meulen, Marjolein C.H.

    2017-01-01

    We previously showed that repetitive cyclic loading of the mouse knee joint causes changes that recapitulate the features of osteoarthritis (OA) in humans. By applying a single loading session, we characterized the temporal progression of the structural and compositional changes in subchondral bone and articular cartilage. We applied loading during a single 5-minute session to the left tibia of adult (26-week-old) C57Bl/6 male mice at a peak load of 9.0N for 1200 cycles. Knee joints were collected at times 0, 1, and 2 weeks after loading. The changes in articular cartilage and subchondral bone were analyzed by histology, immunohistochemistry (caspase-3 and cathepsin K), and microcomputed tomography. At time 0, no change was evident in chondrocyte viability or cartilage or subchondral bone integrity. However, cartilage pathology demonstrated by localized thinning and proteoglycan loss occurred at 1 and 2 weeks after the single session of loading. Transient cancellous bone loss was evident at 1 week, associated with increased osteoclast number. Bone loss was reversed to control levels at 2 weeks. We observed formation of fibrous and cartilaginous tissues at the joint margins at 1 and 2 weeks. Our findings demonstrate that a single session of noninvasive loading leads to the development of OA-like morphological and cellular alterations in articular cartilage and subchondral bone. The loss in subchondral trabecular bone mass and thickness returns to control levels at 2 weeks, whereas the cartilage thinning and proteoglycan loss persist. PMID:26896841

  9. Micromechanical properties of canine femoral articular cartilage following multiple freeze-thaw cycles.

    PubMed

    Peters, Abby E; Comerford, Eithne J; Macaulay, Sophie; Bates, Karl T; Akhtar, Riaz

    2017-07-01

    Tissue material properties are crucial to understanding their mechanical function, both in healthy and diseased states. However, in certain circumstances logistical limitations can prevent testing on fresh samples necessitating one or more freeze-thaw cycles. To date, the nature and extent to which the material properties of articular cartilage are altered by repetitive freezing have not been explored. Therefore, the aim of this study is to quantify how articular cartilage mechanical properties, measured by nanoindentation, are affected by multiple freeze-thaw cycles. Canine cartilage plugs (n = 11) from medial and lateral femoral condyles were submerged in phosphate buffered saline, stored at 3-5°C and tested using nanoindentation within 12h. Samples were then frozen at -20°C and later thawed at 3-5°C for 3h before material properties were re-tested and samples re-frozen under the same conditions. This process was repeated for all 11 samples over three freeze-thaw cycles. Overall mean and standard deviation of shear storage modulus decreased from 1.76 ± 0.78 to 1.21 ± 0.77MPa (p = 0.91), shear loss modulus from 0.42 ± 0.19 to 0.39 ± 0.17MPa (p=0.70) and elastic modulus from 5.13 ± 2.28 to 3.52 ± 2.24MPa (p = 0.20) between fresh and three freeze-thaw cycles respectively. The loss factor increased from 0.31 ± 0.38 to 0.71 ± 1.40 (p = 0.18) between fresh and three freeze-thaw cycles. Inter-sample variability spanned as much as 10.47MPa across freezing cycles and this high-level of biological variability across samples likely explains why overall mean "whole-joint" trends do not reach statistical significance across the storage conditions tested. As a result multiple freeze-thaw cycles cannot be explicitly or statistically linked to mechanical changes within the cartilage. However, the changes in material properties observed herein may be sufficient in magnitude to impact on a variety of clinical and scientific studies of cartilage, and should be considered

  10. The response of bone, articular cartilage and tendon to exercise in the horse

    PubMed Central

    Firth, Elwyn C

    2006-01-01

    Horses can gallop within hours of birth, and may begin training for athletic competition while still growing. This review cites studies on the effects of exercise on bone, tendon and articular cartilage, as detected by clinical and research imaging techniques, tissue biochemical analysis and microscopy of various kinds. For bone, alterations in bone mineral content, mineral density and the morphology of the mineralized tissue are the most common end-points. Apparent bone density increases slightly after athletic training in the cortex, but substantially in the major load paths of the epiphyses and cuboidal bones, despite the lower material density of the new bone, which is deposited subperiosteally and on internal surfaces without prior osteoclastic resorption. With training of greater intensity, adaptive change is supervened by patho-anatomical change in the form of microdamage and frank lesions. In tendon, collagen fibril diameter distribution changes significantly during growth, but not after early training. The exact amount and type of protracted training that does cause reduction in mass average diameter (an early sign of progressive microdamage) have not been defined. Training is associated with an increase in the cross-sectional area of some tendons, possibly owing to slightly greater water content of non-collagenous or newly synthesized matrix. Early training may be associated with greater thickness of hyaline but not calcified articular cartilage, at least in some sites. The age at which adaptation of cartilage to biomechanical influences can occur may thus extend beyond very early life. However, cartilage appears to be the most susceptible of the three tissues to pathological alteration. The effect of training exercise on the anatomical or patho-anatomical features of connective tissue structures is affected by the timing, type and amount of natural or imposed exercise during growth and development which precedes the training. PMID:16637875

  11. Characterizing depth-dependent refractive index of articular cartilage subjected to mechanical wear or enzymic degeneration

    NASA Astrophysics Data System (ADS)

    Wang, Kuyu; Wu, Jianping; Day, Robert; Kirk, Thomas Brett; Hu, Xiaozhi

    2016-09-01

    Utilizing a laser scanning confocal microscope system, the refractive indices of articular cartilage (AC) with mechanical or biochemical degenerations were characterized to investigate whether potential correlations exist between refractive index (RI) and cartilage degeneration. The cartilage samples collected from the medial femoral condyles of kangaroo knees were mechanically degenerated under different loading patterns or digested in trypsin solution with different concentrations. The sequences of RI were then measured from cartilage surface to deep region and the fluctuations of RI were quantified considering combined effects of fluctuating frequency and amplitude. The compositional and microstructural alterations of cartilage samples were assessed with histological methods. Along with the loss of proteoglycans, the average RI of cartilage increased and the local fluctuation of RI became stronger. Short-term high-speed test induced little influence to both the depth fluctuation and overall level of RI. Long-term low-speed test increased the fluctuation of RI but the average RI was barely changed. The results substantially demonstrate that RI of AC varies with both compositional and structural alterations and is potentially an indicator for the degeneration of AC.

  12. Effect of open wedge high tibial osteotomy on the lateral tibiofemoral compartment in sheep. Part II: standard and overcorrection do not cause articular cartilage degeneration.

    PubMed

    Ziegler, Raphaela; Goebel, Lars; Cucchiarini, Magali; Pape, Dietrich; Madry, Henning

    2014-07-01

    To evaluate whether medial open wedge high tibial osteotomy (HTO) results in structural changes in the articular cartilage in the lateral tibiofemoral compartment of adult sheep. Three experimental groups received biplanar osteotomies of the right proximal tibiae: (a) closing wedge HTO (4.5° of tibial varus), (b) opening wedge HTO (4.5° tibial valgus; standard correction), and (c) opening wedge HTO (9.5° of valgus; overcorrection), each of which was compared to the contralateral knees that only received an arthrotomy. After 6 months, the macroscopic and microscopic characteristics of the articular cartilage of the lateral tibiofemoral compartment were assessed. The articular cartilage in the central region of the lateral tibial plateau in sheep had a higher safranin O staining intensity and was 4.6-fold thicker than in the periphery (covered by the lateral meniscus). No topographical variation in the type-II collagen immunoreactivity was seen. All lateral tibial plateaus showed osteoarthritic changes in regions not covered by the lateral meniscus. No osteoarthritis was seen in the peripheral submeniscal regions of the lateral tibial plateau and the lateral femoral condyle. Opening wedge HTO resulting in both standard and overcorrection was not associated with significant macroscopic and microscopic structural changes between groups in the articular cartilage of the lateral tibial plateau and femoral condyle after 6 months in vivo. Opening wedge HTO resulting in both standard and overcorrection is a safe procedure for the articular cartilage in an intact lateral tibiofemoral compartment of adult sheep at 6 months postoperatively.

  13. Cyclic Mechanical Loading Enhances Transport of Antibodies Into Articular Cartilage.

    PubMed

    DiDomenico, Chris D; Xiang Wang, Zhen; Bonassar, Lawrence J

    2017-01-01

    The goal of this study was to characterize antibody penetration through cartilage tissue under mechanical loading. Mechanical stimulation aids in the penetration of some proteins, but this effect has not characterized molecules such as antibodies (>100 kDa), which may hold some clinical value for treating osteoarthritis (OA). For each experiment, fresh articular cartilage plugs were obtained and exposed to fluorescently labeled antibodies while under cyclic mechanical load in unconfined compression for several hours. Penetration of these antibodies was quantified using confocal microscopy, and finite element (FE) simulations were conducted to predict fluid flow patterns within loaded samples. Transport enhancement followed a linear trend with strain amplitude (0.25-5%) and a nonlinear trend with frequency (0.25-2.60 Hz), with maximum enhancement found to be at 5% cyclic strain and 1 Hz, respectively. Regions of highest enhancement of transport within the tissue were associated with the regions of highest interstitial fluid velocity, as predicted from finite-element simulations. Overall, cyclic compression-enhanced antibody transport by twofold to threefold. To our knowledge, this is the first study to test how mechanical stimulation affects the diffusion of antibodies in cartilage and suggest further study into other important factors regarding macromolecular transport.

  14. Evaluation of the Quality, Accuracy, and Readability of Online Patient Resources for the Management of Articular Cartilage Defects.

    PubMed

    Wang, Dean; Jayakar, Rohit G; Leong, Natalie L; Leathers, Michael P; Williams, Riley J; Jones, Kristofer J

    2017-04-01

    Objective Patients commonly use the Internet to obtain their health-related information. The purpose of this study was to investigate the quality, accuracy, and readability of online patient resources for the management of articular cartilage defects. Design Three search terms ("cartilage defect," "cartilage damage," "cartilage injury") were entered into 3 Internet search engines (Google, Bing, Yahoo). The first 25 websites from each search were collected and reviewed. The quality and accuracy of online information were independently evaluated by 3 reviewers using predetermined scoring criteria. The readability was evaluated using the Flesch-Kincaid (FK) grade score. Results Fifty-three unique websites were evaluated. Quality ratings were significantly higher in websites with a FK score >11 compared to those with a score of ≤11 ( P = 0.021). Only 10 websites (19%) differentiated between focal cartilage defects and diffuse osteoarthritis. Of these, 7 (70%) were elicited using the search term "cartilage defect" ( P = 0.038). The average accuracy of the websites was high (11.7 out of maximum 12), and the average FK grade level (13.4) was several grades higher than the recommended level for readable patient education material (eighth grade level). Conclusions The quality and readability of online patient resources for articular cartilage defects favor those with a higher level of education. Additionally, the majority of these websites do not distinguish between focal chondral defects and diffuse osteoarthritis, which can fail to provide appropriate patient education and guidance for available treatment. Clinicians should help guide patients toward high-quality, accurate, and readable online patient education material.

  15. Mechanical Stimulation Protocols of Human Derived Cells in Articular Cartilage Tissue Engineering - A Systematic Review.

    PubMed

    Khozoee, Baktash; Mafi, Pouya; Mafi, Reza; Khan, Wasim S

    2017-01-01

    Mechanical stimulation is a key factor in articular cartilage generation and maintenance. Bioreactor systems have been designed and built in order to deliver specific types of mechanical stimulation. The focus has been twofold, applying a type of preconditioning in order to stimulate cell differentiation, and to simulate in vivo conditions in order to gain further insight into how cells respond to different stimulatory patterns. Due to the complex forces at work within joints, it is difficult to simulate mechanical conditions using a bioreactor. The aim of this review is to gain a deeper understanding of the complexities of mechanical stimulation protocols by comparing those employed in bioreactors in the context of tissue engineering for articular cartilage, and to consider their effects on cultured cells. Allied and Complementary Medicine 1985 to 2016, Ovid MEDLINE[R] 1946 to 2016, and Embase 1974 to 2016 were searched using key terms. Results were subject to inclusion and exclusion criteria, key findings summarised into a table and subsequently discussed. Based on this review it is overwhelmingly clear that mechanical stimulation leads to increased chondrogenic properties in the context of bioreactor articular cartilage tissue engineering using human cells. However, given the variability and lack of controlled factors between research articles, results are difficult to compare, and a standardised method of evaluating stimulation protocols proved challenging. With improved standardisation in mechanical stimulation protocol reporting, bioreactor design and building processes, along with a better understanding of joint behaviours, we hope to perform a meta-analysis on stimulation protocols and methods. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  16. Quantification of the optical surface reflection and surface roughness of articular cartilage using optical coherence tomography

    NASA Astrophysics Data System (ADS)

    Saarakkala, Simo; Wang, Shu-Zhe; Huang, Yan-Ping; Zheng, Yong-Ping

    2009-11-01

    Optical coherence tomography (OCT) is a promising new technique for characterizing the structural changes of articular cartilage in osteoarthritis (OA). The calculation of quantitative parameters from the OCT signal is an important step to develop OCT as an effective diagnostic technique. In this study, two novel parameters for the quantification of optical surface reflection and surface roughness from OCT measurements are introduced: optical surface reflection coefficient (ORC), describing the amount of a ratio of the optical reflection from cartilage surface with respect to that from a reference material, and OCT roughness index (ORI) indicating the smoothness of the cartilage surface. The sensitivity of ORC and ORI to detect changes in bovine articular cartilage samples after enzymatic degradations of collagen and proteoglycans using collagenase and trypsin enzymes, respectively, was tested in vitro. A significant decrease (p < 0.001) in ORC as well as a significant increase (p < 0.001) in ORI was observed after collagenase digestion. After trypsin digestion, no significant changes in ORC or ORI were observed. To conclude, the new parameters introduced were demonstrated to be feasible and sensitive to detect typical OA-like degenerative changes in the collagen network. From the clinical point of view, the quantification of OCT measurements is of great interest since OCT probes have been already miniaturized and applied in patient studies during arthroscopy or open knee surgery in vivo. Further studies are still necessary to demonstrate the clinical capability of the introduced parameters for naturally occurring early OA changes in the cartilage.

  17. Synthesis and characterization of a lubricin mimic (mLub) to reduce friction and adhesion on the articular cartilage surface.

    PubMed

    Lawrence, Alexandra; Xu, Xin; Bible, Melissa D; Calve, Sarah; Neu, Corey P; Panitch, Alyssa

    2015-12-01

    The lubricating proteoglycan, lubricin, facilitates the remarkable low friction and wear properties of articular cartilage in the synovial joints of the body. Lubricin lines the joint surfaces and plays a protective role as a boundary lubricant in sliding contact; decreased expression of lubricin is associated with cartilage degradation and the pathogenesis of osteoarthritis. An unmet need for early osteoarthritis treatment is the development of therapeutic molecules that mimic lubricin function and yet are also resistant to enzymatic degradation common in the damaged joint. Here, we engineered a lubricin mimic (mLub) that is less susceptible to enzymatic degradation and binds to the articular surface to reduce friction. mLub was synthesized using a chondroitin sulfate backbone with type II collagen and hyaluronic acid (HA) binding peptides to promote interaction with the articular surface and synovial fluid constituents. In vitro and in vivo characterization confirmed the binding ability of mLub to isolated type II collagen and HA, and to the cartilage surface. Following trypsin treatment to the cartilage surface, application of mLub, in combination with purified or commercially available hyaluronan, reduced the coefficient of friction, and adhesion, to control levels as assessed over macro-to micro-scales by rheometry and atomic force microscopy. In vivo studies demonstrate an mLub residency time of less than 1 week. Enhanced lubrication by mLub reduces surface friction and adhesion, which may suppress the progression of degradation and cartilage loss in the joint. mLub therefore shows potential for treatment in early osteoarthritis following injury. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. Anatomic variation of depth-dependent mechanical properties in neonatal bovine articular cartilage.

    PubMed

    Silverberg, Jesse L; Dillavou, Sam; Bonassar, Lawrence; Cohen, Itai

    2013-05-01

    Articular cartilage has well known depth-dependent structure and has recently been shown to have similarly non-uniform depth-dependent mechanical properties. Here, we study anatomic variation of the depth-dependent shear modulus and energy dissipation rate in neonatal bovine knees. The regions we specifically focus on are the patellofemoral groove, trochlea, femoral condyle, and tibial plateau. In every sample, we find a highly compliant region within the first 500 µm of tissue measured from the articular surface, where the local shear modulus is reduced by up to two orders of magnitude. Comparing measurements taken from different anatomic sites, we find statistically significant differences localized within the first 50 µm. Histological images reveal these anatomic variations are associated with differences in collagen density and fiber organization. Copyright © 2012 Orthopaedic Research Society.

  19. Zone-specific cell biosynthetic activity in mature bovine articular cartilage: a new method using confocal microscopic stereology and quantitative autoradiography.

    PubMed

    Wong, M; Wuethrich, P; Eggli, P; Hunziker, E

    1996-05-01

    A new methodology was developed to measure spatial variations in chondrocyte/matrix structural parameters and chondrocyte biosynthetic activity in articular cartilage. This technique is based on the use of a laser scanning confocal microscope that can "optically" section chemically fixed, unembedded tissue. The confocal images are used for morphometric measurement of stereologic parameters such as cell density (cells/mm3), cell volume fraction (%), surface density (l/cm), mean cell volume (micron3), and mean cell surface area (micron2). Adjacent pieces of tissue are simultaneously processed for conventional liquid emulsion autoradiography, and a semiautomated grain counting program is used to measure the silver grain density at regions corresponding to the same sites used for structural measurements. An estimate of chondrocyte biosynthetic activity in terms of grains per cell is obtained by dividing the value for grain density by that for cell density. In this paper, the newly developed methodology was applied to characterize the zone-specific behavior of adult articular cartilage in the free-swelling state. Cylinders of young adult bovine articular cartilage were labelled with either [3H]proline or [35S]sulfate, and chondrocyte biosynthesis and structural parameters were measured from the articular surface to the tidemark. The results showed that chondrocytes of the radial zone occupied twice the volume and surface area of the chondrocytes of the superficial zone but were 10 times more synthetically active. This efficient and unbiased technique may prove useful in studying the correlation between mechanically induced changes in cell form and biosynthetic activity within inhomogeneous tissue as well as metabolic changes in cartilage due to ageing and disease.

  20. Site-specific ultrasound reflection properties and superficial collagen content of bovine knee articular cartilage

    NASA Astrophysics Data System (ADS)

    Laasanen, Mikko S.; Saarakkala, Simo; Töyräs, Juha; Rieppo, Jarno; Jurvelin, Jukka S.

    2005-07-01

    Previous quantitative 2D-ultrasound imaging studies have demonstrated that the ultrasound reflection measurement of articular cartilage surface sensitively detects degradation of the collagen network, whereas digestion of cartilage proteoglycans has no significant effect on the ultrasound reflection. In this study, the first aim was to characterize the ability of quantitative 2D-ultrasound imaging to detect site-specific differences in ultrasound reflection and backscattering properties of cartilage surface and cartilage-bone interface at visually healthy bovine knee (n = 30). As a second aim, we studied factors controlling ultrasound reflection properties of an intact cartilage surface. The ultrasound reflection coefficient was determined in time (R) and frequency domains (IRC) at medial femoral condyle, lateral patello-femoral groove, medial tibial plateau and patella using a 20 MHz ultrasound imaging instrument. Furthermore, cartilage surface roughness was quantified by calculating the ultrasound roughness index (URI). The superficial collagen content of the cartilage was determined using a FT-IRIS-technique. A significant site-dependent variation was shown in cartilage thickness, ultrasound reflection parameters, URI and superficial collagen content. As compared to R and IRC, URI was a more sensitive parameter in detecting differences between the measurement sites. Ultrasound reflection parameters were not significantly related to superficial collagen content, whereas the correlation between R and URI was high. Ultrasound reflection at the cartilage-bone interface showed insignificant site-dependent variation. The current results suggest that ultrasound reflection from the intact cartilage surface is mainly dependent on the cartilage surface roughness and the collagen content has a less significant role.

  1. Enhanced cartilage repair in 'healer' mice-New leads in the search for better clinical options for cartilage repair.

    PubMed

    Fitzgerald, Jamie

    2017-02-01

    Adult articular cartilage has a poor capacity to undergo intrinsic repair. Current strategies for the repair of large cartilage defects are generally unsatisfactory because the restored cartilage does not have the same resistance to biomechanical loading as authentic articular cartilage and degrades over time. Recently, an exciting new research direction, focused on intrinsic cartilage regeneration rather than fibrous repair by external means, has emerged. This review explores the new findings in this rapidly moving field as they relate to the clinical goal of restoration of structurally robust, stable and non-fibrous articular cartilage following injury. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. “Soft that molds the hard:” Geometric morphometry of lateral atlantoaxial joints focusing on the role of cartilage in changing the contour of bony articular surfaces

    PubMed Central

    Prasad, Prashant Kumar; Salunke, Pravin; Sahni, Daisy; Kalra, Parveen

    2017-01-01

    Purpose: The existing literature on lateral atlantoaxial joints is predominantly on bony facets and is unable to explain various C1-2 motions observed. Geometric morphometry of facets would help us in understanding the role of cartilages in C1-2 biomechanics/kinematics. Objective: Anthropometric measurements (bone and cartilage) of the atlantoaxial joint and to assess the role of cartilages in joint biomechanics. Materials and Methods: The authors studied 10 cadaveric atlantoaxial lateral joints with the articular cartilage in situ and after removing it, using three-dimensional laser scanner. The data were compared using geometric morphometry with emphasis on surface contours of articulating surfaces. Results: The bony inferior articular facet of atlas is concave in both sagittal and coronal plane. The bony superior articular facet of axis is convex in sagittal plane and is concave (laterally) and convex medially in the coronal plane. The bony articulating surfaces were nonconcordant. The articular cartilages of both C1 and C2 are biconvex in both planes and are thicker than the concavities of bony articulating surfaces. Conclusion: The biconvex structure of cartilage converts the surface morphology of C1-C2 bony facets from concave on concavo-convex to convex on convex. This reduces the contact point making the six degrees of freedom of motion possible and also makes the joint gyroscopic. PMID:29403249

  3. Microfracture technique versus carbon fibre rod implantation for treatment of knee articular cartilage lesions.

    PubMed

    Dasar, U; Gursoy, S; Akkaya, M; Algin, O; Isik, C; Bozkurt, M

    2016-08-01

    To compare the microfracture technique with carbon fibre rod implantation for treatment of knee articular cartilage lesions. 10 men and 30 women aged 22 to 56 (mean, 37.4) years underwent microfracture (n=20) or carbon fibre rod implantation (n=20) for International Cartilage Repair Society grade 3 to 4 knee articular cartilage lesions after a mean of 12.2 months of viscosupplementation and physiotherapy. Clinical outcome at 6 and 12 months was assessed using the Tegner-Lysholm score and modified Cincinnati score. Magnetic resonance imaging (MRI) outcome at 12 months was assessed by a radiologist. The modified magnetic resonance observation of cartilage repair tissue (MOCART) score was evaluated. The 2 groups were comparable in terms of age, body mass index, lesion location, lesion size, duration of symptoms, and coexisting pathology. The microfracture group had a higher preoperative Tegner-Lysholm score (39.4±7.3 vs. 34.4±4.9, p=0.015) and modified Cincinnati score (36.4±7.2 vs. 30.4±4.0, p=0.002) than the carbon fibre rod group. At 12 months, change in both scores was significant within each group (p<0.001) and was higher in the microfracture than carbon fibre rod group (p<0.001). MRI showed minimal regenerative tissue. Lobulation, oedema, and hypertrophy were more commonly found in the regeneration tissue after carbon fibre rod implantation than microfracture. At 12 months, the MOCART score was higher in the microfracture than carbon fibre rod group (59 vs. 47, p<0.001). Microfracture is superior to carbon fibre rod implantation in terms of clinical and radiological outcome.

  4. Treatment of focal articular cartilage lesions of the knee with autogenous osteochondral graftsA 2- to 4-year follow-up study.

    PubMed

    Wang, Ching-Jen

    2002-04-01

    A retrospective study of 15 patients with 16 knees who underwent osteochondral autografts for focal full thickness articular cartilage defects of the knee with 2- to 4-year follow-up showed 80% good or excellent clinical results. There was no correlation of the clinical results with the underlying diagnoses, including osteonecrosis, osteochondritis dessicans and traumatic cartilage defect, or a size of the lesion smaller than 600 mm(2). However, cartilage lesions larger than 600 mm(2) were associated with increasing fibrous tissue formation and fissuring between the grafts and the host tissues and poor results. The improvement in symptoms appeared time-dependent, ranging from 6 to 16 weeks, suggesting that postoperative protection of the graft is warranted. There was no radiographic progression of degenerative changes of the knee on the medium-term follow-up. Therefore, an autogenous osteochondral graft is considered a good method in the treatment of knees with moderately sized articular cartilage defects.

  5. Age-related changes in the articular cartilage of the stifle joint in non-working and working German Shepherd dogs.

    PubMed

    Francuski, J V; Radovanović, A; Andrić, N; Krstić, V; Bogdanović, D; Hadzić, V; Todorović, V; Lazarević Macanović, M; Sourice Petit, S; Beck-Cormier, S; Guicheux, J; Gauthier, O; Kovacević Filipović, M

    2014-11-01

    The aims of this study were to define age-related histological changes in the articular cartilage of the stifle joint in non-chondrodystrophic dogs and to determine whether physical activity has a positive impact on preservation of cartilage structure during ageing. Twenty-eight German shepherd dogs were included in the study. These dogs had no evidence of joint inflammation as defined by clinical assessment, radiology and synovial fluid analysis (specifically absence of synovial fluid serum amyloid A). The dogs were grouped as young working (n ¼ 4), young non-working (n ¼ 5), aged working (n ¼ 13) and aged non-working (n ¼ 6) animals. Gross changes in the stifle joints were recorded and biopsy samples of femoral and tibial articular cartilage were evaluated for thickness; chondrocyte number, density, surface area and morphology; isogenous group morphology; tidemark integrity; subchondral bone structure; presence of proteoglycans/ glycosaminoglycans; and expression of type I, II and X collagens. The major age-related changes, not related to type of physical activity, included elevated chondrocyte density and thinning of tibial cartilage and increased chondrocyte surface area in the superficial and intermediate zone of the femoral cartilage. There was also expression of type X collagen in the femoral and tibial calcified and non-calcified cartilage; however, type X collagen was not detected in the superficial zone of old working dogs. Therefore, ageing, with or without physical activity, leads to slight cartilage degeneration, while physical activity modulates the synthesis of type X collagen in the superficial cartilage zone, partially preserving the structure of hyaline cartilage. 2014 Elsevier Ltd. All rights reserved.

  6. A comparative analysis of 7.0-Tesla magnetic resonance imaging and histology measurements of knee articular cartilage in a canine posterolateral knee injury model: a preliminary analysis.

    PubMed

    Pepin, Scott R; Griffith, Chad J; Wijdicks, Coen A; Goerke, Ute; McNulty, Margaret A; Parker, Josh B; Carlson, Cathy S; Ellermann, Jutta; LaPrade, Robert F

    2009-11-01

    There has recently been increased interest in the use of 7.0-T magnetic resonance imaging for evaluating articular cartilage degeneration and quantifying the progression of osteoarthritis. The purpose of this study was to evaluate articular cartilage cross-sectional area and maximum thickness in the medial compartment of intact and destabilized canine knees using 7.0-T magnetic resonance images and compare these results with those obtained from the corresponding histologic sections. Controlled laboratory study. Five canines had a surgically created unilateral grade III posterolateral knee injury that was followed for 6 months before euthanasia. The opposite, noninjured knee was used as a control. At necropsy, 3-dimensional gradient echo images of the medial tibial plateau of both knees were obtained using a 7.0-T magnetic resonance imaging scanner. Articular cartilage area and maximum thickness in this site were digitally measured on the magnetic resonance images. The proximal tibias were processed for routine histologic analysis with hematoxylin and eosin staining. Articular cartilage area and maximum thickness were measured in histologic sections corresponding to the sites of the magnetic resonance slices. The magnetic resonance imaging results revealed an increase in articular cartilage area and maximum thickness in surgical knees compared with control knees in all specimens; these changes were significant for both parameters (P <.05 for area; P <.01 for thickness). The average increase in area was 14.8% and the average increase in maximum thickness was 15.1%. The histologic results revealed an average increase in area of 27.4% (P = .05) and an average increase in maximum thickness of 33.0% (P = .06). Correlation analysis between the magnetic resonance imaging and histology data revealed that the area values were significantly correlated (P < .01), but the values for thickness obtained from magnetic resonance imaging were not significantly different from the

  7. Micro- and Nanomechanical Analysis of Articular Cartilage by Indentation-Type Atomic Force Microscopy: Validation with a Gel-Microfiber Composite

    PubMed Central

    Loparic, Marko; Wirz, Dieter; Daniels, A.U.; Raiteri, Roberto; VanLandingham, Mark R.; Guex, Geraldine; Martin, Ivan; Aebi, Ueli; Stolz, Martin

    2010-01-01

    Abstract As documented previously, articular cartilage exhibits a scale-dependent dynamic stiffness when probed by indentation-type atomic force microscopy (IT-AFM). In this study, a micrometer-size spherical tip revealed an unimodal stiffness distribution (which we refer to as microstiffness), whereas probing articular cartilage with a nanometer-size pyramidal tip resulted in a bimodal nanostiffness distribution. We concluded that indentation of the cartilage's soft proteoglycan (PG) gel gave rise to the lower nanostiffness peak, whereas deformation of its collagen fibrils yielded the higher nanostiffness peak. To test our hypothesis, we produced a gel-microfiber composite consisting of a chondroitin sulfate-containing agarose gel and a fibrillar poly(ethylene glycol)-terephthalate/poly(butylene)-terephthalate block copolymer. In striking analogy to articular cartilage, the microstiffness distribution of the synthetic composite was unimodal, whereas its nanostiffness exhibited a bimodal distribution. Also, similar to the case with cartilage, addition of the negatively charged chondroitin sulfate rendered the gel-microfiber composite's water content responsive to salt. When the ionic strength of the surrounding buffer solution increased from 0.15 to 2 M NaCl, the cartilage's microstiffness increased by 21%, whereas that of the synthetic biomaterial went up by 31%. When the nanostiffness was measured after the ionic strength was raised by the same amount, the cartilage's lower peak increased by 28%, whereas that of the synthetic biomaterial went up by 34%. Of interest, the higher peak values remained unchanged for both materials. Taken together, these results demonstrate that the nanoscale lower peak is a measure of the soft PG gel, and the nanoscale higher peak measures collagen fibril stiffness. In contrast, the micrometer-scale measurements fail to resolve separate stiffness values for the PG and collagen fibril moieties. Therefore, we propose to use

  8. Hierarchical Structure of Articular Bone-Cartilage Interface and Its Potential Application for Osteochondral Tissue Engineering

    NASA Astrophysics Data System (ADS)

    Bian, Weiguo; Qin, Lian; Li, Dichen; Wang, Jin; Jin, Zhongmin

    2010-09-01

    The artificial biodegradable osteochondral construct is one of mostly promising lifetime substitute in the joint replacement. And the complex hierarchical structure of natural joint is important in developing the osteochondral construct. However, the architecture features of the interface between cartilage and bone, in particular those at the micro-and nano-structural level, remain poorly understood. This paper investigates these structural data of the cartilage-bone interface by micro computerized tomography (μCT) and Scanning Electron Microscope (SEM). The result of μCT shows that important bone parameters and the density of articular cartilage are all related to the position in the hierarchical structure. The conjunctions of bone and cartilage were defined by SEM. All of the study results would be useful for the design of osteochondral construct further manufactured by nano-tech. A three-dimensional model with gradient porous structure is constructed in the environment of Pro/ENGINEERING software.

  9. The collagen structure of equine articular cartilage, characterized using polarization-sensitive optical coherence tomography

    NASA Astrophysics Data System (ADS)

    Ugryumova, Nadya; Attenburrow, Don P.; Winlove, C. Peter; Matcher, Stephen J.

    2005-08-01

    Optical coherence tomography and polarization-sensitive optical coherence tomography images of equine articular cartilage are presented. Measurements were made on intact joint surfaces. Significant (e.g. × 2) variations in the intrinsic birefringence were found over spatial scales of a few millimetres, even on samples taken from young (18 month) animals that appeared visually homogeneous. A comparison of data obtained on a control tissue (equine flexor tendon) further suggests that significant variations in the orientation of the collagen fibres relative to the plane of the joint surface exist. Images of visually damaged cartilage tissue show characteristic features both in terms of the distribution of optical scatterers and of the birefringent components.

  10. Role of Electrostatic Interactions on the Transport of Druglike Molecules in Hydrogel-Based Articular Cartilage Mimics: Implications for Drug Delivery.

    PubMed

    Ye, Fengbin; Baldursdottir, Stefania; Hvidt, Søren; Jensen, Henrik; Larsen, Susan W; Yaghmur, Anan; Larsen, Claus; Østergaard, Jesper

    2016-03-07

    In the field of drug delivery to the articular cartilage, it is advantageous to apply artificial tissue models as surrogates of cartilage for investigating drug transport and release properties. In this study, artificial cartilage models consisting of 0.5% (w/v) agarose gel containing 0.5% (w/v) chondroitin sulfate or 0.5% (w/v) hyaluronic acid were developed, and their rheological and morphological properties were characterized. UV imaging was utilized to quantify the transport properties of the following four model compounds in the agarose gel and in the developed artificial cartilage models: H-Ala-β-naphthylamide, H-Lys-Lys-β-naphthylamide, lysozyme, and α-lactalbumin. The obtained results showed that the incorporation of the polyelectrolytes chondroitin sulfate or hyaluronic acid into agarose gel induced a significant reduction in the apparent diffusivities of the cationic model compounds as compared to the pure agarose gel. The decrease in apparent diffusivity of the cationic compounds was not caused by a change in the gel structure since a similar reduction in apparent diffusivity was not observed for the net negatively charged protein α-lactalbumin. The apparent diffusivity of the cationic compounds in the negatively charged hydrogels was highly dependent on the ionic strength, pointing out the importance of electrostatic interactions between the diffusant and the polyelectrolytes. Solution based affinity studies between the model compounds and the two investigated polyelectrolytes further confirmed the electrostatic nature of their interactions. The results obtained from the UV imaging diffusion studies are important for understanding the effect of drug physicochemical properties on the transport in articular cartilage. The extracted information may be useful in the development of hydrogels for in vitro release testing having features resembling the articular cartilage.

  11. Altered mechano-chemical environment in hip articular cartilage: effect of obesity.

    PubMed

    Travascio, Francesco; Eltoukhy, Moataz; Cami, Sonila; Asfour, Shihab

    2014-10-01

    The production of extracellular matrix (ECM) components of articular cartilage is regulated, among other factors, by an intercellular signaling mechanism mediated by the interaction of cell surface receptors (CSR) with insulin-like growth factor-1 (IGF-1). In ECM, the presence of binding proteins (IGFBP) hinders IGF-1 delivery to CSR. It has been reported that levels of IGF-1 and IGFBP in obese population are, respectively, lower and higher than those found in normal population. In this study, an experimental-numerical approach was adopted to quantify the effect of this metabolic alteration found in obese population on the homeostasis of femoral hip cartilage. A new computational model, based on the mechano-electrochemical mixture theory, was developed to describe competitive binding kinetics of IGF-1 with IGFBP and CSR, and associated glycosaminoglycan (GAG) biosynthesis. Moreover, a gait analysis was carried out on obese and normal subjects to experimentally characterize mechanical loads on hip cartilage during walking. This information was deployed into the model to account for effects of physiologically relevant tissue deformation on GAG production in ECM. Numerical simulations were performed to compare GAG biosynthesis in femoral hip cartilage of normal and obese subjects. Results indicated that the lower ratio of IGF-1 to IGFBP found in obese population reduces cartilage GAG concentration up to 18 % when compared to normal population. Moreover, moderate physical activity, such as walking, has a modest beneficial effect on GAG production. The findings of this study suggest that IGF-1/IGFBP metabolic unbalance should be accounted for when considering the association of obesity with hip osteoarthritis.

  12. Small-Diameter Awls Improve Articular Cartilage Repair After Microfracture Treatment in a Translational Animal Model.

    PubMed

    Orth, Patrick; Duffner, Julia; Zurakowski, David; Cucchiarini, Magali; Madry, Henning

    2016-01-01

    Microfracture is the most commonly applied arthroscopic marrow stimulation procedure. Articular cartilage repair is improved when the subchondral bone is perforated by small-diameter microfracture awls compared with larger awls. Controlled laboratory study. Standardized rectangular (4 × 8 mm) full-thickness chondral defects (N = 24) were created in the medial femoral condyle of 16 adult sheep and debrided down to the subchondral bone plate. Three treatment groups (n = 8 defects each) were tested: 6 microfracture perforations using small-diameter awls (1.0 mm; group 1), large-diameter awls (1.2 mm; group 2), or without perforations (debridement control; group 3). Osteochondral repair was assessed at 6 months in vivo using established macroscopic, histological, immunohistochemical, biochemical, and micro-computed tomography analyses. Compared with control defects, histological cartilage repair was always improved after both microfracture techniques (P < .023). Application of 1.0-mm microfracture awls led to a significantly improved histological overall repair tissue quality (7.02 ± 0.70 vs 9.03 ± 0.69; P = .008) and surface grading (1.05 ± 0.28 vs 2.10 ± 0.19; P = .001) compared with larger awls. The small-diameter awl decreased relative bone volume of the subarticular spongiosa (bone volume/tissue volume ratio: 23.81% ± 3.37% vs 30.58% ± 2.46%; P = .011). Subchondral bone cysts and intralesional osteophytes were frequently observed after either microfracture treatment. Macroscopic grading, DNA, proteoglycan, and type I and type II collagen contents as well as degenerative changes within the adjacent cartilage remained unaffected by the awl diameter. Small-diameter microfracture awls improve articular cartilage repair in the translational sheep model more effectively than do larger awls. These data support the use of small microfracture instruments for the surgical treatment of cartilage defects and warrant prolonged clinical investigations. © 2015 The Author(s).

  13. The effect of variable size posterior wall acetabular fractures on contact characteristics of the hip joint.

    PubMed

    Olson, S A; Bay, B K; Pollak, A N; Sharkey, N A; Lee, T

    1996-01-01

    The indications for open reduction and internal fixation of posterior wall acetabular fractures associated with a clinically stable hip joint are unclear. In previous work a large posterior wall defect (27% articular surface area) resulted in significant alteration of load transmission across the hip; specifically, there was a transition from evenly distributed loading along the acetabular articular surface to loading concentrated mainly in the superior portion of the articular surface during simulated single leg stance. However, the majority of posterior wall fractures involve a smaller amount of the articular surface. Posterior wall acetabular fractures not associated with instability of the hip are commonly treated nonoperatively. This practice does not account for the size of the posterior wall fracture. To study the biomechanical consequences of variably sized articular defects, a laboratory experiment was conducted evaluating three progressively larger posterior wall defects of the acetabulum during simulated single leg stance using superlow Fuji prescale film (Itochu International, New York): (a) 1/3 articular surface width through a 50 degrees arc along the posterior wall of the acetabulum, (b) 2/3, and (c) 3/3 articular width defects through the same 50 degrees arc along the posterior wall of the acetabulum. In the intact acetabulum, 48% of the total articular contact was located in the superior acetabulum. Twenty-eight percent of articular contact was in the anterior wall region of the acetabulum and 24% in the posterior wall region. After the 1/3 width posterior wall defect, 64% of the articular contact was located in the superior acetabulum (p = 0.0011). The 2/3 width posterior wall defect resulted in 71% of articular contact area being located in the superior acetabulum (p = 0.0006). After the 3/3 width posterior wall defect, 77% of articular contact was located in the superior acetabulum, significantly greater than the intact condition (p < 0

  14. T1ρ is superior to T2 mapping for the evaluation of articular cartilage denaturalization with osteoarthritis: radiological-pathological correlation after total knee arthroplasty.

    PubMed

    Takayama, Yukihisa; Hatakenaka, Masamitsu; Tsushima, Hidetoshi; Okazaki, Ken; Yoshiura, Takashi; Yonezawa, Masato; Nishikawa, Kei; Iwamoto, Yukihide; Honda, Hiroshi

    2013-04-01

    We compared the diagnostic performance of T1ρ and T2 mappings in the evaluation of denatured articular cartilage with osteoarthritis of the knee. 2D-Sagittal T1ρ and T2 mappings of the knee were obtained from 16 patients before total knee arthroplasty. After surgery, specimens of the femur and tibia were regionally segmented according to a 5-point scale of the severity of denaturalization. The T1ρ and T2 values in the full thickness of the articular cartilage in each region were measured by two observers. The two mappings were compared for their ability to differentiate between normal and denatured articular cartilage and also for their usefulness in grading the severity of the denaturalization using the area under receiver operating characteristic curves (Az). A p<0.05 was considered significant for each analysis. The T1ρ mapping showed a significantly higher Az value than the T2 mapping for the differentiation between normal and denatured articular cartilage (p<0.05). Regarding the assessment of the severity of denaturalization, T1ρ mapping could differentiate between normal and mild denaturalization (p<0.05), but T2 mapping could not. However, there were no significant differences between the two mappings in the discrimination of mild versus moderate denaturalization or of moderate versus severe denaturalization. The two observers showed good agreement in the results (intraclass correlation coefficient=0.81 for T1ρ and 0.92 for T2). T1ρ mapping is superior to T2 mapping for the evaluation of denatured articular cartilage with osteoarthritis of the knee. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  15. Galectin-3 Binds to Lubricin and Reinforces the Lubricating Boundary Layer of Articular Cartilage.

    PubMed

    Reesink, Heidi L; Bonnevie, Edward D; Liu, Sherry; Shurer, Carolyn R; Hollander, Michael J; Bonassar, Lawrence J; Nixon, Alan J

    2016-05-09

    Lubricin is a mucinous, synovial fluid glycoprotein that enables near frictionless joint motion via adsorption to the surface of articular cartilage and its lubricating properties in solution. Extensive O-linked glycosylation within lubricin's mucin-rich domain is critical for its boundary lubricating function; however, it is unknown exactly how glycosylation facilitates cartilage lubrication. Here, we find that the lubricin glycome is enriched with terminal β-galactosides, known binding partners for a family of multivalent lectins called galectins. Of the galectin family members present in synovial fluid, we find that galectin-3 is a specific, high-affinity binding partner for lubricin. Considering the known ability of galectin-3 to crosslink glycoproteins, we hypothesized that galectins could augment lubrication via biomechanical stabilization of the lubricin boundary layer. We find that competitive inhibition of galectin binding results in lubricin loss from the cartilage surface, and addition of multimeric galectin-3 enhances cartilage lubrication. We also find that galectin-3 has low affinity for the surface layer of osteoarthritic cartilage and has reduced affinity for sialylated O-glycans, a glycophenotype associated with inflammatory conditions. Together, our results suggest that galectin-3 reinforces the lubricin boundary layer; which, in turn, enhances cartilage lubrication and may delay the onset and progression of arthritis.

  16. Galectin-3 Binds to Lubricin and Reinforces the Lubricating Boundary Layer of Articular Cartilage

    PubMed Central

    Reesink, Heidi L.; Bonnevie, Edward D.; Liu, Sherry; Shurer, Carolyn R.; Hollander, Michael J.; Bonassar, Lawrence J.; Nixon, Alan J.

    2016-01-01

    Lubricin is a mucinous, synovial fluid glycoprotein that enables near frictionless joint motion via adsorption to the surface of articular cartilage and its lubricating properties in solution. Extensive O-linked glycosylation within lubricin’s mucin-rich domain is critical for its boundary lubricating function; however, it is unknown exactly how glycosylation facilitates cartilage lubrication. Here, we find that the lubricin glycome is enriched with terminal β-galactosides, known binding partners for a family of multivalent lectins called galectins. Of the galectin family members present in synovial fluid, we find that galectin-3 is a specific, high-affinity binding partner for lubricin. Considering the known ability of galectin-3 to crosslink glycoproteins, we hypothesized that galectins could augment lubrication via biomechanical stabilization of the lubricin boundary layer. We find that competitive inhibition of galectin binding results in lubricin loss from the cartilage surface, and addition of multimeric galectin-3 enhances cartilage lubrication. We also find that galectin-3 has low affinity for the surface layer of osteoarthritic cartilage and has reduced affinity for sialylated O-glycans, a glycophenotype associated with inflammatory conditions. Together, our results suggest that galectin-3 reinforces the lubricin boundary layer; which, in turn, enhances cartilage lubrication and may delay the onset and progression of arthritis. PMID:27157803

  17. Galectin-3 Binds to Lubricin and Reinforces the Lubricating Boundary Layer of Articular Cartilage

    NASA Astrophysics Data System (ADS)

    Reesink, Heidi L.; Bonnevie, Edward D.; Liu, Sherry; Shurer, Carolyn R.; Hollander, Michael J.; Bonassar, Lawrence J.; Nixon, Alan J.

    2016-05-01

    Lubricin is a mucinous, synovial fluid glycoprotein that enables near frictionless joint motion via adsorption to the surface of articular cartilage and its lubricating properties in solution. Extensive O-linked glycosylation within lubricin’s mucin-rich domain is critical for its boundary lubricating function; however, it is unknown exactly how glycosylation facilitates cartilage lubrication. Here, we find that the lubricin glycome is enriched with terminal β-galactosides, known binding partners for a family of multivalent lectins called galectins. Of the galectin family members present in synovial fluid, we find that galectin-3 is a specific, high-affinity binding partner for lubricin. Considering the known ability of galectin-3 to crosslink glycoproteins, we hypothesized that galectins could augment lubrication via biomechanical stabilization of the lubricin boundary layer. We find that competitive inhibition of galectin binding results in lubricin loss from the cartilage surface, and addition of multimeric galectin-3 enhances cartilage lubrication. We also find that galectin-3 has low affinity for the surface layer of osteoarthritic cartilage and has reduced affinity for sialylated O-glycans, a glycophenotype associated with inflammatory conditions. Together, our results suggest that galectin-3 reinforces the lubricin boundary layer; which, in turn, enhances cartilage lubrication and may delay the onset and progression of arthritis.

  18. Feasibility of high-resolution one-dimensional relaxation imaging at low magnetic field using a single-sided NMR scanner applied to articular cartilage.

    PubMed

    Rössler, Erik; Mattea, Carlos; Stapf, Siegfried

    2015-02-01

    Low field Nuclear Magnetic Resonance increases the contrast of the longitudinal relaxation rate in many biological tissues; one prominent example is hyaline articular cartilage. In order to take advantage of this increased contrast and to profile the depth-dependent variations, high resolution parameter measurements are carried out which can be of critical importance in an early diagnosis of cartilage diseases such as osteoarthritis. However, the maximum achievable spatial resolution of parameter profiles is limited by factors such as sensor geometry, sample curvature, and diffusion limitation. In this work, we report on high-resolution single-sided NMR scanner measurements with a commercial device, and quantify these limitations. The highest achievable spatial resolution on the used profiler, and the lateral dimension of the sensitive volume were determined. Since articular cartilage samples are usually bent, we also focus on averaging effects inside the horizontally aligned sensitive volume and their impact on the relaxation profiles. Taking these critical parameters into consideration, depth-dependent relaxation time profiles with the maximum achievable vertical resolution of 20 μm are discussed, and are correlated with diffusion coefficient profiles in hyaline articular cartilage in order to reconstruct T(2) maps from the diffusion-weighted CPMG decays of apparent relaxation rates. Copyright © 2014 Elsevier Inc. All rights reserved.

  19. Feasibility of high-resolution one-dimensional relaxation imaging at low magnetic field using a single-sided NMR scanner applied to articular cartilage

    NASA Astrophysics Data System (ADS)

    Rössler, Erik; Mattea, Carlos; Stapf, Siegfried

    2015-02-01

    Low field Nuclear Magnetic Resonance increases the contrast of the longitudinal relaxation rate in many biological tissues; one prominent example is hyaline articular cartilage. In order to take advantage of this increased contrast and to profile the depth-dependent variations, high resolution parameter measurements are carried out which can be of critical importance in an early diagnosis of cartilage diseases such as osteoarthritis. However, the maximum achievable spatial resolution of parameter profiles is limited by factors such as sensor geometry, sample curvature, and diffusion limitation. In this work, we report on high-resolution single-sided NMR scanner measurements with a commercial device, and quantify these limitations. The highest achievable spatial resolution on the used profiler, and the lateral dimension of the sensitive volume were determined. Since articular cartilage samples are usually bent, we also focus on averaging effects inside the horizontally aligned sensitive volume and their impact on the relaxation profiles. Taking these critical parameters into consideration, depth-dependent relaxation time profiles with the maximum achievable vertical resolution of 20 μm are discussed, and are correlated with diffusion coefficient profiles in hyaline articular cartilage in order to reconstruct T2 maps from the diffusion-weighted CPMG decays of apparent relaxation rates.

  20. A fast quadrature-based numerical method for the continuous spectrum biphasic poroviscoelastic model of articular cartilage.

    PubMed

    Stuebner, Michael; Haider, Mansoor A

    2010-06-18

    A new and efficient method for numerical solution of the continuous spectrum biphasic poroviscoelastic (BPVE) model of articular cartilage is presented. Development of the method is based on a composite Gauss-Legendre quadrature approximation of the continuous spectrum relaxation function that leads to an exponential series representation. The separability property of the exponential terms in the series is exploited to develop a numerical scheme that can be reduced to an update rule requiring retention of the strain history at only the previous time step. The cost of the resulting temporal discretization scheme is O(N) for N time steps. Application and calibration of the method is illustrated in the context of a finite difference solution of the one-dimensional confined compression BPVE stress-relaxation problem. Accuracy of the numerical method is demonstrated by comparison to a theoretical Laplace transform solution for a range of viscoelastic relaxation times that are representative of articular cartilage. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

  1. An integral biochemical analysis of the main constituents of articular cartilage, subchondral and trabecular bone.

    PubMed

    van der Harst, Mark R; Brama, Pieter A J; van de Lest, Chris H A; Kiers, Geesje H; DeGroot, Jeroen; van Weeren, P René

    2004-09-01

    In articular joints, the forces generated by locomotion are absorbed by the whole of cartilage, subchondral bone and underlying trabecular bone. The objective of this study is to test the hypothesis that regional differences in joint loading are related to clear and interrelated differences in the composition of the extracellular matrix (ECM) of all three weight-bearing constituents. Cartilage, subchondral- and trabecular bone samples from two differently loaded sites (site 1, dorsal joint margin; site 2, central area) of the proximal articular surface of 30 macroscopically normal equine first phalanxes were collected. Collagen content, cross-linking (pentosidine, hydroxylysylpyridinoline (HP), lysylpyridinoline (LP)) hydroxylation, and denaturation, as well as glycosaminoglycan (GAG) and DNA content were measured in all three tissues. In addition, bone mineral density (BMD), the percentage of ash and the mineral composition (calcium, magnesium and phosphorus) were determined in the bony samples. For pentosidine cross-links there was an expected correlation with age. Denatured collagen content was significantly higher in cartilage at site 1 than at site 2 and was higher in trabecular bone compared to subchondral bone, with no site differences. There were significant site differences in hydroxylysine (Hyl) concentration and HP cross-links in cartilage that were paralleled in one or both of the bony layers. In subchondral bone there was a positive correlation between total (HP+LP) cross-links and Ca content. For Ca and other minerals there were corresponding site differences in both bony layers. It is concluded that there are distinct differences in distribution of the major biochemical components over both sites in all three layers. These differences show similar patterns in cartilage, subchondral bone and trabecular bone, stressing the functional unity of these tissues. Overall, differences could be interpreted as adaptations to a considerably higher cumulative

  2. Treatment of a Focal Articular Cartilage Defect of the Talus with Polymer-Based Autologous Chondrocyte Implantation: A 12-Year Follow-Up Period.

    PubMed

    Kreuz, Peter Cornelius; Kalkreuth, Richard Horst; Niemeyer, Philipp; Uhl, Markus; Erggelet, Christoph

    Autologous chondrocyte implantation (ACI) is a first-line treatment option for large articular cartilage defects. Although well-established for cartilage defects in the knee, studies of the long-term outcomes of matrix-assisted ACI to treat cartilage defects in the ankle are rare. In the present report, we describe for the first time the long-term clinical and radiologic results 12 years after polymer-based matrix-assisted ACI treat a full-thickness talar cartilage defect in a 25-year-old male patient. The clinical outcome was assessed using the visual analog scale and Freiburg ankle score, magnetic resonance imaging evaluation using the Henderson-Kreuz scoring system and T2 mapping. Clinical assessment revealed improved visual analog scale and Freiburg ankle scores. The radiologic analysis and T2 relaxation time values indicated the formation of hyaline-like repair tissue. Polymer-based autologous chondrocytes has been shown to be a safe and clinically effective long-term treatment of articular cartilage defects in the talus. Copyright © 2017 American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.

  3. Biochemical magnetic resonance imaging of knee articular cartilage: T1rho and T2 mapping as cartilage degeneration biomarkers.

    PubMed

    Le, Jenna; Peng, Qi; Sperling, Karen

    2016-11-01

    Osteoarthritis (OA) is a disease whose hallmark is the degeneration of articular cartilage. There is a worsening epidemic of OA in the United States today, with considerable economic costs. In order to develop more effective treatments for OA, noninvasive biomarkers that permit early diagnosis and treatment monitoring are necessary. T1rho and T2 mapping are two magnetic resonance imaging techniques that have shown great promise as noninvasive biomarkers of cartilage degeneration. Each of the two techniques is endowed with advantages and disadvantages: T1rho can discern earlier biochemical changes of OA than T2 mapping, while T2 mapping is more widely available and can be incorporated into existing imaging protocols in a more time-efficient manner than T1rho. Both techniques have been applied in numerous instances to study how cartilage is affected by OA risk factors, such as age and exercise. Additionally, both techniques have been repeatedly applied to the study of posttraumatic OA in patients with torn anterior cruciate ligaments. © 2016 New York Academy of Sciences.

  4. Articular cartilage scores in cranial cruciate ligament-deficient dogs with or without bucket handle tears of the medial meniscus.

    PubMed

    Kaufman, Kathryn; Beale, Brian S; Thames, Howard D; Saunders, W Brian

    2017-01-01

    To compare articular cartilage scores in cranial cruciate ligament (CCL)-deficient dogs with or without concurrent bucket handle tears (BHT) of the medial meniscus. Retrospective case series. Client-owned dogs treated with arthroscopy and tibial plateau leveling osteotomy or extracapsular repair for complete CCL rupture (290 stifles from 264 dogs). Medical records and arthroscopic images were reviewed. Medial femoral condyle (MFC) and medial tibial plateau (MTP) cartilage was scored using the modified Outerbridge scale. Periarticular osteophytosis (PAO) and injury to the medial meniscus were recorded. Data were analyzed using Student's t-tests, Wilcoxon rank-sum test, and Fisher's exact test for changes in the stifle based on meniscal condition, body weight, and duration of lameness. PAO, MFC, and MTP articular cartilage scores were not significantly different in dogs with or without BHT. There were no significant differences in MFC or MTP scores when dogs were evaluated based on bodyweight and the presence or absence of a BHT. However, PAO formation was significantly increased in dogs weighing >13.6 kg and concurrent meniscal injury vs. dogs weighing <13.6 kg and concurrent meniscal injury (P < .001). Significantly more stifles with chronic lameness (40 of 89; 44.9%) had the highest PAO score of 2 reported compared to only 42 of 182 stifles (23.1%) with acute lameness (P < .001). The presence of a BHT of the medial meniscus was not associated with more severe arthroscopic articular cartilage lesions in the medial joint compartment at the time of surgery. © 2016 The American College of Veterinary Surgeons.

  5. Effect of Treadmill Exercise Timing on Repair of Full-Thickness Defects of Articular Cartilage by Bone-Derived Mesenchymal Stem Cells: An Experimental Investigation in Rats

    PubMed Central

    Li, Xue; Xu, Chang-peng; Cui, Zhuang; Jiang, Nan; Jia, Jun-jie; Yu, Bin

    2014-01-01

    Objective Current medical practice for the treatment of articular cartilage lesions remains a clinical challenge due to the limited self-repair ability of articular cartilage. Both experimental and clinical researches show that moderate exercise can improve articular cartilage repair process. However, optimal timing of moderate exercise is unclear. We aimed to evaluate the effect of timing of moderate treadmill exercise on repair of full-thickness defects of articular cartilage. Design Full-thickness cartilage defects were drilled in the patellar groove of bilateral femoral condyles in a total of 40 male SD rats before they were randomly assigned into four even groups. In sedentary control (SED) group, no exercise was given; in 2-week (2W), 4-week (4W) and 8-week groups, moderate treadmill exercise was initiated respectively two, four and eight weeks after operation. Half of the animals were sacrificed at week 10 after operation and half at week 14 after operation. Femoral condyles were harvested for gross observation and histochemical measurement by O'Driscoll scoring system. Collagen type II was detected by immunohistochemistry and mRNA expressions of aggrecan and collagen type II cartilage by RT-PCR. Results Both 10 and 14 weeks post-operation, the best results were observed in 4W group and the worst results appeared in 2W group. The histochemistry scores and the expressions of collagen type II and aggrecan were significantly higher in 4W group than that in other three groups (P<0.05). Conclusions Moderate exercise at a selected timing (approximately 4 weeks) after injury can significantly promote the healing of cartilage defects but may hamper the repair process if performed too early while delayed intervention by moderate exercise may reduce its benefits in repair of the defects. PMID:24595327

  6. Molecular changes in articular cartilage and subchondral bone in the rat anterior cruciate ligament transection and meniscectomized models of osteoarthritis.

    PubMed

    Pickarski, Maureen; Hayami, Tadashi; Zhuo, Ya; Duong, Le T

    2011-08-24

    Osteoarthritis (OA) is a debilitating, progressive joint disease. Similar to the disease progression in humans, sequential events of early cartilage degradation, subchondral osteopenia followed by sclerosis, and late osteophyte formation were demonstrated in the anterior cruciate ligament transection (ACLT) or ACLT with partial medial meniscectomy (ACLT + MMx) rat OA models. We describe a reliable and consistent method to examine the time dependent changes in the gene expression profiles in articular cartilage and subchondral bone. Local regulation of matrix degradation markers was demonstrated by a significant increase in mRNA levels of aggrecanase-1 and MMP-13 as early as the first week post-surgery, and expression remained elevated throughout the 10 week study. Immunohistochemistry confirmed MMP-13 expression in differentiated chondrocytes and synovial fibroblasts at week-2 and cells within osteophytes at week-10 in the surgically-modified-joints. Concomitant increases in chondrocyte differentiation markers, Col IIA and Sox 9, and vascular invasion markers, VEGF and CD31, peaked around week-2 to -4, and returned to Sham levels at later time points in both models. Indeed, VEGF-positive cells were found in the deep articular chondrocytes adjacent to subchondral bone. Osteoclastic bone resorption markers, cathepsin K and TRAP, were also elevated at week-2. Confirming bone resorption is an early local event in OA progression, cathepsin K positive osteoclasts were found invading the articular cartilage from the subchondral region at week 2. This was followed by late disease events, including subchondral sclerosis and osteophyte formation, as demonstrated by the upregulation of the osteoanabolic markers runx2 and osterix, toward week-4 to 6 post-surgery. In summary, this study demonstrated the temporal and cohesive gene expression changes in articular cartilage and subchondral bone using known markers of OA progression. The findings here support genome-wide profiling

  7. Increasing the Dose of Autologous Chondrocytes Improves Articular Cartilage Repair: Histological and Molecular Study in the Sheep Animal Model.

    PubMed

    Guillén-García, Pedro; Rodríguez-Iñigo, Elena; Guillén-Vicente, Isabel; Caballero-Santos, Rosa; Guillén-Vicente, Marta; Abelow, Stephen; Giménez-Gallego, Guillermo; López-Alcorocho, Juan Manuel

    2014-04-01

    We hypothesized that implanting cells in a chondral defect at a density more similar to that of the intact cartilage could induce them to synthesize matrix with the features more similar to that of the uninjured one. We compared the implantation of different doses of chondrocytes: 1 million (n = 5), 5 million (n = 5), or 5 million mesenchymal cells (n = 5) in the femoral condyle of 15 sheep. Tissue generated by microfracture at the trochlea, and normal cartilage from a nearby region, processed as the tissues resulting from the implantation, were used as references. Histological and molecular (expression of type I and II collagens and aggrecan) studies were performed. The features of the cartilage generated by implantation of mesenchymal cells and elicited by microfractures were similar and typical of a poor repair of the articular cartilage (presence of fibrocartilage, high expression of type I collagen and a low mRNA levels of type II collagen and aggrecan). Nevertheless, in the samples obtained from tissues generated by implantation of chondrocytes, hyaline-like cartilage, cell organization, low expression rates of type I collagen and high levels of mRNA corresponding to type II collagen and aggrecan were observed. These histological features, show less variability and are more similar to those of the normal cartilage used as control in the case of 5 million cells implantation than when 1 million cells were used. The implantation of autologous chondrocytes in type I/III collagen membranes at high density could be a promising tool to repair articular cartilage.

  8. Mechanics and crack formation in the extracellular matrix with articular cartilage as a model system

    NASA Astrophysics Data System (ADS)

    Kearns, Sarah; Silverberg, Jesse; Bonassar, Lawrence; Cohen, Itai; Das, Moumita

    We investigate the mechanical structure-function relations in the extracellular matrix (ECM) with focus on crack formation and failure. As a model system, our study focuses on the ECM in articular cartilage (AC), the tissue that covers the ends of bones, and distributes load in joints including in the knees, shoulders, and hips. The strength, toughness, and crack resistance of native articular cartilage is unparalleled in materials made by humankind. This mechanical response is mainly due to its ECM. The ECM in AC has two major mechanobiological components: a network of the biopolymer collagen and a flexible aggrecan gel. We model this system as a biopolymer network embedded in a swelling gel, and investigate the conditions for the formation and propagation of cracks using a combination of rigidity percolation theory and energy minimization approaches. Our results may provide useful insights into the design principles of the ECM as well as of biomimetic hydrogels that are mechanically robust and can, at the same time, easily adapt to cues in their surroundings. This work was partially supported by a Cottrell College Science Award.

  9. Depth-varying density and organization of chondrocytes in immature and mature bovine articular cartilage assessed by 3d imaging and analysis.

    PubMed

    Jadin, Kyle D; Wong, Benjamin L; Bae, Won C; Li, Kelvin W; Williamson, Amanda K; Schumacher, Barbara L; Price, Jeffrey H; Sah, Robert L

    2005-09-01

    Articular cartilage is a heterogeneous tissue, with cell density and organization varying with depth from the surface. The objectives of the present study were to establish a method for localizing individual cells in three-dimensional (3D) images of cartilage and quantifying depth-associated variation in cellularity and cell organization at different stages of growth. Accuracy of nucleus localization was high, with 99% sensitivity relative to manual localization. Cellularity (million cells per cm3) decreased from 290, 310, and 150 near the articular surface in fetal, calf, and adult samples, respectively, to 120, 110, and 50 at a depth of 1.0 mm. The distance/angle to the nearest neighboring cell was 7.9 microm/31 degrees , 7.1 microm/31 degrees , and 9.1 microm/31 degrees for cells at the articular surface of fetal, calf, and adult samples, respectively, and increased/decreased to 11.6 microm/31 degrees , 12.0 microm/30 degrees , and 19.2 microm/25 degrees at a depth of 0.7 mm. The methodologies described here may be useful for analyzing the 3D cellular organization of cartilage during growth, maturation, aging, degeneration, and regeneration.

  10. Depth-varying density and organization of chondrocytes in immature and mature bovine articular cartilage assessed by 3d imaging and analysis

    NASA Technical Reports Server (NTRS)

    Jadin, Kyle D.; Wong, Benjamin L.; Bae, Won C.; Li, Kelvin W.; Williamson, Amanda K.; Schumacher, Barbara L.; Price, Jeffrey H.; Sah, Robert L.

    2005-01-01

    Articular cartilage is a heterogeneous tissue, with cell density and organization varying with depth from the surface. The objectives of the present study were to establish a method for localizing individual cells in three-dimensional (3D) images of cartilage and quantifying depth-associated variation in cellularity and cell organization at different stages of growth. Accuracy of nucleus localization was high, with 99% sensitivity relative to manual localization. Cellularity (million cells per cm3) decreased from 290, 310, and 150 near the articular surface in fetal, calf, and adult samples, respectively, to 120, 110, and 50 at a depth of 1.0 mm. The distance/angle to the nearest neighboring cell was 7.9 microm/31 degrees , 7.1 microm/31 degrees , and 9.1 microm/31 degrees for cells at the articular surface of fetal, calf, and adult samples, respectively, and increased/decreased to 11.6 microm/31 degrees , 12.0 microm/30 degrees , and 19.2 microm/25 degrees at a depth of 0.7 mm. The methodologies described here may be useful for analyzing the 3D cellular organization of cartilage during growth, maturation, aging, degeneration, and regeneration.

  11. Matrilin-3 codelivery with adipose-derived mesenchymal stem cells promotes articular cartilage regeneration in a rat osteochondral defect model.

    PubMed

    Muttigi, Manjunatha S; Kim, Byoung Ju; Choi, Bogyu; Yoshie, Arai; Kumar, Hemant; Han, Inbo; Park, Hansoo; Lee, Soo-Hong

    2018-03-01

    Matrilin-3 is an essential extracellular matrix component present only in cartilaginous tissues. Matrilin-3 exerts chondroprotective effects by regulating an anti-inflammatory function and extracellular matrix components. We hypothesized that the codelivery of matrilin-3 with infrapatellar adipose-tissue-derived mesenchymal stem cells (Ad-MSCs) may enhance articular cartilage regeneration. Matrilin-3 treatment of Ad-MSCs in serum-free media induced collagen II and aggrecan expression, and matrilin-3 in chondrogenic media also enhanced in vitro chondrogenic differentiation. Next, the in vivo effect of matrilin-3 codelivery with Ad-MSCs on cartilage regeneration was assessed in an osteochondral defect model in Sprague Dawley rats: Ad-MSCs and hyaluronic acid were implanted at the defect site with or without matrilin-3 (140, 280, and 700 ng). Safranin O staining revealed that matrilin-3 (140 and 280 ng) treatment significantly improved cartilage regeneration and glycosaminoglycan accumulation. In the animals treated with 140-ng matrilin-3, in particular, the defect site exhibited complete integration with surrounding tissue and a smooth glistening surface. The International Cartilage Repair Society macroscopic and O'Driscoll microscopic scores for regenerated cartilage were furthermore shown to be considerably higher for this group (matrilin-3; 140 ng) compared with the other groups. Furthermore, the defects treated with 140-ng matrilin-3 revealed significant hyaline-like cartilage regeneration in the osteochondral defect model; in contrast, the defects treated with 700-ng matrilin-3 exhibited drastically reduced cartilage regeneration with mixed hyaline-fibrocartilage morphology. Codelivery of matrilin-3 with Ad-MSCs significantly influenced articular cartilage regeneration, supporting the potential use of this tissue-specific protein for a cartilage-targeted stem cell therapy. Copyright © 2017 John Wiley & Sons, Ltd.

  12. A preclinical evaluation of an autologous living hyaline-like cartilaginous graft for articular cartilage repair: a pilot study.

    PubMed

    Peck, Yvonne; He, Pengfei; Chilla, Geetha Soujanya V N; Poh, Chueh Loo; Wang, Dong-An

    2015-11-09

    In this pilot study, an autologous synthetic scaffold-free construct with hyaline quality, termed living hyaline cartilaginous graft (LhCG), was applied for treating cartilage lesions. Implantation of autologous LhCG was done at load-bearing regions of the knees in skeletally mature mini-pigs for 6 months. Over the course of this study, significant radiographical improvement in LhCG treated sites was observed via magnetic resonance imaging. Furthermore, macroscopic repair was effected by LhCG at endpoint. Microscopic inspection revealed that LhCG engraftment restored cartilage thickness, promoted integration with surrounding native cartilage, produced abundant cartilage-specific matrix molecules, and re-established an intact superficial tangential zone. Importantly, the repair efficacy of LhCG was quantitatively shown to be comparable to native, unaffected cartilage in terms of biochemical composition and biomechanical properties. There were no complications related to the donor site of cartilage biopsy. Collectively, these results imply that LhCG engraftment may be a viable approach for articular cartilage repair.

  13. A preclinical evaluation of an autologous living hyaline-like cartilaginous graft for articular cartilage repair: a pilot study

    PubMed Central

    Peck, Yvonne; He, Pengfei; Chilla, Geetha Soujanya V. N.; Poh, Chueh Loo; Wang, Dong-An

    2015-01-01

    In this pilot study, an autologous synthetic scaffold-free construct with hyaline quality, termed living hyaline cartilaginous graft (LhCG), was applied for treating cartilage lesions. Implantation of autologous LhCG was done at load-bearing regions of the knees in skeletally mature mini-pigs for 6 months. Over the course of this study, significant radiographical improvement in LhCG treated sites was observed via magnetic resonance imaging. Furthermore, macroscopic repair was effected by LhCG at endpoint. Microscopic inspection revealed that LhCG engraftment restored cartilage thickness, promoted integration with surrounding native cartilage, produced abundant cartilage-specific matrix molecules, and re-established an intact superficial tangential zone. Importantly, the repair efficacy of LhCG was quantitatively shown to be comparable to native, unaffected cartilage in terms of biochemical composition and biomechanical properties. There were no complications related to the donor site of cartilage biopsy. Collectively, these results imply that LhCG engraftment may be a viable approach for articular cartilage repair. PMID:26549401

  14. Light Absorptive Properties of Articular Cartilage, ECM Molecules, Synovial Fluid, and Photoinitiators as Potential Barriers to Light-Initiated Polymer Scaffolding Procedures.

    PubMed

    Finch, Anthony J; Benson, Jamie M; Donnelly, Patrick E; Torzilli, Peter A

    2017-06-01

    Objective Many in vivo procedures to repair chondral defects use ultraviolet (UV)-photoinitiated in situ polymerization within the cartilage matrix. Chemical species that absorb UV light might reduce the effectiveness of these procedures by acting as light absorption barriers. This study evaluated whether any of the individual native biochemical components in cartilage and synovial fluid interfered with the absorption of light by common scaffolding photosensitizers. Materials UV-visible spectroscopy was performed on each major component of cartilage in solution, on bovine synovial fluid, and on four photosensitizers, riboflavin, Irgacure 2959, quinine, and riboflavin-5'-phosphate. Molar extinction and absorption coefficients were calculated at wavelengths of maximum absorbance and 365 nm. Intact articular cartilage was also examined. Results The individual major biochemical components of cartilage, Irgacure 2959, and quinine did not exhibit a significant absorption at 365 nm. Riboflavin and riboflavin-5'-phosphate were more effectual light absorbers at 365 nm, compared with the individual native species. Intact cartilage absorbed a significantly greater amount of UV light in comparison with the native species. Conclusion Our results indicate that none of the individual native species in cartilage will interfere with the absorption of UV light at 365 nm by these commonly used photoinitiators. Intact cartilage slices exhibited significant light absorption at 365 nm, while also having distinct absorbance peaks at wavelengths less than 300 nm. Determining the UV absorptive properties of the biomolecules native to articular cartilage and synovial fluid will aid in optimizing scaffolding procedures to ensure sufficient scaffold polymerization at a minimum UV intensity.

  15. Progressive cell-mediated changes in articular cartilage and bone in mice are initiated by a single session of controlled cyclic compressive loading.

    PubMed

    Ko, Frank C; Dragomir, Cecilia L; Plumb, Darren A; Hsia, Allison W; Adebayo, Olufunmilayo O; Goldring, Steven R; Wright, Timothy M; Goldring, Mary B; van der Meulen, Marjolein C H

    2016-11-01

    We previously showed that repetitive cyclic loading of the mouse knee joint causes changes that recapitulate the features of osteoarthritis (OA) in humans. By applying a single loading session, we characterized the temporal progression of the structural and compositional changes in subchondral bone and articular cartilage. We applied loading during a single 5-minute session to the left tibia of adult (26-week-old) C57Bl/6 male mice at a peak load of 9.0N for 1,200 cycles. Knee joints were collected at times 0, 1, and 2 weeks after loading. The changes in articular cartilage and subchondral bone were analyzed by histology, immunohistochemistry (caspase-3 and cathepsin K), and microcomputed tomography. At time 0, no change was evident in chondrocyte viability or cartilage or subchondral bone integrity. However, cartilage pathology demonstrated by localized thinning and proteoglycan loss occurred at 1 and 2 weeks after the single session of loading. Transient cancellous bone loss was evident at 1 week, associated with increased osteoclast number. Bone loss was reversed to control levels at 2 weeks. We observed formation of fibrous and cartilaginous tissues at the joint margins at 1 and 2 weeks. Our findings demonstrate that a single session of noninvasive loading leads to the development of OA-like morphological and cellular alterations in articular cartilage and subchondral bone. The loss in subchondral trabecular bone mass and thickness returns to control levels at 2 weeks, whereas the cartilage thinning and proteoglycan loss persist. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1941-1949, 2016. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  16. Thermal energy effects on articular cartilage: a multidisciplinary evaluation

    NASA Astrophysics Data System (ADS)

    Kaplan, Lee D.; Ernsthausen, John; Ionescu, Dan S.; Studer, Rebecca K.; Bradley, James P.; Chu, Constance R.; Fu, Freddie H.; Farkas, Daniel L.

    2002-05-01

    Partial thickness articular cartilage lesions are commonly encountered in orthopedic surgery. These lesions do not have the ability to heal by themselves, due to lack of vascular supply. Several types of treatment have addressed this problem, including mechanical debridement and thermal chondroplasty. The goal of these treatments is to provide a smooth cartilage surface and prevent propagation of the lesions. Early thermal chondroplasty was performed using lasers, and yielded very mixed results, including severe damage to the cartilage, due to poor control of the induced thermal effects. This led to the development (including commercial) of probes using radiofrequency to generate the thermal effects desired for chondroplasty. Similar concerns over the quantitative aspects and control ability of the induced thermal effects in these treatments led us to test the whole range of complex issues and parameters involved. Our investigations are designed to simultaneously evaluate clinical conditions, instrument variables for existing radiofrequency probes (pressure, speed, distance, dose) as well as the associated basic science issues such as damage temperature and controllability (down to the subcellular level), damage geometry, and effects of surrounding conditions (medium, temperature, flow, pressure). The overall goals of this work are (1) to establish whether thermal chondroplasty can be used in a safe and efficacious manner, and (2) provide a prescription for multi-variable optimization of the way treatments are delivered, based on quantitative analysis. The methods used form an interdisciplinary set, to include precise mechanical actuation, high accuracy temperature and temperature gradient control and measurement, advanced imaging approaches and mathematical modeling.

  17. Transforming growth factor β-induced superficial zone protein accumulation in the surface zone of articular cartilage is dependent on the cytoskeleton.

    PubMed

    McNary, Sean M; Athanasiou, Kyriacos A; Reddi, A Hari

    2014-03-01

    The phenotype of articular chondrocytes is dependent on the cytoskeleton, specifically the actin microfilament architecture. Articular chondrocytes in monolayer culture undergo dedifferentiation and assume a fibroblastic phenotype. This process can be reversed by altering the actin cytoskeleton by treatment with cytochalasin. Whereas dedifferentiation has been studied on chondrocytes isolated from the whole cartilage, the effects of cytoskeletal alteration on specific zones of cells such as superficial zone chondrocytes are not known. Chondrocytes from the superficial zone secrete superficial zone protein (SZP), a lubricating proteoglycan that reduces the coefficient of friction of articular cartilage. A better understanding of this phenomenon may be useful in elucidating chondrocyte dedifferentiation in monolayer and accumulation of the cartilage lubricant SZP, with an eye toward tissue engineering functional articular cartilage. In this investigation, the effects of cytoskeletal modulation on the ability of superficial zone chondrocytes to secrete SZP were examined. Primary superficial zone chondrocytes were cultured in monolayer and treated with a combination of cytoskeleton modifying reagents and transforming growth factor β (TGFβ) 1, a critical regulator of SZP production. Whereas cytochalasin D maintains the articular chondrocyte phenotype, the hallmark of the superficial zone chondrocyte, SZP, was inhibited in the presence of TGFβ1. A decrease in TGFβ1-induced SZP accumulation was also observed when the microtubule cytoskeleton was modified using paclitaxel. These effects of actin and microtubule alteration were confirmed through the application of jasplakinolide and colchicine, respectively. As Rho GTPases regulate actin organization and microtubule polymerization, we hypothesized that the cytoskeleton is critical for TGFβ-induced SZP accumulation. TGFβ-mediated SZP accumulation was inhibited by small molecule inhibitors ML141 (Cdc42), NSC23766 (Rac1

  18. Chronic Changes in the Articular Cartilage and Meniscus Following Traumatic Impact to the Lapine Knee

    PubMed Central

    Fischenich, Kristine M.; Button, Keith D.; Coatney, Garrett A.; Fajardo, Ryan S.; Leikert, Kevin M.; Haut, Roger C.; Haut Donahue, Tammy L.

    2014-01-01

    The objective of this study was to induce anterior cruciate ligament (ACL) and meniscal damage, via a single tibiofemoral compressive impact, in order to document articular cartilage and meniscal changes post impact. Tibiofemoral joints of Flemish Giant rabbits were subjected to a single blunt impact that ruptured the ACL and produced acute meniscal damage. Animals were allowed unrestricted cage activity for 12 weeks before euthanasia. India ink analysis of the articular cartilage revealed higher degrees of surface damage on the impacted tibias (p=0.018) and femurs (p<0.0001) compared to controls. Chronic meniscal damage was most prevalent in the medial central and medial posterior regions. Mechanical tests revealed an overall 19.4% increase in tibial plateau cartilage thickness (p=0.026), 34.8% increase in tibial plateau permeability (p=0.054), 40.8% increase in femoral condyle permeability (p=0.029), and 20.1% decrease in femoral condyle matrix modulus (p=0.012) in impacted joints compared to controls. Both the instantaneous and equilibrium moduli of the lateral and medial menisci were decreased compared to control (p<0.02). Histological analyses revealed significantly increased presence of fissures in the medial femur (p = 0.036). In both the meniscus and cartilage there was a significant decrease in GAG coverage for the impacted limbs. Based on these results it is clear that an unattended combined meniscal and ACL injury results in significant changes to the soft tissues in this experimental joint 12 weeks post injury. Such changes are consistent with a clinical description of mid to late stage PTOA of the knee. PMID:25523754

  19. Knee Pain and Mobility Impairments: Meniscal and Articular Cartilage Lesions Revision 2018.

    PubMed

    Logerstedt, David S; Scalzitti, David A; Bennell, Kim L; Hinman, Rana S; Silvers-Granelli, Holly; Ebert, Jay; Hambly, Karen; Carey, James L; Snyder-Mackler, Lynn; Axe, Michael J; McDonough, Christine M

    2018-02-01

    The Orthopaedic Section of the American Physical Therapy Association (APTA) has an ongoing effort to create evidence-based practice guidelines for orthopaedic physical therapy management of patients with musculoskeletal impairments described in the World Health Organization's International Classification of Functioning, Disability, and Health (ICF). The purpose of these revised clinical practice guidelines is to review recent peer-reviewed literature and make recommendations related to meniscus and articular cartilage lesions. J Orthop Sports Phys Ther. 2018;48(2):A1-A50. doi:10.2519/jospt.2018.0301.

  20. Acetabular labral tears with underlying chondromalacia: a possible association with high-level running.

    PubMed

    Guanche, Carlos A; Sikka, Robby S

    2005-05-01

    The use of hip arthroscopy has helped delineate intra-articular pathology and has enabled clinicians to further elucidate the factors responsible for injuries, such as running. The subtle development of degenerative changes may be a result of repetitive impact loading associated with this sport. This study presents a population of runners with common pathologic acetabular changes. Case series. Eight high-level runners with an average age of 36 years (range, 19 to 45 years) were seen for complaints of increasing hip pain with running without any history of macrotrauma. All of the patients had either run several marathons (4), were triathletes (1), Olympic middle distance runners (1), or had run more than 10 miles per week for longer than 5 years (2). Plain radiographic analysis revealed no degenerative changes and an average center-edge (CE) angle of 36.7 degrees (range, 28 degrees to 44 degrees). All patients underwent hip arthroscopy with labral debridement. In 6 patients (75%), a chondral injury of the acetabular cartilage underlying the labral tear was noted. In addition, 3 patients had ligamentum teres disruptions. It is possible that the development of these tears is the result of subtle instability, which may be exacerbated by running, eventually leading to labral tearing and possible ligamentum teres disruption. While perhaps concurrently, subtle acetabular dysplasia may play a role. Although this study does not confirm an association between running and the development of labral tears or chondral lesions in the hip, it certainly questions whether there is an injury pattern common to this population, a "runner's hip." Level IV.

  1. Assessing the effect of football play on knee articular cartilage using delayed gadolinium-enhanced MRI of cartilage (dGEMRIC).

    PubMed

    Wei, Wenbo; Lambach, Becky; Jia, Guang; Flanigan, David; Chaudhari, Ajit M W; Wei, Lai; Rogers, Alan; Payne, Jason; Siston, Robert A; Knopp, Michael V

    2017-06-01

    The prevalence of cartilage lesions is much higher in football athletes than in the general population. Delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) has been shown to quantify regional variations of glycosaminoglycan (GAG) concentrations which is an indicator of early cartilage degeneration. The goal of this study is to determine whether dGEMRIC can be used to assess the influence in cartilage GAG concentration due to college level football play. Thirteen collegiate football players with one to four years of collegiate football play experience were recruited and both knee joints were scanned using a dedicated 8-channel phased array knee coil on a 3T MRI system. The contrast concentrations within cartilage were calculated based on the T 1 values from dGEMRIC scans. No substantial differences were found in the contrast concentrations between the pre- and post-season across all the cartilage compartments. One year collegiate football players presented an average contrast concentration at the pre-season of 0.116±0.011mM and post-season of 0.116±0.011mM. In players with multiple years of football play, contrast uptake was elevated to 0.141±0.012mM at the pre-season and 0.139±0.012mM at the post-season. The pre-season 0.023±0.016mM and post-season 0.025±0.016mM increase in contrast concentration within the group with multiple years of experience presented with a >20% increase in contrast uptake. This may indicate the gradual, cumulative damage of football play to the articular cartilage over years, even though the effect may not be noticeable after a season of play. Playing collegiate football for a longer period of time may lead to cartilage microstructural alterations, which may be linked to early knee cartilage degeneration. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Depth-Dependent Anisotropies of Amides and Sugar in Perpendicular and Parallel Sections of Articular Cartilage by Fourier Transform Infrared Imaging (FTIRI)

    PubMed Central

    Xia, Yang; Mittelstaedt, Daniel; Ramakrishnan, Nagarajan; Szarko, Matthew; Bidthanapally, Aruna

    2010-01-01

    Full thickness blocks of canine humeral cartilage were microtomed into both perpendicular sections and a series of 100 parallel sections, each 6 μm thick. Fourier Transform Infrared Imaging (FTIRI) was used to image each tissue section eleven times under different infrared polarizations (from 0° to 180° polarization states in 20° increments and with an additional 90° polarization), at a spatial resolution of 6.25 μm and a wavenumber step of 8 cm−1. With increasing depth from the articular surface, amide anisotropies increased in the perpendicular sections and decreased in the parallel sections. Both types of tissue sectioning identified a 90° difference between amide I and amide II in the superficial zone of cartilage. The fibrillar distribution in the parallel sections from the superficial zone was shown to not be random. Sugar had the greatest anisotropy in the upper part of the radial zone in the perpendicular sections. The depth-dependent anisotropic data were fitted with a theoretical equation that contained three signature parameters, which illustrate the arcade structure of collagens with the aid of a fibril model. Infrared imaging of both perpendicular and parallel sections provides the possibility of determining the three-dimensional macromolecular structures in articular cartilage. Being sensitive to the orientation of the macromolecular structure in healthy articular cartilage aids the prospect of detecting the early onset of the tissue degradation that may lead to pathological conditions such as osteoarthritis. PMID:21274999

  3. Attenuation of the progression of articular cartilage degeneration by inhibition of TGF-β1 signaling in a mouse model of osteoarthritis.

    PubMed

    Chen, Rebecca; Mian, Michelle; Fu, Martin; Zhao, Jing Ying; Yang, Liang; Li, Yefu; Xu, Lin

    2015-11-01

    Transforming growth factor beta 1 (TGF-β1) is implicated in osteoarthritis. We therefore studied the role of TGF-β1 signaling in the development of osteoarthritis in a developmental stage-dependent manner. Three different mouse models were investigated. First, the Tgf-β receptor II (Tgfbr2) was specifically removed from the mature cartilage of joints. Tgfbr2-deficient mice were grown to 12 months of age and were then euthanized for collection of knee and temporomandibular joints. Second, Tgfbr2-deficient mice were subjected to destabilization of the medial meniscus (DMM) surgery. Knee joints were then collected from the mice at 8 and 16 weeks after the surgery. Third, wild-type mice were subjected to DMM at the age of 8 weeks. Immediately after the surgery, these mice were treated with the Tgfbr2 inhibitor losartan for 8 weeks and then euthanized for collection of knee joints. All joints were characterized for evidences of articular cartilage degeneration. Initiation or acceleration of articular cartilage degeneration was not observed by the genetic inactivation of Tgfbr2 in the joints at the age of 12 months. In fact, the removal of Tgfbr2 and treatment with losartan both delayed the progression of articular cartilage degeneration induced by DMM compared with control littermates. Therefore, we conclude that inhibition of Tgf-β1 signaling protects adult knee joints in mice against the development of osteoarthritis. Copyright © 2015 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  4. Attenuation of the Progression of Articular Cartilage Degeneration by Inhibition of TGF-β1 Signaling in a Mouse Model of Osteoarthritis

    PubMed Central

    Chen, Rebecca; Mian, Michelle; Fu, Martin; Zhao, Jing Ying; Yang, Liang; Li, Yefu; Xu, Lin

    2016-01-01

    Transforming growth factor beta 1 (TGF-β1) is implicated in osteoarthritis. We therefore studied the role of TGF-β1 signaling in the development of osteoarthritis in a developmental stage-dependent manner. Three different mouse models were investigated. First, the Tgf-β receptor II (Tgfbr2) was specifically removed from the mature cartilage of joints. Tgfbr2-deficient mice were grown to 12 months of age and were then euthanized for collection of knee and temporomandibular joints. Second, Tgfbr2-deficient mice were subjected to destabilization of the medial meniscus (DMM) surgery. Knee joints were then collected from the mice at 8 and 16 weeks after the surgery. Third, wild-type mice were subjected to DMM at the age of 8 weeks. Immediately after the surgery, these mice were treated with the Tgfbr2 inhibitor losartan for 8 weeks and then euthanized for collection of knee joints. All joints were characterized for evidences of articular cartilage degeneration. Initiation or acceleration of articular cartilage degeneration was not observed by the genetic inactivation of Tgfbr2 in the joints at the age of 12 months. In fact, the removal of Tgfbr2 and treatment with losartan both delayed the progression of articular cartilage degeneration induced by DMM compared with control littermates. Therefore, we conclude that inhibition of Tgf-β1 signaling protects adult knee joints in mice against the development of osteoarthritis. PMID:26355014

  5. Depth-Dependent Glycosaminoglycan Concentration in Articular Cartilage by Quantitative Contrast-Enhanced Micro–Computed Tomography

    PubMed Central

    Mittelstaedt, Daniel

    2015-01-01

    Objective A quantitative contrast-enhanced micro–computed tomography (qCECT) method was developed to investigate the depth dependency and heterogeneity of the glycosaminoglycan (GAG) concentration of ex vivo cartilage equilibrated with an anionic radiographic contrast agent, Hexabrix. Design Full-thickness fresh native (n = 19 in 3 subgroups) and trypsin-degraded (n = 6) articular cartilage blocks were imaged using micro–computed tomography (μCT) at high resolution (13.4 μm3) before and after equilibration with various Hexabrix bathing concentrations. The GAG concentration was calculated depth-dependently based on Gibbs-Donnan equilibrium theory. Analysis of variance with Tukey’s post hoc was used to test for statistical significance (P < 0.05) for effect of Hexabrix bathing concentration, and for differences in bulk and zonal GAG concentrations individually and compared between native and trypsin-degraded cartilage. Results The bulk GAG concentration was calculated to be 74.44 ± 6.09 and 11.99 ± 4.24 mg/mL for native and degraded cartilage, respectively. A statistical difference was demonstrated for bulk and zonal GAG between native and degraded cartilage (P < 0.032). A statistical difference was not demonstrated for bulk GAG when comparing Hexabrix bathing concentrations (P > 0.3214) for neither native nor degraded cartilage. Depth-dependent GAG analysis of native cartilage revealed a statistical difference only in the radial zone between 30% and 50% Hexabrix bathing concentrations. Conclusions This nondestructive qCECT methodology calculated the depth-dependent GAG concentration for both native and trypsin-degraded cartilage at high spatial resolution. qCECT allows for more detailed understanding of the topography and depth dependency, which could help diagnose health, degradation, and repair of native and contrived cartilage. PMID:26425259

  6. BioCartilage Improves Cartilage Repair Compared With Microfracture Alone in an Equine Model of Full-Thickness Cartilage Loss.

    PubMed

    Fortier, Lisa A; Chapman, Hannah S; Pownder, Sarah L; Roller, Brandon L; Cross, Jessica A; Cook, James L; Cole, Brian J

    2016-09-01

    Microfracture (MFx) remains a dominant treatment strategy for symptomatic articular cartilage defects. Biologic scaffold adjuncts, such as particulated allograft articular cartilage (BioCartilage) combined with platelet-rich plasma (PRP), offer promise in improving clinical outcomes as an adjunct to MFx. To evaluate the safety, biocompatibility, and efficacy of BioCartilage and PRP for cartilage repair in a preclinical equine model of full-thickness articular cartilage loss. Controlled laboratory study. Two 10-mm-diameter full-thickness cartilage defects were created in 5 horses in the trochlear ridge of both knees: one proximal (high load) and another distal (low load). Complete blood counts were performed on each peripheral blood and resultant PRP sample. In each horse, one knee received MFx with BioCartilage + PRP, and the other knee received MFx alone. Horses were euthanized at 13 months. Outcomes were assessed with serial arthroscopy, magnetic resonance imaging (MRI), micro-computed tomography (micro-CT), and histology. Statistics were performed using a mixed-effects model with response variable contrasts. No complications occurred. PRP generated in all subjects yielded an increase in platelet fold of 3.8 ± 4.7. Leukocyte concentration decreased in PRP samples by an average fold change of 5 ± 0.1. The overall International Cartilage Repair Society repair score in both the proximal and distal defects was significantly higher (better) in the BioCartilage group compared with MFx (proximal BioCartilage: 7.4 ± 0.51, MFx 4.8 ± 0.1, P = .041; distal BioCartilage: 5.6 ± 0.98, MFx 2.6 ± 1.5, P = .022). BioCartilage-treated proximal defects demonstrated improved histologic scores for repair-host integration (BioCartilage, 96 ± 9; MFx, 68 ± 18; P = .02), base integration (BioCartilage, 100 ± 0; MFx, 70 ± 37; P = .04), and formation of collagen type II (BioCartilage, 82 ± 8; MFx, 58 ± 11; P = .05) compared with the positive control. On MRI, T2 relaxation time

  7. Proteoglycan concentrations in healthy and diseased articular cartilage by Fourier transform infrared imaging and principal component regression

    NASA Astrophysics Data System (ADS)

    Yin, Jianhua; Xia, Yang

    2014-12-01

    Fourier transform infrared imaging (FTIRI) combining with principal component regression (PCR) analysis were used to determine the reduction of proteoglycan (PG) in articular cartilage after the transection of the anterior cruciate ligament (ACL). A number of canine knee cartilage sections were harvested from the meniscus-covered and meniscus-uncovered medial tibial locations from the control joints, the ACL joints at three time points after the surgery, and their contralateral joints. The PG loss in the ACL cartilage was related positively to the durations after the surgery. The PG loss in the contralateral knees was less than that of the ACL knees. The PG loss in the meniscus-covered cartilage was less than that of the meniscus-uncovered tissue in both ACL and contralateral knees. The quantitative mapping of PG loss could monitor the disease progression and repair processes in arthritis.

  8. Characterization of articular cartilage and subchondral bone changes in the rat anterior cruciate ligament transection and meniscectomized models of osteoarthritis.

    PubMed

    Hayami, Tadashi; Pickarski, Maureen; Zhuo, Ya; Wesolowski, Gregg A; Rodan, Gideon A; Duong, Le T

    2006-02-01

    Osteoarthritis (OA) is a chronic joint disease characterized by cartilage destruction, subchondral bone sclerosis, and osteophyte formation. Subchondral bone stiffness has been proposed to initiate and/or contribute to cartilage deterioration in OA. The purpose of this study was to characterize subchondral bone remodeling, cartilage damage, and osteophytosis during the disease progression in two models of surgically induced OA. Rat knee joints were subjected either to anterior cruciate ligament transection (ACLT) alone or in combination with resection of medial menisci (ACLT + MMx). Histopathological changes in the surgical joints were compared with sham at 1, 2, 4, 6, and 10 weeks post-surgery. Using a modified Mankin scoring system, we demonstrate that articular cartilage damage occurs within 2 weeks post-surgery in both surgical models. Detectable cartilage surface damage and proteoglycan loss were observed as early as 1 week post-surgery. These were followed by the increases in vascular invasion into cartilage, in loss of chondrocyte number and in cell clustering. Histomorphometric analysis revealed subchondral bone loss in both models within 2 weeks post-surgery followed by significant increases in subchondral bone volume relative to sham up to 10 weeks post-surgery. Incidence of osteophyte formation was optimally observed in ACLT joints at 10 weeks and in ACLT + MMx joints at 6 weeks post-surgery. In summary, the two surgically induced rat OA models share many characteristics seen in human and other animal models of OA, including progressive articular cartilage degradation, subchondral bone sclerosis, and osteophyte formation. Moreover, increased subchondral bone resorption is associated with early development of cartilage lesions, which precedes significant cartilage thinning and subchondral bone sclerosis. Together, these findings support a role for bone remodeling in OA pathogenesis and suggest that these rat models are suitable for evaluating bone

  9. Discrimination of healthy and osteoarthritic articular cartilage by Fourier transform infrared imaging and Fisher’s discriminant analysis

    PubMed Central

    Mao, Zhi-Hua; Yin, Jian-Hua; Zhang, Xue-Xi; Wang, Xiao; Xia, Yang

    2016-01-01

    Fourier transform infrared spectroscopic imaging (FTIRI) technique can be used to obtain the quantitative information of content and spatial distribution of principal components in cartilage by combining with chemometrics methods. In this study, FTIRI combining with principal component analysis (PCA) and Fisher’s discriminant analysis (FDA) was applied to identify the healthy and osteoarthritic (OA) articular cartilage samples. Ten 10-μm thick sections of canine cartilages were imaged at 6.25μm/pixel in FTIRI. The infrared spectra extracted from the FTIR images were imported into SPSS software for PCA and FDA. Based on the PCA result of 2 principal components, the healthy and OA cartilage samples were effectively discriminated by the FDA with high accuracy of 94% for the initial samples (training set) and cross validation, as well as 86.67% for the prediction group. The study showed that cartilage degeneration became gradually weak with the increase of the depth. FTIRI combined with chemometrics may become an effective method for distinguishing healthy and OA cartilages in future. PMID:26977354

  10. Raman Spectroscopy Reveals New Insights into the Zonal Organization of Native and Tissue-Engineered Articular Cartilage

    PubMed Central

    2016-01-01

    Tissue architecture is intimately linked with its functions, and loss of tissue organization is often associated with pathologies. The intricate depth-dependent extracellular matrix (ECM) arrangement in articular cartilage is critical to its biomechanical functions. In this study, we developed a Raman spectroscopic imaging approach to gain new insight into the depth-dependent arrangement of native and tissue-engineered articular cartilage using bovine tissues and cells. Our results revealed previously unreported tissue complexity into at least six zones above the tidemark based on a principal component analysis and k-means clustering analysis of the distribution and orientation of the main ECM components. Correlation of nanoindentation and Raman spectroscopic data suggested that the biomechanics across the tissue depth are influenced by ECM microstructure rather than composition. Further, Raman spectroscopy together with multivariate analysis revealed changes in the collagen, glycosaminoglycan, and water distributions in tissue-engineered constructs over time. These changes were assessed using simple metrics that promise to instruct efforts toward the regeneration of a broad range of tissues with native zonal complexity and functional performance. PMID:28058277

  11. Development of a Novel Large Animal Model to Evaluate Human Dental Pulp Stem Cells for Articular Cartilage Treatment.

    PubMed

    Fernandes, Tiago Lazzaretti; Shimomura, Kazunori; Asperti, Andre; Pinheiro, Carla Cristina Gomes; Caetano, Heloísa Vasconcellos Amaral; Oliveira, Claudia Regina G C M; Nakamura, Norimasa; Hernandez, Arnaldo José; Bueno, Daniela Franco

    2018-05-04

    Chondral lesion is a pathology with high prevalence, reaching as much as 63% of general population and 36% among athletes. The ability of human Dental Pulp Stem Cells (DPSCs) to differentiate into chondroblasts in vitro suggests that this stem cell type may be useful for tissue bioengineering. However, we have yet to identify a study of large animal models in which DPSCs were used to repair articular cartilage. Therefore, this study aimed to describe a novel treatment for cartilage lesion with DPSCs on a large animal model. Mesenchymal stem cells (MSC) were obtained from deciduous teeth and characterized by flow cytometry. DPSCs were cultured and added to a collagen type I/III biomaterial composite scaffold. Brazilian miniature pig (BR-1) was used. A 6-mm diameter, full-thickness chondral defect was created in each posterior medial condyle. The defects were covered with scaffold alone or scaffold + DPSCs on the contralateral side. Animals were euthanized 6 weeks post-surgery. Cartilage defects were analyzed macroscopically and histology according to modified O'Driscoll scoring system. Flow cytometry confirmed characterization of DPSCs as MSCs. Macroscopic and histological findings suggested that this time period was reasonable for evaluating cartilage repair. To our knowledge, this study provides the first description of an animal model using DPSCs to study the differentiation of hyaline articular cartilage in vivo. The animals tolerated the procedure well and did not show clinical or histological rejection of the DPSCs, reinforcing the feasibility of this descriptive miniature pig model for pre-clinical studies.

  12. The short-term effects of running on the deformation of knee articular cartilage and its relationship to biomechanical loads at the knee.

    PubMed

    Boocock, M; McNair, P; Cicuttini, F; Stuart, A; Sinclair, T

    2009-07-01

    To investigate the short-term effects of recreational running on the deformation of knee articular cartilage and to examine the relationship between changes in knee cartilage volume and biomechanical modulators of knee joint load. Twenty healthy volunteers participated in a two phase cross-sectional study. Session 1 involved Magnetic Resonance Imaging (MRI) of femoral and tibial cartilage volumes prior to and following a 30 min period of relaxed sitting, which was directly followed by a recreational run of 5000 steps. Subsequently, all participants undertook a laboratory study of their running gait to compare biomechanical derived measures of knee joint loading with changes in cartilage volume. Estimates of knee joint load were determined using a rigid-link segment, dynamic biomechanical model of the lower limbs and a simplified muscle model. Running resulted in significant deformation of the medial (5.3%, P<0.01) and lateral femoral cartilage (4.0%, P<0.05) and lateral aspect of the tibial cartilage (5.7%, P<0.01), with no significant differences between genders. Maximum compression stress was significantly correlated with percentage changes in lateral femoral cartilage volume (r(2)=0.456, P<0.05). No other biomechanical variables correlated with volume changes. Limited evidence was found linking biomechanical measures of knee joint loading and observed short-term deformation of knee articular cartilage volume following running. Further enhancement of knee muscle modelling and analysis of stress distribution across cartilage are needed if we are to fully understand the contribution of biomechanical factors to knee joint loading and the pathogenesis of knee osteoarthritis (OA).

  13. Widespread epigenomic, transcriptomic and proteomic differences between hip osteophytic and articular chondrocytes in osteoarthritis.

    PubMed

    Steinberg, Julia; Brooks, Roger A; Southam, Lorraine; Bhatnagar, Sahir; Roumeliotis, Theodoros I; Hatzikotoulas, Konstantinos; Zengini, Eleni; Wilkinson, J Mark; Choudhary, Jyoti S; McCaskie, Andrew W; Zeggini, Eleftheria

    2018-05-08

    To identify molecular differences between chondrocytes from osteophytic and articular cartilage tissue from OA patients. We investigated genes and pathways by combining genome-wide DNA methylation, RNA sequencing and quantitative proteomics in isolated primary chondrocytes from the cartilaginous layer of osteophytes and matched areas of low- and high-grade articular cartilage across nine patients with OA undergoing hip replacement surgery. Chondrocytes from osteophytic cartilage showed widespread differences to low-grade articular cartilage chondrocytes. These differences were similar to, but more pronounced than, differences between chondrocytes from osteophytic and high-grade articular cartilage, and more pronounced than differences between high- and low-grade articular cartilage. We identified 56 genes with significant differences between osteophytic chondrocytes and low-grade articular cartilage chondrocytes on all three omics levels. Several of these genes have known roles in OA, including ALDH1A2 and cartilage oligomeric matrix protein, which have functional genetic variants associated with OA from genome-wide association studies. An integrative gene ontology enrichment analysis showed that differences between osteophytic and low-grade articular cartilage chondrocytes are associated with extracellular matrix organization, skeletal system development, platelet aggregation and regulation of ERK1 and ERK2 cascade. We present a first comprehensive view of the molecular landscape of chondrocytes from osteophytic cartilage as compared with articular cartilage chondrocytes from the same joints in OA. We found robust changes at genes relevant to chondrocyte function, providing insight into biological processes involved in osteophyte development and thus OA progression.

  14. Ultrasound elastomicroscopy for articular cartilage: from static to transient and 1D to 2D

    NASA Astrophysics Data System (ADS)

    Zheng, Yongping; Bridal, Sharon L.; Shi, Jun; Saied, Amena; Lu, Minghua; Jaffre, Britta; Mak, Arthur F. T.; Laugier, Pascal; Qin, Ling

    2003-05-01

    Articular cartilage (AC) is a biological weight-bearing tissue covering the ends of articulating bones within synovial joints. Its function very much depends on the unique multi-layered structure and the depth-dependent material properties, which have not been well invetigated nondestructively. In this study, transient depth-dependent material properties of bovine patella cartilage were measured using ultrasound elastomicroscopy methods. A 50 MHz focused ultrasound transducer was used to collect A-mode ultrasound echoes from the articular cartilage during the compression and subsequent force-relaxation. The transient displacements of the cartilage tissues at different depths were calculated from the ultrasound echoes using a cross-correlation technique. It was observed that the strains in the superficial zone were much larger than those in the middle and deep zones as the equilibrium state was approached. The tissues inside the AC layer continued to move during the force-relaxation phase after the compression was completed. This process has been predicted by a biphasic theory. In this study, it has been verified experimentally. It was also observed that the tissue deformations at different depths of AC were much more evenly distributed before force-relaxation. AC specimens were also investigated using a 2D ultrasound elastomicroscopy system that included a 3D translating system for moving the ultrasound transducer over the specimens. B-mode RF ultrasound signals were collected from the specimens under different loading levels applied with a specially designed compressor. Preliminary results demonstrated that the scanning was repeatable with high correlation of radio frequency signals obtained from the same site during different scans when compression level was unchanged (R2 > 0.97). Strains of the AC specimens were mapped using data collected with this ultrasound elastomicroscope. This system can also be potentially used for the assessment of other biological

  15. Articular cartilage degeneration classification by means of high-frequency ultrasound.

    PubMed

    Männicke, N; Schöne, M; Oelze, M; Raum, K

    2014-10-01

    To date only single ultrasound parameters were regarded in statistical analyses to characterize osteoarthritic changes in articular cartilage and the potential benefit of using parameter combinations for characterization remains unclear. Therefore, the aim of this work was to utilize feature selection and classification of a Mankin subset score (i.e., cartilage surface and cell sub-scores) using ultrasound-based parameter pairs and investigate both classification accuracy and the sensitivity towards different degeneration stages. 40 punch biopsies of human cartilage were previously scanned ex vivo with a 40-MHz transducer. Ultrasound-based surface parameters, as well as backscatter and envelope statistics parameters were available. Logistic regression was performed with each unique US parameter pair as predictor and different degeneration stages as response variables. The best ultrasound-based parameter pair for each Mankin subset score value was assessed by highest classification accuracy and utilized in receiver operating characteristics (ROC) analysis. The classifications discriminating between early degenerations yielded area under the ROC curve (AUC) values of 0.94-0.99 (mean ± SD: 0.97 ± 0.03). In contrast, classifications among higher Mankin subset scores resulted in lower AUC values: 0.75-0.91 (mean ± SD: 0.84 ± 0.08). Variable sensitivities of the different ultrasound features were observed with respect to different degeneration stages. Our results strongly suggest that combinations of high-frequency ultrasound-based parameters exhibit potential to characterize different, particularly very early, degeneration stages of hyaline cartilage. Variable sensitivities towards different degeneration stages suggest that a concurrent estimation of multiple ultrasound-based parameters is diagnostically valuable. In-vivo application of the present findings is conceivable in both minimally invasive arthroscopic ultrasound and high-frequency transcutaneous ultrasound

  16. Molecular changes in articular cartilage and subchondral bone in the rat anterior cruciate ligament transection and meniscectomized models of osteoarthritis

    PubMed Central

    2011-01-01

    Background Osteoarthritis (OA) is a debilitating, progressive joint disease. Methods Similar to the disease progression in humans, sequential events of early cartilage degradation, subchondral osteopenia followed by sclerosis, and late osteophyte formation were demonstrated in the anterior cruciate ligament transection (ACLT) or ACLT with partial medial meniscectomy (ACLT + MMx) rat OA models. We describe a reliable and consistent method to examine the time dependent changes in the gene expression profiles in articular cartilage and subchondral bone. Results Local regulation of matrix degradation markers was demonstrated by a significant increase in mRNA levels of aggrecanase-1 and MMP-13 as early as the first week post-surgery, and expression remained elevated throughout the 10 week study. Immunohistochemistry confirmed MMP-13 expression in differentiated chondrocytes and synovial fibroblasts at week-2 and cells within osteophytes at week-10 in the surgically-modified-joints. Concomitant increases in chondrocyte differentiation markers, Col IIA and Sox 9, and vascular invasion markers, VEGF and CD31, peaked around week-2 to -4, and returned to Sham levels at later time points in both models. Indeed, VEGF-positive cells were found in the deep articular chondrocytes adjacent to subchondral bone. Osteoclastic bone resorption markers, cathepsin K and TRAP, were also elevated at week-2. Confirming bone resorption is an early local event in OA progression, cathepsin K positive osteoclasts were found invading the articular cartilage from the subchondral region at week 2. This was followed by late disease events, including subchondral sclerosis and osteophyte formation, as demonstrated by the upregulation of the osteoanabolic markers runx2 and osterix, toward week-4 to 6 post-surgery. Conclusions In summary, this study demonstrated the temporal and cohesive gene expression changes in articular cartilage and subchondral bone using known markers of OA progression. The

  17. MR imaging of post-traumatic articular cartilage injuries confined to the femoral trochlea. Arthroscopic correlation and clinical significance.

    PubMed

    Huegli, Rolf W; Moelleken, Sonja M C; Stork, Alexander; Bonel, Harald M; Bredella, Miriam A; Meckel, Stephan; Genant, Harry K; Tirman, Phillip F J

    2005-01-01

    To assess and describe post-traumatic articular cartilage injuries isolated to the trochlear groove and provide insight into potential mechanism of injury. We retrospectively evaluated MR imaging findings of all knee MRIs performed at our institution over the last 2 years (2450). Thirty patients met the criteria of a cartilage injury confined to the trochlear groove. In 15 cases, which were included in our study, arthroscopic correlation was available. Each plane was evaluated and graded for the presence and appearance of articular cartilage defects using a standard arthroscopic grading scheme adapted to MR imaging. Any additional pathological derangement was documented and information about the mechanism of injury was retrieved by chart review. In all cases the cartilaginous injury was well demonstrated on MRI. In 13 patients additional pathological findings could be observed. The most frequently associated injury was a meniscal tear in nine patients. In eight cases, the arthroscopic grading of the trochlear injury matched exactly with the MRI findings. In the remaining seven cases, the discrepancy between MRI and arthroscopy was never higher than one grade. In 13 out of 15 of patients trauma mechanism could be evaluated. Twelve patients suffered an indirect twisting injury and one suffered a direct trauma to their knee. The findings of this study demonstrate that MR imaging allows reliable grading of isolated injury to the trochlear groove cartilage and assists in directing surgical diagnosis and treatment. These injuries may be the only hyaline cartilage injury in the knee and meniscal tears are a frequently associated finding. Therefore, it is important to search specifically for cartilage injuries of the trochlear groove in patients with anterior knee pain, even if other coexistent pathology could potentially explain the patient's symptoms.

  18. Intra-Articular Cellular Therapy for Osteoarthritis and Focal Cartilage Defects of the Knee: A Systematic Review of the Literature and Study Quality Analysis.

    PubMed

    Chahla, Jorge; Piuzzi, Nicolas S; Mitchell, Justin J; Dean, Chase S; Pascual-Garrido, Cecilia; LaPrade, Robert F; Muschler, George F

    2016-09-21

    Intra-articular cellular therapy injections constitute an appealing strategy that may modify the intra-articular milieu or regenerate cartilage in the settings of osteoarthritis and focal cartilage defects. However, little consensus exists regarding the indications for cellular therapies, optimal cell sources, methods of preparation and delivery, or means by which outcomes should be reported. We present a systematic review of the current literature regarding the safety and efficacy of cellular therapy delivered by intra-articular injection in the knee that provided a Level of Evidence of III or higher. A total of 420 papers were screened. Methodological quality was assessed using a modified Coleman methodology score. Only 6 studies (4 Level II and 2 Level III) met the criteria to be included in this review; 3 studies were on treatment of osteoarthritis and 3 were on treatment of focal cartilage defects. These included 4 randomized controlled studies without blinding, 1 prospective cohort study, and 1 retrospective therapeutic case-control study. The studies varied widely with respect to cell sources, cell characterization, adjuvant therapies, and assessment of outcomes. Outcome was reported in a total of 300 knees (124 in the osteoarthritis studies and 176 in the cartilage defect studies). Mean follow-up was 21.0 months (range, 12 to 36 months). All studies reported improved outcomes with intra-articular cellular therapy and no major adverse events. The mean modified Coleman methodology score was 59.1 ± 16 (range, 32 to 82). The studies of intra-articular cellular therapy injections for osteoarthritis and focal cartilage defects in the human knee suggested positive results with respect to clinical improvement and safety. However, the improvement was modest and a placebo effect cannot be disregarded. The overall quality of the literature was poor, and the methodological quality was fair, even among Level-II and III studies. Effective clinical assessment and

  19. Repair of articular cartilage and subchondral defects in rabbit knee joints with a polyvinyl alcohol/nano-hydroxyapatite/polyamide 66 biological composite material.

    PubMed

    Guo, Tao; Tian, Xiaobin; Li, Bo; Yang, Tianfu; Li, Yubao

    2017-11-15

    This study sought to prepare a new PVA/n-HA/PA66 composite to investigate the repair of articular cartilage and subchondral defects in rabbit knee joints. A 5 × 5 × 5 mm-sized defect was created in the patellofemoral joints of 72 healthy adult New Zealand rabbits. The rabbits were then randomly divided into three groups (n = 24): PVA/n-HA+PA66 group, polyvinyl alcohol (PVA) group, and control (untreated) group. Cylindrical PVA/n-HA+PA66, 5 × 5 mm, comprised an upper PVA layer and a lower n-HA+PA66 layer. Macroscopic and histological evaluations were performed at 4, 8, 12, and 24 weeks, postoperatively. Type II collagen was measured by immunohistochemical staining. The implant/cartilage and bone interfaces were observed by scanning electron microscopy. At 24 weeks postoperatively, the lower PVA/n-HA+PA66 layer became surrounded by cartilage, with no obvious degeneration. In the PVA group, an enlarged space was observed between the implant and the host tissue that had undergone degeneration. In the control group, the articular cartilage had become calcified. In the PVA/n-HA+PA66 group, positive type II collagen staining was observed between the composite and the surrounding cartilage and on the implant surface. In the PVA group, positive staining was slightly increased between the PVA and the surrounding cartilage, but reduced on the PVA surface. In the control group, reduced staining was observed throughout. Scanning electron microscopy showed increased bone tissue in the lower n-HA+PA66 layer that was in close approximation with the upper PVA layer of the composite. In the PVA group, the bone tissue around the material had receded, and in the control group, the defect was filled with bone tissue, while the superior aspect of the defect was filled with disordered, fibrous tissue. The diphase biological composite material PVA/n-HA+PA66 exhibits good histocompatibility and offers a satisfactory substitute for articular cartilage and subchondral bone.

  20. A concurrent computer aided detection (CAD) tool for articular cartilage disease of the knee on MR imaging using active shape models

    NASA Astrophysics Data System (ADS)

    Ramakrishna, Bharath; Saiprasad, Ganesh; Safdar, Nabile; Siddiqui, Khan; Chang, Chein-I.; Siegel, Eliot

    2008-03-01

    Osteoarthritis (OA) is the most common form of arthritis and a major cause of morbidity affecting millions of adults in the US and world wide. In the knee, OA begins with the degeneration of joint articular cartilage, eventually resulting in the femur and tibia coming in contact, and leading to severe pain and stiffness. There has been extensive research examining 3D MR imaging sequences and automatic/semi-automatic techniques for 2D/3D articular cartilage extraction. However, in routine clinical practice the most popular technique still remain radiographic examination and qualitative assessment of the joint space. This may be in large part because of a lack of tools that can provide clinically relevant diagnosis in adjunct (in near real time fashion) with the radiologist and which can serve the needs of the radiologists and reduce inter-observer variation. Our work aims to fill this void by developing a CAD application that can generate clinically relevant diagnosis of the articular cartilage damage in near real time fashion. The algorithm features a 2D Active Shape Model (ASM) for modeling the bone-cartilage interface on all the slices of a Double Echo Steady State (DESS) MR sequence, followed by measurement of the cartilage thickness from the surface of the bone, and finally by the identification of regions of abnormal thinness and focal/degenerative lesions. A preliminary evaluation of CAD tool was carried out on 10 cases taken from the Osteoarthritis Initiative (OAI) database. When compared with 2 board-certified musculoskeletal radiologists, the automatic CAD application was able to get segmentation/thickness maps in little over 60 seconds for all of the cases. This observation poses interesting possibilities for increasing radiologist productivity and confidence, improving patient outcomes, and applying more sophisticated CAD algorithms to routine orthopedic imaging tasks.

  1. The validity and accuracy of MRI arthrogram in the assessment of painful articular disorders of the hip.

    PubMed

    Rajeev, Aysha; Tuinebreijer, Wim; Mohamed, Abdalla; Newby, Mike

    2018-01-01

    The assessment of a patient with chronic hip pain can be challenging. The differential diagnosis of intra-articular pathology causing hip pain can be diverse. These includes conditions such as osteoarthritis, fracture, and avascular necrosis, synovitis, loose bodies, labral tears, articular pathology and, femoro-acetabular impingement. Magnetic resonance imaging (MRI) arthrography of the hip has been widely used now for diagnosis of articular pathology of the hip. A retrospective analysis of 113 patients who had MRI arthrogram and who underwent hip arthroscopy was included in the study. The MRI arthrogram was performed using gadolinium injection and reported by a single radiologist. The findings were then compared to that found on arthroscopy. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), accuracy and 95% confidence interval were calculated for each pathology. Labral tear-sensitivity 84% (74.3-90.5), specificity 64% (40.7-82.8), PPV 91% (82.1-95.8), NPV 48% (29.5-67.5), accuracy 80%. Delamination -sensitivity 7% (0.8-22.1), specificity 98% (91.6-99.7), PPV 50% (6.8-93.2), NPV 74% (65.1-82.2) and accuracy 39%. Chondral changes-sensitivity 25% (13.3-38.9), specificity 83% (71.3-91.1), PPV 52% (30.6-73.2), NPV 59% (48.0-69.2) and accuracy 58%. Femoro-acetabular impingement (CAM deformity)-sensitivity 34% (19.6-51.4), specificity 83% (72.2-90.4), PPV 50% (29.9-70.1), NPV 71% (60.6-80.5) and accuracy 66%. Synovitis-sensitivity 11% (2.3-28.2), specificity 99% (93.6-100), PPV 75% (19.4-99.4), NPV 77% (68.1-84.6) and accuracy 77%. Our study conclusions are MRI arthrogram is a useful investigation tool in detecting labral tears, it is also helpful in the diagnosis of femoro-acetabular impingement. However, when it comes to the diagnosis of chondral changes, defects and cartilage delamination, the sensitivity and accuracy are low.

  2. The Bioactivity of Cartilage Extracellular Matrix in Articular Cartilage Regeneration

    PubMed Central

    Sutherland, Amanda J.; Converse, Gabriel L.; Hopkins, Richard A.; Detamore, Michael S.

    2014-01-01

    Cartilage matrix is a particularly promising acellular material for cartilage regeneration given the evidence supporting its chondroinductive character. The ‘raw materials’ of cartilage matrix can serve as building blocks and signals for enhanced tissue regeneration. These matrices can be created by chemical or physical methods: physical methods disrupt cellular membranes and nuclei but may not fully remove all cell components and DNA, whereas chemical methods when combined with physical methods are particularly effective in fully decellularizing such materials. Critical endpoints include no detectable residual DNA or immunogenic antigens. It is important to first delineate between the sources of the cartilage matrix, i.e., derived from matrix produced by cells in vitro or from native tissue, and then to further characterize the cartilage matrix based on the processing method, i.e., decellularization or devitalization. With these distinctions, four types of cartilage matrices exist: decellularized native cartilage (DCC), devitalized native cartilage (DVC), decellularized cell derived matrix (DCCM), and devitalized cell derived matrix (DVCM). Delivery of cartilage matrix may be a straightforward approach without the need for additional cells or growth factors. Without additional biological additives, cartilage matrix may be attractive from a regulatory and commercialization standpoint. Source and delivery method are important considerations for clinical translation. Only one currently marketed cartilage matrix medical device is decellularized, although trends in filed patents suggest additional decellularized products may be available in the future. To choose the most relevant source and processing for cartilage matrix, qualifying testing needs to include targeting the desired application, optimizing delivery of the material, identify relevant FDA regulations, assess availability of raw materials, and immunogenic properties of the product. PMID:25044502

  3. Isotropic morphometry and multicomponent T1 ρ mapping of human knee articular cartilage in vivo at 3T.

    PubMed

    Baboli, Rahman; Sharafi, Azadeh; Chang, Gregory; Regatte, Ravinder R

    2018-05-02

    The progressive loss of hyaline articular cartilage due to osteoarthritis (OA) changes the functional and biochemical properties of cartilage. Measuring the T 1 ρ along with the morphological assessment can potentially be used as noninvasive biomarkers in detecting early-stage OA. To correlate the biochemical and morphological data, submillimeter isotropic resolution for both studies is required. To implement a high spatial resolution 3D-isotropic-MRI sequence for simultaneous assessment of morphological and biexponential T 1 ρ relaxometry of human knee cartilage in vivo. Prospective. Ten healthy volunteers with no known inflammation, trauma, or pain in the knee. Standard FLASH sequence and customized Turbo-FLASH sequence to acquire 3D-isotropic-T 1 ρ-weighted images on a 3T MRI scanner. The mean volume and thickness along with mono- and biexponential T 1 ρ relaxations were assessed in the articular cartilage of 10 healthy volunteers. Nonparametric rank-sum tests. Bland-Altman analysis and coefficient of variation. The mean monoexponential T 1 ρ relaxation was 40.7 ± 4.8 msec, while the long and short components were 58.2 ± 3.9 msec and 6.5 ± 0.6 msec, respectively. The mean fractions of long and short T 1 ρ relaxation components were 63.7 ± 5.9% and 36.3 ± 5.9%, respectively. Statistically significant (P ≤ 0.03) differences were observed in the monoexponential and long components between some of the regions of interest (ROIs). No gender differences between biexponential components were observed (P > 0.05). Mean cartilage volume and thickness were 25.9 ± 6.4 cm 3 and 2.2 ± 0.7 mm, respectively. Cartilage volume (P = 0.01) and thickness (P = 0.03) were significantly higher in male than female participants across all ROIs. Bland-Altman analysis showed agreement between two morphological methods with limits of agreement between -1000 mm 3 and +1100 mm 3 for volume, and -0.78 mm and +0.46 mm for

  4. Change in joint space width: hyaline articular cartilage loss or alteration in meniscus?

    PubMed

    Hunter, D J; Zhang, Y Q; Tu, X; Lavalley, M; Niu, J B; Amin, S; Guermazi, A; Genant, H; Gale, D; Felson, D T

    2006-08-01

    To explore the relative contribution of hyaline cartilage morphologic features and the meniscus to the radiographic joint space. The Boston Osteoarthritis of the Knee Study is a natural history study of symptomatic knee osteoarthritis (OA). Baseline and 30-month followup assessments included knee magnetic resonance imaging (MRI) and fluoroscopically positioned weight-bearing knee radiographs. Cartilage and meniscal degeneration were scored on MRI in the medial and lateral tibiofemoral joints using a semiquantitative grading system. Meniscal position was measured to the nearest millimeter. The dependent variable was joint space narrowing (JSN) on the plain radiograph (possible range 0-3). The predictor variables were MRI cartilage score, meniscal degeneration, and meniscal position measures. We first conducted a cross-sectional analysis using multivariate regression to determine the relative contribution of meniscal factors and cartilage morphologic features to JSN, adjusting for body mass index (BMI), age, and sex. The same approach was used for change in JSN and change in predictor variables. We evaluated 264 study participants with knee OA (mean age 66.7 years, 59% men, mean BMI 31.4 kg/m(2)). The results from the models demonstrated that meniscal position and meniscal degeneration each contributed to prediction of JSN, in addition to the contribution by cartilage morphologic features. For change in medial joint space, both change in meniscal position and change in articular cartilage score contributed substantially to narrowing of the joint space. The meniscus (both its position and degeneration) accounts for a substantial proportion of the variance explained in JSN, and the change in meniscal position accounts for a substantial proportion of change in JSN.

  5. Cartilage tissue engineering: From biomaterials and stem cells to osteoarthritis treatments.

    PubMed

    Vinatier, C; Guicheux, J

    2016-06-01

    Articular cartilage is a non-vascularized and poorly cellularized connective tissue that is frequently damaged as a result of trauma and degenerative joint diseases such as osteoarthrtis. Because of the absence of vascularization, articular cartilage has low capacity for spontaneous repair. Today, and despite a large number of preclinical data, no therapy capable of restoring the healthy structure and function of damaged articular cartilage is clinically available. Tissue-engineering strategies involving the combination of cells, scaffolding biomaterials and bioactive agents have been of interest notably for the repair of damaged articular cartilage. During the last 30 years, cartilage tissue engineering has evolved from the treatment of focal lesions of articular cartilage to the development of strategies targeting the osteoarthritis process. In this review, we focus on the different aspects of tissue engineering applied to cartilage engineering. We first discuss cells, biomaterials and biological or environmental factors instrumental to the development of cartilage tissue engineering, then review the potential development of cartilage engineering strategies targeting new emerging pathogenic mechanisms of osteoarthritis. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  6. Magnetic resonance imaging for diagnosis and assessment of cartilage defect repairs.

    PubMed

    Marlovits, Stefan; Mamisch, Tallal Charles; Vekszler, György; Resinger, Christoph; Trattnig, Siegfried

    2008-04-01

    Clinical magnetic resonance imaging (MRI) is the method of choice for the non-invasive evaluation of articular cartilage defects and the follow-up of cartilage repair procedures. The use of cartilage-sensitive sequences and a high spatial-resolution technique enables the evaluation of cartilage morphology even in the early stages of disease, as well as assessment of cartilage repair. Sequences that offer high contrast between articular cartilage and adjacent structures, such as the fat-suppressed, 3-dimensional, spoiled gradient-echo sequence and the fast spin-echo sequence, are accurate and reliable for evaluating intrachondral lesions and surface defects of articular cartilage. These sequences can also be performed together in reasonable examination times. In addition to morphology, new MRI techniques provide insight into the biochemical composition of articular cartilage and cartilage repair tissue. These techniques enable the diagnosis of early cartilage degeneration and help to monitor the effect and outcome of various surgical and non-surgical cartilage repair therapies.

  7. Multiscale Mechanics of Articular Cartilage: Potentials and Challenges of Coupling Musculoskeletal, Joint, and Microscale Computational Models

    PubMed Central

    Halloran, J. P.; Sibole, S.; van Donkelaar, C. C.; van Turnhout, M. C.; Oomens, C. W. J.; Weiss, J. A.; Guilak, F.; Erdemir, A.

    2012-01-01

    Articular cartilage experiences significant mechanical loads during daily activities. Healthy cartilage provides the capacity for load bearing and regulates the mechanobiological processes for tissue development, maintenance, and repair. Experimental studies at multiple scales have provided a fundamental understanding of macroscopic mechanical function, evaluation of the micromechanical environment of chondrocytes, and the foundations for mechanobiological response. In addition, computational models of cartilage have offered a concise description of experimental data at many spatial levels under healthy and diseased conditions, and have served to generate hypotheses for the mechanical and biological function. Further, modeling and simulation provides a platform for predictive risk assessment, management of dysfunction, as well as a means to relate multiple spatial scales. Simulation-based investigation of cartilage comes with many challenges including both the computational burden and often insufficient availability of data for model development and validation. This review outlines recent modeling and simulation approaches to understand cartilage function from a mechanical systems perspective, and illustrates pathways to associate mechanics with biological function. Computational representations at single scales are provided from the body down to the microstructure, along with attempts to explore multiscale mechanisms of load sharing that dictate the mechanical environment of the cartilage and chondrocytes. PMID:22648577

  8. Changes in collagen fibril network organization and proteoglycan distribution in equine articular cartilage during maturation and growth

    PubMed Central

    Hyttinen, Mika M; Holopainen, Jaakko; René van Weeren, P; Firth, Elwyn C; Helminen, Heikki J; Brama, Pieter A J

    2009-01-01

    The aim of this study was to record growth-related changes in collagen network organization and proteoglycan distribution in intermittently peak-loaded and continuously lower-level-loaded articular cartilage. Cartilage from the proximal phalangeal bone of the equine metacarpophalangeal joint at birth, at 5, 11 and 18 months, and at 6–10 years of age was collected from two sites. Site 1, at the joint margin, is unloaded at slow gaits but is subjected to high-intensity loading during athletic activity; site 2 is a continuously but less intensively loaded site in the centre of the joint. The degree of collagen parallelism was determined with quantitative polarized light microscopy and the parallelism index for collagen fibrils was computed from the cartilage surface to the osteochondral junction. Concurrent changes in the proteoglycan distribution were quantified with digital densitometry. We found that the parallelism index increased significantly with age (up to 90%). At birth, site 2 exhibited a more organized collagen network than site 1. In adult horses this situation was reversed. The superficial and intermediate zones exhibited the greatest reorganization of collagen. Site 1 had a higher proteoglycan content than site 2 at birth but here too the situation was reversed in adult horses. We conclude that large changes in joint loading during growth and maturation in the period from birth to adulthood profoundly affect the architecture of the collagen network in equine cartilage. In addition, the distribution and content of proteoglycans are modified significantly by altered joint use. Intermittent peak-loading with shear seems to induce higher collagen parallelism and a lower proteoglycan content in cartilage than more constant weight-bearing. Therefore, we hypothesize that the formation of mature articular cartilage with a highly parallel collagen network and relatively low proteoglycan content in the peak-loaded area of a joint is needed to withstand

  9. The effects of different doses of IGF-1 on cartilage and subchondral bone during the repair of full-thickness articular cartilage defects in rabbits.

    PubMed

    Zhang, Z; Li, L; Yang, W; Cao, Y; Shi, Y; Li, X; Zhang, Q

    2017-02-01

    To investigate the effects of different doses of insulin-like growth factor 1 (IGF-1) on the cartilage layer and subchondral bone (SB) during repair of full-thickness articular cartilage (AC) defects. IGF-1-loaded collagen membrane was implanted into full-thickness AC defects in rabbits. The effects of two different doses of IGF-1 on cartilage layer and SB adjacent to the defect, the cartilage structure, formation and integration, and the new SB formation were evaluated at the 1st, 4th and 8th week postoperation. Meanwhile, after 1 week treatment, the relative mRNA expressions in tissues adjacent to the defect, including cartilage and SB were determined by quantitative real-time RT-PCR (qRT-PCR), respectively. Different doses of IGF-1 induced different gene expression profiles in tissues adjacent to the defect and resulted in different repair outcomes. Particularly, at high dose IGF-1 aided cell survival, regulated the gene expressions in cartilage layer adjacent defect and altered ECM composition more effectively, improved the formation and integrity of neo-cartilage. While, at low dose IGF-1 regulated the gene expressions in SB more efficaciously and subsequently promoted the SB remodeling and reconstruction. Different doses of IGF-1 induced different responses of cartilage or SB during the repair of full-thickness AC defects. Particularly, high dose of IGF-1 was more beneficial to the neo-cartilage formation and integration, while low dose of it was more effective for the SB formation. Copyright © 2016 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

  10. Integration of stem cell-derived exosomes with in situ hydrogel glue as a promising tissue patch for articular cartilage regeneration.

    PubMed

    Liu, Xiaolin; Yang, Yunlong; Li, Yan; Niu, Xin; Zhao, Bizeng; Wang, Yang; Bao, Chunyan; Xie, Zongping; Lin, Qiuning; Zhu, Linyong

    2017-03-30

    The regeneration of articular cartilage, which scarcely shows innate self-healing ability, is a great challenge in clinical treatment. Stem cell-derived exosomes (SC-Exos), an important type of extracellular nanovesicle, exhibit great potential for cartilage regeneration to replace stem cell-based therapy. Cartilage regeneration often takes a relatively long time and there is currently no effective administration method to durably retain exosomes at cartilage defect sites to effectively exert their reparative effect. Therefore, in this study, we exploited a photoinduced imine crosslinking hydrogel glue, which presents excellent operation ability, biocompatibility and most importantly, cartilage-integration, as an exosome scaffold to prepare an acellular tissue patch (EHG) for cartilage regeneration. It was found that EHG can retain SC-Exos and positively regulate both chondrocytes and hBMSCs in vitro. Furthermore, EHG can integrate with native cartilage matrix and promote cell deposition at cartilage defect sites, finally resulting in the promotion of cartilage defect repair. The EHG tissue patch therefore provides a novel, cell-free scaffold material for wound repair.

  11. The effect of collagen fibril orientation on the biphasic mechanics of articular cartilage.

    PubMed

    Meng, Qingen; An, Shuqiang; Damion, Robin A; Jin, Zhongmin; Wilcox, Ruth; Fisher, John; Jones, Alison

    2017-01-01

    The highly inhomogeneous distribution of collagen fibrils may have important effects on the biphasic mechanics of articular cartilage. However, the effect of the inhomogeneity of collagen fibrils has mainly been investigated using simplified three-layered models, which may have underestimated the effect of collagen fibrils by neglecting their realistic orientation. The aim of this study was to investigate the effect of the realistic orientation of collagen fibrils on the biphasic mechanics of articular cartilage. Five biphasic material models, each of which included a different level of complexity of fibril reinforcement, were solved using two different finite element software packages (Abaqus and FEBio). Model 1 considered the realistic orientation of fibrils, which was derived from diffusion tensor magnetic resonance images. The simplified three-layered orientation was used for Model 2. Models 3-5 were three control models. The realistic collagen orientations obtained in this study were consistent with the literature. Results from the two finite element implementations were in agreement for each of the conditions modelled. The comparison between the control models confirmed some functions of collagen fibrils. The comparison between Models 1 and 2 showed that the widely-used three-layered inhomogeneous model can produce similar fluid load support to the model including the realistic fibril orientation; however, an accurate prediction of the other mechanical parameters requires the inclusion of the realistic orientation of collagen fibrils. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  12. Deformation of articular cartilage during static loading of a knee joint--experimental and finite element analysis.

    PubMed

    Halonen, K S; Mononen, M E; Jurvelin, J S; Töyräs, J; Salo, J; Korhonen, R K

    2014-07-18

    Novel conical beam CT-scanners offer high resolution imaging of knee structures with i.a. contrast media, even under weight bearing. With this new technology, we aimed to determine cartilage strains and meniscal movement in a human knee at 0, 1, 5, and 30 min of standing and compare them to the subject-specific 3D finite element (FE) model. The FE model of the volunteer׳s knee, based on the geometry obtained from magnetic resonance images, was created to simulate the creep. The effects of collagen fibril network stiffness, nonfibrillar matrix modulus, permeability and fluid flow boundary conditions on the creep response in cartilage were investigated. In the experiment, 80% of the maximum strain in cartilage developed immediately, after which the cartilage continued to deform slowly until the 30 min time point. Cartilage strains and meniscus movement obtained from the FE model matched adequately with the experimentally measured values. Reducing the fibril network stiffness increased the mean strains substantially, while the creep rate was primarily influenced by an increase in the nonfibrillar matrix modulus. Changing the initial permeability and preventing fluid flow through noncontacting surfaces had a negligible effect on cartilage strains. The present results improve understanding of the mechanisms controlling articular cartilage strains and meniscal movements in a knee joint under physiological static loading. Ultimately a validated model could be used as a noninvasive diagnostic tool to locate cartilage areas at risk for degeneration. Copyright © 2014 Elsevier Ltd. All rights reserved.

  13. Local intra-articular injection of resveratrol delays cartilage degeneration in C57BL/6 mice by inducing autophagy via AMPK/mTOR pathway.

    PubMed

    Qin, Na; Wei, Liwei; Li, Wuyin; Yang, Wei; Cai, Litao; Qian, Zhuang; Wu, Shufang

    2017-07-01

    Autophagy is an essential cellular homeostasis mechanism that was found to be compromised in aging and osteoarthritis (OA) cartilage. Previous studies showed that resveratrol can effectively regulate autophagy in other cells. The purpose of this study was to determine whether the chondroprotective effect of resveratrol was related to chondrocyte autophagy and to elucidate underlying mechanisms. OA model was induced by destabilization of the medial meniscus (DMM) in 10-week-old male mice. OA mice were treated with resveratrol with/without 3-MA for 8 weeks beginning 4 weeks after surgery. The local intra-articular injection of resveratrol delayed articular cartilage degradation in DMM-induced OA by OARSI scoring systems and Safranin O-fast green. Resveratrol treatment increased Unc-51-like kinase1, Beclin1, microtubule-associated protein light chain 3, hypoxia inducible factor-1α, phosphorylated AMPK, collagen-2A1, Aggrecan expressions, but decreased hypoxia inducible factor-2α, phosphorylated mTOR, matrix metalloproteinases13 and a disintegrin and metalloproteinase with thrombospondin motifs 5 expressions. The effects of resveratrol were obviously blunted by 3-MA except HIF and AMPK. These findings indicate that resveratrol intra-articular injection delayed articular cartilage degeneration and promoted chondrocyte autophagy in an experimental model of surgical DMM-induced OA, in part via balancing HIF-1α and HIF-2α expressions and thereby regulating AMPK/mTOR signaling pathway. Copyright © 2017 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

  14. Three-Dimensional Bioprinting and Its Potential in the Field of Articular Cartilage Regeneration

    PubMed Central

    Mouser, Vivian H. M.; Levato, Riccardo; Bonassar, Lawrence J.; D’Lima, Darryl D.; Grande, Daniel A.; Klein, Travis J.; Saris, Daniel B. F.; Zenobi-Wong, Marcy; Gawlitta, Debby; Malda, Jos

    2016-01-01

    Three-dimensional (3D) bioprinting techniques can be used for the fabrication of personalized, regenerative constructs for tissue repair. The current article provides insight into the potential and opportunities of 3D bioprinting for the fabrication of cartilage regenerative constructs. Although 3D printing is already used in the orthopedic clinic, the shift toward 3D bioprinting has not yet occurred. We believe that this shift will provide an important step forward in the field of cartilage regeneration. Three-dimensional bioprinting techniques allow incorporation of cells and biological cues during the manufacturing process, to generate biologically active implants. The outer shape of the construct can be personalized based on clinical images of the patient’s defect. Additionally, by printing with multiple bio-inks, osteochondral or zonally organized constructs can be generated. Relevant mechanical properties can be obtained by hybrid printing with thermoplastic polymers and hydrogels, as well as by the incorporation of electrospun meshes in hydrogels. Finally, bioprinting techniques contribute to the automation of the implant production process, reducing the infection risk. To prompt the shift from nonliving implants toward living 3D bioprinted cartilage constructs in the clinic, some challenges need to be addressed. The bio-inks and required cartilage construct architecture need to be further optimized. The bio-ink and printing process need to meet the sterility requirements for implantation. Finally, standards are essential to ensure a reproducible quality of the 3D printed constructs. Once these challenges are addressed, 3D bioprinted living articular cartilage implants may find their way into daily clinical practice. PMID:28934880

  15. Bovine lactoferricin is anti-inflammatory and anti-catabolic in human articular cartilage and synovium.

    PubMed

    Yan, Dongyao; Chen, Di; Shen, Jie; Xiao, Guozhi; van Wijnen, Andre J; Im, Hee-Jeong

    2013-02-01

    Bovine lactoferricin (LfcinB) is a multi-functional peptide derived from proteolytic cleavage of bovine lactoferrin. LfcinB was found to antagonize the biological effects mediated by angiogenic growth factors such as vascular endothelial growth factor (VEGF) and fibroblast growth factor 2 (FGF-2) in endothelial cells. However, the effect of LfcinB on human articular cartilage remained unknown. Here, our findings demonstrate that LfcinB restored the proteoglycan loss promoted by catabolic factors (interleukin-1β) IL-1β and FGF-2 in vitro and ex vivo. Mechanistically, LfcinB attenuated the effects of IL-1β and FGF-2 on the expression of cartilage-degrading enzymes (MMP-1, MMP-3, and MMP-13), destructive cytokines (IL-1β and IL-6), and inflammatory mediators (iNOS and TLR2). LfcinB induced protective cytokine expression (IL-4 and IL-10), and downregulated aggrecanase basal expression. LfcinB specifically activated ERK MAPK and Akt signaling pathways, which may account for its anti-inflammatory activity. We also revealed that LfcinB exerted similar protective effects on human synovial fibroblasts challenged by IL-1β, with minimal cytotoxicity. Collectively, our results suggest that LfcinB possesses potent anti-catabolic and anti-inflammatory bioactivities in human articular tissues, and may be utilized for the prevention and/or treatment of OA in the future. Copyright © 2012 Wiley Periodicals, Inc.

  16. Optimization of Methods for Articular Cartilage Surface Tissue Engineering: Cell Density and Transforming Growth Factor Beta Are Critical for Self-Assembly and Lubricin Secretion.

    PubMed

    Iwasa, Kenjiro; Reddi, A Hari

    2017-07-01

    Lubricin/superficial zone protein (SZP)/proteoglycan4 (PRG4) plays an important role in boundary lubrication in articular cartilage. Lubricin is secreted by superficial zone chondrocytes and synoviocytes of the synovium. The specific objective of this investigation is to optimize the methods for tissue engineering of articular cartilage surface. The aim of this study is to investigate the effect of cell density on the self-assembly of superficial zone chondrocytes and lubricin secretion as a functional assessment. Superficial zone chondrocytes were cultivated as a monolayer at low, medium, and high densities. Chondrocytes at the three different densities were treated with transforming growth factor beta (TGF-β)1 twice a week or daily, and the accumulated lubricin in the culture medium was analyzed by immunoblots and quantitated by enzyme-linked immunosorbent assay (ELISA). Cell numbers in low and medium densities were increased by TGF-β1; whereas cell numbers in high-density cell cultures were decreased by twice-a-week treatment of TGF-β1. On the other hand, the cell numbers were maintained by daily TGF-β treatment. Immunoblots and quantitation of lubricin by ELISA analysis indicated that TGF-β1 stimulated lubricin secretion by superficial zone chondrocytes at all densities with twice-a-week TGF-β treatment. It is noteworthy that the daily treatment of TGF-β1 increased lubricin much higher compared with twice-a-week treatment. These data demonstrate that daily treatment is optimal for the TGF-β1 response in a higher density of monolayer cultures. These findings have implications for self-assembly of surface zone chondrocytes of articular cartilage for application in tissue engineering of articular cartilage surface.

  17. Similar Properties of Chondrocytes from Osteoarthritis Joints and Mesenchymal Stem Cells from Healthy Donors for Tissue Engineering of Articular Cartilage

    PubMed Central

    Fernandes, Amilton M.; Herlofsen, Sarah R.; Karlsen, Tommy A.; Küchler, Axel M.; Fløisand, Yngvar; Brinchmann, Jan E.

    2013-01-01

    Lesions of hyaline cartilage do not heal spontaneously, and represent a therapeutic challenge. In vitro engineering of articular cartilage using cells and biomaterials may prove to be the best solution. Patients with osteoarthritis (OA) may require tissue engineered cartilage therapy. Chondrocytes obtained from OA joints are thought to be involved in the disease process, and thus to be of insufficient quality to be used for repair strategies. Bone marrow (BM) derived mesenchymal stem cells (MSCs) from healthy donors may represent an alternative cell source. We have isolated chondrocytes from OA joints, performed cell culture expansion and tissue engineering of cartilage using a disc-shaped alginate scaffold and chondrogenic differentiation medium. We performed real-time reverse transcriptase quantitative PCR and fluorescence immunohistochemistry to evaluate mRNA and protein expression for a range of molecules involved in chondrogenesis and OA pathogenesis. Results were compared with those obtained by using BM-MSCs in an identical tissue engineering strategy. Finally the two populations were compared using genome-wide mRNA arrays. At three weeks of chondrogenic differentiation we found high and similar levels of hyaline cartilage-specific type II collagen and fibrocartilage-specific type I collagen mRNA and protein in discs containing OA and BM-MSC derived chondrocytes. Aggrecan, the dominant proteoglycan in hyaline cartilage, was more abundantly distributed in the OA chondrocyte extracellular matrix. OA chondrocytes expressed higher mRNA levels also of other hyaline extracellular matrix components. Surprisingly BM-MSC derived chondrocytes expressed higher mRNA levels of OA markers such as COL10A1, SSP1 (osteopontin), ALPL, BMP2, VEGFA, PTGES, IHH, and WNT genes, but lower levels of MMP3 and S100A4. Based on the results presented here, OA chondrocytes may be suitable for tissue engineering of articular cartilage. PMID:23671648

  18. Routine clinical knee MR reports: comparison of diagnostic performance at 1.5 T and 3.0 T for assessment of the articular cartilage.

    PubMed

    Mandell, Jacob C; Rhodes, Jeffrey A; Shah, Nehal; Gaviola, Glenn C; Gomoll, Andreas H; Smith, Stacy E

    2017-11-01

    Accurate assessment of knee articular cartilage is clinically important. Although 3.0 Tesla (T) MRI is reported to offer improved diagnostic performance, literature regarding the clinical impact of MRI field strength is lacking. The purpose of this study is to compare the diagnostic performance of clinical MRI reports for assessment of cartilage at 1.5 and 3.0 T in comparison to arthroscopy. This IRB-approved retrospective study consisted of 300 consecutive knees in 297 patients who had routine clinical MRI and arthroscopy. Descriptions of cartilage from MRI reports of 165 knees at 1.5 T and 135 at 3.0 T were compared with arthroscopy. The sensitivity, specificity, percent of articular surfaces graded concordantly, and percent of articular surfaces graded within one grade of the arthroscopic grading were calculated for each articular surface at 1.5 and 3.0 T. Agreement between MRI and arthroscopy was calculated with the weighted-kappa statistic. Significance testing was performed utilizing the z-test after bootstrapping to obtain the standard error. The sensitivity, specificity, percent of articular surfaces graded concordantly, and percent of articular surfaces graded within one grade were 61.4%, 82.7%, 62.2%, and 77.5% at 1.5 T and 61.8%, 80.6%, 59.5%, and 75.6% at 3.0 T, respectively. The weighted kappa statistic was 0.56 at 1.5 T and 0.55 at 3.0 T. There was no statistically significant difference in any of these parameters between 1.5 and 3.0 T. Factors potentially contributing to the lack of diagnostic advantage of 3.0 T MRI are discussed.

  19. Cell compaction influences the regenerative potential of passaged bovine articular chondrocytes in an ex vivo cartilage defect model.

    PubMed

    Schmutzer, Michael; Aszodi, Attila

    2017-04-01

    The loss and degradation of articular cartilage tissue matrix play central roles in the process of osteoarthritis (OA). New models for evaluating cartilage repair/regeneration are thus of great value for transferring various culture systems into clinically relevant situations. The repair process can be better monitored in ex vivo systems than in in vitro cell cultures. I have therefore established an ex vivo defect model prepared from bovine femoral condyles for evaluating cartilage repair by the implantation of cells cultured in various ways, e.g., monolayer-cultured cells or suspension or pellet cultures of articular bovine chondrocytes representing different cell compactions with variable densities of chondrocytes. I report that the integrin subunit α10 was significantly upregulated in suspension-cultured bovine chondrocytes at passage P2 compared with monolayer-cultured cells at P1 (p = 0.0083) and P2 (p < 0.05). Suspension-cultured cells did not promote cartilage repair when compared with implanted monolayer-cultured chondrocytes and pellets: 24.0 ± 0.66% for suspension cells, 46.4 ± 2.9% for monolayer cells, and 127.64 ± 0.90% for pellets (p < 0.0001) of the original defect volume (percentage of defect). Additional cultivation with chondrogenesis-promoting growth factors TGF-β1 and BMP-2 revealed an enhancing effect on cartilage repair in all settings. The advantage and innovation of this system over in vitro differentiation (e.g., micromass, pellet) assays is the possibility of examining and evaluating cartilage regeneration in an environment in which implanted cells are embedded within native surrounding tissue at the defect site. Such ex vivo explants might serve as a better model system to mimic clinical situations. Copyright © 2017 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

  20. Electromechanical properties of human osteoarthritic and asymptomatic articular cartilage are sensitive and early detectors of degeneration.

    PubMed

    Hadjab, I; Sim, S; Karhula, S S; Kauppinen, S; Garon, M; Quenneville, E; Lavigne, P; Lehenkari, P P; Saarakkala, S; Buschmann, M D

    2018-03-01

    To evaluate cross-correlations of ex vivo electromechanical properties with cartilage and subchondral bone plate thickness, as well as their sensitivity and specificity regarding early cartilage degeneration in human tibial plateau. Six pairs of tibial plateaus were assessed ex vivo using an electromechanical probe (Arthro-BST) which measures a quantitative parameter (QP) reflecting articular cartilage compression-induced streaming potentials. Cartilage thickness was then measured with an automated thickness mapping technique using Mach-1 multiaxial mechanical tester. Subsequently, a visual assessment was performed by an experienced orthopedic surgeon using the International Cartilage Repair Society (ICRS) grading system. Each tibial plateau was finally evaluated with μCT scanner to determine the subchondral-bone plate thickness over the entire surface. Cross-correlations between assessments decreased with increasing degeneration level. Moreover, electromechanical QP and subchondral-bone plate thickness increased strongly with ICRS grade (ρ = 0.86 and ρ = 0.54 respectively), while cartilage thickness slightly increased (ρ = 0.27). Sensitivity and specificity analysis revealed that the electromechanical QP is the most performant to distinguish between different early degeneration stages, followed by subchondral-bone plate thickness and then cartilage thickness. Lastly, effect sizes of cartilage and subchondral-bone properties were established to evaluate whether cartilage or bone showed the most noticeable changes between normal (ICRS 0) and each early degenerative stage. Thus, the effect sizes of cartilage electromechanical QP were almost twice those of the subchondral-bone plate thickness, indicating greater sensitivity of electromechanical measurements to detect early osteoarthritis. The potential of electromechanical properties for the diagnosis of early human cartilage degeneration was highlighted and supported by cartilage thickness and

  1. Compressive and swelling behavior of cuttlebone derived hydroxyapatite loaded PVA hydrogel implants for articular cartilage

    NASA Astrophysics Data System (ADS)

    Kumar, B. Y. Santosh; Kumar, G. C. Mohan; Isloor, Arun M.

    2018-04-01

    Developing a novel antibacterial, nontoxic and biocompatible hydrogel with superior physio mechanical properties is still becoming a challenge. Herein, we synthesize hydroxyapatite (HA) powder from cuttlefish bone and prepare a series of stiff, tough, high strength, biocompatible hydrogel reinforced with HA by integrating glutaraldehyde into PVA/HA. Powder was characterized by SEM and XRD. Compressive strength and swelling properties are studied and compare the results with the properties of healthy natural articular cartilage.

  2. The collagen structure of equine articular cartilage characterized using polarization-sensitive optical coherence tomography and non-linear microscopy

    NASA Astrophysics Data System (ADS)

    Mansfield, Jessica C.; Ugryumova, Nadya; Knapp, Karen M.; Matcher, Stephen J.

    2006-09-01

    Equine articular cartilage has been imaged using both polarization-sensitive optical coherence tomography (PS-OCT) and non-linear microscopy. PS-OCT has been used to spatially map the birefringence in the cartilage and we have found that in the vicinity of the lesion the images display a characteristic disruption in the regular birefringence bands shown by normal cartilage. We also note that significant (e.g. x2) variations in the apparent birefringence of samples taken from young (18 month) animals that otherwise appear visually homogeneous are found over spatial scales of a few millimeters. We have also imaged the cartilage using non-linear microscopy and compare the scans taken with second harmonic generation (SHG) light and the two photon fluorescence (TPF) light. SHG images collected using 800 nm excitation reveals the spatial distribution of collagen fibers, whilst TPF images clearly shows the distribution of intracellular and pericellular fluorophores.

  3. New Frontiers for Cartilage Repair and Protection.

    PubMed

    Zaslav, Kenneth; McAdams, Timothy; Scopp, Jason; Theosadakis, Jason; Mahajan, Vivek; Gobbi, Alberto

    2012-01-01

    Articular cartilage injury is common after athletic injury and remains a difficult treatment conundrum both for the surgeon and athlete. Although recent treatments for damage to articular cartilage have been successful in alleviating symptoms, more durable and complete, long-term articular surface restoration remains the unattained goal. In this article, we look at both new ways to prevent damage to articular surfaces as well as new techniques to recreate biomechanically sound and biochemically true articular surfaces once an athlete injures this surface. This goal should include reproducing hyaline cartilage with a well-integrated and flexible subchondral base and the normal zonal variability in the articular matrix. A number of nonoperative interventions have shown early promise in mitigating cartilage symptoms and in preclinical studies have shown evidence of chondroprotection. These include the use of glucosamine, chondroitin, and other neutraceuticals, viscosupplementation with hyaluronic acid, platelet-rich plasma, and pulsed electromagnetic fields. Newer surgical techniques, some already in clinical study, and others on the horizon offer opportunities to improve the surgical restoration of the hyaline matrix often disrupted in athletic injury. These include new scaffolds, single-stage cell techniques, the use of mesenchymal stem cells, and gene therapy. Although many of these treatments are in the preclinical and early clinical study phase, they offer the promise of better options to mitigate the sequelae of athletically induced cartilage.

  4. Effects of mechanical loading on human mesenchymal stem cells for cartilage tissue engineering.

    PubMed

    Choi, Jane Ru; Yong, Kar Wey; Choi, Jean Yu

    2018-03-01

    Today, articular cartilage damage is a major health problem, affecting people of all ages. The existing conventional articular cartilage repair techniques, such as autologous chondrocyte implantation (ACI), microfracture, and mosaicplasty, have many shortcomings which negatively affect their clinical outcomes. Therefore, it is essential to develop an alternative and efficient articular repair technique that can address those shortcomings. Cartilage tissue engineering, which aims to create a tissue-engineered cartilage derived from human mesenchymal stem cells (MSCs), shows great promise for improving articular cartilage defect therapy. However, the use of tissue-engineered cartilage for the clinical therapy of articular cartilage defect still remains challenging. Despite the importance of mechanical loading to create a functional cartilage has been well demonstrated, the specific type of mechanical loading and its optimal loading regime is still under investigation. This review summarizes the most recent advances in the effects of mechanical loading on human MSCs. First, the existing conventional articular repair techniques and their shortcomings are highlighted. The important parameters for the evaluation of the tissue-engineered cartilage, including chondrogenic and hypertrophic differentiation of human MSCs are briefly discussed. The influence of mechanical loading on human MSCs is subsequently reviewed and the possible mechanotransduction signaling is highlighted. The development of non-hypertrophic chondrogenesis in response to the changing mechanical microenvironment will aid in the establishment of a tissue-engineered cartilage for efficient articular cartilage repair. © 2017 Wiley Periodicals, Inc.

  5. Effects of low molecular weight hyaluronan combined with carprofen on canine osteoarthritis articular chondrocytes and cartilage explants in vitro.

    PubMed

    Euppayo, Thippaporn; Siengdee, Puntita; Buddhachat, Kittisak; Pradit, Waranee; Viriyakhasem, Nawarat; Chomdej, Siriwadee; Ongchai, Siriwan; Harada, Yasuji; Nganvongpanit, Korakot

    2015-09-01

    Intra-articular injection with non-steroidal anti-inflammatory drugs (NSAIDs) is used to treat inflammatory joint disease, but the side effects of NSAIDs include chondrotoxicity. Hyaluronan has shown positive effects on chondrocytes by reducing apoptosis and increasing proteoglycan synthesis. The purposes of this study were to evaluate the effects of low molecular weight hyaluronan (low MW HA), carprofen 25 mg/ml, carprofen 12.5 mg/ml, and a combination of HA and carprofen on canine osteoarthritis (OA) articular chondrocytes and a cartilage explant model in terms of cell viability, extracellular matrix remaining, and gene expression after exposure. In chondrocyte culture, MTT assay was used to evaluate the chondrotoxicity of IC50 and IC80 of carprofen with HA. In cartilage explant culture, two kinds of extracellular matrix (uronic acid and collagen) remaining in cartilage were used to evaluate cartilage damage for 14 d after treatment. Expression of COL2A1, AGG, and MMP3 was used to evaluate the synthesis and degradation of the matrix for 7 d after treatment. In chondrocyte culture, low MW HA could preserve OA chondrocyte viability but could not reduce the chondrotoxicity level of carprofen (P < 0.05). In explant culture, low MW HA combined with 12.5 mg/ml carprofen caused less destruction of uronic acid and collagen structure when compared with the control (P < 0.05). Low MW HA caused high expression levels of COL2A1 and AGG in OA cartilage (P < 0.05); HA combined with carprofen resulted in higher COL2A1 and AGG expression levels than carprofen alone.

  6. Heritability of articular cartilage regeneration and its association with ear wound healing in mice.

    PubMed

    Rai, Muhammad Farooq; Hashimoto, Shingo; Johnson, Eric E; Janiszak, Kara L; Fitzgerald, Jamie; Heber-Katz, Ellen; Cheverud, James M; Sandell, Linda J

    2012-07-01

    Emerging evidence suggests that genetic components contribute significantly to cartilage degeneration in osteoarthritis pathophysiology, but little information is available on the genetics of cartilage regeneration. Therefore, this study was undertaken to investigate cartilage regeneration in genetic murine models using common inbred strains and a set of recombinant inbred (RI) lines generated from LG/J (healer of ear wounds) and SM/J (nonhealer) inbred mouse strains. An acute full-thickness cartilage injury was introduced in the trochlear groove of 8-week-old mice (n=265) through microsurgery. Mouse knee joints were sagittally sectioned and stained with toluidine blue to evaluate regeneration. For the ear wound phenotype, a bilateral 2-mm through-and-through puncture was created in 6-week-old mice (n=229), and healing outcomes were measured after 30 days. Broad-sense heritability and genetic correlations were calculated for both phenotypes. Time-course analysis of the RI mouse lines showed no significant regeneration until 16 weeks after surgery; at that time, the strains could be segregated into 3 categories: good, intermediate, and poor healers. Analysis of heritability (H2) showed that both cartilage regeneration (H2=26%; P=0.006) and ear wound closure (H2=53%; P<0.00001) were significantly heritable. The genetic correlations between the two healing phenotypes for common inbred mouse strains (r=0.92) and RI mouse lines (r=0.86) were found to be extremely high. Our findings indicate that articular cartilage regeneration in mice is heritable, the differences between the mouse lines are due to genetic differences, and a strong genetic correlation between the two phenotypes exists, indicating that they plausibly share a common genetic basis. We therefore surmise that LG/J by SM/J intercross mice can be used to dissect the genetic basis of variation in cartilage regeneration. Copyright © 2012 by the American College of Rheumatology.

  7. A Magnetically Actuated Microscaffold Containing Mesenchymal Stem Cells for Articular Cartilage Repair.

    PubMed

    Go, Gwangjun; Han, Jiwon; Zhen, Jin; Zheng, Shaohui; Yoo, Ami; Jeon, Mi-Jeong; Park, Jong-Oh; Park, Sukho

    2017-07-01

    This study proposes a magnetically actuated microscaffold with the capability of targeted mesenchymal stem cell (MSC) delivery for articular cartilage regeneration. The microscaffold, as a 3D porous microbead, is divided into body and surface portions according to its materials and fabrication methods. The microscaffold body, which consists of poly(lactic-co-glycolic acid) (PLGA), is formed through water-in-oil-in-water emulsion templating, and its surface is coated with amine functionalized magnetic nanoparticles (MNPs) via amino bond formation. The porous PLGA structure of the microscaffold can assist in cell adhesion and migration, and the MNPs on the microscaffold can make it possible to steer using an electromagnetic actuation system that provides external magnetic fields for the 3D locomotion of the microscaffold. As a fundamental test of the magnetic response of the microscaffold, it is characterized in terms of the magnetization curve, velocity, and 3D locomotion of a single microscaffold. In addition, its function with a cargo of MSCs for cartilage regeneration is demonstrated from the proliferation, viability, and chondrogenic differentiation of D1 mouse MSCs that are cultured on the microscaffold. For the feasibility tests for cartilage repair, 2D/3D targeting of multiple microscaffolds with the MSCs is performed to demonstrate targeted stem cell delivery using the microscaffolds and their swarm motion. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. Potential for thermal damage to articular cartilage by PMMA reconstruction of a bone cavity following tumor excision: A finite element study.

    PubMed

    Radev, Boyko R; Kase, Jonathan A; Askew, Michael J; Weiner, Scott D

    2009-05-29

    Benign, giant cell tumors are often treated by intralesional excision and reconstruction with polymethylmethacrylate (PMMA) bone cement. The exothermic reaction of the in-situ polymerizing PMMA is believed to beneficially kill remaining tumor cells. However, at issue is the extent of this necrotic effect into the surrounding normal bone and the adjacent articular cartilage. Finite element analysis (ABAQUS 6.4-1) was used to determine the extent of possible thermal necrosis around prismatically shaped, PMMA implants (8-24cc in volume), placed into a peripheral, sagittally symmetric, metaphyseal defect in the proximal tibia. Temperature/exposure time conditions indicating necrotic potential during the exotherm of the polymerizing bone cement were found in regions of the cancellous bone within 3mm of the superior surface of the PMMA implant. If less than 3mm of cancellous bone existed between the PMMA implant and the subchondral bone layer, regions of the subchondral bone were also exposed to thermally necrotic conditions. However, as long as there were at least 2mm of uniform subchondral bone above the PMMA implant, the necrotic regions did not extend into the overlying articular cartilage. This was the case even when the PMMA was in direct contact with the subchondral bone. If the subchondral bone is not of sufficient thickness, or is not continuous, then care should be taken to protect the articular cartilage from thermal damage as a result of the reconstruction of the tumor cavity with PMMA bone cement.

  9. Mesenchymal stem-cell potential in cartilage repair: an update

    PubMed Central

    Mazor, M; Lespessailles, E; Coursier, R; Daniellou, R; Best, T M; Toumi, H

    2014-01-01

    Articular cartilage damage and subsequent degeneration are a frequent occurrence in synovial joints. Treatment of these lesions is a challenge because this tissue is incapable of quality repair and/or regeneration to its native state. Non-operative treatments endeavour to control symptoms and include anti-inflammatory medications, viscosupplementation, bracing, orthotics and activity modification. Classical surgical techniques for articular cartilage lesions are frequently insufficient in restoring normal anatomy and function and in many cases, it has not been possible to achieve the desired results. Consequently, researchers and clinicians are focusing on alternative methods for cartilage preservation and repair. Recently, cell-based therapy has become a key focus of tissue engineering research to achieve functional replacement of articular cartilage. The present manuscript is a brief review of stem cells and their potential in the treatment of early OA (i.e. articular cartilage pathology) and recent progress in the field. PMID:25353372

  10. Cartilage proteoglycans inhibit fibronectin-mediated adhesion

    NASA Astrophysics Data System (ADS)

    Rich, A. M.; Pearlstein, E.; Weissmann, G.; Hoffstein, S. T.

    1981-09-01

    Normal tissues and organs show, on histological examination, a pattern of cellular and acellular zones that is characteristic and unique for each organ or tissue. This pattern is maintained in health but is sometimes destroyed by disease. For example, in mobile joints, the articular surfaces consist of relatively acellular hyaline cartilage, and the joint space is enclosed by a capsule of loose connective tissue with a lining of fibroblasts and macrophages. In the normal joint these cells are confined to the synovial lining and the articular surface remains acellular. In in vitro culture, macrophages and their precursor monocytes are very adhesive, and fibroblasts can migrate and overgrow surfaces such as collagen or plastic used for tissue culture. The fibroblasts adhere to collagen by means of fibronectin, which they synthesize and secrete1. Because the collagen of cartilage is capable of binding serum fibronectin2 and fibronectin is present in cartilage during its development3, these cells should, in theory, slowly migrate from the synovial lining to the articular surface. It is their absence from the articular cartilage in normal circumstances, and then presence in such pathological states as rheumatoid arthritis, that is striking. We therefore set out to determine whether a component of cartilage could prevent fibroblast adherence in a defined adhesion assay. As normal cartilage is composed of 50% proteoglycans and 50% collagen by dry weight4, we tested the possibility that the proteoglycans in cartilage inhibit fibroblast adhesion to collagen. We present here evidence that fibroblast spreading and adhesion to collagenous substrates is inhibited by cartilage proteoglycans.

  11. Engineered cartilage using primary chondrocytes cultured in a porous cartilage-derived matrix

    PubMed Central

    Cheng, Nai-Chen; Estes, Bradley T; Young, Tai-Horng; Guilak, Farshid

    2011-01-01

    Aim To investigate the cell growth, matrix accumulation and mechanical properties of neocartilage formed by human or porcine articular chondrocytes on a porous, porcine cartilage-derived matrix (CDM) for use in cartilage tissue engineering. Materials & methods We examined the physical properties, cell infiltration and matrix accumulation in different formulations of CDM and selected a CDM made of homogenized cartilage slurry as an appropriate scaffold for long-term culture of human and porcine articular chondrocytes. Results The CDM scaffold supported growth and proliferation of both human and porcine chondrocytes. Histology and immunohistochemistry showed abundant cartilage-specific macromolecule deposition at day 28. Human chondrocytes migrated throughout the CDM, showing a relatively homogeneous distribution of new tissue accumulation, whereas porcine chondrocytes tended to form a proteoglycan-rich layer primarily on the surfaces of the scaffold. Human chondrocyte-seeded scaffolds had a significantly lower aggregate modulus and hydraulic permeability at day 28. Conclusions These data show that a scaffold derived from native porcine articular cartilage can support neocartilage formation in the absence of exogenous growth factors. The overall characteristics and properties of the constructs depend on factors such as the concentration of CDM used, the porosity of the scaffold, and the species of chondrocytes. PMID:21175289

  12. The efficacy of intra-articular hyaluronan injection after the microfracture technique for the treatment of articular cartilage lesions.

    PubMed

    Strauss, Eric; Schachter, Aaron; Frenkel, Sally; Rosen, Jeffrey

    2009-04-01

    Although the exact mechanism of action has yet to be elucidated, recent animal studies have demonstrated chondroprotective and anti-inflammatory properties of hyaluronic acid viscosupplementation. Intra-articular hyaluronic acid after microfracture improves the quality of the repair leading to a more hyaline-like repair tissue with better defect fill and adjacent area integration. Controlled laboratory study. Full-thickness cartilage defects were created in the weightbearing area of the medial femoral condyle in 36 female New Zealand White rabbits. The defects were then treated with surgical microfracture. Eighteen rabbits formed the 3-month cohort and the other 18 formed the 6-month cohort. Within each cohort, 6 rabbits were randomly assigned to receive 3 weekly injections of hyaluronic acid (group A), 5 weekly injections (group B), or control injections of normal saline (group C). At 3 and 6 months postmicrofracture, the animals were sacrificed and the operative knee harvested. Repair tissue was assessed blinded- both grossly, using a modified component of the International Cartilage Repair Society (ICRS) Cartilage Repair Assessment scoring scale, and histologically, using the modified O'Driscoll histological cartilage scoring system. Comparisons were made with respect to gross and histologic findings between treatment groups at each time point. Effects of each treatment type were also evaluated longitudinally by comparing the 3-month results with the 6-month results. Statistical analysis was performed using unpaired Student t tests with significance defined as P < .05. At 3 months, gross and histologic evaluation of the repair tissue demonstrated that the 3-injection group had significantly better fill of the defects and more normal appearing, hyaline-like tissue than controls (a mean ICRS score of 1.92 vs 1.26; P < .05 and a mean modified O'Driscoll score of 10.3 vs 7.6; P < .02). Specimens treated with 5 weekly injections were not significantly improved

  13. Sclerostin Immunoreactivity Increases in Cortical Bone Osteocytes and Decreases in Articular Cartilage Chondrocytes in Aging Mice.

    PubMed

    Thompson, Michelle L; Jimenez-Andrade, Juan Miguel; Mantyh, Patrick W

    2016-03-01

    Sclerostin is a 24-kDa secreted glycoprotein that has been identified as a negative modulator of new bone formation and may play a major role in age-related decline in skeletal function. Although serum levels of sclerostin markedly increase with age, relatively little is known about whether cells in the skeleton change their expression of sclerostin with aging. Using immunohistochemistry and confocal microscopy, we explored sclerostin immunoreactivity (sclerostin-IR) in the femurs of 4-, 9-, and 24-month-old adult C3H/HeJ male mice. In the femur, the only two cell types that expressed detectable levels of sclerostin-IR were bone osteocytes and articular cartilage chondrocytes. At three different sites along the diaphysis of the femur, only a subset of osteocytes expressed sclerostin-IR and the percentage of osteocytes that expressed sclerostin-IR increased from approximately 36% to 48% in 4- vs. 24-month-old mice. In marked contrast, in the same femurs, there were ~40% fewer hypertrophic chondrocytes of articular cartilage that expressed sclerostin-IR when comparing 24- vs. 4-month-old mice. Understanding the mechanism(s) that drive these divergent changes in sclerostin-IR may provide insight into understanding and treating the age-related decline of the skeleton. © 2016 The Histochemical Society.

  14. The structure and function of the pericellular matrix of articular cartilage.

    PubMed

    Wilusz, Rebecca E; Sanchez-Adams, Johannah; Guilak, Farshid

    2014-10-01

    Chondrocytes in articular cartilage are surrounded by a narrow pericellular matrix (PCM) that is both biochemically and biomechanically distinct from the extracellular matrix (ECM) of the tissue. While the PCM was first observed nearly a century ago, its role is still under investigation. In support of early hypotheses regarding its function, increasing evidence indicates that the PCM serves as a transducer of biochemical and biomechanical signals to the chondrocyte. Work over the past two decades has established that the PCM in adult tissue is defined biochemically by several molecular components, including type VI collagen and perlecan. On the other hand, the biomechanical properties of this structure have only recently been measured. Techniques such as micropipette aspiration, in situ imaging, computational modeling, and atomic force microscopy have determined that the PCM exhibits distinct mechanical properties as compared to the ECM, and that these properties are influenced by specific PCM components as well as disease state. Importantly, the unique relationships among the mechanical properties of the chondrocyte, PCM, and ECM in different zones of cartilage suggest that this region significantly influences the stress-strain environment of the chondrocyte. In this review, we discuss recent advances in the measurement of PCM mechanical properties and structure that further increase our understanding of PCM function. Taken together, these studies suggest that the PCM plays a critical role in controlling the mechanical environment and mechanobiology of cells in cartilage and other cartilaginous tissues, such as the meniscus or intervertebral disc. Copyright © 2014 International Society of Matrix Biology. Published by Elsevier B.V. All rights reserved.

  15. The critical size of focal articular cartilage defects is associated with strains in the collagen fibers.

    PubMed

    Heuijerjans, A; Wilson, W; Ito, K; van Donkelaar, C C

    2017-12-01

    The size of full-thickness focal cartilage defect is accepted to be predictive of its fate, but at which size threshold treatment is required is unclear. Clarification of the mechanism behind this threshold effect will help determining when treatment is required. The objective was to investigate the effect of defect size on strains in the collagen fibers and the non-fibrillar matrix of surrounding cartilage. These strains may indicate matrix disruption. Tissue deformation into the defect was expected, stretching adjacent superficial collagen fibers, while an osteochondral implant was expected to prevent these deformations. Finite element simulations of cartilage/cartilage contact for intact, 0.5 to 8mm wide defects and 8mm implant cases were performed. Impact, a load increase to 2MPa in 1ms, and creep loading, a constant load of 0.5MPa for 900s, scenarios were simulated. A composition-based material model for articular cartilage was employed. Impact loading caused low strain levels for all models. Creep loading increased deviatoric strains and collagen strains in the surrounding cartilage. Deviatoric strains increased gradually with defect size, but the surface area at which collagen fiber strains exceeded failure thresholds, abruptly increased for small increases of defect size. This was caused by a narrow distribution of collagen fiber strains resulting from the non-linear stiffness of the fibers. We postulate this might be the mechanism behind the existence of a critical defect size. Filling of the defect with an implant reduced deviatoric and collagen fiber strains towards values for intact cartilage. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. Experimental study on the role of intra-articular injection of MSCs on cartilage regeneration in haemophilia.

    PubMed

    Ravanbod, R; Torkaman, G; Mophid, M; Mohammadali, F

    2015-09-01

    Mesenchymal stem cells (MSCs) therapy is a field in progress in cartilage repair strategies. We tried to investigate the functional properties of the joint and cartilage in experimental haemarthrosis (EH) after MSCs intra-articular (IA) injection. One millilitre of fresh autologous blood was injected twice a week for three consecutive weeks in three groups including control haemophilia 10 days (n = 8), control haemophilia 38 days (n = 8) and MSCs (n = 8) group. In later, 10 days after the end of IA blood injections, MSCs IA injection was performed. Eight animals received no treatment as the normal control group. Thirty-eight days after the end of IA blood injections, animals were sacrificed. Joint friction and stress-relaxation tests were done, inflammatory cytokines of synovial membrane and scanning electron microscopy of the cartilage assessed. Joint friction decreased in MSCs in comparison to other groups and was significant with normal control group, (P = 0.011). The mechanical properties of cartilage showed no significant differences between groups. Tumour necrosis factor alpha and interleukin 1 beta decreased and IL-4 very slightly increased in MSCs in comparison to the time-matched control group. Scanning electron microscopy enabled acquisition of good structural properties of the surface and layers of the cartilage after MSCs injection. The hole induced in the medial plateau of the tibia bones, after inducing haemarthrosis, were covered with cartilage-like structure. The results showed that MSCs IA injection has some beneficial effects on cartilage structure and function in haemarthrosis model and is promising in patients with haemophilia. © 2015 John Wiley & Sons Ltd.

  17. Multiphasic modeling of charged solute transport across articular cartilage: Application of multi-zone finite-bath model.

    PubMed

    Arbabi, Vahid; Pouran, Behdad; Weinans, Harrie; Zadpoor, Amir A

    2016-06-14

    Charged and uncharged solutes penetrate through cartilage to maintain the metabolic function of chondrocytes and to possibly restore or further breakdown the cartilage tissue in different stages of osteoarthritis. In this study the transport of charged solutes across the various zones of cartilage was quantified, taken into account the physicochemical interactions between the solute and the cartilage constituents. A multiphasic finite-bath finite element (FE) model was developed to simulate equine cartilage diffusion experiments that used a negatively charged contrast agent (ioxaglate) in combination with serial micro-computed tomography (micro-CT) to measure the diffusion. By comparing the FE model with the experimental data both the diffusion coefficient of ioxaglate and the fixed charge density (FCD) were obtained. In the multiphasic model, cartilage was divided into multiple (three) zones to help understand how diffusion coefficient and FCD vary across cartilage thickness. The direct effects of charged solute-FCD interaction on diffusion were investigated by comparing the diffusion coefficients derived from the multiphasic and biphasic-solute models. We found a relationship between the FCD obtained by the multiphasic model and ioxaglate partitioning obtained from micro-CT experiments. Using our multi-zone multiphasic model, diffusion coefficient of the superficial zone was up to ten-fold higher than that of the middle zone, while the FCD of the middle zone was up to almost two-fold higher than that of the superficial zone. In conclusion, the developed finite-bath multiphasic model provides us with a non-destructive method by which we could obtain both diffusion coefficient and FCD of different cartilage zones. The outcomes of the current work will also help understand how charge of the bath affects the diffusion of a charged molecule and also predict the diffusion behavior of a charged solute across articular cartilage. Copyright © 2016 Elsevier Ltd. All

  18. Gene Therapy for Cartilage Repair

    PubMed Central

    Madry, Henning; Orth, Patrick; Cucchiarini, Magali

    2011-01-01

    The concept of using gene transfer strategies for cartilage repair originates from the idea of transferring genes encoding therapeutic factors into the repair tissue, resulting in a temporarily and spatially defined delivery of therapeutic molecules to sites of cartilage damage. This review focuses on the potential benefits of using gene therapy approaches for the repair of articular cartilage and meniscal fibrocartilage, including articular cartilage defects resulting from acute trauma, osteochondritis dissecans, osteonecrosis, and osteoarthritis. Possible applications for meniscal repair comprise meniscal lesions, meniscal sutures, and meniscal transplantation. Recent studies in both small and large animal models have demonstrated the applicability of gene-based approaches for cartilage repair. Chondrogenic pathways were stimulated in the repair tissue and in osteoarthritic cartilage using genes for polypeptide growth factors and transcription factors. Although encouraging data have been generated, a successful translation of gene therapy for cartilage repair will require an ongoing combined effort of orthopedic surgeons and of basic scientists. PMID:26069580

  19. Suppression of glycosaminoglycan synthesis by articular cartilage, but not of hyaluronic acid synthesis by synovium, after exposure to radiation

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Hugenberg, S.T.; Myers, S.L.; Brandt, K.D.

    1989-04-01

    We recently found that injection of 2 mCi of yttrium 90 (90Y; approximately 23,000 rads) into normal canine knees stimulated glycosaminoglycan (GAG) synthesis by femoral condylar cartilage. The present investigation was conducted to determine whether radiation affects cartilage metabolism directly. Rates of GAG synthesis and degradation in normal canine articular cartilage were studied following irradiation. Cultured synovium from the same knees was treated similarly, to determine the effects of irradiation on hyaluronic acid synthesis. Twenty-four hours after exposure to 1,000 rads, 10,000 rads, or 50,000 rads, 35S-GAG synthesis by the cartilage was 93%, 69%, and 37%, respectively, of that inmore » control, nonirradiated cartilage. The effect was not rapidly reversible: 120 hours after exposure to 50,000 rads, GAG synthesis remained at only 28% of the control level. Autoradiography showed marked suppression of 35S uptake by chondrocytes after irradiation. Cartilage GAG degradation was also increased following irradiation: 4 hours and 8 hours after exposure to 50,000 rads, the cartilage GAG concentration was only 66% and 54%, respectively, of that at time 0, while corresponding values for control, nonirradiated cartilage were 90% and 87%. In contrast to its effects on cartilage GAG metabolism, radiation at these levels had no effect on synovial hyaluronic acid synthesis.« less

  20. Hypoxia Potentiates Anabolic Effects of Exogenous Hyaluronic Acid in Rat Articular Cartilage

    PubMed Central

    Ichimaru, Shohei; Nakagawa, Shuji; Arai, Yuji; Kishida, Tsunao; Shin-Ya, Masaharu; Honjo, Kuniaki; Tsuchida, Shinji; Inoue, Hiroaki; Fujiwara, Hiroyoshi; Shimomura, Seiji; Mazda, Osam; Kubo, Toshikazu

    2016-01-01

    Hyaluronic acid (HA) is used clinically to treat osteoarthritis (OA), but its pharmacological effects under hypoxic conditions remain unclear. Articular chondrocytes in patients with OA are exposed to a hypoxic environment. This study investigated whether hypoxia could potentiate the anabolic effects of exogenous HA in rat articular cartilage and whether these mechanisms involved HA receptors. HA under hypoxic conditions significantly enhanced the expression of extracellular matrix genes and proteins in explant culture, as shown by real-time reverse transcription-polymerase chain reaction (RT-PCR), Western blotting, and dimethylmethylene blue (DMMB) assays. Staining with Safranin-O and immunohistochemical staining with antibody to type II collagen were also enhanced in pellet culture. The expression of CD44 was increased by hypoxia and significantly suppressed by transfection with siRNAs targeting hypoxia-inducible factor 1 alpha (siHIF-1α). These findings indicate that hypoxia potentiates the anabolic effects of exogenous HA by a mechanism in which HIF-1α positively regulates the expression of CD44, enhancing the binding affinity for exogenous HA. The anabolic effects of exogenous HA may increase as OA progresses. PMID:27347945

  1. Advances in the Surgical Management of Articular Cartilage Defects: Autologous Chondrocyte Implantation Techniques in the Pipeline.

    PubMed

    Stein, Spencer; Strauss, Eric; Bosco, Joseph

    2013-01-01

    The purpose of this review is to gain insight into the latest methods of articular cartilage implantation (ACI) and to detail where they are in the Food and Drug Administration approval and regulatory process. A PubMed search was performed using the phrase "Autologous Chondrocyte Implantation" alone and with the words second generation and third generation. Additionally, clinicaltrials.gov was searched for the names of the seven specific procedures and the parent company websites were referenced. Two-Stage Techniques: BioCart II uses a FGF2v1 culture and a fibrinogen, thrombin matrix, whereas Hyalograft-C uses a Hyaff 11 matrix. MACI uses a collagen I/III matrix. Cartipatch consists of an agarose-alginate hydrogel. Neocart uses a high-pressure bioreactor for culturing with a type I collagen matrix. ChondroCelect makes use of a gene expression analysis to predict chondrocyte proliferation and has demonstrated significant clinical improvement, but failed to show superiority to microfracture in a phase III trial. One Step Technique: CAIS is an ACI procedure where harvested cartilage is minced and implanted into a matrix for defect filling. As full thickness defects in articular cartilage continue to pose a challenge to treat, new methods of repair are being researched. Later generation ACI has been developed to address the prevalence of fibrocartilage with microfracture and the complications associated with the periosteal flap of first generation ACI such as periosteal hypertrophy. The procedures and products reviewed here represent advances in tissue engineering, scaffolds and autologous chondrocyte culturing that may hold promise in our quest to alter the natural history of symptomatic chondral disease.

  2. Diagnostic accuracy of 3.0 Tesla magnetic resonance imaging for the detection of articular cartilage lesions of the talus.

    PubMed

    Gatlin, Coley C; Matheny, Lauren M; Ho, Charles P; Johnson, Nicholas S; Clanton, Thomas O

    2015-03-01

    Talar chondral defects can be a source of persistent ankle pain and disability. If untreated, there is an increased risk of osteoarthritis. The purpose of our study was to determine diagnostic accuracy of 3T MRI in detecting Outerbridge grades 3 and 4 articular cartilage lesions of the talus in a clinical setting, utilizing a standardized clinical MRI protocol. Patients who had a 3T ankle MRI and subsequent ankle surgery, by a single surgeon, were included in this study. MRI exams were performed 180 days or less before surgery. Seventy-nine ankles in 78 patients (mean age of 42.3 years) were included in this study. Mean body mass index was 26.3. A standard clinical MRI exam was performed on a 3T MRI scanner. Mean days from MRI to surgery was 39 days. All MRI exams were read and findings recorded by a musculoskeletal radiologist. Arthroscopic examination was performed by a single orthopaedic surgeon. Detailed arthroscopic findings and demographic data were collected prospectively and stored in a data registry. Of the 78 patients, 31 (39.2%) reported previous ankle surgery. Pain was the primary reason for seeking medical attention as reported by 95% of patients, followed by instability in 44% and loss of function with 42%. Prevalence of Outerbridge grade 3 and 4 talar articular cartilage defects identified at arthroscopy was 17.7%. The 3T MRI demonstrated a sensitivity of 0.714, specificity of 0.738, positive predictive value of 0.370, and negative predictive value of 0.923. Sensitivity and specificity levels were acceptable for detection of grades 3 and 4 articular cartilage defects of the talar dome using 3T MRI. The high negative predictive value may be beneficial in preoperative planning. While these values are acceptable, a high index of suspicion should be maintained in the appropriate clinical setting. © The Author(s) 2014.

  3. Reconstruction of cartilage with clonal mesenchymal stem cell-acellular dermal matrix in cartilage defect model in nonhuman primates.

    PubMed

    Ma, Anlun; Jiang, Li; Song, Lijun; Hu, Yanxin; Dun, Hao; Daloze, Pierre; Yu, Yonglin; Jiang, Jianyuan; Zafarullah, Muhammad; Chen, Huifang

    2013-07-01

    Articular cartilage defects are commonly associated with trauma, inflammation and osteoarthritis. Mesenchymal stem cell (MSC)-based therapy is a promising novel approach for repairing articular cartilage. Direct intra-articular injection of uncommitted MSCs does not regenerate high-quality cartilage. This study explored utilization of a new three-dimensional, selected chondrogenic clonal MSC-loaded monkey acellular dermal matrix (MSC-ADM) scaffold to repair damaged cartilage in an experimental model of knee joint cartilage defect in Cynomolgus monkeys. MSCs were characterized for cell size, cell yield, phenotypes, proliferation and chondrogenic differentiation capacity. Chondrogenic differentiation assays were performed at different MSC passages by sulfated glycosaminoglycans (sGAG), collagen, and fluorescence activated cell sorter (FACS) analysis. Selected chondrogenic clonal MSCs were seeded onto ADM scaffold with the sandwich model and MSC-loaded ADM grafts were analyzed by confocal microscopy and scanning electron microscopy. Cartilage defects were treated with normal saline, clonal MSCs and clonal MSC-ADM grafts, respectively. The clinical parameters, and histological and immunohistochemical examinations were evaluated at weeks 8, 16, 24 post-treatment, respectively. Polyclonal and clonal MSCs could differentiate into the chondrogenic lineage after stimulation with suitable chondrogenic factors. They expressed mesenchymal markers and were negative for hematopoietic markers. Articular cartilage defects were considerably improved and repaired by selected chondrogenic clonal MSC-based treatment, particularly, in MSC-ADM-treated group. The histological scores in MSC-ADM-treated group were consistently higher than those of other groups. Our results suggest that selected chondrogenic clonal MSC-loaded ADM grafts could improve the cartilage lesions in Cynomolgus monkey model, which may be applicable for repairing similar human cartilage defects. Copyright © 2013

  4. Computational Wear Simulation of Patellofemoral Articular Cartilage during In Vitro Testing

    PubMed Central

    Li, Lingmin; Patil, Shantanu; Steklov, Nick; Bae, Won; Temple-Wong, Michele; D'Lima, Darryl D.; Sah, Robert L.; Fregly, Benjamin J.

    2011-01-01

    Though changes in normal joint motions and loads (e.g., following anterior cruciate ligament injury) contribute to the development of knee osteoarthritis, the precise mechanism by which these changes induce osteoarthritis remains unknown. As a first step toward identifying this mechanism, this study evaluates computational wear simulations of a patellofemoral joint specimen wear tested on a knee simulator machine. A multi-body dynamic model of the specimen mounted in the simulator machine was constructed in commercial computer-aided engineering software. A custom elastic foundation contact model was used to calculate contact pressures and wear on the femoral and patellar articular surfaces using geometry created from laser scan and MR data. Two different wear simulation approaches were investigated – one that wore the surface geometries gradually over a sequence of 10 one-cycle dynamic simulations (termed the “progressive” approach), and one that wore the surface geometries abruptly using results from a single one-cycle dynamic simulation (termed the “non-progressive” approach). The progressive approach with laser scan geometry reproduced the experimentally measured wear depths and areas for both the femur and patella. The less costly non-progressive approach predicted deeper wear depths, especially on the patella, but had little influence on predicted wear areas. Use of MR data for creating the articular and subchondral bone geometry altered wear depth and area predictions by at most 13%. These results suggest that MR-derived geometry may be sufficient for simulating articular cartilage wear in vivo and that a progressive simulation approach may be needed for the patella and tibia since both remain in continuous contact with the femur. PMID:21453922

  5. Computational wear simulation of patellofemoral articular cartilage during in vitro testing.

    PubMed

    Li, Lingmin; Patil, Shantanu; Steklov, Nick; Bae, Won; Temple-Wong, Michele; D'Lima, Darryl D; Sah, Robert L; Fregly, Benjamin J

    2011-05-17

    Though changes in normal joint motions and loads (e.g., following anterior cruciate ligament injury) contribute to the development of knee osteoarthritis, the precise mechanism by which these changes induce osteoarthritis remains unknown. As a first step toward identifying this mechanism, this study evaluates computational wear simulations of a patellofemoral joint specimen wear tested on a knee simulator machine. A multibody dynamic model of the specimen mounted in the simulator machine was constructed in commercial computer-aided engineering software. A custom elastic foundation contact model was used to calculate contact pressures and wear on the femoral and patellar articular surfaces using geometry created from laser scan and MR data. Two different wear simulation approaches were investigated--one that wore the surface geometries gradually over a sequence of 10 one-cycle dynamic simulations (termed the "progressive" approach), and one that wore the surface geometries abruptly using results from a single one-cycle dynamic simulation (termed the "non-progressive" approach). The progressive approach with laser scan geometry reproduced the experimentally measured wear depths and areas for both the femur and patella. The less costly non-progressive approach predicted deeper wear depths, especially on the patella, but had little influence on predicted wear areas. Use of MR data for creating the articular and subchondral bone geometry altered wear depth and area predictions by at most 13%. These results suggest that MR-derived geometry may be sufficient for simulating articular cartilage wear in vivo and that a progressive simulation approach may be needed for the patella and tibia since both remain in continuous contact with the femur. Copyright © 2011 Elsevier Ltd. All rights reserved.

  6. Time-dependent changes in gene expression induced in vitro by interleukin-1β in equine articular cartilage.

    PubMed

    Löfgren, Maria; Svala, Emilia; Lindahl, Anders; Skiöldebrand, Eva; Ekman, Stina

    2018-05-01

    Osteoarthritis is an inflammatory and degenerative joint disease commonly affecting horses. To identify genes of relevance for cartilage pathology in osteoarthritis we studied the time-course effects of interleukin (IL)-1β on equine articular cartilage. Articular cartilage explants from the distal third metacarpal bone were collected postmortem from three horses without evidence of joint disease. The explants were stimulated with IL-1β for 27 days and global gene expression was measured by microarray. Gene expression was compared to that of unstimulated explants at days 3, 9, 15, 21 and 27. Release of inflammatory proteins was measured using Proximity Extension Assay. Stimulation with IL-1β led to time-dependent changes in gene expression related to inflammation, the extracellular matrix (ECM), and phenotypic alterations. Gene expression and protein release of cytokines, chemokines, and matrix-degrading enzymes increased in the stimulated explants. Collagen type II was downregulated from day 15, whereas other ECM molecules were downregulated earlier. In contrast molecules involved in ECM signaling (perlecan, chondroitin sulfate proteoglycan 4, and syndecan 4) were upregulated. At the late time points, genes related to a chondrogenic phenotype were downregulated, and genes related to a hypertrophic phenotype were upregulated, suggesting a transition towards hypertrophy later in the culturing period. The data suggest that this in vitro model mimics time course events of in vivo inflammation in OA and it may be valuable as an in vitro tool to test treatments and to study disease mechanisms. Copyright © 2018 Elsevier Ltd. All rights reserved.

  7. Effect of intra-articular administration of superparamagnetic iron oxide nanoparticles (SPIONs) for MRI assessment of the cartilage barrier in a large animal model

    PubMed Central

    Hall, Sarah; Xia, Xin-Rui; Schwarz, Tobias

    2017-01-01

    Early diagnosis of cartilage disease at a time when changes are limited to depletion of extracellular matrix components represents an important diagnostic target to reduce patient morbidity. This report is to present proof of concept for nanoparticle dependent cartilage barrier imaging in a large animal model including the use of clinical magnetic resonance imaging (MRI). Conditioned (following matrix depletion) and unconditioned porcine metacarpophalangeal cartilage was evaluated on the basis of fluorophore conjugated 30 nm and 80 nm spherical gold nanoparticle permeation and multiphoton laser scanning and bright field microscopy after autometallographic particle enhancement. Consequently, conditioned and unconditioned joints underwent MRI pre- and post-injection with 12 nm superparamagnetic iron oxide nanoparticles (SPIONs) to evaluate particle permeation in the context of matrix depletion and use of a clinical 1.5 Tesla MRI scanner. To gauge the potential pro-inflammatory effect of intra-articular nanoparticle delivery co-cultures of equine synovium and cartilage tissue were exposed to an escalating dose of SPIONs and IL-6, IL-10, IFN-γ and PGE2 were assessed in culture media. The chemotactic potential of growth media samples was subsequently assessed in transwell migration assays on isolated equine neutrophils. Results demonstrate an increase in MRI signal following conditioning of porcine joints which suggests that nanoparticle dependent compositional cartilage imaging is feasible. Tissue culture and neutrophil migration assays highlight a dose dependent inflammatory response following SPION exposure which at the imaging dose investigated was not different from controls. The preliminary safety and imaging data support the continued investigation of nanoparticle dependent compositional cartilage imaging. To our knowledge, this is the first report in using SPIONs as intra-articular MRI contrast agent for studying cartilage barrier function, which could

  8. A phenotypic comparison of intervertebral disc and articular cartilage cells in the rat

    PubMed Central

    Lee, Cynthia R.; Sakai, Daisuke; Nakai, Tomoko; Toyama, Kanae; Mochida, Joji; Alini, Mauro

    2007-01-01

    The basic molecular characteristics of intervertebral disc cells are still poorly defined. This study compared the phenotypes of nucleus pulposus (NP), annulus fibrosus (AF) and articular cartilage (AC) cells using rat coccygeal discs and AC from both young and aged animals and a combination of microarray, real-time RT-PCR and immunohistochemistry. Microarray analysis identified 63 genes with at least a fivefold difference in fluorescence intensity between the NP and AF cells and 41 genes with a fivefold or greater difference comparing NP cells and articular chondrocytes. In young rats, the relative mRNA levels, assessed by real-time RT-PCR, of annexin A3, glypican 3 (gpc3), keratin 19 (k19) and pleiotrophin (ptn) were significantly higher in NP compared to AF and AC samples. Furthermore, vimentin (vim) mRNA was higher in NP versus AC, and expression levels of cartilage oligomeric matrix protein (comp) and matrix gla protein (mgp) were lower in NP versus AC. Higher NP levels of comp and mgp mRNA and higher AF levels of gpc3, k19, mgp and ptn mRNA were found in aged compared to young tissue. However, the large differences between NP and AC expression of gpc3 and k19 were obvious even in the aged animals. Furthermore, the differences in expression levels of gpc3 and k19 were also evident at the protein level, with intense immunostaining for both proteins in NP and non-existent immunoreaction in AF and AC. Future studies using different species are required to evaluate whether the expression of these molecules can be used to characterize NP cells and distinguish them from other chondrocyte-like cells. PMID:17786487

  9. In vivo comparison of delayed gadolinium-enhanced MRI of cartilage and delayed quantitative CT arthrography in imaging of articular cartilage.

    PubMed

    Hirvasniemi, J; Kulmala, K A M; Lammentausta, E; Ojala, R; Lehenkari, P; Kamel, A; Jurvelin, J S; Töyräs, J; Nieminen, M T; Saarakkala, S

    2013-03-01

    To compare delayed gadolinium-enhanced magnetic resonance imaging (MRI) of cartilage (dGEMRIC) and delayed quantitative computed tomography (CT) arthrography (dQCTA) to each other, and their association to arthroscopy. Additionally, the relationship between dGEMRIC with intravenous (dGEMRIC(IV)) and intra-articular contrast agent administration (dGEMRIC(IA)) was determined. Eleven patients with knee pain were scanned at 3 T MRI and 64-slice CT before arthroscopy. dQCTA was performed at 5 and 45 min after intra-articular injection of ioxaglate. Both dGEMRIC(IV) and dGEMRIC(IA) were performed at 90 min after gadopentetate injection. dGEMRIC indices and change in relaxation rates (ΔR(1)) were separately calculated for dGEMRIC(IV) and dGEMRIC(IA). dGEMRIC and dQCTA parameters were calculated for predetermined sites at the knee joint that were International Cartilage Repair Society (ICRS) graded in arthroscopy. dQCTA normalized with the contrast agent concentration in synovial fluid (SF) and dGEMRIC(IV) correlated significantly, whereas dGEMRIC(IA) correlated with the normalized dQCTA only when dGEMRIC(IA) was also normalized with the contrast agent concentration in SF. Correlation was strongest between normalized dQCTA at 45 min and ΔR(1,IV) (r(s) = 0.72 [95% CI 0.56-0.83], n = 49, P < 0.01) and ΔR(1,IA) normalized with ΔR(1) in SF (r(s) = 0.70 [0.53-0.82], n = 52, P < 0.01). Neither dGEMRIC nor dQCTA correlated with arthroscopic grading. dGEMRIC(IV) and non-normalized dGEMRIC(IA) were not related while ΔR(1,IV) correlated with normalized ΔR(1,IA) (r(s) = 0.52 [0.28-0.70], n = 50, P < 0.01). This study suggests that dQCTA is in best agreement with dGEMRIC(IV) at 45 min after CT contrast agent injection. dQCTA and dGEMRIC were not related to arthroscopy, probably because the remaining cartilage is analysed in dGEMRIC and dQCTA, whereas in arthroscopy the absence of cartilage defines the grading. The findings indicate the importance to take

  10. Development of a cellularly degradable PEG hydrogel to promote articular cartilage extracellular matrix deposition.

    PubMed

    Sridhar, Balaji V; Brock, John L; Silver, Jason S; Leight, Jennifer L; Randolph, Mark A; Anseth, Kristi S

    2015-04-02

    Healing articular cartilage remains a significant clinical challenge because of its limited self-healing capacity. While delivery of autologous chondrocytes to cartilage defects has received growing interest, combining cell-based therapies with scaffolds that capture aspects of native tissue and promote cell-mediated remodeling could improve outcomes. Currently, scaffold-based therapies with encapsulated chondrocytes permit matrix production; however, resorption of the scaffold does not match the rate of production by cells leading to generally low extracellular matrix outputs. Here, a poly (ethylene glycol) (PEG) norbornene hydrogel is functionalized with thiolated transforming growth factor (TGF-β1) and cross-linked by an MMP-degradable peptide. Chondrocytes are co-encapsulated with a smaller population of mesenchymal stem cells, with the goal of stimulating matrix production and increasing bulk mechanical properties of the scaffold. The co-encapsulated cells cleave the MMP-degradable target sequence more readily than either cell population alone. Relative to non-degradable gels, cellularly degraded materials show significantly increased glycosaminoglycan and collagen deposition over just 14 d of culture, while maintaining high levels of viability and producing a more widely-distributed matrix. These results indicate the potential of an enzymatically degradable, peptide-functionalized PEG hydrogel to locally influence and promote cartilage matrix production over a short period. Scaffolds that permit cell-mediated remodeling may be useful in designing treatment options for cartilage tissue engineering applications. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  11. Mesenchymal stem cell-based repair of articular cartilage with polyglycolic acid-hydroxyapatite biphasic scaffold.

    PubMed

    Zhou, X Z; Leung, V Y; Dong, Q R; Cheung, K M; Chan, D; Lu, W W

    2008-06-01

    This study investigates the capacity of a composite scaffold composed of polyglycolic acid-hydroxyapatite (PGA-HA) and autologous mesenchymal stem cells (MSCs) to promote repair of osteochondral defects. MSCs from culture-expanded rabbits were seeded onto a PGA and HA scaffold. After a 72-hour co-culture period, the cell-adhered PGA and HA were joined together, forming an MSCs-PGA-HA composite. Full-thickness cartilage defects in the intercondylar fossa of the femur were then implanted with the MSC-PGA-HA composite, the PGA-HA scaffold only, or they were left empty (n=20). Animals were sacrificed 16 or 32 weeks after surgery and the gross appearance of the defects was evaluated. The specimens were examined histologically for morphologic features, and stained immunohistochemically for type 2 collagen. Specimens of the MSCs-PGA-HA composite implantation group demonstrated hyaline cartilage and a complete subchondral bone formation. At 16 weeks post-implantation, significant integration of the newly formed tissue with surrounding normal cartilage and subchondral bone was observed when compared to the two control groups. At 32 weeks, no sign of progressive degeneration of the newly formed tissue was found. A significant difference in histological grading score was found compared with the control groups. The novel MSCs-seeded, PGA-HA biphasic graft facilitated both articular cartilage and subchondral bone regeneration in an animal model and might serve as a new approach for clinical applications.

  12. Biologic injections for osteoarthritis and articular cartilage damage: can we modify disease?

    PubMed

    Shi, Weilong J; Tjoumakaris, Fotios P; Lendner, Mayan; Freedman, Kevin B

    2017-09-01

    The purpose of the present investigation is to conduct a systematic review of the literature to review the clinical results of platelet rich plasma (PRP) and mesenchymal stem cell treatments (MSC) (biologics) for articular cartilage lesions and osteoarthritis of the knee. A search of the PubMed, EMBASE, and Cochrane databases was performed to identify studies involving biologic therapy for osteoarthritis or osteochondral defects. Only Level I-III clinical trials with at least 3-month follow-up were included. Outcome data was gathered on any patient-completed surveys, 2nd look arthroscopy, follow-up imaging, biopsy/histology results, and any adverse effects of treatment. Thirty-three articles met our inclusion criteria. There was a total of 21 PRP studies in the study. All PRP studies showed clinical improvement with PRP therapies in outcomes surveys measuring patient satisfaction, pain, and function. Two studies reported no significant difference in improvement compared to hyaluronic acid (HA). Similarly, the 7/9 MSC studies showed improvement. One study found BM-MSC implantation was not significantly superior to matrix assisted chondrocyte implantation (MACI), while one reported peripheral blood stem cells (PBSC) did not significantly improve outcomes over HA. Of the three studies looking at a combination of MSC/PRP, two found MSC/PRP combination did not improve outcomes compared to MSC or PRP therapy alone. The one PRP study that had a 2nd look arthroscopy reported increases cartilage regeneration with PRP. All 8 MSC studies with follow-up MRI and all 7 MSC studies with 2nd look arthroscopy showed improvement in cartilage regeneration in terms of coverage, fill of the defect, and/or firmness of the new cartilage. Current data suggests that, of the two treatments, MSC provides more significant disease modifying effect; however, further research needs to be done to compare these two treatments and determine if there is a synergetic effect when combined.

  13. Effects of refrigeration and freezing on the electromechanical and biomechanical properties of articular cartilage.

    PubMed

    Changoor, Adele; Fereydoonzad, Liah; Yaroshinsky, Alex; Buschmann, Michael D

    2010-06-01

    In vitro electromechanical and biomechanical testing of articular cartilage provide critical information about the structure and function of this tissue. Difficulties obtaining fresh tissue and lengthy experimental testing procedures often necessitate a storage protocol, which may adversely affect the functional properties of cartilage. The effects of storage at either 4°C for periods of 6 days and 12 days, or during a single freeze-thaw cycle at -20°C were examined in young bovine cartilage. Non-destructive electromechanical measurements and unconfined compression testing on 3 mm diameter disks were used to assess cartilage properties, including the streaming potential integral (SPI), fibril modulus (Ef), matrix modulus (Em), and permeability (k). Cartilage disks were also examined histologically. Compared with controls, significant decreases in SPI (to 32.3±5.5% of control values, p<0.001), Ef (to 31.3±41.3% [corrected] of control values, p=0.046), Em (to 6.4±8.5% of control values, p<0.0001), and an increase in k (to 2676.7±2562.0% of control values, p=0.004) were observed at day 12 of refrigeration at 4°C, but no significant changes were detected at day 6. A trend toward detecting a decrease in SPI (to 94.2±6.2% of control values, p=0.083) was identified following a single freeze-thaw cycle, but no detectable changes were observed for any biomechanical parameters. All numbers are mean±95% confidence interval. These results indicate that fresh cartilage can be stored in a humid chamber at 4°C for a maximum of 6 days with no detrimental effects to cartilage electromechanical and biomechanical properties, while one freeze-thaw cycle produces minimal deterioration of biomechanical and electromechanical properties. A comparison to literature suggested that particular attention should be paid to the manner in which specimens are thawed after freezing, specifically by minimizing thawing time at higher temperatures.

  14. High throughput proteomic analysis of the secretome in an explant model of articular cartilage inflammation

    PubMed Central

    Clutterbuck, Abigail L.; Smith, Julia R.; Allaway, David; Harris, Pat; Liddell, Susan; Mobasheri, Ali

    2011-01-01

    This study employed a targeted high-throughput proteomic approach to identify the major proteins present in the secretome of articular cartilage. Explants from equine metacarpophalangeal joints were incubated alone or with interleukin-1beta (IL-1β, 10 ng/ml), with or without carprofen, a non-steroidal anti-inflammatory drug, for six days. After tryptic digestion of culture medium supernatants, resulting peptides were separated by HPLC and detected in a Bruker amaZon ion trap instrument. The five most abundant peptides in each MS scan were fragmented and the fragmentation patterns compared to mammalian entries in the Swiss-Prot database, using the Mascot search engine. Tryptic peptides originating from aggrecan core protein, cartilage oligomeric matrix protein (COMP), fibronectin, fibromodulin, thrombospondin-1 (TSP-1), clusterin (CLU), cartilage intermediate layer protein-1 (CILP-1), chondroadherin (CHAD) and matrix metalloproteinases MMP-1 and MMP-3 were detected. Quantitative western blotting confirmed the presence of CILP-1, CLU, MMP-1, MMP-3 and TSP-1. Treatment with IL-1β increased MMP-1, MMP-3 and TSP-1 and decreased the CLU precursor but did not affect CILP-1 and CLU levels. Many of the proteins identified have well-established extracellular matrix functions and are involved in early repair/stress responses in cartilage. This high throughput approach may be used to study the changes that occur in the early stages of osteoarthritis. PMID:21354348

  15. Carnosic acid attenuates cartilage degeneration through induction of heme oxygenase-1 in human articular chondrocytes.

    PubMed

    Ishitobi, Hiroyuki; Sanada, Yohei; Kato, Yoshio; Ikuta, Yasunari; Shibata, Sachi; Yamasaki, Satoshi; Lotz, Martin K; Matsubara, Kiminori; Miyaki, Shigeru; Adachi, Nobuo

    2018-04-17

    Osteoarthritis (OA) is common age-associated disease, and associated with joint pain, mobility limitations and compromised overall quality of life. OA treatment is currently limited to pain management and joint arthroplasty at end stage disease. Oxidative damage to cartilage extracellular matrix and cells is an important mechanism in joint aging and OA pathogenesis. Evidence from in vitro and in vivo models of OA suggests that pharmaceuticals and natural compounds with antioxidant properties reduce expression of mediators of OA pathogenesis and OA severity in animal models. Among the signaling pathways that control cellular protective mechanisms against oxygen radical damage is heme oxygenase-1 (HO-1). We recently report HO-1 reduced OA severity in a mouse model. This led to the hypothesis that compounds that increase HO-1 expression have therapeutic potential in OA. Carnosic acid (CA), a natural diterpene with oxidant activity, is prevents cartilage degeneration though induction of HO-1. CA induced HO-1 and miR-140 expression in human articular chondrocytes, and cartilage degeneration was attenuated by CA treatment. Induced HO-1 by CA was in part associated with downregulation via miR-140 binding to 3'UTR of BTB and CNC homology 1 (BACH1). These findings suggest that CA attenuates cartilage degradation through HO-1 upregulation and has potential as a supplement for OA prevention. Copyright © 2018 Elsevier B.V. All rights reserved.

  16. [Technique and value of direct MR arthrography applying articular distraction].

    PubMed

    Becce, Fabio; Wettstein, Michael; Guntern, Daniel; Mouhsine, Elyazid; Palhais, Nuno; Theumann, Nicolas

    2010-02-24

    Direct MR arthrography has a better diagnostic accuracy than MR imaging alone. However, contrast material is not always homogeneously distributed in the articular space. Lesions of cartilage surfaces or intra-articular soft tissues can thus be misdiagnosed. Concomitant application of axial traction during MR arthrography leads to articular distraction. This enables better distribution of contrast material in the joint and better delineation of intra-articular structures. Therefore, this technique improves detection of cartilage lesions. Moreover, the axial stress applied on articular structures may reveal lesions invisible on MR images without traction. Based on our clinical experience, we believe that this relatively unknown technique is promising and should be further developed.

  17. Inhibition of integrative cartilage repair by proteoglycan 4 in synovial fluid.

    PubMed

    Englert, Carsten; McGowan, Kevin B; Klein, Travis J; Giurea, Alexander; Schumacher, Barbara L; Sah, Robert L

    2005-04-01

    To determine the effects of the articular cartilage surface, as well as synovial fluid (SF) and its components, specifically proteoglycan 4 (PRG4) and hyaluronic acid (HA), on integrative cartilage repair in vitro. Blocks of calf articular cartilage were harvested, some with the articular surface intact and others without. Some of the latter types of blocks were pretreated with trypsin, and then with bovine serum albumin, SF, PRG4, or HA. Immunolocalization of PRG4 on cartilage surfaces was performed after treatment. Pairs of similarly treated cartilage blocks were incubated in partial apposition for 2 weeks in medium supplemented with serum and (3)H-proline. Following culture, mechanical integration between apposed cartilage blocks was assessed by measuring adhesive strength, and protein biosynthesis and deposition were determined by incorporated (3)H-proline. Samples with articular surfaces in apposition exhibited little integrative repair compared with samples with cut surfaces in apposition. PRG4 was immunolocalized at the articular cartilage surface, but not in deeper, cut surfaces (without treatment). Cartilage samples treated with trypsin and then with SF or PRG4 exhibited an inhibition of integrative repair and positive immunostaining for PRG4 at treated surfaces compared with normal cut cartilage samples, while samples treated with HA exhibited neither inhibited integrative repair nor PRG4 at the tissue surfaces. Deposition of newly synthesized protein was relatively similar under conditions in which integration differed significantly. These results support the concept that PRG4 in SF, which normally contributes to cartilage lubrication, can inhibit integrative cartilage repair. This has the desirable effect of preventing fusion of apposing surfaces of articulating cartilage, but has the undesirable effect of inhibiting integrative repair.

  18. Effect of open wedge high tibial osteotomy on the lateral tibiofemoral compartment in sheep. Part III: analysis of the microstructure of the subchondral bone and correlations with the articular cartilage and meniscus.

    PubMed

    Ziegler, Raphaela; Goebel, Lars; Seidel, Roland; Cucchiarini, Magali; Pape, Dietrich; Madry, Henning

    2015-09-01

    First, to evaluate whether medial open wedge high tibial osteotomy (HTO) induces alterations of the microstructure of the lateral tibial subchondral bone plate of sheep. Second, to test the hypothesis that specific correlations exist between topographical structural alterations of the subchondral bone, the cartilage and the lateral meniscus. Three experimental groups received biplanar osteotomies of the right proximal tibiae: (a) closing wedge HTO (4.5° of tibial varus), (b) opening wedge HTO (4.5° tibial valgus; standard correction) and (c) opening wedge HTO (9.5° of valgus; overcorrection), each of which was compared to the non-osteotomised contralateral proximal tibiae. After 6 months, subchondral bone structure indices were measured by computed tomography. Correlations between the subchondral bone, the articular cartilage and the lateral meniscus were determined. Increased loading by valgus overcorrection led to an enlarged specific bone surface (BS/BV) in the subarticular spongiosa compared with unloading by varisation. The subchondral bone plate was 3.9-fold thicker in the central region of the lateral tibial plateau than in the submeniscal periphery. Its thickness in the central region significantly correlated with the thickness of the articular cartilage. In the submeniscal region, such correlation did not exist. In general, a higher degree of osteoarthritis (OA) correlated with alterations of the subchondral bone plate microstructure. OA of the submeniscal articular cartilage also correlated with worse matrix staining of the lateral meniscus. Osteoarthritis changes are associated with alterations of the subchondral bone plate microstructure. Specific topographical relationships exist in the central region between the articular cartilage and subchondral bone plate thickness, and in the submeniscal periphery between and the articular cartilage and lateral meniscus. From a clinical perspective, the combined follow-up data from this and the previous two

  19. Direct hip joint distraction during acetabular fracture surgery using the AO universal manipulator.

    PubMed

    Calafi, L Afshin; Routt, M L Chip

    2010-02-01

    Certain acetabular fractures may necessitate distraction of the hip joint for removal of intra-articular debris and assessment of reduction. Distraction can be accomplished by manual traction, using a traction table or an AO universal manipulator (UM). The UM is a relatively simple and an inexpensive device that can provide focal distraction in a controlled manner without the risks associated with the use of a traction table. We describe a technique using the UM for hip joint distraction during acetabular fracture surgery through a Kocher-Langenbeck surgical exposure.

  20. Articular Cartilage of the Human Knee Joint: In Vivo Multicomponent T2 Analysis at 3.0 T

    PubMed Central

    Choi, Kwang Won; Samsonov, Alexey; Spencer, Richard G.; Wilson, John J.; Block, Walter F.; Kijowski, Richard

    2015-01-01

    Purpose To compare multicomponent T2 parameters of the articular cartilage of the knee joint measured by using multicomponent driven equilibrium single-shot observation of T1 and T2 (mcDESPOT) in asymptomatic volunteers and patients with osteoarthritis. Materials and Methods This prospective study was performed with institutional review board approval and with written informed consent from all subjects. The mcDESPOT sequence was performed in the knee joint of 13 asymptomatic volunteers and 14 patients with osteoarthritis of the knee. Single-component T2 (T2Single), T2 of the fast-relaxing water component (T2F) and of the slow-relaxing water component (T2S), and the fraction of the fast-relaxing water component (FF) of cartilage were measured. Wilcoxon rank-sum tests and multivariate linear regression models were used to compare mcDESPOT parameters between volunteers and patients with osteoarthritis. Receiver operating characteristic analysis was used to assess diagnostic performance with mcDESPOT parameters for distinguishing morphologically normal cartilage from morphologically degenerative cartilage identified at magnetic resonance imaging in eight cartilage subsections of the knee joint. Results Higher cartilage T2Single (P < .001), lower cartilage FF (P < .001), and similar cartilage T2F (P = .079) and T2S (P = .124) values were seen in patients with osteoarthritis compared with those in asymptomatic volunteers. Differences in T2Single and FF remained significant (P < .05) after consideration of age differences between groups of subjects. Diagnostic performance was higher with FF than with T2Single for distinguishing between normal and degenerative cartilage (P < .05), with greater areas under the curve at receiver operating characteristic analysis. Conclusion Patients with osteoarthritis of the knee had significantly higher cartilage T2Single and significantly lower cartilage FF than did asymptomatic volunteers, and receiver operating characteristic analysis

  1. Application of a Three-Dimensional Poroelastic BEM to Modeling the Biphasic Mechanics of Cell-Matrix Interactions in Articular Cartilage (REVISION)

    PubMed Central

    Haider, Mansoor A.; Guilak, Farshid

    2009-01-01

    Articular cartilage exhibits viscoelasticity in response to mechanical loading that is well described using biphasic or poroelastic continuum models. To date, boundary element methods (BEMs) have not been employed in modeling biphasic tissue mechanics. A three dimensional direct poroelastic BEM, formulated in the Laplace transform domain, is applied to modeling stress relaxation in cartilage. Macroscopic stress relaxation of a poroelastic cylinder in uni-axial confined compression is simulated and validated against a theoretical solution. Microscopic cell deformation due to poroelastic stress relaxation is also modeled. An extended Laplace inversion method is employed to accurately represent mechanical responses in the time domain. PMID:19851478

  2. Application of a Three-Dimensional Poroelastic BEM to Modeling the Biphasic Mechanics of Cell-Matrix Interactions in Articular Cartilage (REVISION).

    PubMed

    Haider, Mansoor A; Guilak, Farshid

    2007-06-15

    Articular cartilage exhibits viscoelasticity in response to mechanical loading that is well described using biphasic or poroelastic continuum models. To date, boundary element methods (BEMs) have not been employed in modeling biphasic tissue mechanics. A three dimensional direct poroelastic BEM, formulated in the Laplace transform domain, is applied to modeling stress relaxation in cartilage. Macroscopic stress relaxation of a poroelastic cylinder in uni-axial confined compression is simulated and validated against a theoretical solution. Microscopic cell deformation due to poroelastic stress relaxation is also modeled. An extended Laplace inversion method is employed to accurately represent mechanical responses in the time domain.

  3. Comparison of 1.5- and 3-T MR imaging for evaluating the articular cartilage of the knee.

    PubMed

    Van Dyck, Pieter; Kenis, Christoph; Vanhoenacker, Filip M; Lambrecht, Valérie; Wouters, Kristien; Gielen, Jan L; Dossche, Lieven; Parizel, Paul M

    2014-06-01

    The aim of this prospective study was to compare routine MRI scans of the knee at 1.5 and 3 T obtained in the same individuals in terms of their performance in the diagnosis of cartilage lesions. One hundred patients underwent MRI of the knee at 1.5 and 3 T and subsequent knee arthroscopy. All MR examinations consisted of multiplanar 2D turbo spin-echo sequences. Three radiologists independently graded all articular surfaces of the knee joint seen at MRI. With arthroscopy as the reference standard, the sensitivity, specificity, and accuracy of 1.5- and 3-T MRI for detecting cartilage lesions and the proportion of correctly graded cartilage lesions within the knee joint were determined and compared using resampling statistics. For all readers and surfaces combined, the respective sensitivity, specificity, and accuracy for detecting all grades of cartilage lesions in the knee joint using MRI were 60, 96, and 87% at 1.5 T and 69, 96, and 90% at 3 T. There was a statistically significant improvement in sensitivity (p < 0.05), but not specificity or accuracy (n.s.) for the detection of cartilage lesions at 3 T. There was also a statistically significant (p < 0.05) improvement in the proportion of correctly graded cartilage lesions at 3 T as compared to 1.5 T. A 3-T MR protocol significantly improves diagnostic performance for the purpose of detecting cartilage lesions within the knee joint, when compared with a similar protocol performed at 1.5 T. III.

  4. Subwavelength hyperspectral THz studies of articular cartilage.

    PubMed

    Stantchev, Rayko I; Mansfield, Jessica C; Edginton, Ryan S; Hobson, Peter; Palombo, Francesca; Hendry, Euan

    2018-05-02

    Terahertz-spectroscopy probes dynamics and spectral response of collective vibrational modes in condensed phase, which can yield insight into composition and topology. However, due to the long wavelengths employed (λ = 300 μm at 1THz), diffraction limited imaging is typically restricted to spatial resolutions around a millimeter. Here, we demonstrate a new form of subwavelength hyperspectral, polarization-resolved THz imaging which employs an optical pattern projected onto a 6 μm-thin silicon wafer to achieve near-field modulation of a co-incident THz pulse. By placing near-field scatterers, one can measure the interaction of object with the evanescent THz fields. Further, by measuring the temporal evolution of the THz field a sample's permittivity can be extracted with 65 μm spatial resolution due to the presence of evanescent fields. Here, we present the first application of this new approach to articular cartilage. We show that the THz permittivity in this material varies progressively from the superficial zone to the deep layer, and that this correlates with a change in orientation of the collagen fibrils that compose the extracellular matrix (ECM) of the tissue. Our approach enables direct interrogation of the sample's biophysical properties, in this case concerning the structure and permittivity of collagen fibrils and their anisotropic organisation in connective tissue.

  5. Gene Expression in Human Meniscal Tears has Limited Association with Early Degenerative Changes in Knee Articular Cartilage

    PubMed Central

    Brophy, Robert H.; Sandell, Linda J.; Cheverud, James M.; Rai, Muhammad Farooq

    2018-01-01

    Purpose/Aim Meniscus tears are a common injury to the knee associated with the development of osteoarthritis. Gene expression in the injured meniscus may be associated with early degeneration in the articular cartilage. The purpose of this study was to test the hypothesis that gene expression in meniscus tears is associated with early degenerative changes in the articular cartilage at the time of partial meniscectomy. Materials and Methods Torn meniscus was removed at the time of partial meniscectomy in 63 patients without radiographic osteoarthritis. Meniscal mRNA expression was measured by quantitative PCR for multiple molecular markers of osteoarthritis and cartilage homeostasis. The presence of early degenerative changes in the knee was recorded by X-ray (N=63), magnetic resonance imaging (MRI, N=48) and arthroscopy (N=63). Gene expression was tested for correlation with the presence/absence of degenerative changes after adjusting for age, sex and body mass index. Results Overall gene expression varied significantly with degenerative changes based on X-ray (P=0.047) and MRI (P=0.018). The linear combination of gene variation was also significant. However, only adiponectin (ADIPOQ) (P=0.015) was expressed at a significantly lower level in patients with chondrosis on MRI while the expression of ADIPOQ (P=0.035) and resistin (RETN) (P=0.017) was higher in patients with early degenerative changes on X-ray. Conclusions There is an overall association of gene expression in meniscal tears to early degenerative changes in the knee, but only a limited number of specific genes demonstrate this relationship. The roles of adiponectin and resistin in knee injury and osteoarthritis deserve further study. PMID:27435997

  6. Nonlinear mechanical response of the extracellular matrix: learning from articular cartilage

    NASA Astrophysics Data System (ADS)

    Kearns, Sarah; Das, Moumita

    2015-03-01

    We study the mechanical structure-function relations in the extracellular matrix (ECM) with focus on nonlinear shear and compression response. As a model system, our study focuses on the ECM in articular cartilage tissue which has two major mechanobiological components: a network of the biopolymer collagen that acts as a stiff, reinforcing matrix, and a flexible aggrecan network that facilitates deformability. We model this system as a double network hydrogel made of interpenetrating networks of stiff and flexible biopolymers respectively. We study the linear and nonlinear mechanical response of the model ECM to shear and compression forces using a combination of rigidity percolation theory and energy minimization approaches. Our results may provide useful insights into the design principles of the ECM as well as biomimetic hydrogels that are mechanically robust and can, at the same time, easily adapt to cues in their surroundings.

  7. Accessing 3D Location of Standing Pelvis: Relative Position of Sacral Plateau and Acetabular Cavities versus Pelvis

    PubMed Central

    Berthonnaud, E.; Hilmi, R.; Dimnet, J.

    2012-01-01

    The goal of this paper is to access to pelvis position and morphology in standing posture and to determine the relative locations of their articular surfaces. This is obtained from coupling biplanar radiography and bone modeling. The technique involves different successive steps. Punctual landmarks are first reconstructed, in space, from their projected images, identified on two orthogonal standing X-rays. Geometric models, of global pelvis and articular surfaces, are determined from punctual landmarks. The global pelvis is represented as a triangle of summits: the two femoral head centers and the sacral plateau center. The two acetabular cavities are modeled as hemispheres. The anterior sacral plateau edge is represented by an hemi-ellipsis. The modeled articular surfaces are projected on each X-ray. Their optimal location is obtained when the projected contours of their models best fit real outlines identified from landmark images. Linear and angular parameters characterizing the position of global pelvis and articular surfaces are calculated from the corresponding sets of axis. Relative positions of sacral plateau, and acetabular cavities, are then calculated. Two hundred standing pelvis, of subjects and scoliotic patients, have been studied. Examples are presented. They focus upon pelvis orientations, relative positions of articular surfaces, and pelvis asymmetries. PMID:22567279

  8. Up-regulated expression of cartilage intermediate-layer protein and ANK in articular hyaline cartilage from patients with calcium pyrophosphate dihydrate crystal deposition disease.

    PubMed

    Hirose, Jun; Ryan, Lawrence M; Masuda, Ikuko

    2002-12-01

    Excess accumulation of extracellular inorganic pyrophosphate (ePPi) in aged human cartilage is crucial in calcium pyrophosphate dihydrate (CPPD) crystal formation in cartilage matrix. Two sources of ePPi are ePPi-generating ectoenzymes (NTPPPH) and extracellular transport of intracellular PPi by ANK. This study was undertaken to evaluate the role of NTPPPH and ANK in ePPi elaboration, by investigating expression of NTPPPH enzymes (cartilage intermediate-layer protein [CILP] and plasma cell membrane glycoprotein 1 [PC-1]) and ANK in human chondrocytes from osteoarthritic (OA) articular cartilage containing CPPD crystals and without crystals. Chondrocytes were harvested from knee cartilage at the time of arthroplasty (OA with CPPD crystals [CPPD], n = 8; OA without crystals [OA], n = 10). Normal adult human chondrocytes (n = 1) were used as a control. Chondrocytes were cultured with transforming growth factor beta1 (TGFbeta1), which stimulates ePPi elaboration, and/or insulin-like growth factor 1 (IGF-1), which inhibits ePPi elaboration. NTPPPH and ePPi were measured in the media at 48 hours. Media CILP, PC-1, and ANK were determined by dot-immunoblot analysis. Chondrocyte messenger RNA (mRNA) was extracted for reverse transcriptase-polymerase chain reaction to study expression of mRNA for CILP, PC-1, and ANK. NTPPPH and ANK mRNA and protein were also studied in fresh frozen cartilage. Basal ePPi elaboration and NTPPPH activity in conditioned media from CPPD chondrocytes were elevated compared with normal chondrocytes, and tended to be higher compared with OA chondrocytes. Basal expression of mRNA for CILP (chondrocytes) and ANK (cartilage) was higher in both CPPD chondrocytes and CPPD cartilage extract than in OA or normal samples. PC-1 mRNA was less abundant in CPPD chondrocytes and cartilage extract than in OA chondrocytes and extract, although the difference was not significant. CILP, PC-1, and ANK protein levels were similar in CPPD, OA, and normal chondrocytes

  9. Revisiting spatial distribution and biochemical composition of calcium-containing crystals in human osteoarthritic articular cartilage.

    PubMed

    Nguyen, Christelle; Bazin, Dominique; Daudon, Michel; Chatron-Colliet, Aurore; Hannouche, Didier; Bianchi, Arnaud; Côme, Dominique; So, Alexander; Busso, Nathalie; Busso, Nathalie; Lioté, Frédéric; Ea, Hang-Korng

    2013-01-01

    upregulated in OA chondrocytes isolated from CaC crystal-containing cartilages. CaC crystal deposition is a widespread phenomenon in human OA articular cartilage involving the entire knee cartilage including macroscopically normal and less weight-bearing zones. Cartilage calcification is associated with altered expression of genes involved in the mineralisation process.

  10. Automating measurement of subtle changes in articular cartilage from MRI of the knee by combining 3D image registration and segmentation

    NASA Astrophysics Data System (ADS)

    Lynch, John A.; Zaim, Souhil; Zhao, Jenny; Peterfy, Charles G.; Genant, Harry K.

    2001-07-01

    In osteoarthritis, articular cartilage loses integrity and becomes thinned. This usually occurs at sites which bear weight during normal use. Measurement of such loss from MRI scans, requires precise and reproducible techniques, which can overcome the difficulties of patient repositioning within the scanner. In this study, we combine a previously described technique for segmentation of cartilage from MRI of the knee, with a technique for 3D image registration that matches localized regions of interest at followup and baseline. Two patients, who had recently undergone meniscal surgery, and developed lesions during the 12 month followup period were examined. Image registration matched regions of interest (ROI) between baseline and followup, and changes within the cartilage lesions were estimate to be about a 16% reduction in cartilage volume within each ROI. This was more than 5 times the reproducibility of the measurement, but only represented a change of between 1 and 2% in total femoral cartilage volume. Changes in total cartilage volume may be insensitive for quantifying changes in cartilage morphology. A combined used of automated image segmentation, with 3D image registration could be a useful tool for the precise and sensitive measurement of localized changes in cartilage from MRI of the knee.

  11. Biochemical and Cellular Assessment of Acetabular Chondral Flaps Identified During Hip Arthroscopy.

    PubMed

    Hariri, Sanaz; Truntzer, Jeremy; Smith, Robert Lane; Safran, Marc R

    2015-06-01

    To analyze chondral flaps debrided during hip arthroscopy to determine their biochemical and cellular composition. Thirty-one full-thickness acetabular chondral flaps were collected during hip arthroscopy. Biochemical analysis was undertaken in 21 flaps from 20 patients, and cellular viability was determined in 10 flaps from 10 patients. Biochemical analysis included concentrations of (1) DNA (an indicator of chondrocyte content), (2) hydroxyproline (an indicator of collagen content), and (3) glycosaminoglycan (an indicator of chondrocyte biosynthesis). Higher values for these parameters indicated more healthy tissue. The flaps were examined to determine the percentage of viable chondrocytes. The percentage of acetabular chondral flap specimens that had concentrations within 1 SD of the mean values reported in previous normal cartilage studies was 38% for DNA, 0% for glycosaminoglycan, and 43% for hydroxyproline. The average cellular viability of our acetabular chondral flap specimens was 39% (SD, 14%). Only 2 of the 10 specimens had more than half the cells still viable. There was no correlation between (1) the gross examination of the joint or knowledge of the patient's demographic characteristics and symptoms and (2) biochemical properties and cell viability of the flap, with one exception: a degenerative appearance of the surrounding cartilage correlated with a higher hydroxyproline concentration. Although full-thickness acetabular chondral flaps can appear normal grossly, the biochemical properties and percentage of live chondrocytes in full-thickness chondral flaps encountered in hip arthroscopy show that this tissue is not normal. There has been recent interest in repairing chondral flaps encountered during hip arthroscopy. These data suggest that acetabular chondral flaps are not biochemically and cellularly normal. Although these flaps may still be valuable mechanically and/or as a scaffold in some conductive or inductive capacity, further study is

  12. Multiparametric MRI Assessment of Human Articular Cartilage Degeneration: Correlation with Quantitative Histology and Mechanical Properties

    PubMed Central

    Rautiainen, Jari; Nissi, Mikko J.; Salo, Elli-Noora; Tiitu, Virpi; Finnilä, Mikko A.J.; Aho, Olli-Matti; Saarakkala, Simo; Lehenkari, Petri; Ellermann, Jutta; Nieminen, Miika T.

    2014-01-01

    Purpose To evaluate the sensitivity of quantitative MRI techniques (T1, T1,Gd, T2, continous wave (CW) T1ρ dispersion, adiabatic T1ρ, adiabatic T2ρ, RAFF and inversion-prepared magnetization transfer (MT)) for assessment of human articular cartilage with varying degrees of natural degeneration. Methods Osteochondral samples (n = 14) were obtained from the tibial plateaus of patients undergoing total knee replacement. MRI of the specimens was performed at 9.4 T and the relaxation time maps were evaluated in the cartilage zones. For reference, quantitative histology, OARSI grading and biomechanical measurements were performed and correlated with MRI findings. Results All MRI parameters, except T1,Gd, showed statistically significant differences in tangential and full-thickness ROIs between early and advanced osteoarthritis (OA) groups, as classified by OARSI grading. CW-T1ρ showed significant dispersion in all ROIs and featured classical laminar structure of cartilage with spin-lock powers below 1000 Hz. Adiabatic T1ρ, T2ρ, CW-T1ρ, MT and RAFF correlated strongly with OARSI grade and biomechanical parameters. Conclusion MRI parameters were able to differentiate between early and advanced OA. Furthermore, rotating frame methods, namely adiabatic T1ρ, adiabatic T2ρ, CW-T1ρ and RAFF, as well as MT experiment correlated strongly with biomechanical parameters and OARSI grade, suggesting high sensitivity of the parameters for cartilage degeneration. PMID:25104181

  13. Wrist Traction During MR Arthrography Improves Detection of Triangular Fibrocartilage Complex and Intrinsic Ligament Tears and Visibility of Articular Cartilage.

    PubMed

    Lee, Ryan K L; Griffith, James F; Ng, Alex W H; Nung, Ryan C H; Yeung, David K W

    2016-01-01

    The purpose of this study was to assess the effects of traction during MR arthrography of the wrist on joint space widening, cartilage visibility, and detection of tears of the triangular fibrocartilage complex (TFCC) and intrinsic ligaments. A prospective study included 40 wrists in 39 patients (25 men, 14 women; mean age, 35 years). MR arthrography was performed with a 3-T MRI system with and without axial traction. Two radiologists independently measured wrist and carpal joint space widths and semiquantitatively graded articular cartilage visibility. Using conventional arthrography as the reference standard and working in consensus, they assessed for the presence of tears of the TFCC, lunotriquetral ligament (LTL), and scapholunate ligament (SLL). Visibility of a tear before traction was compared with visibility after traction. With traction, all joint spaces in the wrist and carpus were significantly widened (change, 0.15-1.01 mm; all p < 0.006). Subjective cartilage visibility of all joint spaces improved after traction (all p ≤ 0.048) except for that of the radioscaphoid space, which was well visualized even before traction. Conventional arthrography depicted 24 TFCC tears, seven LTL tears, and three SLL tears. The accuracy of tear detection improved after traction for the TFCC (98% after traction vs 83% before traction), the LTL (100% vs 88%), and the SLL (100% vs 95%). Tear visibility improved after traction for 54% of TFCC tears, 71% of LTL tears, and 66% of SLL tears. Wrist MR arthrography with axial traction significantly improved the visibility of articular cartilage and the detection and visibility of tears of the TFCC and intrinsic ligaments. The results favor more widespread use of traction during MR arthrography of the wrist.

  14. Deficiency of Hyaluronan Synthase 1 (Has1) Results in Chronic Joint Inflammation and Widespread Intra-Articular Fibrosis in a Murine Model of Knee Joint Cartilage Damage

    PubMed Central

    Chan, Deva D.; Xiao, Wenfeng; Li, Jun; de la Motte, Carol A.; Sandy, John D.; Plaas, Anna

    2015-01-01

    Objective Articular cartilage defects commonly result from traumatic injury and predispose to degenerative joint diseases. To test the hypothesis that aberrant healing responses and chronic inflammation lead to osteoarthritis, we examined spatiotemporal changes in joint tissues after cartilage injury in murine knees. Since intra-articular injection of hyaluronan (HA) can attenuate injury-induced osteoarthritis in wild-type (WT) mice, we investigated a role for HA in the response to cartilage injury in mice lacking HA synthase 1 (Has1−/−). Design Femoral groove cartilage of WT and Has1−/− mice was debrided to generate a non-bleeding wound. Macroscopic imaging, histology, and gene expression were used to evaluate naïve, sham-operated, and injured joints. Results Acute responses (1–2 weeks) in injured joints from WT mice included synovial hyperplasia with HA deposition and joint-wide increases in expression of genes associated with inflammation, fibrosis, and extracellular matrix (ECM) production. By 4 weeks, some resurfacing of damaged cartilage occurred, and early cell responses were normalized. Cartilage damage in Has1−/− mice also induced early responses; however, at 4 weeks, inflammation and fibrosis genes remained elevated with widespread cartilage degeneration and fibrotic scarring in the synovium and joint capsule. Conclusions We conclude that the ineffective repair of injured cartilage in Has1−/− joints can be at least partly explained by the markedly enhanced expression of particular genes in pathways linked to ECM turnover, IL-17/IL-6 cytokine signaling, and apoptosis. Notably, Has1 ablation does not alter gross HA content in the ECM, suggesting that HAS1 has a unique function in the metabolism of inflammatory HA matrices. PMID:26521733

  15. Mechano growth factor (MGF) and transforming growth factor (TGF)-β3 functionalized silk scaffolds enhance articular hyaline cartilage regeneration in rabbit model.

    PubMed

    Luo, Ziwei; Jiang, Li; Xu, Yan; Li, Haibin; Xu, Wei; Wu, Shuangchi; Wang, Yuanliang; Tang, Zhenyu; Lv, Yonggang; Yang, Li

    2015-06-01

    Damaged cartilage has poor self-healing ability and usually progresses to scar or fibrocartilaginous tissue, and finally degenerates to osteoarthritis (OA). Here we demonstrated that one of alternative isoforms of IGF-1, mechano growth factor (MGF) acted synergistically with transforming growth factor β3 (TGF-β3) embedded in silk fibroin scaffolds to induce chemotactic homing and chondrogenic differentiation of mesenchymal stem cells (MSCs). Combination of MGF and TGF-β3 significantly increased cell recruitment up to 1.8 times and 2 times higher than TGF-β3 did in vitro and in vivo. Moreover, MGF increased Collagen II and aggrecan secretion of TGF-β3 induced hMSCs chondrogenesis, but decreased Collagen I in vitro. Silk fibroin (SF) scaffolds have been widely used for tissue engineering, and we showed that methanol treated pured SF scaffolds were porous, similar to compressive module of native cartilage, slow degradation rate and excellent drug released curves. At 7 days after subcutaneous implantation, TGF-β3 and MGF functionalized silk fibroin scaffolds (STM) recruited more CD29+/CD44+cells (P<0.05). Similarly, more cartilage-like extracellular matrix and less fibrillar collagen were detected in STM scaffolds than that in TGF-β3 modified scaffolds (ST) at 2 months after subcutaneous implantation. When implanted into articular joints in a rabbit osteochondral defect model, STM scaffolds showed the best integration into host tissues, similar architecture and collagen organization to native hyaline cartilage, as evidenced by immunostaining of aggrecan, collagen II and collagen I, as well as Safranin O and Masson's trichrome staining, and histological evalution based on the modified O'Driscoll histological scoring system (P<0.05), indicating that MGF and TGF-β3 might be a better candidate for cartilage regeneration. This study demonstrated that TGF-β3 and MGF functionalized silk fibroin scaffolds enhanced endogenous stem cell recruitment and facilitated in

  16. Micromechanical response of articular cartilage to tensile load measured using nonlinear microscopy.

    PubMed

    Bell, J S; Christmas, J; Mansfield, J C; Everson, R M; Winlove, C P

    2014-06-01

    Articular cartilage (AC) is a highly anisotropic biomaterial, and its complex mechanical properties have been a topic of intense investigation for over 60 years. Recent advances in the field of nonlinear optics allow the individual constituents of AC to be imaged in living tissue without the need for exogenous contrast agents. Combining mechanical testing with nonlinear microscopy provides a wealth of information about microscopic responses to load. This work investigates the inhomogeneous distribution of strain in loaded AC by tracking the movement and morphological changes of individual chondrocytes using point pattern matching and Bayesian modeling. This information can be used to inform models of mechanotransduction and pathogenesis, and is readily extendable to various other connective tissues. Copyright © 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  17. Bovine lactoferricin, an antimicrobial peptide, is anti-inflammatory and anti-catabolic in human articular cartilage and synovium

    PubMed Central

    Yan, Dongyao; Chen, Di; Shen, Jie; Xiao, Guozhi; van Wijnen, Andre J; Im, Hee-Jeong

    2012-01-01

    Bovine lactoferricin (LfcinB) is a multi-functional peptide derived from proteolytic cleavage of bovine lactoferrin. LfcinB was found to antagonize the biological effects mediated by angiogenic growth factors such as vascular endothelial growth factor (VEGF) and fibroblast growth factor 2 (FGF-2) in endothelial cells. However, the effect of LfcinB on human articular cartilage remained unknown. Here, our findings demonstrate that LfcinB restored the proteoglycan loss promoted by catabolic factors (interleukin-1 β) IL-1β and FGF-2 in vitro and ex vivo. Mechanistically, LfcinB attenuated the effects of IL-1β and FGF-2 on the expression of cartilage-degrading enzymes (MMP-1, MMP-3, and MMP-13), destructive cytokines (IL-1β and IL-6), and inflammatory mediators (iNOS and TLR2). LfcinB induced protective cytokine expression (IL-4 and IL-10), and downregulated aggrecanase basal expression. LfcinB specifically activated ERK MAPK and Akt signaling pathways, which may account for its anti-inflammatory activity. We also revealed that LfcinB exerted similar protective effects on human synovial fibroblasts challenged by IL-1β, with minimal cytotoxicity. Collectively, our results suggest that LfcinB possesses potent anti-catabolic and anti-inflammatory bioactivities in human articular tissues, and may be utilized for the prevention and/or treatment of OA in the future. PMID:22740381

  18. Application of an acoustofluidic perfusion bioreactor for cartilage tissue engineering.

    PubMed

    Li, Siwei; Glynne-Jones, Peter; Andriotis, Orestis G; Ching, Kuan Y; Jonnalagadda, Umesh S; Oreffo, Richard O C; Hill, Martyn; Tare, Rahul S

    2014-12-07

    Cartilage grafts generated using conventional static tissue engineering strategies are characterised by low cell viability, suboptimal hyaline cartilage formation and, critically, inferior mechanical competency, which limit their application for resurfacing articular cartilage defects. To address the limitations of conventional static cartilage bioengineering strategies and generate robust, scaffold-free neocartilage grafts of human articular chondrocytes, the present study utilised custom-built microfluidic perfusion bioreactors with integrated ultrasound standing wave traps. The system employed sweeping acoustic drive frequencies over the range of 890 to 910 kHz and continuous perfusion of the chondrogenic culture medium at a low-shear flow rate to promote the generation of three-dimensional agglomerates of human articular chondrocytes, and enhance cartilage formation by cells of the agglomerates via improved mechanical stimulation and mass transfer rates. Histological examination and assessment of micromechanical properties using indentation-type atomic force microscopy confirmed that the neocartilage grafts were analogous to native hyaline cartilage. Furthermore, in the ex vivo organ culture partial thickness cartilage defect model, implantation of the neocartilage grafts into defects for 16 weeks resulted in the formation of hyaline cartilage-like repair tissue that adhered to the host cartilage and contributed to significant improvements to the tissue architecture within the defects, compared to the empty defects. The study has demonstrated the first successful application of the acoustofluidic perfusion bioreactors to bioengineer scaffold-free neocartilage grafts of human articular chondrocytes that have the potential for subsequent use in second generation autologous chondrocyte implantation procedures for the repair of partial thickness cartilage defects.

  19. Dietary variation and mechanical properties of articular cartilage in the temporomandibular joint: implications for the role of plasticity in mechanobiology and pathobiology.

    PubMed

    Ravosa, Matthew J; Kane, Robert J

    2017-10-01

    Due to their nature as tissue composites, skeletal joints pose an additional challenge in terms of evaluating the functional significance of morphological variation in their bony and cartilaginous components in response to altered loading conditions. Arguably, this complexity requires more direct means of investigating joint plasticity and performance than typically employed to analyze macro- and micro-anatomical phenomena. To address a significant gap in our understanding of the plasticity of the mammalian temporomandibular joint (TMJ), we investigated the histology and mechanical properties of condylar articular cartilage in rabbits subjected to long-term variation in diet-induced masticatory stresses, specifically cyclical loading. Three cohorts of male weanlings were raised for six months on different diets until adulthood. Following euthanasia, the TMJ condyles on one side were dissected away, fixed, decalcified, dehydrated, embedded and sectioned. Safranin O staining was employed to identify variation in proteoglycan content, which in turn was used to predict patterns of articular cartilage stiffness in contralateral condylar specimens for each treatment group. Hematoxylin and eosin staining was used to quantify diet-induced changes in chondrocyte hypertrophy and cellularity. Mechanical tests document significant decreases in articular cartilage stiffness corresponding to patterns of extracellular matrix relative protein abundance in rabbits subjected to greater cyclical loading. This indicates that TMJs routinely subjected to higher masticatory stresses due to a challenging diet eventually develop postnatal decreases in the ability to counter compressive loads during postcanine biting and chewing. These findings provide novel information regarding TMJ performance, with broader implications about the costs and benefits of phenotypic plasticity as well as implications for how such biological processes affect connective tissue mechanobiology and pathobiology

  20. Chondrocalcinosis of the hyaline cartilage of the knee: MRI manifestations.

    PubMed

    Beltran, J; Marty-Delfaut, E; Bencardino, J; Rosenberg, Z S; Steiner, G; Aparisi, F; Padrón, M

    1998-07-01

    To determine the ability of MRI to detect the presence of crystals of calcium pyrophosphate in the articular cartilage of the knee. The MR studies of 12 knees (11 cases) were reviewed retrospectively and correlated with radiographs (12 cases) and the findings at arthroscopy (2 cases) and surgery (1 case). A total of 72 articular surfaces were evaluated. Radiographic, surgical or arthroscopic demonstration of chondrocalcinosis was used as the gold standard. Additionally, two fragments of the knee of a patient who underwent total knee replacement and demonstrated extensive chondrocalcinosis were studied with radiography and MRI using spin-echo T1-, T2- and proton-density-weighted images as well as two- and three-dimensional fat saturation (2D and 3D Fat Sat) gradient recalled echo (GRE) and STIR sequences. MRI revealed multiple hypointense foci within the articular cartilage in 34 articular surfaces, better shown on 2D and 3D GRE sequences. Radiographs showed 12 articular surfaces with chondrocalcinosis. In three cases with arthroscopic or surgical correlation, MRI demonstrated more diffuse involvement of the articular cartilage than did the radiographs. The 3D Fat Sat GRE sequences were the best for demonstrating articular calcification in vitro. In no case was meniscal calcification identified with MRI. Hyperintense halos around some of the calcifications were seen on the MR images. MRI can depict articular cartilage calcification as hypointense foci using GRE techniques. Differential diagnosis includes loose bodies, post-surgical changes, marginal osteophytes and hemosiderin deposition.

  1. Non-destructive electromechanical assessment (Arthro-BST) of human articular cartilage correlates with histological scores and biomechanical properties.

    PubMed

    Sim, S; Chevrier, A; Garon, M; Quenneville, E; Yaroshinsky, A; Hoemann, C D; Buschmann, M D

    2014-11-01

    The hand-held Arthro-BST™ device is used to map electromechanical properties of articular cartilage. The purpose of the study was to evaluate correlation of electromechanical properties with histological, biochemical and biomechanical properties of cartilage. Electromechanical properties (quantitative parameter (QP)) of eight human distal femurs were mapped manually ex vivo using the Arthro-BST (1 measure/site, 5 s/measure, 3209 sites). Osteochondral cores were then harvested from different areas on the femurs and assessed with the Mankin histological score. Prior to histoprocessing, cores were tested in unconfined compression. A subset of the cores was analyzed with polarized light microscopy (PLM) to assess collagen structure. Biochemical assays were done on additional cores to obtain water content and glycosaminoglycan (GAG) content. The QP corresponding to each core was calculated by averaging all QPs collected within 6 mm of the core center. The electromechanical QP correlated strongly with both the Mankin score and the PLM score (r = 0.73, P < 0.0001 and r = -0.70, P < 0.0001 respectively) thus accurately reflecting tissue quality and collagen architecture. Electromechanical QP also correlated strongly with biomechanical properties including fibril modulus (r = -0.76, P < 0.0001), matrix modulus (r = -0.69, P < 0.0001), and log of permeability (r = 0.72, P < 0.0001). The QP correlated weakly with GAG per wet weight and with water content (r = -0.50, P < 0.0003 and r = 0.39, P < 0.006 respectively). Non-destructive electromechanical QP measurements correlate strongly with histological scores and biomechanical parameters providing a rapid and reliable assessment of articular cartilage quality. Copyright © 2014 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

  2. Concepts in Gene Therapy for Cartilage Repair

    PubMed Central

    Steinert, Andre F.; Nöth, Ulrich; Tuan, Rocky S.

    2009-01-01

    Summary Once articular cartilage is injured, it has a very limited capacity for self-repair. Although current surgical therapeutic procedures to cartilage repair are clinically useful, they cannot restore a normal articular surface. Current research offers a growing number of bioactive reagents, including proteins and nucleic acids, that may be used to augment different aspects of the repair process. As these agents are difficult to administer effectively, gene transfer approaches are being developed to provide their sustained synthesis at sites of repair. To augment regeneration of articular cartilage, therapeutic genes can be delivered to the synovium, or directly to the cartilage lesion. Gene delivery to the cells of the synovial lining is generally considered more suitable for chondroprotective approaches, based on the expression of anti-inflammatory mediators. Gene transfer targeted to cartilage defects can be achieved by either direct vector administration to cells located at or surrounding the defects, or by transplantation of genetically modified chondrogenic cells into the defect. Several studies have shown that exogenous cDNAs encoding growth factors can be delivered locally to sites of cartilage damage, where they are expressed at therapeutically relevant levels. Furthermore, data is beginning to emerge indicating, that efficient delivery and expression of these genes is capable of influencing a repair response toward the synthesis of a more hyaline cartilage repair tissue in vivo. This review presents the current status of gene therapy for cartilage healing and highlights some of the remaining challenges. PMID:18313477

  3. Mesenchyme-specific knockout of ESET histone methyltransferase causes ectopic hypertrophy and terminal differentiation of articular chondrocytes.

    PubMed

    Lawson, Kevin A; Teteak, Colin J; Zou, Junhui; Hacquebord, Jacques; Ghatan, Andrew; Zielinska-Kwiatkowska, Anna; Fernandes, Russell J; Chansky, Howard A; Yang, Liu

    2013-11-08

    The exact molecular mechanisms governing articular chondrocytes remain unknown in skeletal biology. In this study, we have found that ESET (an ERG-associated protein with a SET domain, also called SETDB1) histone methyltransferase is expressed in articular cartilage. To test whether ESET regulates articular chondrocytes, we carried out mesenchyme-specific deletion of the ESET gene in mice. ESET knock-out did not affect generation of articular chondrocytes during embryonic development. Two weeks after birth, there was minimal qualitative difference at the knee joints between wild-type and ESET knock-out animals. At 1 month, ectopic hypertrophy, proliferation, and apoptosis of articular chondrocytes were seen in the articular cartilage of ESET-null animals. At 3 months, additional signs of terminal differentiation such as increased alkaline phosphatase activity and an elevated level of matrix metalloproteinase (MMP)-13 were found in ESET-null cartilage. Staining for type II collagen and proteoglycan revealed that cartilage degeneration became progressively worse from 2 weeks to 12 months at the knee joints of ESET knock-out mutants. Analysis of over 14 pairs of age- and sex-matched wild-type and knock-out mice indicated that the articular chondrocyte phenotype in ESET-null mutants is 100% penetrant. Our results demonstrate that expression of ESET plays an essential role in the maintenance of articular cartilage by preventing articular chondrocytes from terminal differentiation and may have implications in joint diseases such as osteoarthritis.

  4. T2 values of articular cartilage in clinically relevant subregions of the asymptomatic knee.

    PubMed

    Surowiec, Rachel K; Lucas, Erin P; Fitzcharles, Eric K; Petre, Benjamin M; Dornan, Grant J; Giphart, J Erik; LaPrade, Robert F; Ho, Charles P

    2014-06-01

    In order for T2 mapping to become more clinically applicable, reproducible subregions and standardized T2 parameters must be defined. This study sought to: (1) define clinically relevant subregions of knee cartilage using bone landmarks identifiable on both MR images and during arthroscopy and (2) determine healthy T2 values and T2 texture parameters within these subregions. Twenty-five asymptomatic volunteers (age 18-35) were evaluated with a sagittal T2 mapping sequence. Manual segmentation was performed by three raters, and cartilage was divided into twenty-one subregions modified from the International Cartilage Repair Society Articular Cartilage Mapping System. Mean T2 values and texture parameters (entropy, variance, contrast, homogeneity) were recorded for each subregion, and inter-rater and intra-rater reliability was assessed. The central regions of the condyles had significantly higher T2 values than the posterior regions (P < 0.05) and higher variance than the posterior region on the medial side (P < 0.001). The central trochlea had significantly greater T2 values than the anterior and posterior condyles. The central lateral plateau had lower T2 values, lower variance, higher homogeneity, and lower contrast than nearly all subregions in the tibia. The central patellar regions had higher entropy than the superior and inferior regions (each P ≤ 0.001). Repeatability was good to excellent for all subregions. Significant differences in mean T2 values and texture parameters were found between subregions in this carefully selected asymptomatic population, which suggest that there is normal variation of T2 values within the knee joint. The clinically relevant subregions were found to be robust as demonstrated by the overall high repeatability.

  5. Evaluation of the articular cartilage of the knee joint: value of adding a T2 mapping sequence to a routine MR imaging protocol.

    PubMed

    Kijowski, Richard; Blankenbaker, Donna G; Munoz Del Rio, Alejandro; Baer, Geoffrey S; Graf, Ben K

    2013-05-01

    To determine whether the addition of a T2 mapping sequence to a routine magnetic resonance (MR) imaging protocol could improve diagnostic performance in the detection of surgically confirmed cartilage lesions within the knee joint at 3.0 T. This prospective study was approved by the institutional review board, and the requirement to obtain informed consent was waived. The study group consisted of 150 patients (76 male and 74 female patients with an average age of 41.2 and 41.5 years, respectively) who underwent MR imaging and arthroscopy of the knee joint. MR imaging was performed at 3.0 T by using a routine protocol with the addition of a sagittal T2 mapping sequence. Images from all MR examinations were reviewed in consensus by two radiologists before surgery to determine the presence or absence of cartilage lesions on each articular surface, first by using the routine MR protocol alone and then by using the routine MR protocol with T2 maps. Each articular surface was then evaluated at arthroscopy. Generalized estimating equation models were used to compare the sensitivity and specificity of the routine MR imaging protocol with and without T2 maps in the detection of surgically confirmed cartilage lesions. The sensitivity and specificity in the detection of 351 cartilage lesions were 74.6% and 97.8%, respectively, for the routine MR protocol alone and 88.9% and 93.1% for the routine MR protocol with T2 maps. Differences in sensitivity and specificity were statistically significant (P < .001). The addition of T2 maps to the routine MR imaging protocol significantly improved the sensitivity in the detection of 24 areas of cartilage softening (from 4.2% to 62%, P < .001), 41 areas of cartilage fibrillation (from 20% to 66%, P < .001), and 96 superficial partial-thickness cartilage defects (from 71% to 88%, P = .004). The addition of a T2 mapping sequence to a routine MR protocol at 3.0 T improved sensitivity in the detection of cartilage lesions within the knee

  6. Human Cartilage-Derived Progenitor Cells From Committed Chondrocytes for Efficient Cartilage Repair and Regeneration

    PubMed Central

    Jiang, Yangzi; Cai, Youzhi; Zhang, Wei; Yin, Zi; Hu, Changchang; Tong, Tong; Lu, Ping; Zhang, Shufang; Neculai, Dante

    2016-01-01

    Articular cartilage is not a physiologically self-renewing tissue. Injury of cartilage often progresses from the articular surface to the subchondral bone, leading to pathogenesis of tissue degenerative diseases, such as osteoarthritis. Therapies to treat cartilage defects using autologous chondrocyte-based tissue engineering have been developed and used for more than 20 years; however, the challenge of chondrocyte expansion in vitro remains. A promising cell source, cartilage stem/progenitor cells (CSPCs), has attracted recent attention. Because their origin and identity are still unclear, the application potential of CSPCs is under active investigation. Here we have captured the emergence of a group of stem/progenitor cells derived from adult human chondrocytes, highlighted by dynamic changes in expression of the mature chondrocyte marker, COL2, and mesenchymal stromal/stem cell (MSC) marker, CD146. These cells are termed chondrocyte-derived progenitor cells (CDPCs). The stem cell-like potency and differentiation status of CDPCs were determined by physical and biochemical cues during culture. A low-density, low-glucose 2-dimensional culture condition (2DLL) was critical for the emergence and proliferation enhancement of CDPCs. CDPCs showed similar phenotype as bone marrow mesenchymal stromal/stem cells but exhibited greater chondrogenic potential. Moreover, the 2DLL-cultured CDPCs proved efficient in cartilage formation both in vitro and in vivo and in repairing large knee cartilage defects (6–13 cm2) in 15 patients. These findings suggest a phenotype conversion between chondrocytes and CDPCs and provide conditions that promote the conversion. These insights expand our understanding of cartilage biology and may enhance the success of chondrocyte-based therapies. Significance Injury of cartilage, a non-self-repairing tissue, often progresses to pathogenesis of degenerative joint diseases, such as osteoarthritis. Although tissue-derived stem cells have been shown

  7. Human Cartilage-Derived Progenitor Cells From Committed Chondrocytes for Efficient Cartilage Repair and Regeneration.

    PubMed

    Jiang, Yangzi; Cai, Youzhi; Zhang, Wei; Yin, Zi; Hu, Changchang; Tong, Tong; Lu, Ping; Zhang, Shufang; Neculai, Dante; Tuan, Rocky S; Ouyang, Hong Wei

    2016-06-01

    Articular cartilage is not a physiologically self-renewing tissue. Injury of cartilage often progresses from the articular surface to the subchondral bone, leading to pathogenesis of tissue degenerative diseases, such as osteoarthritis. Therapies to treat cartilage defects using autologous chondrocyte-based tissue engineering have been developed and used for more than 20 years; however, the challenge of chondrocyte expansion in vitro remains. A promising cell source, cartilage stem/progenitor cells (CSPCs), has attracted recent attention. Because their origin and identity are still unclear, the application potential of CSPCs is under active investigation. Here we have captured the emergence of a group of stem/progenitor cells derived from adult human chondrocytes, highlighted by dynamic changes in expression of the mature chondrocyte marker, COL2, and mesenchymal stromal/stem cell (MSC) marker, CD146. These cells are termed chondrocyte-derived progenitor cells (CDPCs). The stem cell-like potency and differentiation status of CDPCs were determined by physical and biochemical cues during culture. A low-density, low-glucose 2-dimensional culture condition (2DLL) was critical for the emergence and proliferation enhancement of CDPCs. CDPCs showed similar phenotype as bone marrow mesenchymal stromal/stem cells but exhibited greater chondrogenic potential. Moreover, the 2DLL-cultured CDPCs proved efficient in cartilage formation both in vitro and in vivo and in repairing large knee cartilage defects (6-13 cm(2)) in 15 patients. These findings suggest a phenotype conversion between chondrocytes and CDPCs and provide conditions that promote the conversion. These insights expand our understanding of cartilage biology and may enhance the success of chondrocyte-based therapies. Injury of cartilage, a non-self-repairing tissue, often progresses to pathogenesis of degenerative joint diseases, such as osteoarthritis. Although tissue-derived stem cells have been shown to

  8. Scaffold-assisted cartilage tissue engineering using infant chondrocytes from human hip cartilage.

    PubMed

    Kreuz, P C; Gentili, C; Samans, B; Martinelli, D; Krüger, J P; Mittelmeier, W; Endres, M; Cancedda, R; Kaps, C

    2013-12-01

    Studies about cartilage repair in the hip and infant chondrocytes are rare. The aim of our study was to evaluate the use of infant articular hip chondrocytes for tissue engineering of scaffold-assisted cartilage grafts. Hip cartilage was obtained from five human donors (age 1-10 years). Expanded chondrocytes were cultured in polyglycolic acid (PGA)-fibrin scaffolds. De- and re-differentiation of chondrocytes were assessed by histological staining and gene expression analysis of typical chondrocytic marker genes. In vivo, cartilage matrix formation was assessed by histology after subcutaneous transplantation of chondrocyte-seeded PGA-fibrin scaffolds in immunocompromised mice. The donor tissue was heterogenous showing differentiated articular cartilage and non-differentiated tissue and considerable expression of type I and II collagens. Gene expression analysis showed repression of typical chondrocyte and/or mesenchymal marker genes during cell expansion, while markers were re-induced when expanded cells were cultured in PGA-fibrin scaffolds. Cartilage formation after subcutaneous transplantation of chondrocyte loaded PGA-fibrin scaffolds in nude mice was variable, with grafts showing resorption and host cell infiltration or formation of hyaline cartilage rich in type II collagen. Addition of human platelet rich plasma (PRP) to cartilage grafts resulted robustly in formation of hyaline-like cartilage that showed type II collagen and regions with type X collagen. These results suggest that culture of expanded and/or de-differentiated infant hip cartilage cells in PGA-fibrin scaffolds initiates chondrocyte re-differentiation. The heterogenous donor tissue containing immature chondrocytes bears the risk of cartilage repair failure in vivo, which may be possibly overcome by the addition of PRP. Copyright © 2013 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

  9. Chondrogenic properties of collagen type XI, a component of cartilage extracellular matrix.

    PubMed

    Li, Ang; Wei, Yiyong; Hung, Clark; Vunjak-Novakovic, Gordana

    2018-08-01

    Cartilage extracellular matrix (ECM) has been used for promoting tissue engineering. However, the exact effects of ECM on chondrogenesis and the acting mechanisms are not well understood. In this study, we investigated the chondrogenic effects of cartilage ECM on human mesenchymal stem cells (MSCs) and identified the contributing molecular components. To this end, a preparation of articular cartilage ECM was supplemented to pellets of chondrogenically differentiating MSCs, pellets of human chondrocytes, and bovine articular cartilage explants to evaluate the effects on cell proliferation and the production of cartilaginous matrix. Selective enzymatic digestion and screening of ECM components were conducted to identify matrix molecules with chondrogenic properties. Cartilage ECM promoted MSC proliferation, production of cartilaginous matrix, and maturity of chondrogenic differentiation, and inhibited the hypertrophic differentiation of MSC-derived chondrocytes. Selective digestion of ECM components revealed a contributory role of collagens in promoting chondrogenesis. The screening of various collagen subtypes revealed strong chondrogenic effect of collagen type XI. Finally, collagen XI was found to promote production and inhibit degradation of cartilage matrix in human articular chondrocyte pellets and bovine articular cartilage explants. Our results indicate that cartilage ECM promotes chondrogenesis and inhibits hypertrophic differentiation in MSCs. Collagen type XI is the ECM component that has the strongest effects on enhancing the production and inhibiting the degradation of cartilage matrix. Copyright © 2018 Elsevier Ltd. All rights reserved.

  10. Characterization of cells from pannus-like tissue over articular cartilage of advanced osteoarthritis.

    PubMed

    Yuan, G-H; Tanaka, M; Masuko-Hongo, K; Shibakawa, A; Kato, T; Nishioka, K; Nakamura, H

    2004-01-01

    To identify the characteristics of cells isolated from pannus-like soft tissue on osteoarthritic cartilage (OA pannus cells), and to evaluate the role of this tissue in osteoarthritis (OA). OA pannus cells were isolated from pannus-like tissues in five joints obtained during arthroplasty. The phenotypic features of the isolated cells were characterized by safranin-O staining and immunohistochemical studies. Expression of MMP-1, MMP-3 and MMP-13 was also assessed using reverse transcriptase-polymerase chain reactions (RT-PCR), enzyme-linked immunosorbent assay (ELISA) and immunocytochemistry. Foci and plaque formation of pannus-like tissue over cartilage surface were found in 15 of 21 (71.4%) OA joints macroscopically, and among them, only five samples had enough tissue to be isolated. OA pannus cells were positive for type I collagen and vimentin, besides they also expressed type II collagen and aggrecan mRNA. Spontaneous expression of MMP-1, MMP-3 and MMP-13 was detected in OA pannus cells. Similar or higher levels of MMPs were detected in the supernatant of cultured OA pannus cells compared to OA chondrocytes, and among these MMP-3 levels were relatively higher in OA pannus cells. Immunohistochemically, MMP-3 positive cells located preferentially in pannus-like tissue on the border of original hyaline cartilage. Our results showed that OA pannus cells shared the property of mesenchymal cells and chondrocytes; however, their origin seemed different from chondrocytes or synoviocytes. The spontaneous expression of MMPs suggests that they are involved in the articular degradation in OA.

  11. Harnessing biomechanics to develop cartilage regeneration strategies.

    PubMed

    Athanasiou, Kyriacos A; Responte, Donald J; Brown, Wendy E; Hu, Jerry C

    2015-02-01

    As this review was prepared specifically for the American Society of Mechanical Engineers H.R. Lissner Medal, it primarily discusses work toward cartilage regeneration performed in Dr. Kyriacos A. Athanasiou's laboratory over the past 25 years. The prevalence and severity of degeneration of articular cartilage, a tissue whose main function is largely biomechanical, have motivated the development of cartilage tissue engineering approaches informed by biomechanics. This article provides a review of important steps toward regeneration of articular cartilage with suitable biomechanical properties. As a first step, biomechanical and biochemical characterization studies at the tissue level were used to provide design criteria for engineering neotissues. Extending this work to the single cell and subcellular levels has helped to develop biochemical and mechanical stimuli for tissue engineering studies. This strong mechanobiological foundation guided studies on regenerating hyaline articular cartilage, the knee meniscus, and temporomandibular joint (TMJ) fibrocartilage. Initial tissue engineering efforts centered on developing biodegradable scaffolds for cartilage regeneration. After many years of studying scaffold-based cartilage engineering, scaffoldless approaches were developed to address deficiencies of scaffold-based systems, resulting in the self-assembling process. This process was further improved by employing exogenous stimuli, such as hydrostatic pressure, growth factors, and matrix-modifying and catabolic agents, both singly and in synergistic combination to enhance neocartilage functional properties. Due to the high cell needs for tissue engineering and the limited supply of native articular chondrocytes, costochondral cells are emerging as a suitable cell source. Looking forward, additional cell sources are investigated to render these technologies more translatable. For example, dermis isolated adult stem (DIAS) cells show potential as a source of

  12. Comparison of Two Methods for Calculating the Frictional Properties of Articular Cartilage Using a Simple Pendulum and Intact Mouse Knee Joints

    PubMed Central

    Drewniak, Elizabeth I.; Jay, Gregory D.; Fleming, Braden C.; Crisco, Joseph J.

    2009-01-01

    In attempts to better understand the etiology of osteoarthritis, a debilitating joint disease that results in the degeneration of articular cartilage in synovial joints, researchers have focused on joint tribology, the study of joint friction, lubrication, and wear. Several different approaches have been used to investigate the frictional properties of articular cartilage. In this study, we examined two analysis methods for calculating the coefficient of friction (μ) using a simple pendulum system and BL6 murine knee joints (n=10) as the fulcrum. A Stanton linear decay model (Lin μ) and an exponential model that accounts for viscous damping (Exp μ) were fit to the decaying pendulum oscillations. Root mean square error (RMSE), asymptotic standard error (ASE), and coefficient of variation (CV) were calculated to evaluate the fit and measurement precision of each model. This investigation demonstrated that while Lin μ was more repeatable, based on CV (5.0% for Lin μ; 18% for Exp μ), Exp μ provided a better fitting model, based on RMSE (0.165° for Exp μ; 0.391° for Lin μ) and ASE (0.033 for Exp μ; 0.185 for Lin μ), and had a significantly lower coefficient of friction value (0.022±0.007 for Exp μ; 0.042±0.016 for Lin μ) (p=0.001). This study details the use of a simple pendulum for examining cartilage properties in situ that will have applications investigating cartilage mechanics in a variety of species. The Exp μ model provided a more accurate fit to the experimental data for predicting the frictional properties of intact joints in pendulum systems. PMID:19632680

  13. Caprine articular, meniscus and intervertebral disc cartilage: an integral analysis of collagen network and chondrocytes.

    PubMed

    Vonk, Lucienne A; Kroeze, Robert Jan; Doulabi, Behrouz Zandieh; Hoogendoorn, Roel J; Huang, Chunling; Helder, Marco N; Everts, Vincent; Bank, Ruud A

    2010-04-01

    Cartilage is a tissue with only limited reparative capacities. A small part of its volume is composed of cells, the remaining part being the hydrated extracellular matrix (ECM) with collagens and proteoglycans as its main constituents. The functioning of cartilage depends heavily on its ECM. Although it is known that the various (fibro)cartilaginous tissues (articular cartilage, annulus fibrosus, nucleus pulposus, and meniscus) differ from one each other with respect to their molecular make-up, remarkable little quantitative information is available with respect to its biochemical constituents, such as collagen content, or the various posttranslational modifications of collagen. Furthermore, we have noticed that tissue-engineering strategies to replace cartilaginous tissues pay in general little attention to the biochemical differences of the tissues or the phenotypical differences of the (fibro)chondrocytes under consideration. The goal of this paper is therefore to provide quantitative biochemical data from these tissues as a reference for further studies. We have chosen the goat as the source of these tissues, as this animal is widely accepted as an animal model in orthopaedic studies, e.g. in the field of cartilage degeneration and tissue engineering. Furthermore, we provide data on mRNA levels (from genes encoding proteins/enzymes involved in the synthesis and degradation of the ECM) from (fibro)chondrocytes that are freshly isolated from these tissues and from the same (fibro)chondrocytes that are cultured for 18 days in alginate beads. Expression levels of genes involved in the cross-linking of collagen were different between cells isolated from various cartilaginous tissues. This opens the possibility to include more markers than the commonly used chondrogenic markers type II collagen and aggrecan for cartilage tissue-engineering applications. Copyright 2009 Elsevier B.V. All rights reserved.

  14. Cartilage tissue engineering: recent advances and perspectives from gene regulation/therapy.

    PubMed

    Li, Kuei-Chang; Hu, Yu-Chen

    2015-05-01

    Diseases in articular cartilages affect millions of people. Despite the relatively simple biochemical and cellular composition of articular cartilages, the self-repair ability of cartilage is limited. Successful cartilage tissue engineering requires intricately coordinated interactions between matrerials, cells, biological factors, and phycial/mechanical factors, and still faces a multitude of challenges. This article presents an overview of the cartilage biology, current treatments, recent advances in the materials, biological factors, and cells used in cartilage tissue engineering/regeneration, with strong emphasis on the perspectives of gene regulation (e.g., microRNA) and gene therapy. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. Success Rates and Immunologic Responses of Autogenic, Allogenic, and Xenogenic Treatments to Repair Articular Cartilage Defects

    PubMed Central

    Revell, Christopher M.

    2009-01-01

    This review examines current approaches available for articular cartilage repair, not only in terms of their regeneration potential, but also as a function of immunologic response. Autogenic repair techniques, including osteochondral plug transplantation, chondrocyte implantation, and microfracture, are the most widely accepted clinical treatment options due to the lack of immunogenic reactions, but only moderate graft success rates have been reported. Although suspended allogenic chondrocytes are shown to evoke an immune response upon implantation, allogenic osteochondral plugs and tissue-engineered grafts using allogenic chondrocytes exhibit a tolerable immunogenic response. Additionally, these repair techniques produce neotissue with success rates approaching those of currently available autogenic repair techniques, while simultaneously obviating their major hindrance of donor tissue scarcity. To date, limited research has been performed with xenogenic tissue, although several studies demonstrate the potential for its long-term success. This article focuses on the various treatment options for cartilage repair and their associated success rates and immunologic responses. PMID:19063664

  16. High Density Infill in Cracks and Protrusions from the Articular Calcified Cartilage in Osteoarthritis in Standardbred Horse Carpal Bones

    PubMed Central

    Laverty, Sheila; Lacourt, Mathieu; Gao, Chan; Henderson, Janet E.; Boyde, Alan

    2015-01-01

    We studied changes in articular calcified cartilage (ACC) and subchondral bone (SCB) in the third carpal bones (C3) of Standardbred racehorses with naturally-occurring repetitive loading-induced osteoarthritis (OA). Two osteochondral cores were harvested from dorsal sites from each of 15 post-mortem C3 and classified as control or as showing early or advanced OA changes from visual inspection. We re-examined X-ray micro-computed tomography (µCT) image sets for the presence of high-density mineral infill (HDMI) in ACC cracks and possible high-density mineralized protrusions (HDMP) from the ACC mineralizing (tidemark) front (MF) into hyaline articular cartilage (HAC). We hypothesized and we show that 20-µm µCT resolution in 10-mm diameter samples is sufficient to detect HDMI and HDMP: these are lost upon tissue decalcification for routine paraffin wax histology owing to their predominant mineral content. The findings show that µCT is sufficient to discover HDMI and HDMP, which were seen in 2/10 controls, 6/9 early OA and 8/10 advanced OA cases. This is the first report of HDMI and HDMP in the equine carpus and in the Standardbred breed and the first to rely solely on µCT. HDMP are a candidate cause for mechanical tissue destruction in OA. PMID:25927581

  17. The present state of treatments for articular cartilage defects in the knee

    PubMed Central

    Perera, JR; Gikas, PD; Bentley, G

    2012-01-01

    INTRODUCTION Chondral and osteochondral lesions of the knee are notoriously difficult to treat due to the poor healing capacity of articular cartilage and the hostile environment of moving joints, ultimately causing disabling pain and early osteoarthritis. There are many different reconstructive techniques used currently but few are proven to be of value. However, some have been shown to produce a better repair with hyaline-like cartilage rather than fibrocartilage. METHODS A systematic search of all available online databases including PubMed, MEDLINE® and Embase™ was undertaken using several keywords. All the multiple treatment options and methods available were considered. These were summarised and the evidence for and against them was scrutinised. RESULTS A total of 460 articles were identified after cross-referencing the database searches using the keywords. These revealed that autologous and matrix assisted chondrocyte implantation demonstrated both ‘good to excellent’ histological results and significant improvement in clinical outcomes. CONCLUSIONS Autologous and matrix assisted chondrocyte implantation have been shown to treat symptomatic lesions successfully with significant histological and clinical improvement. There is, however, still a need for further randomised clinical trials, perfecting the type of scaffold and the use of adjuncts such as growth factors. A list of recommendations for treatment and the potential future trends of managing these lesions are given. PMID:22943326

  18. Whole-body vibration of mice induces articular cartilage degeneration with minimal changes in subchondral bone.

    PubMed

    McCann, M R; Yeung, C; Pest, M A; Ratneswaran, A; Pollmann, S I; Holdsworth, D W; Beier, F; Dixon, S J; Séguin, C A

    2017-05-01

    Low-amplitude, high-frequency whole-body vibration (WBV) has been adopted for the treatment of musculoskeletal diseases including osteoarthritis (OA); however, there is limited knowledge of the direct effects of vibration on joint tissues. Our recent studies revealed striking damage to the knee joint following exposure of mice to WBV. The current study examined the effects of WBV on specific compartments of the murine tibiofemoral joint over 8 weeks, including microarchitecture of the tibia, to understand the mechanisms associated with WBV-induced joint damage. Ten-week-old male CD-1 mice were exposed to WBV (45 Hz, 0.3 g peak acceleration; 30 min/day, 5 days/week) for 4 weeks, 8 weeks, or 4 weeks WBV followed by 4 weeks recovery. The knee joint was evaluated histologically for tissue damage. Architecture of the subchondral bone plate, subchondral trabecular bone, primary and secondary spongiosa of the tibia was assessed using micro-CT. Meniscal tears and focal articular cartilage damage were induced by WBV; the extent of damage increased between 4 and 8-week exposures to WBV. WBV did not alter the subchondral bone plate, or trabecular bone of the tibial spongiosa; however, a transient increase was detected in the subchondral trabecular bone volume and density. The lack of WBV-induced changes in the underlying subchondral bone suggests that damage to the articular cartilage may be secondary to the meniscal injury we detected. Our findings underscore the need for further studies to assess the safety of WBV in the human population to avoid long-term joint damage. Copyright © 2016 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

  19. T1ρ Dispersion in Articular Cartilage

    PubMed Central

    Besier, Thor F.; Pauly, John M.; Smith, R. Lane; Delp, Scott L.; Beaupre, Gary S.; Gold, Garry E.

    2015-01-01

    Objective This study assessed T1ρ relaxation dispersion, measured by magnetic resonance imaging (MRI), as a tool to noninvasively evaluate cartilage material and biochemical properties. The specific objective was to answer two questions: (1) does cartilage initial elastic modulus (E0) correlate with T1ρ dispersion effects and (2) does collagen or proteoglycan content correlate with T1ρ dispersion effects? Design Cadaveric patellae with and without visible cartilage damage on conventional MR were included. T2 and T1ρ relaxation times at 500 and 1000 Hz spin-lock field amplitudes were measured. We estimated T1ρ dispersion effects by measuring T1ρ relaxation time at 500 and 1000 Hz and T2 relaxation time and using a new tool, the ratio T1ρ/T2. Cartilage initial elastic modulus, E0, was measured from initial response of mechanical indentation creep tests. Collagen and proteoglycan contents were measured at the indentation test sites; proteoglycan content was measured by their covalently linked sulfated glycosaminoglycans (sGAG). Pearson correlation coefficients were determined, taking into account the clustering of multiple samples within a single patella specimen. Results Cartilage initial elastic modulus, E0, increased with decreasing values of T1ρ/T2 measurements at both 500 Hz (P = 0.034) and 1000 Hz (P = 0.022). 1/T1ρ relaxation time (500 Hz) increased with increasing sGAG content (P = 0.041). Conclusions T1ρ/T2 ratio, a new tool, and cartilage initial elastic modulus are both measures of water–protein interactions, are dependent on the cartilage structure, and were correlated in this study. PMID:26069714

  20. What is the effect of matrices on cartilage repair? A systematic review.

    PubMed

    Wylie, James D; Hartley, Melissa K; Kapron, Ashley L; Aoki, Stephen K; Maak, Travis G

    2015-05-01

    Articular cartilage has minimal endogenous ability to undergo repair. Multiple chondral restoration strategies have been attempted with varied results. The purpose of our review was to determine: (1) Does articular chondrocyte transplantation or matrix-assisted articular chondrocyte transplantation provide better patient-reported outcomes scores, MRI morphologic measurements, or histologic quality of repair tissue compared with microfracture in prospective comparative studies of articular cartilage repair; and (2) which available matrices for matrix-assisted articular chondrocyte transplantation show the best patient-reported outcomes scores, MRI morphologic measurements, or histologic quality of repair tissue? We conducted a systematic review of PubMed, CINAHL, and MEDLINE from March 2004 to February 2014 using keywords determined to be important for articular cartilage repair, including "cartilage", "chondral", "cell source", "chondrocyte", "matrix", "augment", "articular", "joint", "repair", "treatment", "regeneration", and "restoration" to find articles related to cell-based articular cartilage repair of the knee. The articles were reviewed by two authors (JDW, MKH), our study exclusion criteria were applied, and articles were determined to be relevant (or not) to the research questions. The Methodological Index for Nonrandomized Studies (MINORS) scale was used to judge the quality of nonrandomized manuscripts used in this review and the Jadad score was used to judge the quality of randomized trials. Seventeen articles were reviewed for the first research question and 83 articles were reviewed in the second research question from 301 articles identified in the original systematic search. The average MINORS score was 9.9 (62%) for noncomparative studies and 16.1 (67%) for comparative studies. The average Jadad score was 2.3 for the randomized studies. Articular chondrocyte transplantation shows better patient-reported outcomes at 5 years in patients without

  1. PEDF Is Associated with the Termination of Chondrocyte Phenotype and Catabolism of Cartilage Tissue.

    PubMed

    Klinger, P; Lukassen, S; Ferrazzi, F; Ekici, A B; Hotfiel, T; Swoboda, B; Aigner, T; Gelse, K

    2017-01-01

    Objective. To investigate the expression and target genes of pigment epithelium-derived factor (PEDF) in cartilage and chondrocytes, respectively. Methods. We analyzed the expression pattern of PEDF in different human cartilaginous tissues including articular cartilage, osteophytic cartilage, and fetal epiphyseal and growth plate cartilage, by immunohistochemistry and quantitative real-time (qRT) PCR. Transcriptome analysis after stimulation of human articular chondrocytes with rhPEDF was performed by RNA sequencing (RNA-Seq) and confirmed by qRT-PCR. Results. Immunohistochemically, PEDF could be detected in transient cartilaginous tissue that is prone to undergo endochondral ossification, including epiphyseal cartilage, growth plate cartilage, and osteophytic cartilage. In contrast, PEDF was hardly detected in healthy articular cartilage and in the superficial zone of epiphyses, regions that are characterized by a permanent stable chondrocyte phenotype. RNA-Seq analysis and qRT-PCR demonstrated that rhPEDF significantly induced the expression of a number of matrix-degrading factors including SAA1, MMP1, MMP3, and MMP13. Simultaneously, a number of cartilage-specific genes including COL2A1, COL9A2, COMP, and LECT were among the most significantly downregulated genes. Conclusions. PEDF represents a marker for transient cartilage during all neonatal and postnatal developmental stages and promotes the termination of cartilage tissue by upregulation of matrix-degrading factors and downregulation of cartilage-specific genes. These data provide the basis for novel strategies to stabilize the phenotype of articular cartilage and prevent its degradation.

  2. Manifold learning for automatically predicting articular cartilage morphology in the knee with data from the osteoarthritis initiative (OAI)

    NASA Astrophysics Data System (ADS)

    Donoghue, C.; Rao, A.; Bull, A. M. J.; Rueckert, D.

    2011-03-01

    Osteoarthritis (OA) is a degenerative, debilitating disease with a large socio-economic impact. This study looks to manifold learning as an automatic approach to harness the plethora of data provided by the Osteoarthritis Initiative (OAI). We construct several Laplacian Eigenmap embeddings of articular cartilage appearance from MR images of the knee using multiple MR sequences. A region of interest (ROI) defined as the weight bearing medial femur is automatically located in all images through non-rigid registration. A pairwise intensity based similarity measure is computed between all images, resulting in a fully connected graph, where each vertex represents an image and the weight of edges is the similarity measure. Spectral analysis is then applied to these pairwise similarities, which acts to reduce the dimensionality non-linearly and embeds these images in a manifold representation. In the manifold space, images that are close to each other are considered to be more "similar" than those far away. In the experiment presented here we use manifold learning to automatically predict the morphological changes in the articular cartilage by using the co-ordinates of the images in the manifold as independent variables for multiple linear regression. In the study presented here five manifolds are generated from five sequences of 390 distinct knees. We find statistically significant correlations (up to R2 = 0.75), between our predictors and the results presented in the literature.

  3. Intra-articular TSG-6 delivery from heparin-based microparticles reduces cartilage damage in a rat model of osteoarthritis.

    PubMed

    Tellier, Liane E; Treviño, Elda A; Brimeyer, Alexandra L; Reece, David S; Willett, Nick J; Guldberg, Robert E; Temenoff, Johnna S

    2018-05-01

    As a potential treatment for osteoarthritis (OA), we have developed injectable and hydrolytically degradable heparin-based biomaterials with tunable sulfation for the intra-articular delivery of tumor necrosis factor-alpha stimulated gene-6 (TSG-6), a protein known to inhibit plasmin which may degrade extracellular matrix within OA joints. We first assessed the effect of heparin sulfation on TSG-6 anti-plasmin activity and found that while fully sulfated (Hep) and heparin desulfated at only the N position (Hep-N) significantly enhanced TSG-6 bioactivity in vitro, fully desulfated heparin (Hep-) had no effect, indicating that heparin sulfation plays a significant role in modulating TSG-6 bioactivity. Next, TSG-6 loaded, degradable 10 wt% Hep-N microparticles (MPs) were delivered via intra-articular injection into the knee at 1, 7, and 15 days following medial meniscal transection (MMT) injury in a rat model. After 21 days, cartilage thickness, volume, and attenuation were significantly increased with soluble TSG-6, indicating degenerative changes. In contrast, no significant differences were observed with TSG-6 loaded MP treatment, demonstrating that TSG-6 loaded MPs reduced cartilage damage following MMT injury. Ultimately, our results indicate that Hep-N can enhance TSG-6 anti-plasmin activity and that Hep-N-based biomaterials may be an effective method for TSG-6 delivery to treat OA.

  4. Improvement of arthroscopic cartilage stiffness probe using amorphous diamond coating.

    PubMed

    Töyräs, Juha; Korhonen, Rami K; Voutilainen, Tanja; Jurvelin, Jukka S; Lappalainen, Reijo

    2005-04-01

    During arthroscopic evaluation of articular cartilage unstable contact and even slipping of the measurement instrument on the tissue surface may degrade the reproducibility of the measurement. The main aim of the present study was to achieve more stable contact by controlling the friction between articular cartilage surface and the arthroscopic cartilage stiffness probe (Artscan 200, Artscan Oy, Helsinki, Finland) using amorphous diamond (AD) coating. In order to obtain surfaces with different average roughnesses (R(a)), polished stainless steel disks were coated with AD by using the filtered pulsed arc-discharge (FPAD) method. Dynamic coefficient of friction (mu) between the articular cartilage (n = 8) and the coated plates along one non-coated plate was then determined. The friction between AD and cartilage could be controlled over a wide range (mu = 0.027-0.728, p < 0.05, Wilcoxon test) by altering the roughness. Possible deterioration of cartilage was investigated by measuring surface roughness after friction tests and comparing it with the roughness of the adjacent, untested samples (n = 8). Importantly, even testing with the roughest AD (R(a) = 1250 nm) did not damage articular surface. On the basis of the friction measurements, a proper AD coating was selected for the stiffness probe. The performance of coated and non-coated probe was compared by measuring bovine osteochondral samples (n = 22) with both instruments. The reproducibility of the stiffness measurements was significantly better with the AD-coated probe (CV% = 4.7) than with the uncoated probe (CV% = 8.2). To conclude, AD coating can be used to safely control dynamic friction with articular surface. Sufficient friction between articular surface and reference plate of the arthroscopic probe improves significantly reproducibility of the stiffness measurements. (c) 2005 Wiley Periodicals, Inc.

  5. Hyaluronan injection in murine osteoarthritis prevents TGFbeta 1-induced synovial neovascularization and fibrosis and maintains articular cartilage integrity by a CD44-dependent mechanism

    PubMed Central

    2012-01-01

    Introduction The mechanism by which intra-articular injection of hyaluronan (HA) ameliorates joint pathology is unknown. Animal studies have shown that HA can reduce synovial activation, periarticular fibrosis and cartilage erosion; however, its specific effects on the different cell types involved remain unclear. We have used the TTR (TGFbeta1 injection and Treadmill Running) model of murine osteoarthritis (OA), which exhibits many OA-like changes, including synovial activation, to examine in vivo tissue-specific effects of intra-articular HA. Methods The kinetics of clearance of fluorotagged HA from joints was examined with whole-body imaging. Naïve and treated knee joints were examined macroscopically for cartilage erosion, meniscal damage and fibrosis. Quantitative histopathology was done with Safranin O for cartilage and with Hematoxylin & Eosin for synovium. Gene expression in joint tissues for Acan, Col1a1, Col2a1, Col3a1, Col5a1, Col10a1, Adamts5 and Mmp13 was done by quantitative PCR. The abundance and distribution of aggrecan, collagen types I, II, III, V and X, ADAMTS5 and MMP13 were examined by immunohistochemistry. Results Injected HA showed a half-life of less than 2 h in the murine knee joint. At the tissue level, HA protected against neovascularization and fibrosis of the meniscus/synovium and maintained articular cartilage integrity in wild-type but not in Cd44 knockout mice. HA injection enhanced the expression of chondrogenic genes and proteins and blocked that of fibrogenic/degradative genes and proteins in cartilage/subchondral bone, whereas it blocked activation of both groups in meniscus/synovium. In all locations it reduced the expression/protein for Mmp13 and blocked Adamts5 expression but not its protein abundance in the synovial lining. Conclusions The injection of HA, 24 h after TGFbeta1 injection, inhibited the cascade of OA-like joint changes seen after treadmill use in the TTR model of OA. In terms of mechanism, tissue protection by

  6. Exogenous fibroblast growth factor 9 attenuates cartilage degradation and aggravates osteophyte formation in post-traumatic osteoarthritis.

    PubMed

    Zhou, S; Wang, Z; Tang, J; Li, W; Huang, J; Xu, W; Luo, F; Xu, M; Wang, J; Wen, X; Chen, L; Chen, H; Su, N; Shen, Y; Du, X; Xie, Y; Chen, L

    2016-12-01

    The aim of the present study is to investigate the effects of exogenous fibroblast growth factor (FGF)9 on the progression of post-traumatic osteoarthritis (OA). The expression of FGF9 in articular cartilage with OA is detected by immunohistochemistry (IHC). The effects of intra-articular exogenous FGF9 injection on post-traumatic OA induced by the destabilization of the medial meniscus (DMM) surgery are evaluated. Cartilage changes and osteophyte formation in knee joints are investigated by histological analysis. Changes in subchondral bone are evaluated by microcomputed tomography (micro-CT). The effect of exogenous FGF9 on an interleukin-1β (IL-1β)-induced ex vivo OA model of human articular cartilage tissues is also evaluated. FGF9 expression was down-regulated in articular chondrocytes of OA but ectopically induced at sites of osteophyte formation. Intra-articular injection of exogenous FGF9 attenuated articular cartilage degradation in mice after DMM surgery. Exogenous FGF9 suppressed collagen X and MMP13 expressions in OA cartilage, while promoted collagen II expression. Similar results were observed in IL-1β-induced ex vivo OA model. Intra-articular injection of FGF9 had no significant effect on the subchondral bone of knee joints after DMM surgery, but aggravated osteophyte formation. The expressions of SOX9 and collagen II, and cell proliferation were up-regulated at sites of initial osteophyte formation in mice with exogenous FGF9 treatment. Intra-articular injection of exogenous FGF9 delays articular cartilage degradation in post-traumatic OA, while aggravates osteophyte formation. Copyright © 2016. Published by Elsevier Ltd.

  7. Spatially localized structure-function relations in the elastic properties of sheared articular cartilage

    NASA Astrophysics Data System (ADS)

    Silverberg, Jesse; Bonassar, Lawrence; Cohen, Itai

    2013-03-01

    Contemporary developments in therapeutic tissue engineering have been enabled by basic research efforts in the field of biomechanics. Further integration of technology in medicine requires a deeper understanding of the mechanical properties of soft biological materials and the structural origins of their response under extreme stresses and strains. Drawing on the science generated by the ``Extreme Mechanics'' community, we present experimental results on the mechanical properties of articular cartilage, a hierarchically structured soft biomaterial found in the joints of mammalian long bones. Measurements of the spatially localized structure and mechanical properties will be compared with theoretical descriptions based on networks of deformed rods, poro-visco-elasticity, and standard continuum models. Discrepancies between experiment and theory will be highlighted, and suggestions for how models can be improved will be given.

  8. The biomechanical ambiguity of the articular surface.

    PubMed Central

    Kamalanathan, S; Broom, N D

    1993-01-01

    A series of micromechanical tests carried out on the articular surface of cartilage have provided an accurate description of the mechanical properties of any one site with respect to the orientation framework obtained from its characteristic split-line direction. Ultrastructural studies revealed little evidence that the split-line direction correlated strongly with any preferred alignment of fibrils. This paper therefore offers a new interpretation of the biomechanical significance of the widely used split-line test for the articular surface of cartilage. Images Fig. 9 Fig. 2 Fig. 6 Fig. 7 Fig. 8 Fig. 10 Fig. 11 PMID:8300433

  9. Induction of spontaneous hyaline cartilage regeneration using a double-network gel: efficacy of a novel therapeutic strategy for an articular cartilage defect.

    PubMed

    Kitamura, Nobuto; Yasuda, Kazunori; Ogawa, Munehiro; Arakaki, Kazunobu; Kai, Shuken; Onodera, Shin; Kurokawa, Takayuki; Gong, Jian Ping

    2011-06-01

    A double-network (DN) gel, which was composed of poly-(2-acrylamido-2-methylpropanesulfonic acid) and poly-(N,N'-dimetyl acrylamide) (PAMPS/PDMAAm), has the potential to induce chondrogenesis both in vitro and in vivo. To establish the efficacy of a therapeutic strategy for an articular cartilage defect using a DN gel. Controlled laboratory study. A 4.3-mm-diameter osteochondral defect was created in rabbit trochlea. A DN gel plug was implanted into the defect of the right knee so that a defect 2 mm in depth remained after surgery. An untreated defect of the left knee provided control data. The osteochondral defects created were examined by histological and immunohistochemical evaluations, surface assessment using confocal laser scanning microscopy, and real-time polymerase chain reaction (PCR) analysis at 4 and 12 weeks. Samples were quantitatively evaluated with 2 scoring systems reported by Wayne et al and O'Driscoll et al. The DN gel-implanted defect was filled with a sufficient volume of the hyaline cartilage tissue rich in proteoglycan and type 2 collagen. Quantitative evaluation using the grading scales revealed a significantly higher score in the DN gel-implanted defects compared with the untreated control at each period (P < .0001). The mean relative values of type 2 collagen mRNAs in the regenerated tissue were obviously higher in the DN gel-implanted defect than in the untreated control at each period. The mean surface roughness of the untreated control was significantly higher than the normal cartilage at 12 weeks (P = .0106), while there was no statistical difference between the DN gel-implanted and normal knees. This study using the mature rabbit femoral trochlea osteochondral defect model demonstrated that DN gel implantation is an effective treatment to induce cartilage regeneration in vivo without any cultured cells or mammalian-derived scaffolds. This study has prompted us to develop a potential innovative strategy to repair cartilage lesions in

  10. Mechanical Testing of Hydrogels in Cartilage Tissue Engineering: Beyond the Compressive Modulus

    PubMed Central

    Xiao, Yinghua; Friis, Elizabeth A.; Gehrke, Stevin H.

    2013-01-01

    Injuries to articular cartilage result in significant pain to patients and high medical costs. Unfortunately, cartilage repair strategies have been notoriously unreliable and/or complex. Biomaterial-based tissue-engineering strategies offer great promise, including the use of hydrogels to regenerate articular cartilage. Mechanical integrity is arguably the most important functional outcome of engineered cartilage, although mechanical testing of hydrogel-based constructs to date has focused primarily on deformation rather than failure properties. In addition to deformation testing, as the field of cartilage tissue engineering matures, this community will benefit from the addition of mechanical failure testing to outcome analyses, given the crucial clinical importance of the success of engineered constructs. However, there is a tremendous disparity in the methods used to evaluate mechanical failure of hydrogels and articular cartilage. In an effort to bridge the gap in mechanical testing methods of articular cartilage and hydrogels in cartilage regeneration, this review classifies the different toughness measurements for each. The urgency for identifying the common ground between these two disparate fields is high, as mechanical failure is ready to stand alongside stiffness as a functional design requirement. In comparing toughness measurement methods between hydrogels and cartilage, we recommend that the best option for evaluating mechanical failure of hydrogel-based constructs for cartilage tissue engineering may be tensile testing based on the single edge notch test, in part because specimen preparation is more straightforward and a related American Society for Testing and Materials (ASTM) standard can be adopted in a fracture mechanics context. PMID:23448091

  11. Mechanical testing of hydrogels in cartilage tissue engineering: beyond the compressive modulus.

    PubMed

    Xiao, Yinghua; Friis, Elizabeth A; Gehrke, Stevin H; Detamore, Michael S

    2013-10-01

    Injuries to articular cartilage result in significant pain to patients and high medical costs. Unfortunately, cartilage repair strategies have been notoriously unreliable and/or complex. Biomaterial-based tissue-engineering strategies offer great promise, including the use of hydrogels to regenerate articular cartilage. Mechanical integrity is arguably the most important functional outcome of engineered cartilage, although mechanical testing of hydrogel-based constructs to date has focused primarily on deformation rather than failure properties. In addition to deformation testing, as the field of cartilage tissue engineering matures, this community will benefit from the addition of mechanical failure testing to outcome analyses, given the crucial clinical importance of the success of engineered constructs. However, there is a tremendous disparity in the methods used to evaluate mechanical failure of hydrogels and articular cartilage. In an effort to bridge the gap in mechanical testing methods of articular cartilage and hydrogels in cartilage regeneration, this review classifies the different toughness measurements for each. The urgency for identifying the common ground between these two disparate fields is high, as mechanical failure is ready to stand alongside stiffness as a functional design requirement. In comparing toughness measurement methods between hydrogels and cartilage, we recommend that the best option for evaluating mechanical failure of hydrogel-based constructs for cartilage tissue engineering may be tensile testing based on the single edge notch test, in part because specimen preparation is more straightforward and a related American Society for Testing and Materials (ASTM) standard can be adopted in a fracture mechanics context.

  12. [Study on shape and structure of calcified cartilage zone in normal human knee joint].

    PubMed

    Wang, Fuyou; Yang, Liu; Duan, Xiaojun; Tan, Hongbo; Dai, Gang

    2008-05-01

    To explore the shape and structure of calcified cartilage zone and its interface between the non-calcified articular cartilage and subchondral bone plate. The normal human condyles of femur (n=20) were obtained from the tissue bank donated by the residents, 10 males and 10 females, aged 17-45 years. The longitudinal and transverse paraffin sections were prepared by the routine method. The shape and structure of calcified cartilage zone were observed with the Safranin O/fast green and von kossa stain method. The interface conjunction among zones of cartilage was researched by SEM and the 3D structural model was established by serial sections and modeling technique. Articular bone-cartilage safranin O/fast green staining showed that cartilage was stained red and subchondral bone was stained blue. The calcified cartilage zone was located between the tidemark and cement line. Von kossa staining showed that calcified cartilage zone was stained black and sharpness of structure border. Upper interface gomphosised tightly with the non-calcified cartilage by the wave shaped tidemark and lower interface anchored tightly with the subchondral bone by the uneven comb shaped cement line. The non-calcified cartilage zone was interlocked tightly in the manner of "ravine-engomphosis" by the calcified cartilage zone as observed under SEM, and the subchondral bone was anchored tightly in the manner of"comb-anchor" by the in the calcified cartilage zone 3D reconstruction model. The calcified cartilage zone is an important structure in the articular cartilage. The articular cartilage is fixed firmly into subchondral bone plate by the distinctive conjunct interfaces of calcified cartilage zone.

  13. HYDROSTATIC PRESSURIZATION AND DEPLETION OF TRAPPED LUBRICANT POOL DURING CREEP CONTACT OF A RIPPLED INDENTER AGAINST A BIPHASIC ARTICULAR CARTILAGE LAYER

    PubMed Central

    Soltz, Michael A.; Basalo, Ines M.; Ateshian, Gerard A.

    2010-01-01

    This study presents an analysis of the contact of a rippled rigid impermeable indenter against a cartilage layer, which represents a first simulation of the contact of rough cartilage surfaces with lubricant entrapment. Cartilage was modeled with the biphasic theory for hydrated soft tissues, to account for fluid flow into or out of the lubricant pool. The findings of this study demonstrate that under contact creep, the trapped lubricant pool gets depleted within a time period on the order of seconds or minutes as a result of lubricant flow into the articular cartilage. Prior to depletion, hydrostatic fluid load across the contact interface may be enhanced by the presence of the trapped lubricant pool, depending on the initial geometry of the lubricant pool. According to friction models based on the biphasic nature of the tissue, this enhancement in fluid load support produces a smaller minimum friction coefficient than would otherwise be predicted without a lubricant pool. The results of this study support the hypothesis that trapped lubricant decreases the initial friction coefficient following load application, independently of squeeze-film lubrication effects. PMID:14618917

  14. Physiological loading of joints prevents cartilage degradation through CITED2.

    PubMed

    Leong, Daniel J; Li, Yong H; Gu, Xiang I; Sun, Li; Zhou, Zuping; Nasser, Philip; Laudier, Damien M; Iqbal, Jameel; Majeska, Robert J; Schaffler, Mitchell B; Goldring, Mary B; Cardoso, Luis; Zaidi, Mone; Sun, Hui B

    2011-01-01

    Both overuse and disuse of joints up-regulate matrix metalloproteinases (MMPs) in articular cartilage and cause tissue degradation; however, moderate (physiological) loading maintains cartilage integrity. Here, we test whether CBP/p300-interacting transactivator with ED-rich tail 2 (CITED2), a mechanosensitive transcriptional coregulator, mediates this chondroprotective effect of moderate mechanical loading. In vivo, hind-limb immobilization of Sprague-Dawley rats up-regulates MMP-1 and causes rapid, histologically detectable articular cartilage degradation. One hour of daily passive joint motion prevents these changes and up-regulates articular cartilage CITED2. In vitro, moderate (2.5 MPa, 1 Hz) intermittent hydrostatic pressure (IHP) treatment suppresses basal MMP-1 expression and up-regulates CITED2 in human chondrocytes, whereas high IHP (10 MPa) down-regulates CITED2 and increases MMP-1. Competitive binding and transcription assays demonstrate that CITED2 suppresses MMP-1 expression by competing with MMP transactivator, Ets-1 for its coactivator p300. Furthermore, CITED2 up-regulation in vitro requires the p38δ isoform, which is specifically phosphorylated by moderate IHP. Together, these studies identify a novel regulatory pathway involving CITED2 and p38δ, which may be critical for the maintenance of articular cartilage integrity under normal physical activity levels.

  15. Intra-articular administration of hyaluronic acid increases the volume of the hyaline cartilage regenerated in a large osteochondral defect by implantation of a double-network gel.

    PubMed

    Fukui, Takaaki; Kitamura, Nobuto; Kurokawa, Takayuki; Yokota, Masashi; Kondo, Eiji; Gong, Jian Ping; Yasuda, Kazunori

    2014-04-01

    Implantation of PAMPS/PDMAAm double-network (DN) gel can induce hyaline cartilage regeneration in the osteochondral defect. However, it is a problem that the volume of the regenerated cartilage tissue is gradually reduced at 12 weeks. This study investigated whether intra-articular administration of hyaluronic acid (HA) increases the volume of the cartilage regenerated with the DN gel at 12 weeks. A total of 48 rabbits were used in this study. A cylindrical osteochondral defect created in the bilateral femoral trochlea was treated with DN gel (Group DN) or left without any implantation (Group C). In both Groups, we injected 1.0 mL of HA in the left knee, and 1.0 mL of saline solution in the right knee. Quantitative histological evaluations were performed at 2, 4, and 12 weeks, and PCR analysis was performed at 2 and 4 weeks after surgery. In Group DN, the proteoglycan-rich area was significantly greater in the HA-injected knees than in the saline-injected knees at 12 weeks (P = 0.0247), and expression of type 2 collagen, aggrecan, and Sox9 mRNAs was significantly greater in the HA-injected knees than in the saline-injected knees at 2 weeks (P = 0.0475, P = 0.0257, P = 0.0222, respectively). The intra-articular administration of HA significantly enhanced these gene expression at 2 weeks and significantly increased the volume of the hyaline cartilage regenerated by implantation of a DN gel at 12 weeks. This information is important to develop an additional method to increase the volume of the hyaline cartilage tissue in a potential cartilage regeneration strategy using the DN gel.

  16. Treatment of Focal Articular Cartilage Defects in the Knee

    PubMed Central

    Magnussen, Robert A.; Dunn, Warren R.; Carey, James L.

    2008-01-01

    We asked whether autologous chondrocyte implantation or osteochondral autograft transfer yields better clinical outcomes compared with one another or with traditional abrasive techniques for treatment of isolated articular cartilage defects and whether lesion size influences this clinical outcome. We performed a literature search and identified five randomized, controlled trials and one prospective comparative trial evaluating these treatment techniques in 421 patients. The operative procedures included autologous chondrocyte implantation, osteochondral autograft transfer, matrix-induced autologous chondrocyte implantation, and microfracture. Minimum followup was 1 year (mean, 1.7 years; range, 1–3 years). All studies documented greater than 95% followup for clinical outcome measures. No technique consistently had superior results compared with the others. Outcomes for microfracture tended to be worse in larger lesions. All studies reported improvement in clinical outcome measures in all treatment groups when compared with preoperative assessment; however, no control (nonoperative) groups were used in any of the studies. A large prospective trial investigating these techniques with the addition of a control group would be the best way to definitively address the clinical questions. Level of Evidence: Level II, therapeutic study. See the Guidelines for Authors for a complete description of levels of evidence. PMID:18196358

  17. Exercise-driven metabolic pathways in healthy cartilage.

    PubMed

    Blazek, A D; Nam, J; Gupta, R; Pradhan, M; Perera, P; Weisleder, N L; Hewett, T E; Chaudhari, A M; Lee, B S; Leblebicioglu, B; Butterfield, T A; Agarwal, S

    2016-07-01

    Exercise is vital for maintaining cartilage integrity in healthy joints. Here we examined the exercise-driven transcriptional regulation of genes in healthy rat articular cartilage to dissect the metabolic pathways responsible for the potential benefits of exercise. Transcriptome-wide gene expression in the articular cartilage of healthy Sprague-Dawley female rats exercised daily (low intensity treadmill walking) for 2, 5, or 15 days was compared to that of non-exercised rats, using Affymetrix GeneChip arrays. Database for Annotation, Visualization and Integrated Discovery (DAVID) was used for Gene Ontology (GO)-term enrichment and Functional Annotation analysis of differentially expressed genes (DEGs). Kyoto Encyclopedia of Genes and Genome (KEGG) pathway mapper was used to identify the metabolic pathways regulated by exercise. Microarray analysis revealed that exercise-induced 644 DEGs in healthy articular cartilage. The DAVID bioinformatics tool demonstrated high prevalence of functional annotation clusters with greater enrichment scores and GO-terms associated with extracellular matrix (ECM) biosynthesis/remodeling and inflammation/immune response. The KEGG database revealed that exercise regulates 147 metabolic pathways representing molecular interaction networks for Metabolism, Genetic Information Processing, Environmental Information Processing, Cellular Processes, Organismal Systems, and Diseases. These pathways collectively supported the complex regulation of the beneficial effects of exercise on the cartilage. Overall, the findings highlight that exercise is a robust transcriptional regulator of a wide array of metabolic pathways in healthy cartilage. The major actions of exercise involve ECM biosynthesis/cartilage strengthening and attenuation of inflammatory pathways to provide prophylaxis against onset of arthritic diseases in healthy cartilage. Copyright © 2016 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights

  18. A study on role of triiodothyronine (T3) hormone on the improvement of articular cartilage surface architecture.

    PubMed

    Jia, Pei-Tong; Zhang, Xing-Lin; Zuo, Hai-Ning; Lu, Xing; Gai, Peng-Zhou

    2017-10-02

    The present study was aimed to investigate the effect of triiodothyronine (T3) on the improvement of articular cartilage surface architecture at in vitro level. The T3 hormone was applied to neo-tissues in the range of 50, 100, 150 and 200ng/ml for 5 weeks. At the end of the treatment, biochemical and histological evaluation was carried out in the neo-tissues. T3 hormone application significantly increased the collagen production in neo-cartilage tissues. The properties of tensile and compressive were significantly increased compared to the controls. However, T3 hormone application also induced hypertrophy. At the higher dose concentration of T3 hormone application, tensile and compressive properties were tremendously increased 4.3 and 4.6 fold respectively. Taking all these data together, it suggested that the T3 hormone application could be a potential agent to increase the functional properties such tensile and compressive in neo-tissues. Copyright © 2017 Elsevier GmbH. All rights reserved.

  19. Direct bone morphogenetic protein 2 and Indian hedgehog gene transfer for articular cartilage repair using bone marrow coagulates.

    PubMed

    Sieker, J T; Kunz, M; Weißenberger, M; Gilbert, F; Frey, S; Rudert, M; Steinert, A F

    2015-03-01

    Bone morphogenetic protein 2 (BMP-2, encoded by BMP2) and Indian hedgehog protein (IHH, encoded by IHH) are well known regulators of chondrogenesis and chondrogenic hypertrophy. Despite being a potent chondrogenic factor BMP-2 was observed to induce chondrocyte hypertrophy in osteoarthritis (OA), growth plate cartilage and adult mesenchymal stem cells (MSCs). IHH might induce chondrogenic differentiation through different intracellular signalling pathways without inducing subsequent chondrocyte hypertrophy. The primary objective of this study is to test the efficacy of direct BMP2 and IHH gene delivery via bone marrow coagulates to influence histological repair cartilage quality in vivo. Vector-laden autologous bone marrow coagulates with 10(11) adenoviral vector particles encoding BMP2, IHH or the Green fluorescent protein (GFP) were delivered to 3.2 mm osteochondral defects in the trochlea of rabbit knees. After 13 weeks the histological repair cartilage quality was assessed using the ICRS II scoring system and the type II collagen positive area. IHH treatment resulted in superior histological repair cartilage quality than GFP controls in all of the assessed parameters (with P < 0.05 in five of 14 assessed parameters). Results of BMP2 treatment varied substantially, including severe intralesional bone formation in two of six joints after 13 weeks. IHH gene transfer is effective to improve repair cartilage quality in vivo, whereas BMP2 treatment, carried the risk intralesional bone formation. Therefore IHH protein can be considered as an attractive alternative candidate growth factor for further preclinical research and development towards improved treatments for articular cartilage defects. Copyright © 2014 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

  20. Coculture of human mesenchymal stem cells and articular chondrocytes reduces hypertrophy and enhances functional properties of engineered cartilage.

    PubMed

    Bian, Liming; Zhai, David Y; Mauck, Robert L; Burdick, Jason A

    2011-04-01

    Mesenchymal stem cells (MSCs) are being recognized as a viable cell source for cartilage repair; however, it still remains a challenge to recapitulate the functional properties of native articular cartilage using only MSCs. Additionally, MSCs may exhibit a hypertrophic phenotype under chondrogenic induction, resulting in calcification after ectopic transplantation. With this in mind, the objective of this study was to assess whether the addition of chondrocytes to MSC cultures influences the properties of tissue-engineered cartilage and MSC hypertrophy when cultured in hyaluronic acid hydrogels. Mixed cell populations (human MSCs and human chondrocytes at a ratio of 4:1) were encapsulated in the hydrogels and exhibited significantly higher Young's moduli, dynamic moduli, glycosaminoglycan levels, and collagen content than did constructs seeded with only MSCs or chondrocytes. Furthermore, the deposition of collagen X, a marker of MSC hypertrophy, was significantly lower in the coculture constructs than in the constructs seeded with MSCs alone. When MSCs and chondrocytes were cultured in distinct gels, but in the same wells, there was no improvement in biomechanical and biochemical properties of the engineered tissue, implying that a close proximity is essential. This approach can be used to improve the properties and prevent calcification of engineered cartilage formed from MSC-seeded hydrogels with the addition of lower fractions of chondrocytes, leading to improved clinical outcomes.

  1. Cell-based cartilage repair strategies in the horse.

    PubMed

    Ortved, Kyla F; Nixon, Alan J

    2016-02-01

    Damage to the articular cartilage surface is common in the equine athlete and, due to the poor intrinsic healing capabilities of cartilage, can lead to osteoarthritis (OA). Joint disease and OA are the leading cause of retirement in equine athletes and currently there are no effective treatments to stop the progression of OA. Several different cell-based strategies have been investigated to bolster the weak regenerative response of chondrocytes. Such techniques aim to restore the articular surface and prevent further joint degradation. Cell-based cartilage repair strategies include enhancement of endogenous repair mechanisms by recruitment of stem cells from the bone marrow following perforation of the subchondral bone plate; osteochondral implantation; implantation of chondrocytes that are maintained in defects by either a membrane cover or scaffold, and transplantation of mesenchymal stem cells into cartilage lesions. More recently, bioengineered cartilage and scaffoldless cartilage have been investigated for enhancing repair. This review article focuses on the multitude of cell-based repair techniques for cartilage repair across several species, with special attention paid to the horse. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. Co-Expression and Co-Localization of Cartilage Glycoproteins CHI3L1 and Lubricin in Osteoarthritic Cartilage: Morphological, Immunohistochemical and Gene Expression Profiles

    PubMed Central

    Szychlinska, Marta Anna; Trovato, Francesca Maria; Di Rosa, Michelino; Malaguarnera, Lucia; Puzzo, Lidia; Leonardi, Rosy; Castrogiovanni, Paola; Musumeci, Giuseppe

    2016-01-01

    Osteoarthritis is the most common human arthritis characterized by degeneration of articular cartilage. Several studies reported that levels of human cartilage glycoprotein chitinase 3-like-1 (CHI3L1) are known as a potential marker for the activation of chondrocytes and the progression of Osteoarthritis (OA), whereas lubricin appears to be chondroprotective. The aim of this study was to investigate the co-expression and co-localization of CHI3L1 and lubricin in normal and osteoarthritic rat articular cartilage to correlate their modified expression to a specific grade of OA. Samples of normal and osteoarthritic rat articular cartilage were analyzed by the Kellgren–Lawrence OA severity scores, the Kraus’ modified Mankin score and the Histopathology Osteoarthritis Research Society International (OARSI) system for histomorphometric evaluations, and through CHI3L1 and lubricin gene expression, immunohistochemistry and double immuno-staining analysis. The immunoexpression and the mRNA levels of lubricin increased in normal cartilage and decreased in OA cartilage (normal vs. OA, p < 0.01). By contrast, the immunoexpression and the mRNA levels of CHI3L1 increased in OA cartilage and decreased in normal cartilage (normal vs. OA, p < 0.01). Our findings are consistent with reports suggesting that these two glycoproteins are functionally associated with the development of OA and in particular with grade 2/3 of OA, suggesting that in the future they could be helpful to stage the severity and progression of the disease. PMID:26978347

  3. Histochemistry as a Unique Approach for Investigating Normal and Osteoarthritic Cartilage

    PubMed Central

    Musumeci, G.; Castrogiovanni, P.; Mazzone, V.; Szychlinska, M. A.; Castorina, S.; Loreto, C.

    2014-01-01

    In this review article, we describe benefits and disadvantages of the established histochemical methods for studying articular cartilage tissue under normal, pathological and experimental conditions. We illustrate the current knowledge on cartilage tissue based on histological and immunohistochemical aspects, and in conclusion we provide a short overview on the degeneration of cartilage, such as osteoarthritis. Adult articular cartilage has low capacity to repair itself, and thus even minor injuries may lead to progressive damage and osteoarthritic joint degeneration, resulting in significant pain and disability. Numerous efforts have been made to implement the knowledge in the study of cartilage in the last years, and histochemistry proved to be an especially powerful tool to this aim. PMID:24998926

  4. Reconstruction of Hyaline Cartilage Deep Layer Properties in 3-Dimensional Cultures of Human Articular Chondrocytes.

    PubMed

    Nanduri, Vibudha; Tattikota, Surendra Mohan; T, Avinash Raj; Sriramagiri, Vijaya Rama Rao; Kantipudi, Suma; Pande, Gopal

    2014-06-01

    Articular cartilage (AC) injuries and malformations are commonly noticed because of trauma or age-related degeneration. Many methods have been adopted for replacing or repairing the damaged tissue. Currently available AC repair methods, in several cases, fail to yield good-quality long-lasting results, perhaps because the reconstructed tissue lacks the cellular and matrix properties seen in hyaline cartilage (HC). To reconstruct HC tissue from 2-dimensional (2D) and 3-dimensional (3D) cultures of AC-derived human chondrocytes that would specifically exhibit the cellular and biochemical properties of the deep layer of HC. Descriptive laboratory study. Two-dimensional cultures of human AC-derived chondrocytes were established in classical medium (CM) and newly defined medium (NDM) and maintained for a period of 6 weeks. These cells were suspended in 2 mm-thick collagen I gels, placed in 24-well culture inserts, and further cultured up to 30 days. Properties of chondrocytes, grown in 2D cultures and the reconstructed 3D cartilage tissue, were studied by optical and scanning electron microscopic techniques, immunohistochemistry, and cartilage-specific gene expression profiling by reverse transcription polymerase chain reaction and were compared with those of the deep layer of native human AC. Two-dimensional chondrocyte cultures grown in NDM, in comparison with those grown in CM, showed more chondrocyte-specific gene activity and matrix properties. The NDM-grown chondrocytes in 3D cultures also showed better reproduction of deep layer properties of HC, as confirmed by microscopic and gene expression analysis. The method used in this study can yield cartilage tissue up to approximately 1.6 cm in diameter and 2 mm in thickness that satisfies the very low cell density and matrix composition properties present in the deep layer of normal HC. This study presents a novel and reproducible method for long-term culture of AC-derived chondrocytes and reconstruction of cartilage

  5. Combating Osteoarthritis through Stem Cell Therapies by Rejuvenating Cartilage: A Review

    PubMed Central

    Dubey, Navneet Kumar; Mishra, Viraj Krishna; Dubey, Rajni; Syed-Abdul, Shabbir; Wang, Joseph R.; Wang, Peter D.

    2018-01-01

    Knee osteoarthritis (OA) is a chronic degenerative disorder which could be distinguished by erosion of articular cartilage, pain, stiffness, and crepitus. Not only aging-associated alterations but also the metabolic factors such as hyperglycemia, dyslipidemia, and obesity affect articular tissues and may initiate or exacerbate the OA. The poor self-healing ability of articular cartilage due to limited regeneration in chondrocytes further adversely affects the osteoarthritic microenvironment. Traditional and current surgical treatment procedures for OA are limited and incapable to reverse the damage of articular cartilage. To overcome these limitations, cell-based therapies are currently being employed to repair and regenerate the structure and function of articular tissues. These therapies not only depend upon source and type of stem cells but also on environmental conditions, growth factors, and chemical and mechanical stimuli. Recently, the pluripotent and various multipotent mesenchymal stem cells have been employed for OA therapy, due to their differentiation potential towards chondrogenic lineage. Additionally, the stem cells have also been supplemented with growth factors to achieve higher healing response in osteoarthritic cartilage. In this review, we summarized the current status of stem cell therapies in OA pathophysiology and also highlighted the potential areas of further research needed in regenerative medicine. PMID:29765416

  6. Reference genes for normalization of gene expression studies in human osteoarthritic articular cartilage.

    PubMed

    Pombo-Suarez, Manuel; Calaza, Manuel; Gomez-Reino, Juan J; Gonzalez, Antonio

    2008-01-29

    Assessment of gene expression is an important component of osteoarthritis (OA) research, greatly improved by the development of quantitative real-time PCR (qPCR). This technique requires normalization for precise results, yet no suitable reference genes have been identified in human articular cartilage. We have examined ten well-known reference genes to determine the most adequate for this application. Analyses of expression stability in cartilage from 10 patients with hip OA, 8 patients with knee OA and 10 controls without OA were done with classical statistical tests and the software programs geNorm and NormFinder. Results from the three methods of analysis were broadly concordant. Some of the commonly used reference genes, GAPDH, ACTB and 18S RNA, performed poorly in our analysis. In contrast, the rarely used TBP, RPL13A and B2M genes were the best. It was necessary to use together several of these three genes to obtain the best results. The specific combination depended, to some extent, on the type of samples being compared. Our results provide a satisfactory set of previously unused reference genes for qPCR in hip and knee OA This confirms the need to evaluate the suitability of reference genes in every tissue and experimental situation before starting the quantitative assessment of gene expression by qPCR.

  7. Spaceflight-Relevant Challenges of Radiation and/or Reduced Weight Bearing Cause Arthritic Responses in Knee Articular Cartilage.

    PubMed

    Willey, J S; Kwok, A T; Moore, J E; Payne, V; Lindburg, C A; Balk, S A; Olson, J; Black, P J; Walb, M C; Yammani, R R; Munley, M T

    2016-10-01

    acute degenerative and pre-arthritic changes in the knee articular cartilage of rats. A return to normal weight bearing resulted in some recovery from cartilage degradation. However, radiation delivered as both a single challenge and when combined with HLU resulted in chronic cartilage damage. These findings suggest that radiation exposure during spaceflight leads to and/or impairs recovery of cartilage upon return to reloading, generating long-term joint problems for astronauts.

  8. Effect of gender and sports on the risk of full-thickness articular cartilage lesions in anterior cruciate ligament-injured knees: a nationwide cohort study from Sweden and Norway of 15 783 patients.

    PubMed

    Røtterud, Jan Harald; Sivertsen, Einar A; Forssblad, Magnus; Engebretsen, Lars; Årøen, Asbjørn

    2011-07-01

    The presence of an articular cartilage lesion in anterior cruciate ligament-injured knees is considered a predictor of osteoarthritis. This study was undertaken to evaluate risk factors for full-thickness articular cartilage lesions in anterior cruciate ligament-injured knees, in particular the role of gender and the sport causing the initial injury. Cohort study (prognosis); Level of evidence, 2. Primary unilateral anterior cruciate ligament reconstructions prospectively registered in the Swedish and the Norwegian National Knee Ligament Registry during 2005 through 2008 were included (N = 15 783). Logistic regression analyses were used to evaluate risk factors for cartilage lesions. A total of 1012 patients (6.4%) had full-thickness cartilage lesions. The median time from injury to surgery was 9 months (range, 0 days-521 months). Male patients had an increased odds of full-thickness cartilage lesions compared with females (odds ratio = 1.22; 95% confidence interval, 1.04-1.42). In males, team handball had an increase in the odds of full-thickness cartilage lesions compared with soccer (odds ratio = 2.36; 95% confidence interval, 1.33-4.19). Among female patients, no sport investigated showed a significant decrease or increase in the odds of full-thickness cartilage lesions. The odds of a full-thickness cartilage lesion increased by 1.006 (95% confidence interval, 1.005-1.008) for each month elapsed from time of injury until anterior cruciate ligament reconstruction when all patients were considered, while time from injury to surgery did not affect the odds significantly in those patients reconstructed within 1 year of injury (odds ratio = 0.98; 95% confidence interval, 0.95-1.02). Previous surgery increased the odds of having a full-thickness cartilage lesion (odds ratio = 1.40; 95% confidence interval, 1.21-1.63). One year of increasing patient age also increased the odds (odds ratio = 1.05; 95% confidence interval, 1.05-1.06). Male gender is associated with an

  9. Mapping the spatiotemporal evolution of solute transport in articular cartilage explants reveals how cartilage recovers fluid within the contact area during sliding.

    PubMed

    Graham, Brian T; Moore, Axel C; Burris, David L; Price, Christopher

    2018-04-11

    The interstitial fluid within articular cartilage shields the matrix from mechanical stresses, reduces friction and wear, enables biochemical processes, and transports solutes into and out of the avascular extracellular matrix. The balanced competition between fluid exudation and recovery under load is thus critical to the mechanical and biological functions of the tissue. We recently discovered that sliding alone can induce rapid solute transport into buried cartilage contact areas via a phenomenon termed tribological rehydration. In this study, we use in situ confocal microscopy measurements to track the spatiotemporal propagation of a small neutral solute into the buried contact area to clarify the fluid mechanics underlying the tribological rehydration phenomenon. Sliding experiments were interrupted by periodic static loading to enable scanning of the entire contact area. Spatiotemporal patterns of solute transport combined with tribological data suggested pressure driven flow through the extracellular matrix from the contact periphery rather than into the surface via a fluid film. Interestingly, these testing interruptions also revealed dynamic, repeatable and history-independent fluid loss and recovery processes consistent with those observed in vivo. Unlike the migrating contact area, which preserves hydration by moving faster than interstitial fluid can flow, our results demonstrate that the stationary contact area can maintain and actively recover hydration through a dynamic competition between load-induced exudation and sliding-induced recovery. The results demonstrate that sliding contributes to the recovery of fluid and solutes by cartilage within the contact area while clarifying the means by which it occurs. Copyright © 2018 Elsevier Ltd. All rights reserved.

  10. First and second order stereology of hyaline cartilage: Application on mice femoral cartilage.

    PubMed

    Noorafshan, Ali; Niazi, Behnam; Mohamadpour, Masoomeh; Hoseini, Leila; Hoseini, Najmeh; Owji, Ali Akbar; Rafati, Ali; Sadeghi, Yasaman; Karbalay-Doust, Saied

    2016-11-01

    Stereological techniques could be considered in research on cartilage to obtain quantitative data. The present study aimed to explain application of the first- and second-order stereological methods on articular cartilage of mice and the methods applied on the mice exposed to cadmium (Cd). The distal femoral articular cartilage of BALB/c mice (control and Cd-treated) was removed. Then, volume and surface area of the cartilage and number of chondrocytes were estimated using Cavalieri and optical dissector techniques on isotropic uniform random sections. Pair-correlation function [g(r)] and cross-correlation function were calculated to express the spatial arrangement of chondrocytes-chondrocytes and chondrocytes-matrix (chondrocyte clustering/dispersing), respectively. The mean±standard deviation of the cartilage volume, surface area, and thickness were 1.4±0.1mm 3 , 26.2±5.4mm 2 , and 52.8±6.7μm, respectively. Besides, the mean number of chondrocytes was 680±200 (×10 3 ). The cartilage volume, cartilage surface area, and number of chondrocytes were respectively reduced by 25%, 27%, and 27% in the Cd-treated mice in comparison to the control animals (p<0.03). Estimates of g(r) for the cells and matrix against the dipole distances, r, have been plotted. This plot showed that the chondrocytes and the matrix were neither dispersed nor clustered in the two study groups. Application of design-based stereological methods and also evaluation of spatial arrangement of the cartilage components carried potential advantages for investigating the cartilage in different joint conditions. Chondrocyte clustering/dispersing and cellularity can be evaluated in cartilage assessment in normal or abnormal situations. Copyright © 2016 Elsevier GmbH. All rights reserved.

  11. High resolution MRI imaging at 9.4 Tesla of the osteochondral unit in a translational model of articular cartilage repair.

    PubMed

    Goebel, Lars; Müller, Andreas; Bücker, Arno; Madry, Henning

    2015-04-16

    Non-destructive structural evaluation of the osteochondral unit is challenging. Here, the capability of high-field magnetic resonance imaging (μMRI) at 9.4 Tesla (T) was explored to examine osteochondral repair ex vivo in a preclinical large animal model. A specific aim of this study was to detect recently described alterations of the subchondral bone associated with cartilage repair. Osteochondral samples of medial femoral condyles from adult ewes containing full-thickness articular cartilage defects treated with marrow stimulation were obtained after 6 month in vivo and scanned in a 9.4 T μMRI. Ex vivo imaging of small osteochondral samples (typical volume: 1-2 cm(3)) at μMRI was optimised by variation of repetition time (TR), time echo (TE), flip angle (FA), spatial resolution and number of excitations (NEX) from standard MultiSliceMultiEcho (MSME) and three-dimensional (3D) spoiled GradientEcho (SGE) sequences. A 3D SGE sequence with the parameters: TR = 10 ms, TE = 3 ms, FA = 10°, voxel size = 120 × 120 × 120 μm(3) and NEX = 10 resulted in the best fitting for sample size, image quality, scanning time and artifacts. An isovolumetric voxel shape allowed for multiplanar reconstructions. Within the osteochondral unit articular cartilage, cartilaginous repair tissue and bone marrow could clearly be distinguished from the subchondral bone plate and subarticular spongiosa. Specific alterations of the osteochondral unit associated with cartilage repair such as persistent drill holes, subchondral bone cysts, sclerosis of the subchondral bone plate and of the subarticular spongiosa and intralesional osteophytes were precisely detected. High resolution, non-destructive ex vivo analysis of the entire osteochondral unit in a preclinical large animal model that is sufficient for further analyses is possible using μMRI at 9.4 T. In particular, 9.4 T is capable of accurately depicting alterations of the subchondral bone that are associated with

  12. What lies beneath: sub-articular long bone shape scaling in eutherian mammals and saurischian dinosaurs suggests different locomotor adaptations for gigantism.

    PubMed

    Bonnan, Matthew F; Wilhite, D Ray; Masters, Simon L; Yates, Adam M; Gardner, Christine K; Aguiar, Adam

    2013-01-01

    Eutherian mammals and saurischian dinosaurs both evolved lineages of huge terrestrial herbivores. Although significantly more saurischian dinosaurs were giants than eutherians, the long bones of both taxa scale similarly and suggest that locomotion was dynamically similar. However, articular cartilage is thin in eutherian mammals but thick in saurischian dinosaurs, differences that could have contributed to, or limited, how frequently gigantism evolved. Therefore, we tested the hypothesis that sub-articular bone, which supports the articular cartilage, changes shape in different ways between terrestrial mammals and dinosaurs with increasing size. Our sample consisted of giant mammal and reptile taxa (i.e., elephants, rhinos, sauropods) plus erect and non-erect outgroups with thin and thick articular cartilage. Our results show that eutherian mammal sub-articular shape becomes narrow with well-defined surface features as size increases. In contrast, this region in saurischian dinosaurs expands and remains gently convex with increasing size. Similar trends were observed in non-erect outgroup taxa (monotremes, alligators), showing that the trends we report are posture-independent. These differences support our hypothesis that sub-articular shape scales differently between eutherian mammals and saurischian dinosaurs. Our results show that articular cartilage thickness and sub-articular shape are correlated. In mammals, joints become ever more congruent and thinner with increasing size, whereas archosaur joints remained both congruent and thick, especially in sauropods. We suggest that gigantism occurs less frequently in mammals, in part, because joints composed of thin articular cartilage can only become so congruent before stress cannot be effectively alleviated. In contrast, frequent gigantism in saurischian dinosaurs may be explained, in part, by joints with thick articular cartilage that can deform across large areas with increasing load.

  13. What Lies Beneath: Sub-Articular Long Bone Shape Scaling in Eutherian Mammals and Saurischian Dinosaurs Suggests Different Locomotor Adaptations for Gigantism

    PubMed Central

    Bonnan, Matthew F.; Wilhite, D. Ray; Masters, Simon L.; Yates, Adam M.; Gardner, Christine K.; Aguiar, Adam

    2013-01-01

    Eutherian mammals and saurischian dinosaurs both evolved lineages of huge terrestrial herbivores. Although significantly more saurischian dinosaurs were giants than eutherians, the long bones of both taxa scale similarly and suggest that locomotion was dynamically similar. However, articular cartilage is thin in eutherian mammals but thick in saurischian dinosaurs, differences that could have contributed to, or limited, how frequently gigantism evolved. Therefore, we tested the hypothesis that sub-articular bone, which supports the articular cartilage, changes shape in different ways between terrestrial mammals and dinosaurs with increasing size. Our sample consisted of giant mammal and reptile taxa (i.e., elephants, rhinos, sauropods) plus erect and non-erect outgroups with thin and thick articular cartilage. Our results show that eutherian mammal sub-articular shape becomes narrow with well-defined surface features as size increases. In contrast, this region in saurischian dinosaurs expands and remains gently convex with increasing size. Similar trends were observed in non-erect outgroup taxa (monotremes, alligators), showing that the trends we report are posture-independent. These differences support our hypothesis that sub-articular shape scales differently between eutherian mammals and saurischian dinosaurs. Our results show that articular cartilage thickness and sub-articular shape are correlated. In mammals, joints become ever more congruent and thinner with increasing size, whereas archosaur joints remained both congruent and thick, especially in sauropods. We suggest that gigantism occurs less frequently in mammals, in part, because joints composed of thin articular cartilage can only become so congruent before stress cannot be effectively alleviated. In contrast, frequent gigantism in saurischian dinosaurs may be explained, in part, by joints with thick articular cartilage that can deform across large areas with increasing load. PMID:24130690

  14. Contour interpolated radial basis functions with spline boundary correction for fast 3D reconstruction of the human articular cartilage from MR images

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Javaid, Zarrar; Unsworth, Charles P., E-mail: c.unsworth@auckland.ac.nz; Boocock, Mark G.

    2016-03-15

    Purpose: The aim of this work is to demonstrate a new image processing technique that can provide a “near real-time” 3D reconstruction of the articular cartilage of the human knee from MR images which is user friendly. This would serve as a point-of-care 3D visualization tool which would benefit a consultant radiologist in the visualization of the human articular cartilage. Methods: The authors introduce a novel fusion of an adaptation of the contour method known as “contour interpolation (CI)” with radial basis functions (RBFs) which they describe as “CI-RBFs.” The authors also present a spline boundary correction which further enhancesmore » volume estimation of the method. A subject cohort consisting of 17 right nonpathological knees (ten female and seven male) is assessed to validate the quality of the proposed method. The authors demonstrate how the CI-RBF method dramatically reduces the number of data points required for fitting an implicit surface to the entire cartilage, thus, significantly improving the speed of reconstruction over the comparable RBF reconstruction method of Carr. The authors compare the CI-RBF method volume estimation to a typical commercial package (3D DOCTOR), Carr’s RBF method, and a benchmark manual method for the reconstruction of the femoral, tibial, and patellar cartilages. Results: The authors demonstrate how the CI-RBF method significantly reduces the number of data points (p-value < 0.0001) required for fitting an implicit surface to the cartilage, by 48%, 31%, and 44% for the patellar, tibial, and femoral cartilages, respectively. Thus, significantly improving the speed of reconstruction (p-value < 0.0001) by 39%, 40%, and 44% for the patellar, tibial, and femoral cartilages over the comparable RBF model of Carr providing a near real-time reconstruction of 6.49, 8.88, and 9.43 min for the patellar, tibial, and femoral cartilages, respectively. In addition, it is demonstrated how the CI-RBF method matches the

  15. Cartilage repair and joint preservation: medical and surgical treatment options.

    PubMed

    Madry, Henning; Grün, Ulrich Wolfgang; Knutsen, Gunnar

    2011-10-01

    Articular cartilage defects are most often caused by trauma and osteoarthritis and less commonly by metabolic disorders of the subchondral bone, such as osteonecrosis and osteochondritis dissecans. Such defects do not heal spontaneously in adults and can lead to secondary osteoarthritis. Medications are indicated for symptomatic relief. Slow-acting drugs in osteoarthritis (SADOA), such as glucosamine and chondroitin, are thought to prevent cartilage degeneration. Reconstructive surgical treatment strategies aim to form a repair tissue or to unload compartments of the joint with articular cartilage damage. In this article, we selectively review the pertinent literature, focusing on original publications of the past 5 years and older standard texts. Particular attention is paid to guidelines and clinical studies with a high level of evidence, along with review articles, clinical trials, and book chapters. There have been only a few randomized trials of medical versus surgical treatments. Pharmacological therapies are now available that are intended to treat the cartilage defect per se, rather than the associated symptoms, yet none of them has yet been shown to slow or reverse the progression of cartilage destruction. Surgical débridement of cartilage does not prevent the progression of osteoarthritis and is thus not recommended as the sole treatment. Marrow-stimulating procedures and osteochondral grafts are indicated for small focal articular cartilage defects, while autologous chondrocyte implantationis mainly indicated for larger cartilage defects. These surgical reconstructive techniques play a lesser role in the treatment of osteoarthritis. Osteotomy near the knee joint is indicated for axial realignment when unilateral osteoarthritis of the knee causes axis deviation. Surgical reconstructive techniques can improve joint function and thereby postpone the need for replacement of the articular surface with an artificial joint.

  16. Toward patient-specific articular contact mechanics

    PubMed Central

    Ateshian, Gerard A.; Henak, Corinne R.; Weiss, Jeffrey A.

    2015-01-01

    The mechanics of contacting cartilage layers is fundamentally important to understanding the development, homeostasis and pathology of diarthrodial joints. Because of the highly nonlinear nature of both the materials and the contact problem itself, numerical methods such as the finite element method are typically incorporated to obtain solutions. Over the course of five decades, we have moved from an initial qualitative understanding of articular cartilage material behavior to the ability to perform complex, three-dimensional contact analysis, including multiphasic material representations. This history includes the development of analytical and computational contact analysis methods that now provide the ability to perform highly nonlinear analyses. Numerical implementations of contact analysis based on the finite element method are rapidly advancing and will soon enable patient-specific analysis of joint contact mechanics using models based on medical image data. In addition to contact stress on the articular surfaces, these techniques can predict variations in strain and strain through the cartilage layers, providing the basis to predict damage and failure. This opens up exciting areas for future research and application to patient-specific diagnosis and treatment planning applied to a variety of pathologies that affect joint function and cartilage homeostasis. PMID:25698236

  17. Reaction-Diffusion-Delay Model for EPO/TNF-α Interaction in articular cartilage lesion abatement

    PubMed Central

    2012-01-01

    Background Injuries to articular cartilage result in the development of lesions that form on the surface of the cartilage. Such lesions are associated with articular cartilage degeneration and osteoarthritis. The typical injury response often causes collateral damage, primarily an effect of inflammation, which results in the spread of lesions beyond the region where the initial injury occurs. Results and discussion We present a minimal mathematical model based on known mechanisms to investigate the spread and abatement of such lesions. The first case corresponds to the parameter values listed in Table 1, while the second case has parameter values as in Table 2. In particular we represent the "balancing act" between pro-inflammatory and anti-inflammatory cytokines that is hypothesized to be a principal mechanism in the expansion properties of cartilage damage during the typical injury response. We present preliminary results of in vitro studies that confirm the anti-inflammatory activities of the cytokine erythropoietin (EPO). We assume that the diffusion of cytokines determine the spatial behavior of injury response and lesion expansion so that a reaction diffusion system involving chemical species and chondrocyte cell state population densities is a natural way to represent cartilage injury response. We present computational results using the mathematical model showing that our representation is successful in capturing much of the interesting spatial behavior of injury associated lesion development and abatement in articular cartilage. Further, we discuss the use of this model to study the possibility of using EPO as a therapy for reducing the amount of inflammation induced collateral damage to cartilage during the typical injury response. Table 1 Model Parameter Values for Results in Figure 5 Table of Parameter Values Corresponding to Simulations in Figure 5 Parameter Value Units Reason D R 0.1 c m 2 day Determined from [13] D M 0.05 c m 2 day Determined from [13

  18. Spatially resolved elemental distributions in articular cartilage

    NASA Astrophysics Data System (ADS)

    Reinert, T.; Reibetanz, U.; Vogt, J.; Butz, T.; Werner, A.; Gründer, W.

    2001-07-01

    In this study, the nuclear microprobe technique is employed to analyse the chemistry of joint cartilage in order to correlate internal structures of the collagen network with the elemental distribution. The samples were taken from pig's knee joint. 30 μm thick coronar cross-sections were prepared by means of cryosectioning and freeze-drying. We performed simultaneously particle induced X-ray emission (PIXE), Rutherford backscattering spectrometry (RBS) and elastic recoil detection analysis (ERDA). Thus we obtained spatially resolved distributions of the elements H, C, N, O, P, S, Cl, K and Ca. The main components of the organic matrix are H, C, N and O. It was shown that their relations vary with the cartilage structures. It could be shown that zones with aligned collagen fibrils contain less sulphur and potassium but more chlorine. The higher chlorine concentration is remarkable because newest biochemical studies found that hypochloric acid is involved in cartilage degradation. Furthermore, the calcium distribution is still of great interest. Its correlation to structural changes inside the cartilage is still being discussed. It could be disproved that zones of higher calcium concentration are related to the aligned structures of the collagen network.

  19. Physiological loading of joints prevents cartilage degradation through CITED2

    PubMed Central

    Leong, Daniel J.; Li, Yong H.; Gu, Xiang I.; Sun, Li; Zhou, Zuping; Nasser, Philip; Laudier, Damien M.; Iqbal, Jameel; Majeska, Robert J.; Schaffler, Mitchell B.; Goldring, Mary B.; Cardoso, Luis; Zaidi, Mone; Sun, Hui B.

    2011-01-01

    Both overuse and disuse of joints up-regulate matrix metalloproteinases (MMPs) in articular cartilage and cause tissue degradation; however, moderate (physiological) loading maintains cartilage integrity. Here, we test whether CBP/p300-interacting transactivator with ED-rich tail 2 (CITED2), a mechanosensitive transcriptional coregulator, mediates this chondroprotective effect of moderate mechanical loading. In vivo, hind-limb immobilization of Sprague-Dawley rats up-regulates MMP-1 and causes rapid, histologically detectable articular cartilage degradation. One hour of daily passive joint motion prevents these changes and up-regulates articular cartilage CITED2. In vitro, moderate (2.5 MPa, 1 Hz) intermittent hydrostatic pressure (IHP) treatment suppresses basal MMP-1 expression and up-regulates CITED2 in human chondrocytes, whereas high IHP (10 MPa) down-regulates CITED2 and increases MMP-1. Competitive binding and transcription assays demonstrate that CITED2 suppresses MMP-1 expression by competing with MMP transactivator, Ets-1 for its coactivator p300. Furthermore, CITED2 up-regulation in vitro requires the p38δ isoform, which is specifically phosphorylated by moderate IHP. Together, these studies identify a novel regulatory pathway involving CITED2 and p38δ, which may be critical for the maintenance of articular cartilage integrity under normal physical activity levels.—Leong, D. J., Li, Y. H., Gu, X. I., Sun, L., Zhou, Z., Nasser, P., Laudier, D. M., Iqbal, J., Majeska, R. J., Schaffler, M. B., Goldring, M. B., Cardoso, L., Zaidi, M., Sun, H. B. Physiological loading of joints prevents cartilage degradation through CITED2. PMID:20826544

  20. Matrix Disruptions, Growth, and Degradation of Cartilage with Impaired Sulfation*

    PubMed Central

    Mertz, Edward L.; Facchini, Marcella; Pham, Anna T.; Gualeni, Benedetta; De Leonardis, Fabio; Rossi, Antonio; Forlino, Antonella

    2012-01-01

    Diastrophic dysplasia (DTD) is an incurable recessive chondrodysplasia caused by mutations in the SLC26A2 transporter responsible for sulfate uptake by chondrocytes. The mutations cause undersulfation of glycosaminoglycans in cartilage. Studies of dtd mice with a knock-in Slc26a2 mutation showed an unusual progression of the disorder: net undersulfation is mild and normalizing with age, but the articular cartilage degrades with age and bones develop abnormally. To understand underlying mechanisms, we studied newborn dtd mice. We developed, verified and used high-definition infrared hyperspectral imaging of cartilage sections at physiological conditions, to quantify collagen and its orientation, noncollagenous proteins, and chondroitin chains, and their sulfation with 6-μm spatial resolution and without labeling. We found that chondroitin sulfation across the proximal femur cartilage varied dramatically in dtd, but not in the wild type. Corresponding undersulfation of dtd was mild in most regions, but strong in narrow articular and growth plate regions crucial for bone development. This undersulfation correlated with the chondroitin synthesis rate measured via radioactive sulfate incorporation, explaining the sulfation normalization with age. Collagen orientation was reduced, and the reduction correlated with chondroitin undersulfation. Such disorientation involved the layer of collagen covering the articular surface and protecting cartilage from degradation. Malformation of this layer may contribute to the degradation progression with age and to collagen and proteoglycan depletion from the articular region, which we observed in mice already at birth. The results provide clues to in vivo sulfation, DTD treatment, and cartilage growth. PMID:22556422

  1. Acetabular Cup Revision.

    PubMed

    Kim, Young-Ho

    2017-09-01

    The use of acetabular cup revision arthroplasty is on the rise as demands for total hip arthroplasty, improved life expectancies, and the need for individual activity increase. For an acetabular cup revision to be successful, the cup should gain stable fixation within the remaining supportive bone of the acetabulum. Since the patient's remaining supportive acetabular bone stock plays an important role in the success of revision, accurate classification of the degree of acetabular bone defect is necessary. The Paprosky classification system is most commonly used when determining the location and degree of acetabular bone loss. Common treatment options include: acetabular liner exchange, high hip center, oblong cup, trabecular metal cup with augment, bipolar cup, bulk structural graft, cemented cup, uncemented cup including jumbo cup, acetabular reinforcement device (cage), trabecular metal cup cage. The optimal treatment option is dependent upon the degree of the discontinuity, the amount of available bone stock and the likelihood of achieving stable fixation upon supportive host bone. To achieve successful acetabular cup revision, accurate evaluation of bone defect preoperatively and intraoperatively, proper choice of method of acetabular revision according to the evaluation of acetabular bone deficiency, proper technique to get primary stability of implant such as precise grafting technique, and stable fixation of implant are mandatory.

  2. On mechanical mechanism of damage evolution in articular cartilage.

    PubMed

    Men, Yu-Tao; Jiang, Yan-Long; Chen, Ling; Zhang, Chun-Qiu; Ye, Jin-Duo

    2017-09-01

    Superficial lesions of cartilage are the direct indication of osteoarthritis. To investigate the mechanical mechanism of cartilage with micro-defect under external loading, a new plain strain numerical model with micro-defect was proposed and damage evolution progression in cartilage over time has been simulated, the parameter were studied including load style, velocity of load and degree of damage. The new model consists of the hierarchical structure of cartilage and depth-dependent arched fibers. The numerical results have shown that not only damage of the cartilage altered the distribution of the stress but also matrix and fiber had distinct roles in affecting cartilage damage, and damage in either matrix or fiber could promote each other. It has been found that the superficial cracks in cartilage spread preferentially along the tangent direction of the fibers. It is the arched distribution form of fibers that affects the crack spread of cartilage, which has been verified by experiment. During the process of damage evolution, its extension direction and velocity varied constantly with the damage degree. The rolling load could cause larger stress and strain than sliding load. Strain values of the matrix initially increased and then decreased gradually with the increase of velocity, and velocity had a greater effect on matrix than fibers. Damage increased steadily before reaching 50%, sharply within 50 to 85%, and smoothly and slowly after 85%. The finding of the paper may help to understand the mechanical mechanism why the cracks in cartilage spread preferentially along the tangent direction of the fibers. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Tissue-engineered cartilage with inducible and tunable immunomodulatory properties.

    PubMed

    Glass, Katherine A; Link, Jarrett M; Brunger, Jonathan M; Moutos, Franklin T; Gersbach, Charles A; Guilak, Farshid

    2014-07-01

    The pathogenesis of osteoarthritis is mediated in part by inflammatory cytokines including interleukin-1 (IL-1), which promote degradation of articular cartilage and prevent human mesenchymal stem cell (MSC) chondrogenesis. In this study, we combined gene therapy and functional tissue engineering to develop engineered cartilage with immunomodulatory properties that allow chondrogenesis in the presence of pathologic levels of IL-1 by inducing overexpression of IL-1 receptor antagonist (IL-1Ra) in MSCs via scaffold-mediated lentiviral gene delivery. A doxycycline-inducible vector was used to transduce MSCs in monolayer or within 3D woven PCL scaffolds to enable tunable IL-1Ra production. In the presence of IL-1, IL-1Ra-expressing engineered cartilage produced cartilage-specific extracellular matrix, while resisting IL-1-induced upregulation of matrix metalloproteinases and maintaining mechanical properties similar to native articular cartilage. The ability of functional engineered cartilage to deliver tunable anti-inflammatory cytokines to the joint may enhance the long-term success of therapies for cartilage injuries or osteoarthritis. Copyright © 2014 Elsevier Ltd. All rights reserved.

  4. Tissue-engineered cartilage with inducible and tunable immunomodulatory properties

    PubMed Central

    Glass, Katherine A.; Link, Jarrett M.; Brunger, Jonathan M.; Moutos, Franklin T.; Gersbach, Charles A.; Guilak, Farshid

    2014-01-01

    The pathogenesis of osteoarthritis is mediated in part by inflammatory cytokines including interleukin-1 (IL-1), which promote degradation of articular cartilage and prevent human mesenchymal stem cell (MSC) chondrogenesis. In this study, we combined gene therapy and functional tissue engineering to develop engineered cartilage with immunomodulatory properties that allow chondrogenesis in the presence of pathologic levels of IL-1 by inducing overexpression of IL-1 receptor antagonist (IL-1Ra) in MSCs via scaffold-mediated lentiviral gene delivery. A doxycycline-inducible vector was used to transduce MSCs in monolayer or within 3D woven PCL scaffolds to enable tunable IL-1Ra production. In the presence of IL-1, IL-1Ra-expressing engineered cartilage produced cartilage-specific extracellular matrix, while resisting IL-1-induced upregulation of matrix metalloproteinases and maintaining mechanical properties similar to native articular cartilage. The ability of functional engineered cartilage to deliver tunable anti-inflammatory cytokines to the joint may enhance the long-term success of therapies for cartilage injuries or osteoarthritis. PMID:24767790

  5. An overview of cartilage tissue engineering.

    PubMed

    Kim, H W; Han, C D

    2000-12-01

    Articular cartilage regeneration refers to the formation of new tissue that is indistinguishable from the native articular cartilage with respect to zonal organization, biochemical composition, and mechanical properties. Due to a limited capacity to repair cartilage, scar tissue frequently has a poorly organized structure and lacks the functional characteristics of normal cartilage. The degree of success to date achieved using a purely cell- or biological-based approach has been modest. Potentially the development of a hybrid strategy, whereby, chondrocytes or chondrogenic stem cells are combined with a matrix, making cartilage in vitro, which is then subsequently transplanted, offers a route towards a new successful treatment modality. The success of this approach depends upon the material being biocompatible, processable into a suitable three-dimensional structure and eventually biodegradable without harmful effects. In addition, the material should have a sufficient porosity to facilitate high cell loading and tissue ingrowth, and it should be able to support cell proliferation, differentiation, and function. The cell-polymer-bioreactor system provides a basis for studying the structural and functional properties of the cartilaginous matrix during its development, because tissue concentrations of glycosaminoglycan and collagen can be modulated by altering the conditions of tissue cultivation.

  6. Co-culture systems-based strategies for articular cartilage tissue engineering.

    PubMed

    Zhang, Yu; Guo, Weimin; Wang, Mingjie; Hao, Chunxiang; Lu, Liang; Gao, Shuang; Zhang, Xueliang; Li, Xu; Chen, Mingxue; Li, Penghao; Jiang, Peng; Lu, Shibi; Liu, Shuyun; Guo, Quanyi

    2018-03-01

    Cartilage engineering facilitates repair and regeneration of damaged cartilage using engineered tissue that restores the functional properties of the impaired joint. The seed cells used most frequently in tissue engineering, are chondrocytes and mesenchymal stem cells. Seed cells activity plays a key role in the regeneration of functional cartilage tissue. However, seed cells undergo undesirable changes after in vitro processing procedures, such as degeneration of cartilage cells and induced hypertrophy of mesenchymal stem cells, which hinder cartilage tissue engineering. Compared to monoculture, which does not mimic the in vivo cellular environment, co-culture technology provides a more realistic microenvironment in terms of various physical, chemical, and biological factors. Co-culture technology is used in cartilage tissue engineering to overcome obstacles related to the degeneration of seed cells, and shows promise for cartilage regeneration and repair. In this review, we focus first on existing co-culture systems for cartilage tissue engineering and related fields, and discuss the conditions and mechanisms thereof. This is followed by methods for optimizing seed cell co-culture conditions to generate functional neo-cartilage tissue, which will lead to a new era in cartilage tissue engineering. © 2017 Wiley Periodicals, Inc.

  7. T2* Mapping of the Hip in Asymptomatic Volunteers with Normal Cartilage Morphology: An Analysis of Regional and Age-Dependent Distribution.

    PubMed

    Hesper, Tobias; Schleich, Christoph; Buchwald, Alexander; Hosalkar, Harish S; Antoch, Gerald; Krauspe, Rüdiger; Zilkens, Christoph; Bittersohl, Bernd

    2018-01-01

    Objective To assess age-dependent and regional differences in T2* relaxation measurements in hip joint cartilage of asymptomatic volunteers at 3 T. Design Three age cohorts (cohort 1: age 20-30 years, 15 individuals; cohort 2: age 30-40 years, 17 individuals; cohort 3: age 40-50 years, 15 individuals) were enrolled. T2* values were obtained in the central and peripheral cartilage of the acetabulum and the femoral head in 7 regions (anterior to superior and posterior). Results T2* did not differ among age cohorts in acetabular cartilage (cohort 1: 24.65 ± 6.56 ms, cohort 2: 24.70 ± 4.83 ms, cohort 3: 25.81 ± 5.10 ms, P = 0.10) and femoral head cartilage (cohort 1: 27.08 ± 8.24 ms, cohort 2: 25.90 ± 7.82 ms, cohort 3: 26.50 ± 5.61 ms, P = 0.34). Analysis of the regional T2* distribution pattern indicates increased T2* values in the anterior, anterior-superior, superior-anterior, and the posterior-superior aspects of acetabular and femoral head cartilage. For acetabular cartilage, higher values were observed in the central region (25.90 ± 4.80 ms vs. 24.21 ± 4.05 ms, P < 0.0001) whereas femoral head cartilage did not reveal such differences (26.62 ± 5.74 ms vs. 26.37 ± 5.89 ms, P = 0.44). Conclusions The T2* analysis of presumably healthy hip joint cartilage does not seem to be stratified according to age in this population. Regional T2* variation throughout hip joint cartilage is apparent in this modality.

  8. [Creation of artificial cartilage by nanotechnology].

    PubMed

    Murosaki, Takayuki; Gong, Jian Ping; Osada, Yoshihito

    2006-02-01

    Artificial joints are made from hard and dry materials like metal or ceramics, although these artificial joints have several problems such as bacterial infection, high surface friction and wear, lack in shock-absorption. From this viewpoint, hydrogels have a high potential as substitutes for articular cartilage, although most of them suffer from lack of mechanical strength. In our recent study, we have found hydrogels, that exhibit high fracture strength as several tens of megapascals, extremely low coefficient of friction as 10(-4), high wear resistance, and with biocompatibility. These gels might open new era of soft and wet materials as substitutes for articular cartilage and other tissues.

  9. Diffusion tensor imaging of articular cartilage at 3T correlates with histology and biomechanics in a mechanical injury model.

    PubMed

    Ferizi, Uran; Rossi, Ignacio; Lee, Youjin; Lendhey, Matin; Teplensky, Jason; Kennedy, Oran D; Kirsch, Thorsten; Bencardino, Jenny; Raya, José G

    2017-07-01

    We establish a mechanical injury model for articular cartilage to assess the sensitivity of diffusion tensor imaging (DTI) in detecting cartilage damage early in time. Mechanical injury provides a more realistic model of cartilage degradation compared with commonly used enzymatic degradation. Nine cartilage-on-bone samples were obtained from patients undergoing knee replacement. The 3 Tesla DTI (0.18 × 0.18 × 1 mm 3 ) was performed before, 1 week, and 2 weeks after (zero, mild, and severe) injury, with a clinical radial spin-echo DTI (RAISED) sequence used in our hospital. We performed stress-relaxation tests and used a quasilinear-viscoelastic (QLV) model to characterize cartilage mechanical properties. Serial histology sections were dyed with Safranin-O and given an OARSI grade. We then correlated the changes in DTI parameters with the changes in QLV-parameters and OARSI grades. After severe injury the mean diffusivity increased after 1 and 2 weeks, whereas the fractional anisotropy decreased after 2 weeks (P < 0.05). The QLV-parameters and OARSI grades of the severe injury group differed from the baseline with statistical significance. The changes in mean diffusivity across all the samples correlated with the changes in the OARSI grade (r = 0.72) and QLV-parameters (r = -0.75). DTI is sensitive in tracking early changes after mechanical injury, and its changes correlate with changes in biomechanics and histology. Magn Reson Med 78:69-78, 2017. © 2016 International Society for Magnetic Resonance in Medicine. © 2016 International Society for Magnetic Resonance in Medicine.

  10. Characterization of Selective Exosite-Binding Inhibitors of Matrix Metalloproteinase 13 That Prevent Articular Cartilage Degradation in Vitro

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Spicer, Timothy P.; Jiang, Jianwen; Taylor, Alexander B.

    Matrix metalloproteinase 13 (MMP-13) has been shown to be the main collagenase responsible for degradation of articular cartilage during osteoarthritis and therefore represents a target for drug development. Here, as a result of high-throughput screening and structure$-$activity relationship studies, we identified a novel, highly selective class of MMP-13 inhibitors (compounds 1 (Q), 2 (Q1), and 3 (Q2)). Mechanistic characterization revealed a noncompetitive nature of these inhibitors with binding constants in the low micromolar range. Crystallographic analyses revealed two binding modes for compound 2 in the MMP-13 S 1' subsite and in an S 1/S 2* subsite. Type II collagen- andmore » cartilage-protective effects exhibited by compounds 1, 2, and 3 suggested that these compounds might be efficacious in future in vivo studies. Lastly, these compounds were also highly selective when tested against a panel of 30 proteases, which, in combination with a good CYP inhibition profile, suggested low off-target toxicity and drug$-$drug interactions in humans.« less

  11. Characterization of Selective Exosite-Binding Inhibitors of Matrix Metalloproteinase 13 That Prevent Articular Cartilage Degradation in Vitro

    DOE PAGES

    Spicer, Timothy P.; Jiang, Jianwen; Taylor, Alexander B.; ...

    2014-10-20

    Matrix metalloproteinase 13 (MMP-13) has been shown to be the main collagenase responsible for degradation of articular cartilage during osteoarthritis and therefore represents a target for drug development. Here, as a result of high-throughput screening and structure$-$activity relationship studies, we identified a novel, highly selective class of MMP-13 inhibitors (compounds 1 (Q), 2 (Q1), and 3 (Q2)). Mechanistic characterization revealed a noncompetitive nature of these inhibitors with binding constants in the low micromolar range. Crystallographic analyses revealed two binding modes for compound 2 in the MMP-13 S 1' subsite and in an S 1/S 2* subsite. Type II collagen- andmore » cartilage-protective effects exhibited by compounds 1, 2, and 3 suggested that these compounds might be efficacious in future in vivo studies. Lastly, these compounds were also highly selective when tested against a panel of 30 proteases, which, in combination with a good CYP inhibition profile, suggested low off-target toxicity and drug$-$drug interactions in humans.« less

  12. The 3-D collagen structure of equine articular cartilage, characterized using variable-angle-of-incidence polarization-sensitive optical coherence tomography

    NASA Astrophysics Data System (ADS)

    Ugryumova, Nadya; Gangnus, Sergei V.; Matcher, Stephen J.

    2005-08-01

    Polarization-sensitive optical coherence tomography has been used to spatially map the birefringence of equine articular cartilage. Images obtained in the vicinity of visible osteoarthritic lesions display a characteristic disruption of the regular birefringence bands shown by normal cartilage. We also note that significant (e.g. ×2) variations in the apparent birefringence of samples taken from young (18 month) animals that otherwise appear visually homogeneous are found over spatial scales of a few millimeters. We suggest that whilst some of this variation may be due to changes in the intrinsic birefringence of the tissue, the 3-D orientation of the collagen fibers relative to the plane of the joint surface should also be taken into account. We propose a method based on multiple angles of illumination to determine the polar angle of the collagen fibers.

  13. Variable angle-of-incidence polarization-sensitive optical coherence tomography: its use to study the 3D collagen structure of equine articular cartilage

    NASA Astrophysics Data System (ADS)

    Ugryumova, Nadya; Gangnus, Sergei V.; Matcher, Stephen J.

    2006-02-01

    Polarization-sensitive optical coherence tomography has been used to spatially map the birefringence of equine articular cartilage. The polar orientation of the collagen fibers relative to the plane of the joint surface must be taken into account if a quantitative measurement of true birefringence is required. Using a series of images taken at different angles of illumination, we determine the fiber polar angle and true birefringence at one site on a sample of equine cartilage, on the assumption that the fibers lie within the plane of imaging. We propose a more general method based on the extended Jones matrix formalism to determine both the polar and azimuthal orientation of the collagen fibers as well as the true birefringence as functions of depth.

  14. Growth factor transgenes interactively regulate articular chondrocytes.

    PubMed

    Shi, Shuiliang; Mercer, Scott; Eckert, George J; Trippel, Stephen B

    2013-04-01

    Adult articular chondrocytes lack an effective repair response to correct damage from injury or osteoarthritis. Polypeptide growth factors that stimulate articular chondrocyte proliferation and cartilage matrix synthesis may augment this response. Gene transfer is a promising approach to delivering such factors. Multiple growth factor genes regulate these cell functions, but multiple growth factor gene transfer remains unexplored. We tested the hypothesis that multiple growth factor gene transfer selectively modulates articular chondrocyte proliferation and matrix synthesis. We tested the hypothesis by delivering combinations of the transgenes encoding insulin-like growth factor I (IGF-I), fibroblast growth factor-2 (FGF-2), transforming growth factor beta1 (TGF-β1), bone morphogenetic protein-2 (BMP-2), and bone morphogenetic protien-7 (BMP-7) to articular chondrocytes and measured changes in the production of DNA, glycosaminoglycan, and collagen. The transgenes differentially regulated all these chondrocyte activities. In concert, the transgenes interacted to generate widely divergent responses from the cells. These interactions ranged from inhibitory to synergistic. The transgene pair encoding IGF-I and FGF-2 maximized cell proliferation. The three-transgene group encoding IGF-I, BMP-2, and BMP-7 maximized matrix production and also optimized the balance between cell proliferation and matrix production. These data demonstrate an approach to articular chondrocyte regulation that may be tailored to stimulate specific cell functions, and suggest that certain growth factor gene combinations have potential value for cell-based articular cartilage repair. Copyright © 2012 Wiley Periodicals, Inc.

  15. Treatment of Knee Osteochondral Lesions Using a Novel Clot of Autologous Plasma Rich in Growth Factors Mixed with Healthy Hyaline Cartilage Chips and Intra-Articular Injection of PRGF

    PubMed Central

    Alentorn-Geli, Eduard; Steinbacher, Gilbert; Álvarez-Díaz, Pedro; Cuscó, Xavier; Seijas, Roberto; Barastegui, David; Navarro, Jordi; Laiz, Patricia; García-Balletbó, Montserrat

    2017-01-01

    Knee cartilage or osteochondral lesions are common and challenging injuries. To date, most symptomatic lesions warrant surgical treatment. We present two cases of patients with knee osteochondral defects treated with a one-step surgical procedure consisting of an autologous-based matrix composed of healthy hyaline cartilage chips, mixed plasma poor-rich in platelets clot, and plasma rich in growth factors (PRGF). Both patients returned to playing soccer at the preinjury activity level and demonstrated excellent defect filling in both magnetic resonance imaging and second-look arthroscopy (in one of them). The use of a clot of autologous plasma poor in platelets with healthy hyaline cartilage chips and intra-articular injection of plasma rich in platelets is an effective, easy, and cheap option to treat knee cartilage injuries in young and athletic patients. PMID:28798878

  16. Treatment of Knee Osteochondral Lesions Using a Novel Clot of Autologous Plasma Rich in Growth Factors Mixed with Healthy Hyaline Cartilage Chips and Intra-Articular Injection of PRGF.

    PubMed

    Cugat, Ramón; Alentorn-Geli, Eduard; Steinbacher, Gilbert; Álvarez-Díaz, Pedro; Cuscó, Xavier; Seijas, Roberto; Barastegui, David; Navarro, Jordi; Laiz, Patricia; García-Balletbó, Montserrat

    2017-01-01

    Knee cartilage or osteochondral lesions are common and challenging injuries. To date, most symptomatic lesions warrant surgical treatment. We present two cases of patients with knee osteochondral defects treated with a one-step surgical procedure consisting of an autologous-based matrix composed of healthy hyaline cartilage chips, mixed plasma poor-rich in platelets clot, and plasma rich in growth factors (PRGF). Both patients returned to playing soccer at the preinjury activity level and demonstrated excellent defect filling in both magnetic resonance imaging and second-look arthroscopy (in one of them). The use of a clot of autologous plasma poor in platelets with healthy hyaline cartilage chips and intra-articular injection of plasma rich in platelets is an effective, easy, and cheap option to treat knee cartilage injuries in young and athletic patients.

  17. The Role of Inorganic Polyphosphates in the Formation of Bioengineered Cartilage Incorporating a Zone of Calcified Cartilage In Vitro

    NASA Astrophysics Data System (ADS)

    St-Pierre, Jean-Philippe

    The development of bioengineered cartilage for replacement of damaged articular cartilage has gained momentum in recent years. One such approach has been developed in the Kandel lab, whereby cartilage is formed by seeding primary articular chondrocytes on the top surface of a porous biodegradable calcium polyphosphate (CPP) bone substitute, permitting anchorage of the tissue within the pores of the substrate; however, the interfacial shear properties of the tissue-substrate interface of these biphasic constructs are 1 to 2 orders of magnitude lower than the native cartilage-subchondral bone interface. To overcome this limitation, a strategy was devised to generate a zone of calcified cartilage (ZCC), thereby mimicking the native architecture of the osteochondral junction; however, the ZCC was located slightly above the cartilage-CPP interface. Thus, it was hypothesized that polyphosphate released from the CPP substrate and accumulating in the tissue inhibits the formation of the ZCC at the tissue-substrate interface. Based on this information, a strategy was devised to generate biphasic constructs incorporating a properly located ZCC. This approach involved the application of a thin calcium phosphate film to the surfaces of porous CPP via a sol-gel procedure, thereby limiting the accumulation of polyphosphate in the cartilaginous tissue. This modification to the substrate surface did not negatively impact the quality of the in vitro-formed cartilage tissue or the ZCC. Interfacial shear testing of biphasic constructs demonstrated significantly improved interfacial shear properties in the presence of a properly located ZCC. These studies also led to the observation that chondrocytes produce endogenous polyphosphate and that its levels in deep zone cartilage appear inversely related to mineral deposition within the tissue. Using an in vitro model of cartilage calcification, it was demonstrated that polyphosphate levels are modulated in part by the inhibitory effects

  18. Unique glycosignature for intervertebral disc and articular cartilage cells and tissues in immaturity and maturity.

    PubMed

    Collin, E C; Kilcoyne, M; White, S J; Grad, S; Alini, M; Joshi, L; Pandit, A S

    2016-03-11

    In this study, on/off markers for intervertebral disc (IVD) and articular cartilage (AC) cells (chondrocytes) and distinct glycoprofiles of cell and tissue-types were identified from immaturity to maturity. Three and eleven month-old ovine IVD and AC tissues were histochemically profiled with a panel of lectins and antibodies. Relationships between tissue and cell types were analysed by hierarchical clustering. Chondroitin sulfate (CS) composition of annulus fibrosus (AF), nucleus pulposus (NP) and AC tissues was determined by HPLC analysis. Clear on/off cell type markers were identified, which enabled the discrimination of chondrocytes, AF and NP cells. AF and NP cells were distinguishable using MAA, SNA-I, SBA and WFA lectins, which bound to both NP cells and chondrocytes but not AF cells. Chondrocytes were distinguished from NP and AF cells with a specific binding of LTA and PNA lectins to chondrocytes. Each tissue showed a unique CS composition with a distinct switch in sulfation pattern in AF and NP tissues upon disc maturity while cartilage maintained the same sulfation pattern over time. In conclusion, distinct glycoprofiles for cell and tissue-types across age groups were identified in addition to altered CS composition and sulfation patterns for tissue types upon maturity.

  19. Early Changes of Articular Cartilage and Subchondral Bone in The DMM Mouse Model of Osteoarthritis.

    PubMed

    Fang, Hang; Huang, Lisi; Welch, Ian; Norley, Chris; Holdsworth, David W; Beier, Frank; Cai, Daozhang

    2018-02-12

    To examine the early changes of articular cartilage and subchondral bone in the DMM mouse model of osteoarthritis, mice were subjected to DMM or SHAM surgery and sacrificed at 2-, 5- and 10-week post-surgery. Catwalk gait analyses, Micro-Computed Tomography, Toluidine Blue, Picrosirius Red and Tartrate-Resistant Acid Phosphatase (TRAP) staining were used to investigate gait patterns, joint morphology, subchondral bone, cartilage, collagen organization and osteoclasts activity, respectively. Results showed OA progressed over 10-week time-course. Gait disparity occurred only at 10-week post-surgery. Osteophyte formed at 2-week post-surgery. BMDs of DMM showed no statistical differences comparing to SHAM at 2 weeks, but BV/TV is much higher in DMM mice. Increased BMD was clearly found at 5- and 10-week post-surgery in DMM mice. TRAP staining showed increased osteoclast activity at the site of osteophyte formation of DMM joints at 5- and 10-week time points. These results showed that subchondral bone turnover might occurred earlier than 2 weeks in this mouse DMM model. Gait disparity only occurred at later stage of OA in DMM mice. Notably, patella dislocation could occur in some of the DMM mice and cause a different pattern of OA in affected knee.

  20. 3D Printing of Cytocompatible Water-Based Light-Cured Polyurethane with Hyaluronic Acid for Cartilage Tissue Engineering Applications

    PubMed Central

    Shie, Ming-You; Chang, Wen-Ching; Wei, Li-Ju; Huang, Yu-Hsin; Chen, Chien-Han; Shih, Cheng-Ting; Chen, Yi-Wen; Shen, Yu-Fang

    2017-01-01

    Diseases in articular cartilages have affected millions of people globally. Although the biochemical and cellular composition of articular cartilages is relatively simple, there is a limitation in the self-repair ability of the cartilage. Therefore, developing strategies for cartilage repair is very important. Here, we report on a new liquid resin preparation process of water-based polyurethane based photosensitive materials with hyaluronic acid with application of the materials for 3D printed customized cartilage scaffolds. The scaffold has high cytocompatibility and is one that closely mimics the mechanical properties of articular cartilages. It is suitable for culturing human Wharton’s jelly mesenchymal stem cells (hWJMSCs) and the cells in this case showed an excellent chondrogenic differentiation capacity. We consider that the 3D printing hybrid scaffolds may have potential in customized tissue engineering and also facilitate the development of cartilage tissue engineering. PMID:28772498