Biochemical and biomechanical characterisation of equine cervical facet joint cartilage.

PubMed

O'Leary, S A; White, J L; Hu, J C; Athanasiou, K A

2018-04-15

The equine cervical facet joint is a site of significant pathology. Located bilaterally on the dorsal spine, these diarthrodial joints work in conjunction with the intervertebral disc to facilitate appropriate spinal motion. Despite the high prevalence of pathology in this joint, the facet joint is understudied and thus lacking in viable treatment options. The goal of this study was to characterise equine facet joint cartilage and provide a comprehensive database describing the morphological, histological, biochemical and biomechanical properties of this tissue. Descriptive cadaver studies. A total of 132 facet joint surfaces were harvested from the cervical spines of six skeletally mature horses (11 surfaces per animal) for compiling biomechanical and biochemical properties of hyaline cartilage of the equine cervical facet joints. Gross morphometric measurements and histological staining were performed on facet joint cartilage. Creep indentation and uniaxial strain-to-failure testing were used to determine the biomechanical compressive and tensile properties. Biochemical assays included quantification of total collagen, sulfated glycosaminoglycan and DNA content. The facet joint surfaces were ovoid in shape with a flat articular surface. Histological analyses highlighted structures akin to articular cartilage of other synovial joints. In general, biomechanical and biochemical properties did not differ significantly between the inferior and superior joint surfaces as well as among spinal levels. Interestingly, compressive and tensile properties of cervical facet articular cartilage were lower than those of articular cartilage from other previously characterised equine joints. Removal of the superficial zone reduced the tissue's tensile strength, suggesting that this zone is important for the tensile integrity of the tissue. Facet surfaces were sampled at a single, central location and do not capture the potential topographic variation in cartilage properties. This is the first study to report the properties of equine cervical facet joint cartilage and may serve as the foundation for the development of future tissue-engineered replacements as well as other treatment strategies. © 2018 EVJ Ltd.

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.

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.

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.

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

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.

Laser surface modification of decellularized extracellular cartilage matrix for cartilage tissue engineering.

PubMed

Goldberg-Bockhorn, Eva; Schwarz, Silke; Subedi, Rachana; Elsässer, Alexander; Riepl, Ricarda; Walther, Paul; Körber, Ludwig; Breiter, Roman; Stock, Karl; Rotter, Nicole

2018-02-01

The implantation of autologous cartilage as the gold standard operative procedure for the reconstruction of cartilage defects in the head and neck region unfortunately implicates a variety of negative effects at the donor site. Tissue-engineered cartilage appears to be a promising alternative. However, due to the complex requirements, the optimal material is yet to be determined. As demonstrated previously, decellularized porcine cartilage (DECM) might be a good option to engineer vital cartilage. As the dense structure of DECM limits cellular infiltration, we investigated surface modifications of the scaffolds by carbon dioxide (CO 2 ) and Er:YAG laser application to facilitate the migration of chondrocytes inside the scaffold. After laser treatment, the scaffolds were seeded with human nasal septal chondrocytes and analyzed with respect to cell migration and formation of new extracellular matrix proteins. Histology, immunohistochemistry, SEM, and TEM examination revealed an increase of the scaffolds' surface area with proliferation of cell numbers on the scaffolds for both laser types. The lack of cytotoxic effects was demonstrated by standard cytotoxicity testing. However, a thermal denaturation area seemed to hinder the migration of the chondrocytes inside the scaffolds, even more so after CO 2 laser treatment. Therefore, the Er:YAG laser seemed to be better suitable. Further modifications of the laser adjustments or the use of alternative laser systems might be advantageous for surface enlargement and to facilitate migration of chondrocytes into the scaffold in one step.

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 tissue engineering of articular cartilage that begins to explore and incorporate methods of lubrication. PMID:21955119

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.

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

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.

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.

Influence of Structure and Composition on Dynamic Viscoelastic Property of Cartilaginous Tissue: Criteria for Classification between Hyaline Cartilage and Fibrocartilage Based on Mechanical Function

NASA Astrophysics Data System (ADS)

Miyata, Shogo; Tateishi, Tetsuya; Furukawa, Katsuko; Ushida, Takashi

Recently, many types of methodologies have been developed to regenerate articular cartilage. It is important to assess whether the reconstructed cartilaginous tissue has the appropriate mechanical functions to qualify as hyaline (articular) cartilage. In some cases, the reconstructed tissue may become fibrocartilage and not hyaline cartilage. In this study, we determined the dynamic viscoelastic properties of these two types of cartilage by using compression and shear tests, respectively. Hyaline cartilage specimens were harvested from the articular surface of bovine knee joints and fibrocartilage specimens were harvested from the meniscus tissue of the same. The results of this study revealed that the compressive energy dissipation of hyaline cartilage showed a strong dependence on testing frequency at low frequencies, while that of fibrocartilage did not. Therefore, the compressive energy dissipation that is indicated by the loss tangent could become the criterion for the in vitro assessment of the mechanical function of regenerated cartilage.

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.

Improved Mesenchymal Stem Cells Attachment and In Vitro Cartilage Tissue Formation on Chitosan-Modified Poly(l-Lactide-co-Epsilon-Caprolactone) Scaffold

PubMed Central

Wu, Yingnan; Li, Chao; Zhang, Tianting; Zou, Yu; Hui, James H.P.; Lee, Eng Hin

2012-01-01

Considering the load-bearing physiological requirement of articular cartilage, scaffold for cartilage tissue engineering should exhibit appropriate mechanical responses as natural cartilage undergoing temporary deformation on loading with little structural collapse, and recovering to the original geometry on unloading. A porous elastomeric poly l-lactide-co-ɛ-caprolactone (PLCL) was generated and crosslinked at the surface to chitosan to improve its wettability. Human bone marrow derived mesenchymal stem cells (MSC) attachment, morphological change, proliferation and in vitro cartilage tissue formation on the chitosan-modified PLCL scaffold were compared with the unmodified PLCL scaffold. Chitosan surface promoted more consistent and even distribution of the seeded MSC within the scaffold. MSC rapidly adopted a distinct spread-up morphology on attachment on the chitosan-modified PLCL scaffold with the formation of F-actin stress fiber which proceeded to cell aggregation; an event much delayed in the unmodified PLCL. Enhanced cartilage formation on the chitosan-modified PLCL was shown by real-time PCR analysis, histological and immunochemistry staining and biochemical assays of the cartilage extracellular matrix components. The Young's modulus of the derived cartilage tissues on the chitosan-modified PLCL scaffold was significantly increased and doubled that of the unmodified PLCL. Our results show that chitosan modification of the PLCL scaffold improved the cell compatibility of the PLCL scaffold without significant alteration of the physical elastomeric properties of PLCL and resulted in the formation of cartilage tissue of better quality. PMID:21902611

Effect of disulfide bonding and multimerization on proteoglycan 4's cartilage boundary lubricating ability and adsorption.

PubMed

Abubacker, Saleem; Ponjevic, Dragana; Ham, Hyun O; Messersmith, Phillip B; Matyas, John R; Schmidt, Tannin A

2016-01-01

The objectives of this study were to assess the cartilage boundary lubricating ability of (1) nonreduced (NR) disulfide-bonded proteoglycan 4 (PRG4) multimers versus PRG4 monomers and (2) NR versus reduced and alkylated (R/A) PRG4 monomers and to assess (3) the ability of NR PRG4 multimers versus monomers to adsorb to an articular cartilage surface. PRG4 was separated into two preparations, PRG4 multimer enriched (PRG4Multi+) and PRG4 multimer deficient (PRG4Multi-), using size exclusion chromatography (SEC) and characterized by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). The cartilage boundary lubricating ability of PRG4Multi+ and PRG4Multi- was compared at a physiological concentration (450 μg/mL) and assessed over a range of concentrations (45, 150, and 450 μg/mL). R/A and NR PRG4Multi- were evaluated at 450 μg/mL. Immunohistochemistry with anti-PRG4 antibody 4D6 was performed to visualize the adsorption of PRG4 preparations to the surface of articular cartilage explants. Separation into enriched populations of PRG4Multi+ and PRG4Multi- was achieved using SEC and was confirmed by SDS-PAGE. PRG4Multi+ and PRG4Multi- both functioned as effective friction-reducing cartilage boundary lubricants at 450 μg/mL, with PRG4Multi+ being more effective than PRG4Multi-. PRG4Multi+ lubricated in a dose-dependent manner, however, PRG4Multi- did not. R/A PRG4Multi- lubricated similar to NR PRG4Multi-. PRG4-containing solutions showed 4D6 immunoreactivity at the articular surface; the immunoreactive intensity of PRG4Multi+ appeared to be similar to SF, whereas PRG4Multi- appeared to have less intensity. These results demonstrate that the intermolecular disulfide-bonded multimeric structure of PRG4 is important for its ability to adsorb to a cartilage surface and function as a boundary lubricant. These findings contribute to a greater understanding of the molecular basis of cartilage boundary lubrication of PRG4. Elucidating the PRG4 structure-lubrication function relationship will further contribute to the understanding of PRG4's role in diarthrodial joint homeostasis and disease.

A novel in vitro bovine cartilage punch model for assessing the regeneration of focal cartilage defects with biocompatible bacterial nanocellulose.

PubMed

Pretzel, David; Linss, Stefanie; Ahrem, Hannes; Endres, Michaela; Kaps, Christian; Klemm, Dieter; Kinne, Raimund W

2013-01-01

Current therapies for articular cartilage defects fail to achieve qualitatively sufficient tissue regeneration, possibly because of a mismatch between the speed of cartilage rebuilding and the resorption of degradable implant polymers. The present study focused on the self-healing capacity of resident cartilage cells in conjunction with cell-free and biocompatible (but non-resorbable) bacterial nanocellulose (BNC). This was tested in a novel in vitro bovine cartilage punch model. Standardized bovine cartilage discs with a central defect filled with BNC were cultured for up to eight weeks with/without stimulation with transforming growth factor-β1 (TGF-β1. Cartilage formation and integrity were analyzed by histology, immunohistochemistry and electron microscopy. Content, release and neosynthesis of the matrix molecules proteoglycan/aggrecan, collagen II and collagen I were also quantified. Finally, gene expression of these molecules was profiled in resident chondrocytes and chondrocytes migrated onto the cartilage surface or the implant material. Non-stimulated and especially TGF-β1-stimulated cartilage discs displayed a preserved structural and functional integrity of the chondrocytes and surrounding matrix, remained vital in long-term culture (eight weeks) without signs of degeneration and showed substantial synthesis of cartilage-specific molecules at the protein and mRNA level. Whereas mobilization of chondrocytes from the matrix onto the surface of cartilage and implant was pivotal for successful seeding of cell-free BNC, chondrocytes did not immigrate into the central BNC area, possibly due to the relatively small diameter of its pores (2 to 5 μm). Chondrocytes on the BNC surface showed signs of successful redifferentiation over time, including increase of aggrecan/collagen type II mRNA, decrease of collagen type I mRNA and initial deposition of proteoglycan and collagen type II in long-term high-density pellet cultures. Although TGF-β1 stimulation showed protective effects on matrix integrity, effects on other parameters were limited. The present bovine cartilage punch model represents a robust, reproducible and highly suitable tool for the long-term culture of cartilage, maintaining matrix integrity and homoeostasis. As an alternative to animal studies, this model may closely reflect early stages of cartilage regeneration, allowing the evaluation of promising biomaterials with/without chondrogenic factors.

Structural and in vivo mechanical characterization of canine patellar cartilage: a closed chondromalacia patellae model.

PubMed

LaBerge, M; Audet, J; Drouin, G; Rivard, C H

1993-01-01

The purpose of this project was to study the relationship between the structure of the patellar cartilage and its response to static compressive loading with a closed chondromalacia patellae model. An animal model was used to induce degeneration of the patella that was monitored quantitatively and qualitatively as a function of time. Ten adult mongrel dogs had their left patellofemoral groove replaced by a customized metallic implant covered with a thin film of polyethylene for periods of 3 months (five dogs) and 6 months (five dogs). An indenter was designed to perform mechanical indentation testing on the patellar cartilage in situ. The animals were anesthetized and the response of patellar cartilage to a static compressive load of 4.5 MPa was monitored for 20 min and its relaxation after load removal for 20 min. Indentation tests were performed every 3 months of the implantation period. At the end of the implantation period, the patellae were processed for histology, and sections were stained with Safranin-O indicative of the proteoglycans content. Macroscopically, no apparent degeneration or fibrillation of the patellar surfaces was observed after 3 or 6 months of implantation. However, the patellar surface showed a change in coloration after 6 months. A 17 +/- 3% and 37 +/- 8% deformation of the cartilage were calculated for the 3-month and 6-month specimens, respectively. Histologically, a progressive loss of proteoglycans was observed in the matrix as a function of implantation time. These results indicated that an increase in cartilage compliance is associated with an intrinsic remodeling of the cartilage matrix and that these changes might occur without external signs of degeneration and can be quantified.

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.

Investigation of Migration and Differentiation of Human Mesenchymal Stem Cells on Five-Layered Collagenous Electrospun Scaffold Mimicking Native Cartilage Structure.

PubMed

Reboredo, Jenny W; Weigel, Tobias; Steinert, Andre; Rackwitz, Lars; Rudert, Maximilian; Walles, Heike

2016-09-01

Cartilage degeneration is the major cause of chronic pain, lost mobility, and reduced quality of life for over estimated 150 million osteoarthritis sufferers worldwide. Despite intensive research, none of the available therapies can restore the hyaline cartilage surface beyond just fibrous repair. To overcome these limitations, numerous cell-based approaches for cartilage repair are being explored that aim to provide an appropriate microenvironment for chondrocyte maintenance and differentiation of multipotent mesenchymal stem cells (MSCs) toward the chondrogenic lineage. Articular cartilage is composed of highly organized collagen network that entails the tissue into four distinct zones and each zone into three different regions based on differences in matrix morphology and biochemistry. Current cartilage implants cannot establish the hierarchical tissue organization that seems critical for normal cartilage function. Therefore, in this study, a structured, multilayered collagen scaffold designed for the replacement of damaged cartilage is presented that allows repopulation by host cells and synthesis of a new natural matrix. By using the electrospinning method, the potential to engineer a scaffold consisting of two different collagen types is obtained. With the developed collagen scaffold, a five-layered biomaterial is created that has the potency to induce the differentiation of human bone marrow derived MSCs toward the chondrogenic lineage. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Accuracy of magnetic resonance imaging to detect cartilage loss in severe osteoarthritis of the first carpometacarpal joint: comparison with histological evaluation.

PubMed

Saltzherr, Michael S; Coert, J Henk; Selles, Ruud W; van Neck, Johan W; Jaquet, Jean-Bart; van Osch, Gerjo J V M; Oei, Edwin H G; Luime, Jolanda J; Muradin, Galied S R

2017-03-14

Magnetic resonance imaging (MRI) is increasingly used for research in hand osteoarthritis, but imaging the thin cartilage layers in the hand joints remains challenging. We therefore assessed the accuracy of MRI in detecting cartilage loss in patients with symptomatic osteoarthritis of the first carpometacarpal (CMC1) joint. Twelve patients scheduled for trapeziectomy to treat severe symptomatic osteoarthritis of the CMC1 joint underwent a preoperative high resolution 3D spoiled gradient (SPGR) MRI scan. Subsequently, the resected trapezium was evaluated histologically. The sections were scored for cartilage damage severity (Osteoarthritis Research Society International (OARSI) score), and extent of damage (percentage surface area). Each MRI scan was scored for the area of normal cartilage, partial cartilage loss and full cartilage loss. The percentages of the total surface area with any cartilage loss and full-thickness cartilage loss were calculated using MRI and histological evaluation. MRI and histological evaluation both identified large areas of overall cartilage loss. The median (IQR) surface area of any cartilage loss on MRI was 98% (82-100%), and on histological assessment 96% (87-98%). However, MRI underestimated the extent of full-thickness cartilage loss. The median (IQR) surface area of full-thickness cartilage loss on MRI was 43% (22-70%), and on histological evaluation 79% (67-85%). The difference was caused by a thin layer of high signal on the articulating surface, which was interpreted as damaged cartilage on MRI but which was not identified on histological evaluation. Three-dimensional SPGR MRI of the CMC1 joint demonstrates overall cartilage damage, but underestimates full-thickness cartilage loss in patients with advanced osteoarthritis.

Shaping skeletal growth by modular regulatory elements in the Bmp5 gene.

PubMed

Guenther, Catherine; Pantalena-Filho, Luiz; Kingsley, David M

2008-12-01

Cartilage and bone are formed into a remarkable range of shapes and sizes that underlie many anatomical adaptations to different lifestyles in vertebrates. Although the morphological blueprints for individual cartilage and bony structures must somehow be encoded in the genome, we currently know little about the detailed genomic mechanisms that direct precise growth patterns for particular bones. We have carried out large-scale enhancer surveys to identify the regulatory architecture controlling developmental expression of the mouse Bmp5 gene, which encodes a secreted signaling molecule required for normal morphology of specific skeletal features. Although Bmp5 is expressed in many skeletal precursors, different enhancers control expression in individual bones. Remarkably, we show here that different enhancers also exist for highly restricted spatial subdomains along the surface of individual skeletal structures, including ribs and nasal cartilages. Transgenic, null, and regulatory mutations confirm that these anatomy-specific sequences are sufficient to trigger local changes in skeletal morphology and are required for establishing normal growth rates on separate bone surfaces. Our findings suggest that individual bones are composite structures whose detailed growth patterns are built from many smaller lineage and gene expression domains. Individual enhancers in BMP genes provide a genomic mechanism for controlling precise growth domains in particular cartilages and bones, making it possible to separately regulate skeletal anatomy at highly specific locations in the body.

In Vitro Mimetic Models for the Bone-Cartilage Interface Regeneration.

PubMed

Bicho, Diana; Pina, Sandra; Oliveira, J Miguel; Reis, Rui L

2018-01-01

In embryonic development, pure cartilage structures are in the basis of bone-cartilage interfaces. Despite this fact, the mature bone and cartilage structures can vary greatly in composition and function. Nevertheless, they collaborate in the osteochondral region to create a smooth transition zone that supports the movements and forces resulting from the daily activities. In this sense, all the hierarchical organization is involved in the maintenance and reestablishment of the equilibrium in case of damage. Therefore, this interface has attracted a great deal of interest in order to understand the mechanisms of regeneration or disease progression in osteoarthritis. With that purpose, in vitro tissue models (either static or dynamic) have been studied. Static in vitro tissue models include monocultures, co-cultures, 3D cultures, and ex vivo cultures, mostly cultivated in flat surfaces, while dynamic models involve the use of bioreactors and microfluidic systems. The latter have emerged as alternatives to study the cellular interactions in a more authentic manner over some disadvantages of the static models. The current alternatives of in vitro mimetic models for bone-cartilage interface regeneration are overviewed and discussed herein.

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.

Combining μX-ray fluorescence, μXANES and μXRD to shed light on Zn2+ cations in cartilage and meniscus calcifications.

PubMed

Dessombz, Arnaud; Nguyen, Christelle; Ea, Hang-Korng; Rouzière, Stephan; Foy, Eddy; Hannouche, Didier; Réguer, Solene; Picca, Frederic-Emmanuel; Thiaudière, Dominique; Lioté, Frédéric; Daudon, Michel; Bazin, Dominique

2013-10-01

We aimed to examine the presence of Zn, a trace element, in osteoarthritis (OA) cartilage and meniscus from patients undergoing total knee joint replacement for primary OA. We mapped Ca(2+) and Zn(2+) at the mesoscopic scale by X-ray fluorescence microanalysis (μX-ray) to determine the spatial distribution of the 2 elements in cartilage, μX-ray absorption near edge structure spectroscopy to identify the Zn species, and μX-ray diffraction to determine the chemical nature of the calcification. Fourier transform infrared spectroscopy was used to determine the chemical composition of cartilage and meniscus. Ca(2+) showed a heterogeneous spatial distribution corresponding to the calcifications within cartilage (or meniscus) or at their surface. At least 2 Zn(2+) species were present: the first may correspond to Zn embedded in protein (different Zn metalloproteins are known to prevent calcification in biological tissues), and the second may be associated with a Zn trap in or at the surface of the calcification. Calcification present in OA cartilage may significantly modify the spatial distribution of Zn; part of the Zn may be trapped in the calcification and may alter the associated biological function of Zn metalloproteins. Copyright © 2013 Elsevier GmbH. All rights reserved.

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

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.

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.

Solute Transport of Negatively Charged Contrast Agents Across Articular Surface of Injured Cartilage.

PubMed

Kokkonen, H T; Chin, H C; Töyräs, J; Jurvelin, J S; Quinn, T M

2017-04-01

Solute transport through the extracellular matrix (ECM) is crucial to chondrocyte metabolism. Cartilage injury affects solute transport in cartilage due to alterations in ECM structure and solute-matrix interactions. Therefore, cartilage injury may be detected by using contrast agent-based clinical imaging. In the present study, effects of mechanical injury on transport of negatively charged contrast agents in cartilage were characterized. Using cartilage plugs injured by mechanical compression protocol, effective partition coefficients and diffusion fluxes of iodine- and gadolinium-based contrast agents were measured using high resolution microCT imaging. For all contrast agents studied, effective diffusion fluxes increased significantly, particularly at early times during the diffusion process (38 and 33% increase after 4 min, P < 0.05 for iodine and Gd-DTPA; and 76% increase after 10 min for diatrizoate, P < 0.05). Effective partition coefficients were unaffected in mechanically injured cartilage. Mechanical injury reduced PG content and collagen integrity in cartilage superficial zone. This study suggests that alterations in contrast agent diffusion flux, a non-equilibrium transport parameter, provides a more sensitive indicator for assessment of cartilage matrix integrity than partition coefficient and the equilibrium distribution of solute. These findings may help in developing clinical methods of contrast agent-based imaging to detect cartilage injury.

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.

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.

Nano Scale Mechanical Analysis of Biomaterials Using Atomic Force Microscopy

NASA Astrophysics Data System (ADS)

Dutta, Diganta

The atomic force microscope (AFM) is a probe-based microscope that uses nanoscale and structural imaging where high resolution is desired. AFM has also been used in mechanical, electrical, and thermal engineering applications. This unique technique provides vital local material properties like the modulus of elasticity, hardness, surface potential, Hamaker constant, and the surface charge density from force versus displacement curve. Therefore, AFM was used to measure both the diameter and mechanical properties of the collagen nanostraws in human costal cartilage. Human costal cartilage forms a bridge between the sternum and bony ribs. The chest wall of some humans is deformed due to defective costal cartilage. However, costal cartilage is less studied compared to load bearing cartilage. Results show that there is a difference between chemical fixation and non-chemical fixation treatments. Our findings imply that the patients' chest wall is mechanically weak and protein deposition is abnormal. This may impact the nanostraws' ability to facilitate fluid flow between the ribs and the sternum. At present, AFM is the only tool for imaging cells' ultra-structure at the nanometer scale because cells are not homogeneous. The first layer of the cell is called the cell membrane, and the layer under it is made of the cytoskeleton. Cancerous cells are different from normal cells in term of cell growth, mechanical properties, and ultra-structure. Here, force is measured with very high sensitivity and this is accomplished with highly sensitive probes such as a nano-probe. We performed experiments to determine ultra-structural differences that emerge when such cancerous cells are subject to treatments such as with drugs and electric pulses. Jurkat cells are cancerous cells. These cells were pulsed at different conditions. Pulsed and non-pulsed Jurkat cell ultra-structures were investigated at the nano meter scale using AFM. Jurkat cell mechanical properties were measured under different conditions. In addition, AFM was used to measure the charge density of cell surface in physiological conditions. We found that the treatments changed the cancer cells' ultra-structural and mechanical properties at the nanometer scale. Finally, we used AFM to characterize many non-biological materials with relevance to biomedical science. Various metals, polymers, and semi-conducting materials were characterized in air and multiple liquid media through AFM - techniques from which a plethora of industries can benefit. This applies especially to the fledging solar industry which has found much promise in nanoscopic insights. Independent of the material being examined, a reliable method to measure the surface force between a nano probe and a sample surface in a variety of ionic concentrations was also found in the process of procuring these measurements. The key findings were that the charge density increases with the increase of the medium's ionic concentration.

Determination of characteristics of degenerative joint disease using optical coherence tomography and polarization sensitive optical coherence tomography.

PubMed

Xie, Tuqiang; Guo, Shuguang; Zhang, Jun; Chen, Zhongping; Peavy, George M

2006-10-01

Previous studies have demonstrated that optical coherence tomography (OCT) could be used to delineate alterations in the microstructure of cartilage, and have suggested that changes in the polarization state of light as detected by OCT could provide information on the birefringence properties of articular cartilage as influenced by disease. In this study we have used both OCT and polarization sensitive optical coherence tomography (PS-OCT) technologies to evaluate normal and abnormal bovine articular cartilage according to established structural, organizational, and birefringent characteristics of degenerative joint disease (DJD) in order to determine if this technology can be used to differentiate various stages of DJD as a minimally invasive imaging tool. Fresh bovine femoral-tibial joints were obtained from an abattoir, and 45 cartilage specimens were harvested from 8 tibial plateaus. Whole ex vivo specimens of normal and degenerative articular cartilage were imaged by both OCT and PS-OCT, then fixed and processed for histological evaluation. OCT/PS-OCT images and corresponding histology sections of each specimen were scored according to a modified Mankin structural grading scale and compared. OCT and PS-OCT imaging allowed structural evaluation of intact articular cartilage along a 6 mm surface length to a depth of 2 mm with a transverse resolution of 12 microm and an axial resolution of 10 microm. The OCT and PS-OCT images demonstrated characteristic alterations in the structure of articular cartilage with a high correlation to histological evaluation (kappa = 0.776). The OCT images were able to demonstrate early to advanced structural changes of articular cartilage while the optical phase retardation images obtained by PS-OCT imaging were able to discriminate areas where disorganization of the cartilage matrix was present, however, these characteristics are much different than those reported where OCT images alone were used to characterize tissue birefringence. No evidence of differences in OCT or PS-OCT images were detected between specimens of similar structural characteristics where proteoglycan was judged present or absent by safranin-O Fast Green staining. The combined use of OCT and PS-OCT technologies to obtain images from a single system is able to demonstrate and discriminate between characteristics of very early stages of surface irregularities not previously reported for OCT imaging, to deep clefts and collagen matrix disorganization for tissue at depths of up to 2 mm with good correlation to histology. PS-OCT and accumulated optical phase retardation images of articular cartilage as constructed from alterations in Stokes vector parameters appear to give a valuable but different assessment of alterations in tissue birefringence and organization than have been reported for OCT images obtained with the use of polarized or non-polarized light sources. This is the first time that alterations in the polarization state of light reflected from within the tissue have been demonstrated to be consistent with changes observed in the orientation and organization of the collagen matrix in advanced stages of DJD. The degree of phase transformation of light reflected from within the tissue as determined by PS-OCT imaging does not appear to be altered by the presence or absence of proteoglycan.

Micrometer scale guidance of mesenchymal stem cells to form structurally oriented large-scale tissue engineered cartilage.

PubMed

Chou, Chih-Ling; Rivera, Alexander L; Williams, Valencia; Welter, Jean F; Mansour, Joseph M; Drazba, Judith A; Sakai, Takao; Baskaran, Harihara

2017-09-15

Current clinical methods to treat articular cartilage lesions provide temporary relief of the symptoms but fail to permanently restore the damaged tissue. Tissue engineering, using mesenchymal stem cells (MSCs) combined with scaffolds and bioactive factors, is viewed as a promising method for repairing cartilage injuries. However, current tissue engineered constructs display inferior mechanical properties compared to native articular cartilage, which could be attributed to the lack of structural organization of the extracellular matrix (ECM) of these engineered constructs in comparison to the highly oriented structure of articular cartilage ECM. We previously showed that we can guide MSCs undergoing chondrogenesis to align using microscale guidance channels on the surface of a two-dimensional (2-D) collagen scaffold, which resulted in the deposition of aligned ECM within the channels and enhanced mechanical properties of the constructs. In this study, we developed a technique to roll 2-D collagen scaffolds containing MSCs within guidance channels in order to produce a large-scale, three-dimensional (3-D) tissue engineered cartilage constructs with enhanced mechanical properties compared to current constructs. After rolling the MSC-scaffold constructs into a 3-D cylindrical structure, the constructs were cultured for 21days under chondrogenic culture conditions. The microstructure architecture and mechanical properties of the constructs were evaluated using imaging and compressive testing. Histology and immunohistochemistry of the constructs showed extensive glycosaminoglycan (GAG) and collagen type II deposition. Second harmonic generation imaging and Picrosirius red staining indicated alignment of neo-collagen fibers within the guidance channels of the constructs. Mechanical testing indicated that constructs containing the guidance channels displayed enhanced compressive properties compared to control constructs without these channels. In conclusion, using a novel roll-up method, we have developed large scale MSC based tissue-engineered cartilage that shows microscale structural organization and enhanced compressive properties compared to current tissue engineered constructs. Tissue engineered cartilage constructs made with human mesenchymal stem cells (hMSCs), scaffolds and bioactive factors are a promising solution to treat cartilage defects. A major disadvantage of these constructs is their inferior mechanical properties compared to the native tissue, which is likely due to the lack of structural organization of the extracellular matrix of the engineered constructs. In this study, we developed three-dimensional (3-D) cartilage constructs from rectangular scaffold sheets containing hMSCs in micro-guidance channels and characterized their mechanical properties and metabolic requirements. The work led to a novel roll-up method to embed 2-D microscale structures in 3-D constructs. Further, micro-guidance channels incorporated within the 3-D cartilage constructs led to the production of aligned cell-produced matrix and enhanced mechanical function. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Quantitative assessment of optical properties in healthy cartilage and repair tissue by optical coherence tomography and histology (Conference Presentation)

NASA Astrophysics Data System (ADS)

Jansen, Sanne M. A.; Cernohorsky, Paul; de Bruin, Daniel M.; van der Pol, Edwin; Savci-Heijink, Cemile D.; Strackee, Simon D.; Faber, Dirk J.; van Leeuwen, Ton G.

2016-02-01

Quantification of the OCT signal is an important step toward clinical implementation of a diagnostic tool in cartilage imaging. Discrimination of structural cartilage differences in patients with osteoarthritis is critical, yet challenging. This study assesses the variation in the optical attenuation coefficient (μOCT) between healthy cartilage, repair tissue, bone and layers within repair tissue in a controlled setting. OCT and histology was used to assess goat talus articular surfaces in which central osteochondral defects were created. Exact matches of OCT and histology were selected for research. μOCT measurements were taken from healthy cartilage, repair tissue and bone. Measured μOCT in healthy cartilage was higher compared to both repair tissue and bone tissue. Two possible mechanisms for the difference in attenuation were investigated. We studied morphological parameters in terms of nucleus count, nucleus size and inter-nucleus distance. Collagen content in healthy cartilage and repair tissue was assessed using polarization microscopy. Quantitative analysis of the nuclei did not demonstrate a difference in nucleus size and count between healthy cartilage and repair tissue. In healthy cartilage, cells were spaced farther apart and had a lower variation in local nuclear density compared to repair tissue. Polarization microscopy suggested higher collagen content in healthy cartilage compared to repair tissue. μOCT measurements can distinguish between healthy cartilage, repair tissue and bone. Results suggest that cartilage OCT attenuation measurements could be of great impact in clinical diagnostics of osteoarthritis.

Optimization of the arthroscopic indentation instrument for the measurement of thin cartilage stiffness

NASA Astrophysics Data System (ADS)

Lyyra-Laitinen, Tiina; Niinimäki, Mia; Töyräs, Juha; Lindgren, Reijo; Kiviranta, Ilkka; Jurvelin, Jukka S.

1999-10-01

Structural alterations associated with early, mostly reversible, degeneration of articular cartilage induce tissue softening, generally preceding fibrillation and, thus, visible changes of the cartilage surface. We have already developed an indentation instrument for measuring arthroscopic stiffness of cartilage with typical thickness >2 mm. The aim of this study was to extend the applicability of the instrument for the measurement of thin (<2 mm) cartilage stiffness. Variations in cartilage thickness, which will not be known during arthroscopy, can nonetheless affect the indentation measurement, and therefore optimization of the indenter dimensions is necessary. First, we used theoretical and finite element models to compare plane-ended and spherical-ended indenters and, then, altered the dimensions to determine the optimal indenter for thin cartilage measurements. Finally, we experimentally validated the optimized indenter using bovine humeral head cartilage. Reference unconfined compression measurements were carried out with a material testing device. The spherical-ended indenter was more insensitive to the alterations in cartilage thickness (20% versus 39% in the thickness range 1.5-5 mm) than the plane-ended indenter. For thin cartilage, the optimal dimensions for the spherical-ended indenter were 0.5 mm for diameter and 0.1 mm for height. The experimental stiffness measurements with this indenter correlated well with the reference measurements (r = 0.811, n = 31, p<0.0001) in the cartilage thickness range 0.7-1.8 mm. We conclude that the optimized indenter is reliable and well suited for the measurement of thin cartilage stiffness.

Mesenchymal Stem Cells in Oriented PLGA/ACECM Composite Scaffolds Enhance Structure-Specific Regeneration of Hyaline Cartilage in a Rabbit Model

PubMed Central

Guo, Weimin; Zheng, Xifu; Zhang, Weiguo; Chen, Mingxue; Wang, Zhenyong; Hao, Chunxiang; Huang, Jingxiang; Yuan, Zhiguo; Zhang, Yu; Wang, Mingjie; Peng, Jiang; Wang, Aiyuan; Wang, Yu; Sui, Xiang; Xu, Wenjing

2018-01-01

Articular cartilage lacks a blood supply and nerves. Hence, articular cartilage regeneration remains a major challenge in orthopedics. Decellularized extracellular matrix- (ECM-) based strategies have recently received particular attention. The structure of native cartilage exhibits complex zonal heterogeneity. Specifically, the development of a tissue-engineered scaffold mimicking the aligned structure of native cartilage would be of great utility in terms of cartilage regeneration. Previously, we fabricated oriented PLGA/ACECM (natural, nanofibrous, articular cartilage ECM) composite scaffolds. In vitro, we found that the scaffolds not only guided seeded cells to proliferate in an aligned manner but also exhibited high biomechanical strength. To detect whether oriented cartilage regeneration was possible in vivo, we used mesenchymal stem cell (MSC)/scaffold constructs to repair cartilage defects. The results showed that cartilage defects could be completely regenerated. Histologically, these became filled with hyaline cartilage and subchondral bone. Moreover, the aligned structure of cartilage was regenerated and was similar to that of native tissue. In conclusion, the MSC/scaffold constructs enhanced the structure-specific regeneration of hyaline cartilage in a rabbit model and may be a promising treatment strategy for the repair of human cartilage defects. PMID:29666653

Mesenchymal Stem Cells in Oriented PLGA/ACECM Composite Scaffolds Enhance Structure-Specific Regeneration of Hyaline Cartilage in a Rabbit Model.

PubMed

Guo, Weimin; Zheng, Xifu; Zhang, Weiguo; Chen, Mingxue; Wang, Zhenyong; Hao, Chunxiang; Huang, Jingxiang; Yuan, Zhiguo; Zhang, Yu; Wang, Mingjie; Peng, Jiang; Wang, Aiyuan; Wang, Yu; Sui, Xiang; Xu, Wenjing; Liu, Shuyun; Lu, Shibi; Guo, Quanyi

2018-01-01

Articular cartilage lacks a blood supply and nerves. Hence, articular cartilage regeneration remains a major challenge in orthopedics. Decellularized extracellular matrix- (ECM-) based strategies have recently received particular attention. The structure of native cartilage exhibits complex zonal heterogeneity. Specifically, the development of a tissue-engineered scaffold mimicking the aligned structure of native cartilage would be of great utility in terms of cartilage regeneration. Previously, we fabricated oriented PLGA/ACECM (natural, nanofibrous, articular cartilage ECM) composite scaffolds. In vitro, we found that the scaffolds not only guided seeded cells to proliferate in an aligned manner but also exhibited high biomechanical strength. To detect whether oriented cartilage regeneration was possible in vivo, we used mesenchymal stem cell (MSC)/scaffold constructs to repair cartilage defects. The results showed that cartilage defects could be completely regenerated. Histologically, these became filled with hyaline cartilage and subchondral bone. Moreover, the aligned structure of cartilage was regenerated and was similar to that of native tissue. In conclusion, the MSC/scaffold constructs enhanced the structure-specific regeneration of hyaline cartilage in a rabbit model and may be a promising treatment strategy for the repair of human cartilage defects.

A subdivision-based parametric deformable model for surface extraction and statistical shape modeling of the knee cartilages

NASA Astrophysics Data System (ADS)

Fripp, Jurgen; Crozier, Stuart; Warfield, Simon K.; Ourselin, Sébastien

2006-03-01

Subdivision surfaces and parameterization are desirable for many algorithms that are commonly used in Medical Image Analysis. However, extracting an accurate surface and parameterization can be difficult for many anatomical objects of interest, due to noisy segmentations and the inherent variability of the object. The thin cartilages of the knee are an example of this, especially after damage is incurred from injuries or conditions like osteoarthritis. As a result, the cartilages can have different topologies or exist in multiple pieces. In this paper we present a topology preserving (genus 0) subdivision-based parametric deformable model that is used to extract the surfaces of the patella and tibial cartilages in the knee. These surfaces have minimal thickness in areas without cartilage. The algorithm inherently incorporates several desirable properties, including: shape based interpolation, sub-division remeshing and parameterization. To illustrate the usefulness of this approach, the surfaces and parameterizations of the patella cartilage are used to generate a 3D statistical shape model.

INTERACTION OF LASER RADIATION WITH MATTER: Calculation of the kinetics of heating and structural changes in the cartilaginous tissue under the action of laser radiation

NASA Astrophysics Data System (ADS)

Sobol', E. N.; Kitai, M. S.

1998-07-01

A theoretical model is developed for the calculation of the temperature fields and determination of the size of a zone with structural changes in the cartilaginous tissue. The model is based on a simultaneous analysis of the heat and mass transfer processes and it takes into account the bulk absorption of laser radiation by the tissue, surface evaporation of water, and temperature dependences of the diffusion coefficients. It is assumed that under the influence of a phase transition between free and bound water, caused by heating of the cartilage to 70°C, the proteoglycans of the cartilage matrix become mobile and, as a result of such mass transfer, structural changes are induced in the cartilaginous tissue causing relaxation of stresses or denaturation. It is shown that the maximum temperature is then reached not on the irradiated surface but at some distance from it, and that the size of the zones of structural changes (denaturation depth) depends strongly on the energy density of the laser radiation and its wavelength, on the duration of the irradiation, and on the cartilage thickness. This model makes it possible to calculate the temperature fields and the depth of structural changes in laser-induced relaxation of stresses and changes in the shape of the cartilaginous tissue.

The amphoteric effect on friction between the bovine cartilage/cartilage surfaces under slightly sheared hydration lubrication mode.

PubMed

Pawlak, Zenon; Gadomski, Adam; Sojka, Michal; Urbaniak, Wieslaw; Bełdowski, Piotr

2016-10-01

The amphoteric effect on the friction between the bovine cartilage/cartilage contacts has been found to be highly sensitive to the pH of an aqueous solution. The cartilage surface was characterized using a combination of the pH, wettability, as well as the interfacial energy and friction coefficient testing methods to support lamellar-repulsive mechanism of hydration lubrication. It has been confirmed experimentally that phospholipidic multi-bilayers are essentially described as lamellar frictionless lubricants protecting the surface of the joints against wear. At the hydrophilicity limit, the low friction would then be due to (a) lamellar slippage of bilayers and (b) a short-range (nanometer-scale) repulsion between the interfaces of negatively charged (PO4(-)) cartilage surfaces, and in addition, contribution of the extracellular matrix (ECM) collagen fibers, hyaluronate, proteoglycans aggregates (PGs), glycoprotein termed lubricin and finally, lamellar PLs phases. In this paper we demonstrate experimentally that the pH sensitivity of cartilage to friction provides a novel concept in joint lubrication on charged surfaces. Copyright © 2016 Elsevier B.V. All rights reserved.

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.

[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.

Two-photon excitation laser scanning microscopy of rabbit nasal septal cartilage following Nd:YAG-laser-mediated stress relaxation

NASA Astrophysics Data System (ADS)

Kim, Charlton C.; Wallace, Vincent P.; Coleno, Mariah L.; Dao, Xavier; Tromberg, Bruce J.; Wong, Brian J.

2000-04-01

Laser irradiation of hyaline cartilage result in stable shape changes due to temperature dependent stress relaxation. In this study, we determined the structural changes in chondrocytes within rabbit nasal septal cartilage tissue over a 12-day period using a two-photon laser scanning microscope (TPM) following Nd:YAG laser irradiation. During laser irradiation surface temperature, stress relaxation, and diffuse reflectance, were measured dynamically. Each specimen received one or two sequential laser exposures. The cartilage reached a peak surface temperature of about 61 degrees C during irradiation. Cartilage denatured in 50 percent EtOH was used as a positive control. TPM was performed to detect the fluorescence emission from the chondrocytes. Images of chondrocytes were obtained at depths up to 150 microns, immediately following laser exposure, and also following 12 days in culture. Few differences in the pattern or intensity of fluorescence was observed between controls and irradiated specimens imaged immediately following exposure, regardless of the number of laser pulses. However, following twelve days in tissue culture, the irradiated specimens increase, whereas the native tissue diminishes, in intensity and distribution of fluorescence in the cytoplasm. In contrast, the positive control shows only extracellular matrices and empty lacuna, feature consistent with cell membrane lysis.

Simultaneous segmentation of the bone and cartilage surfaces of a knee joint in 3D

NASA Astrophysics Data System (ADS)

Yin, Y.; Zhang, X.; Anderson, D. D.; Brown, T. D.; Hofwegen, C. Van; Sonka, M.

2009-02-01

We present a novel framework for the simultaneous segmentation of multiple interacting surfaces belonging to multiple mutually interacting objects. The method is a non-trivial extension of our previously reported optimal multi-surface segmentation. Considering an example application of knee-cartilage segmentation, the framework consists of the following main steps: 1) Shape model construction: Building a mean shape for each bone of the joint (femur, tibia, patella) from interactively segmented volumetric datasets. Using the resulting mean-shape model - identification of cartilage, non-cartilage, and transition areas on the mean-shape bone model surfaces. 2) Presegmentation: Employment of iterative optimal surface detection method to achieve approximate segmentation of individual bone surfaces. 3) Cross-object surface mapping: Detection of inter-bone equidistant separating sheets to help identify corresponding vertex pairs for all interacting surfaces. 4) Multi-object, multi-surface graph construction and final segmentation: Construction of a single multi-bone, multi-surface graph so that two surfaces (bone and cartilage) with zero and non-zero intervening distances can be detected for each bone of the joint, according to whether or not cartilage can be locally absent or present on the bone. To define inter-object relationships, corresponding vertex pairs identified using the separating sheets were interlinked in the graph. The graph optimization algorithm acted on the entire multiobject, multi-surface graph to yield a globally optimal solution. The segmentation framework was tested on 16 MR-DESS knee-joint datasets from the Osteoarthritis Initiative database. The average signed surface positioning error for the 6 detected surfaces ranged from 0.00 to 0.12 mm. When independently initialized, the signed reproducibility error of bone and cartilage segmentation ranged from 0.00 to 0.26 mm. The results showed that this framework provides robust, accurate, and reproducible segmentation of the knee joint bone and cartilage surfaces of the femur, tibia, and patella. As a general segmentation tool, the developed framework can be applied to a broad range of multi-object segmentation problems.

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 cues for cells. We used microindentation to map the time-dependent properties of untreated and trypsin treated cartilage throughout each cartilage zone. Unlike conventional approaches that combine viscoelastic and poroelastic behaviors into a single framework, we deconvoluted the mechanical response into separate contributions to time-dependent behavior. Poroelastic effects in all cartilage zones dominated the time-dependent behavior of articular cartilage, and a model that incorporates tension-compression nonlinearity best represented cartilage mechanical behavior. These results can be used to assess the success of regeneration and repair approaches, as design targets for tissue engineering, and for development of accurate computational models. Copyright © 2017 Acta Materialia Inc. All rights reserved.

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.

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

Innovative application of optical techniques to comprehensive study of the etiology of osteoarthritis

NASA Astrophysics Data System (ADS)

Ugryumova, Nadya; Matcher, Stephen J.

2006-08-01

Osteoarthritis is a painful condition, causing restricted mobility in the articular joints. In this paper we present a review of different optical techniques that might be used to clarify the etiology of degeneration of connective joint tissues, such as bone and articular cartilage. Significant correlation (R2 = 0.8) between bone mineral density and scattering coefficient of cortical bone tissue are found by using Integrating Sphere Technique. Optical Coherence Tomography and Polarization-Sensitive Optical Coherence Tomography images of cartilage tissue are presented. They were performed as series of angle-dependant measurements for different location along the surface. Method for spatial mapping the birefringence of equine articular cartilage is proposed. Variations in band spacing of birefringence obtained from visually healthy and abnormal cartilage samples are compared. Visible osteoarthritic lesions are characterized by a loss of the regular birefringence bands shown by normal cartilage. We discuss the hypothesis that some of these variations may be due to changes in intrinsic structure of tissue.

An overview of multiphase cartilage mechanical modelling and its role in understanding function and pathology.

PubMed

Klika, Václav; Gaffney, Eamonn A; Chen, Ying-Chun; Brown, Cameron P

2016-09-01

There is a long history of mathematical and computational modelling with the objective of understanding the mechanisms governing cartilage׳s remarkable mechanical performance. Nonetheless, despite sophisticated modelling development, simulations of cartilage have consistently lagged behind structural knowledge and thus the relationship between structure and function in cartilage is not fully understood. However, in the most recent generation of studies, there is an emerging confluence between our structural knowledge and the structure represented in cartilage modelling. This raises the prospect of further refinement in our understanding of cartilage function and also the initiation of an engineering-level understanding for how structural degradation and ageing relates to cartilage dysfunction and pathology, as well as informing the potential design of prospective interventions. Aimed at researchers entering the field of cartilage modelling, we thus review the basic principles of cartilage models, discussing the underlying physics and assumptions in relatively simple settings, whilst presenting the derivation of relatively parsimonious multiphase cartilage models consistent with our discussions. We proceed to consider modern developments that start aligning the structure captured in the models with observed complexities. This emphasises the challenges associated with constitutive relations, boundary conditions, parameter estimation and validation in cartilage modelling programmes. Consequently, we further detail how both experimental interrogations and modelling developments can be utilised to investigate and reduce such difficulties before summarising how cartilage modelling initiatives may improve our understanding of cartilage ageing, pathology and intervention. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Polyester type polyHIPE scaffolds with an interconnected porous structure for cartilage regeneration

NASA Astrophysics Data System (ADS)

Naranda, Jakob; Sušec, Maja; Maver, Uroš; Gradišnik, Lidija; Gorenjak, Mario; Vukasović, Andreja; Ivković, Alan; Rupnik, Marjan Slak; Vogrin, Matjaž; Krajnc, Peter

2016-06-01

Development of artificial materials for the facilitation of cartilage regeneration remains an important challenge in orthopedic practice. Our study investigates the potential for neocartilage formation within a synthetic polyester scaffold based on the polymerization of high internal phase emulsions. The fabrication of polyHIPE polymer (PHP) was specifically tailored to produce a highly porous (85%) structure with the primary pore size in the range of 50-170 μm for cartilage tissue engineering. The resulting PHP scaffold was proven biocompatible with human articular chondrocytes and viable cells were observed within the materials as evaluated using the Live/Dead assay and histological analysis. Chondrocytes with round nuclei were organized into multicellular layers on the PHP surface and were observed to grow approximately 300 μm into the scaffold interior. The accumulation of collagen type 2 was detected using immunohistochemistry and chondrogenic specific genes were expressed with favorable collagen type 2 to 1 ratio. In addition, PHP samples are biodegradable and their baseline mechanical properties are similar to those of native cartilage, which enhance chondrocyte cell growth and proliferation.

Polyester type polyHIPE scaffolds with an interconnected porous structure for cartilage regeneration

PubMed Central

Naranda, Jakob; Sušec, Maja; Maver, Uroš; Gradišnik, Lidija; Gorenjak, Mario; Vukasović, Andreja; Ivković, Alan; Rupnik, Marjan Slak; Vogrin, Matjaž; Krajnc, Peter

2016-01-01

Development of artificial materials for the facilitation of cartilage regeneration remains an important challenge in orthopedic practice. Our study investigates the potential for neocartilage formation within a synthetic polyester scaffold based on the polymerization of high internal phase emulsions. The fabrication of polyHIPE polymer (PHP) was specifically tailored to produce a highly porous (85%) structure with the primary pore size in the range of 50–170 μm for cartilage tissue engineering. The resulting PHP scaffold was proven biocompatible with human articular chondrocytes and viable cells were observed within the materials as evaluated using the Live/Dead assay and histological analysis. Chondrocytes with round nuclei were organized into multicellular layers on the PHP surface and were observed to grow approximately 300 μm into the scaffold interior. The accumulation of collagen type 2 was detected using immunohistochemistry and chondrogenic specific genes were expressed with favorable collagen type 2 to 1 ratio. In addition, PHP samples are biodegradable and their baseline mechanical properties are similar to those of native cartilage, which enhance chondrocyte cell growth and proliferation. PMID:27340110

Characterization of the surface and interfacial properties of the lamina splendens

NASA Astrophysics Data System (ADS)

Rexwinkle, Joe T.; Hunt, Heather K.; Pfeiffer, Ferris M.

2017-06-01

Joint disease affects approximately 52.5 million patients in the United States alone, costing 80.8 billion USD in direct healthcare costs. The development of treatment programs for joint disease and trauma requires accurate assessment of articular cartilage degradation. The articular cartilage is the interfacial tissue between articulating surfaces, such as bones, and acts as low-friction interfaces. Damage to the lamina splendens, which is the articular cartilage's topmost layer, is an early indicator of joint degradation caused by injury or disease. By gaining comprehensive knowledge on the lamina splendens, particularly its structure and interfacial properties, researchers could enhance the accuracy of human and animal biomechanical models, as well as develop appropriate biomimetic materials for replacing damaged articular cartilage, thereby leading to rational treatment programs for joint disease and injury. Previous studies that utilize light, electron, and force microscopy techniques have found that the lamina splendens is composed of collagen fibers oriented parallel to the cartilage surface and encased in a proteoglycan matrix. Such orientation maximizes wear resistance and proteoglycan retention while promoting the passage of nutrients and synovial fluid. Although the structure of the lamina splendens has been explored in the literature, the low-friction interface of this tissue remains only partially characterized. Various functional models are currently available for the interface, such as pure boundary lubrication, thin films exuded under pressure, and sheets of trapped proteins. Recent studies suggest that each of these lubrication models has certain advantages over one another. Further research is needed to fully model the interface of this tissue. In this review, we summarize the methods for characterizing the lamina splendens and the results of each method. This paper aims to serve as a resource for existing studies to date and a roadmap of the investigations needed to gain further insight into the lamina splendens and the progression of joint disease.

Medial Meniscal Extrusion Relates to Cartilage Loss in Specific Femorotibial Subregions- Data from the Osteoarthritis Initiative

PubMed Central

Bloecker, K.; Wirth, W.; Guermazi, A.; Hunter, DJ; Resch, H.; Hochreiter, J.; Eckstein, F.

2015-01-01

Objective Medial meniscal extrusion is known to be related to structural progression of knee OA. However, it is unclear whether medial meniscal extrusion is more strongly associated with cartilage loss in certain medial femorotibial subregions than to others. Methods Segmentation of the medial tibial and femoral cartilage (baseline; 1-year follow-up) and the medial meniscus (baseline) was performed in 60 participants with frequent knee pain (age 61.3±9.2y, BMI 31.3±3.9 kg/m2) and with unilateral medial radiographic joint space narrowing (JSN) grade 1–3, using double echo steady state MR-images. Medial meniscal extrusion distance and extrusion area (%) between the external meniscal and tibial margin at baseline, and longitudinal medial cartilage loss in eight anatomical subregions were determined. Results A significant association (Pearson correlation coefficient) was seen between medial meniscus extrusion area in JSN knees and cartilage loss over one year throughout the entire medial femorotibial compartment. The strongest correlation was with cartilage loss in the external medial tibia (r=−0.34 [p<0.01] in JSN, and r=−0.30 [p=0.02] in noJSN knees). Conclusion Medial meniscus extrusion was associated with subsequent medial cartilage loss. The external medial tibial cartilage may be particularly vulnerable to thinning once the meniscus extrudes and its surface is “exposed” to direct, non-physiological, cartilage-cartilage contact. PMID:25988986

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

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.

[The three-dimensional simulation of arytenoid cartilage movement].

PubMed

Zhang, Jun; Wang, Xuefeng

2011-08-01

Exploring the characteristics of arytenoid cartilage movement. Using Pro/ENGINEER (Pro/E) software, the cricoid cartilage, arytenoid cartilage and vocal cords were simulated to the three-dimensional reconstruction, by analyzing the trajectory of arytenoid cartilage in the joint surface from the cricoid cartilage and arytenoid cartilage composition. The 3D animation simulation showed the normal movement patterns of the vocal cords and the characteristics of vocal cords movement in occasion of arytenoid cartilage dislocation vividly. The three-dimensional model has clinical significance for arytenoid cartilage movement disorders.

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.

Simple geometry tribological study of osteochondral graft implantation in the knee.

PubMed

Bowland, Philippa; Ingham, Eileen; Fisher, John; Jennings, Louise M

2018-03-01

Robust preclinical test methods involving tribological simulations are required to investigate and understand the tribological function of osteochondral repair interventions in natural knee tissues. The aim of this study was to investigate the effects of osteochondral allograft implantation on the local tribology (friction, surface damage, wear and deformation) of the tissues in the natural knee joint using a simple geometry, reciprocating pin-on-plate friction simulator. In addition, the study aimed to assess the ability of osteochondral grafts to restore a low surface damage, deformation and wear articulation when compared to the native state. A method was developed to characterise and quantify surface damage wear and deformation of the opposing cartilage-bone pin surface using a non-contacting optical profiler (Alicona Infinite Focus). Porcine 12 mm diameter cartilage-bone pins were reciprocated against bovine cartilage-bone plates that had 6 mm diameter osteochondral allografts, cartilage defects or stainless steel pins (positive controls) inserted centrally. Increased levels of surface damage with changes in geometry were not associated with significant increases in the coefficient of dynamic friction. Significant damage to the opposing cartilage surface was observed in the positive control groups. Cartilage damage, deformation and wear (as measured by change in geometry) in the xenograft (2.4 mm 3 ) and cartilage defect (0.99 mm 3 ) groups were low and not significantly different (p > 0.05) compared to the negative control in either group. The study demonstrated the potential of osteochondral grafts to restore the congruent articular surface and biphasic tribology of the natural joint. An optical method has been developed to characterise cartilage wear, damage and deformation that can be applied to the tribological assessment of osteochondral grafts in a whole natural knee joint simulation model.

Simple geometry tribological study of osteochondral graft implantation in the knee

PubMed Central

Bowland, Philippa; Ingham, Eileen; Fisher, John; Jennings, Louise M

2018-01-01

Robust preclinical test methods involving tribological simulations are required to investigate and understand the tribological function of osteochondral repair interventions in natural knee tissues. The aim of this study was to investigate the effects of osteochondral allograft implantation on the local tribology (friction, surface damage, wear and deformation) of the tissues in the natural knee joint using a simple geometry, reciprocating pin-on-plate friction simulator. In addition, the study aimed to assess the ability of osteochondral grafts to restore a low surface damage, deformation and wear articulation when compared to the native state. A method was developed to characterise and quantify surface damage wear and deformation of the opposing cartilage-bone pin surface using a non-contacting optical profiler (Alicona Infinite Focus). Porcine 12 mm diameter cartilage-bone pins were reciprocated against bovine cartilage-bone plates that had 6 mm diameter osteochondral allografts, cartilage defects or stainless steel pins (positive controls) inserted centrally. Increased levels of surface damage with changes in geometry were not associated with significant increases in the coefficient of dynamic friction. Significant damage to the opposing cartilage surface was observed in the positive control groups. Cartilage damage, deformation and wear (as measured by change in geometry) in the xenograft (2.4 mm3) and cartilage defect (0.99 mm3) groups were low and not significantly different (p > 0.05) compared to the negative control in either group. The study demonstrated the potential of osteochondral grafts to restore the congruent articular surface and biphasic tribology of the natural joint. An optical method has been developed to characterise cartilage wear, damage and deformation that can be applied to the tribological assessment of osteochondral grafts in a whole natural knee joint simulation model. PMID:29375001

Menopause is associated with articular cartilage degeneration: a clinical study of knee joint in 860 women.

PubMed

Lou, Chao; Xiang, Guangheng; Weng, Qiaoyou; Chen, Zhaojie; Chen, Deheng; Wang, Qingqing; Zhang, Di; Zhou, Bin; He, Dengwei; Chen, Hongliang

2016-11-01

The purpose of this study was to investigate the association between menopause and severity of knee joint cartilage degeneration using a magnetic resonance imaging-based six-level grading system, with six cartilage surfaces, the medial and lateral femoral condyle, the femoral trochlea, the medial and lateral tibia plateau, and the patella. The study cohort comprised 860 healthy women (age 36-83 y), and 5,160 cartilage surfaces were analyzed. Age, weight, height, age at natural menopause, and years since menopause (YSM) were obtained. Cartilage degeneration was assessed using a magnetic resonance imaging-based six-level grading system. After removing the age, height, and weight effects, postmenopausal women had more severe cartilage degeneration than pre- and perimenopausal women (P < 0.001). A positive trend was observed between YSM and severity of cartilage degeneration (P < 0.05). Postmenopausal women were divided into seven subgroups by every five YSM. When YSM was less than 25 years, the analysis of covariance indicated a significant difference in medial tibia plateau, medial femoral condyle, trochlea, patella, and total surfaces (P < 0.05 or 0.01) between every two groups. When YSM was more than 25 years, the significant difference, however, disappeared in these four surfaces (P > 0.05). No significant difference was observed in lateral tibia plateau and lateral femoral condyle in postmenopausal women. Menopause is associated with cartilage degeneration of knee joint. After menopause, cartilage showed progressive severe degeneration that occurred in the first 25 YSM, suggesting estrogen deficiency might be a risk factor of cartilage degeneration of the knee joint. Further studies are needed to investigate whether age or menopause plays a more important role in the progression of cartilage degeneration in the knee joint.

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 coefficient of cartilage, which were linearly correlated, increased with increasing Outerbridge stages in postcollapse AVN. The underlying mechanism of these results can be related to proteoglycan loss within the articular cartilage that is also observed in osteoarthritis. With regard to the tribological properties, the cartilage degeneration mechanism in AVN was similar to that of osteoarthritis without reversibility.

Similar hyaline-like cartilage repair of osteochondral defects in rabbits using isotropic and anisotropic collagen scaffolds.

PubMed

de Mulder, Eric L W; Hannink, Gerjon; van Kuppevelt, Toin H; Daamen, Willeke F; Buma, Pieter

2014-02-01

Lesions in knee joint articular cartilage (AC) have limited repair capacity. Many clinically available treatments induce a fibrous-like cartilage repair instead of hyaline cartilage. To induce hyaline cartilage repair, we hypothesized that type I collagen scaffolds with fibers aligned perpendicular to the AC surface would result in qualitatively better tissue repair due to a guided cellular influx from the subchondral bone. By specific freezing protocols, type I collagen scaffolds with isotropic and anisotropic fiber architectures were produced. Rabbits were operated on bilaterally and two full thickness defects were created in each knee joint. The defects were filled with (1) an isotropic scaffold, (2) an anisotropic scaffold with pores parallel to the cartilage surface, and (3) an anisotropic scaffold with pores perpendicular to the cartilage surface. Empty defects served as controls. After 4 (n=13) and 12 (n=13) weeks, regeneration was scored qualitatively and quantitatively using histological analysis and a modified O'Driscoll score. After 4 weeks, all defects were completely filled with partially differentiated hyaline cartilage tissue. No differences in O'Driscoll scores were measured between empty defects and scaffold types. After 12 weeks, all treatments led to hyaline cartilage repair visualized by increased glycosaminoglycan staining. Total scores were significantly increased for parallel anisotropic and empty defects over time (p<0.05). The results indicate that collagen scaffolds allow the formation of hyaline-like cartilage repair. Fiber architecture had no effect on cartilage repair.

[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.

Correlation and sex differences between ankle and knee cartilage morphology determined by quantitative magnetic resonance imaging

PubMed Central

Eckstein, F; Siedek, V; Glaser, C; Al-Ali, D; Englmeier, K; Reiser, M; Graichen, H

2004-01-01

Objective: To study the correlation between ankle and knee cartilage morphology to test the hypothesis that knee joint cartilage loss in gonarthritis can be estimated retrospectively using quantitative MRI analysis of the knee and ankle and established regression equations; and to test the hypothesis that sex differences in joint surface area are larger in the knee than the ankle, which may explain the greater incidence of knee osteoarthritis in elderly women than in elderly men. Methods: Sagittal MR images (3D FLASH WE) of the knee and hind foot were acquired in 29 healthy subjects (14 women, 15 men; mean (SD) age, 25 (3) years), with no signs joint disease. Cartilage volume, thickness, and joint surface area were determined in the knee, ankle, and subtalar joint. Results: Knee cartilage volumes and joint surface areas showed only moderate correlations with those of the ankle and subtalar joint (r = 0.33 to 0.81). The correlations of cartilage thickness between the two joints were weaker still (r = –0.05 to 0.53). Sex differences in cartilage morphology at the knee and the ankle were similar, with surface areas being –17.5% to –23.5% lower in women than in men. Conclusions: Only moderate correlations in cartilage morphology of healthy subjects were found between knee and ankle. It is therefore impractical to estimate knee joint cartilage loss a posteriori in cross sectional studies by measuring the hind foot and then applying a scaling factor. Sex differences in cartilage morphology do not explain differences in osteoarthritis incidence between men and women in the knee and ankle. PMID:15479900

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.

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

A new injectable biphasic hydrogel based on partially hydrolyzed polyacrylamide and nano hydroxyapatite, crosslinked with chromium acetate, as scaffold for cartilage regeneration

NASA Astrophysics Data System (ADS)

Koushki, N.; Tavassoli, H.; Katbab, A. A.; Katbab, P.; Bonakdar, S.

2015-05-01

Polymer scaffolds are applied in the field of tissue engineering as three dimensional structures to organize cells and present stimuli to direct generation of a desired damaged tissue. In situ gelling scaffolds have attracted great attentions, as they are structurally similar to the extra cellular matrix (ECM). In the present work, attempts have been made to design and fabricate a new injectable and crosslinkable biphasic hydrogel based on partially hydrolyzed polyacrylamide (HPAM), chromium acetate as crosslink agent and nanocrystalline hydroxyapatite (nHAp) as reinforcing and bioactive agent for repair and regeneration of damaged cartilage. The distinct characteristic of HPAM is the presence of carboxylate anion groups on its backbone which allows to engineer the structure of the hydrogel for the desired bioactivity with appropriate cells differentiation towards both soft and hard (bone) tissues. The synthesized hydrogel exhibited bifunctional behavior which was derived by its biphasic structure in which one phase was loaded with nano hydroxyapatite to provide integration capability by subchondral bones and fix the hydrogel at cartilage defect without a need for suturing. The other phase differentiates the rabbit adipogenic mesenchymal stem cells (MSCs) towards soft tissue. Rheomechanical spectrometry (RMS) was employed to study the kinetic of the gelation including induction time and rate, as well as to measure the ultimate elastic modulus of the optimum crosslinked hydrogel. Surface tension measurement was also performed to tailor the surface characteristics of the gels. In vitro culturing of the cells inside the crosslinked hydrogel revealed high viability and high differentiation of the encapsulated rabbit stem cells, providing that the chromium acetate level was kept below 0.2 wt%. Based on the obtained results, the designed and fabricated biphasic hydrogel exhibited high potential as carrier for the stem cells for cartilage tissue engineering application with excellent injectability.

Motion of the Tympanic Membrane after Cartilage Tympanoplasty Determined by Stroboscopic Holography

PubMed Central

Aarnisalo, Antti A.; Cheng, Jeffrey T.; Ravicz, Michael E.; Furlong, Cosme; Merchant, Saumil N.; Rosowski, John J.

2009-01-01

Stroboscopic holography was used to quantify dynamic deformations of the tympanic membrane (TM) of the entire surface of the TM before and after cartilage tympanoplasty of the posterior or posterior-superior part of the TM. Cartilage is widely used in tympanoplasties to provide mechanical stability for the TM. Three human cadaveric temporal bones were used. A 6 mm × 3 mm oval cartilage graft was placed through the widely opened facial recess onto the medial surface of the posterior or posterior-superior part of the TM. The graft was either in contact with the bony tympanic rim and manubrium or not. Graft thickness was either 0.5 or 1.0 mm. Stroboscopic holography produced displacement amplitude and phase maps of the TM surface in response to stimulus sound. Sound stimuli were 0.5, 1, 4 and 7 (or 8) kHz tones. Middle ear impedance was measured from the motion of the entire TM. Cartilage placement generally produced reductions in the motion of the TM apposed to the cartilage, especially at 4 kHz and 7 or 8 kHz. Some parts of the TM showed altered motion compared to the control in all three cases. In general, middle ear impedance was either unchanged or increased somewhat after cartilage reconstruction both at low (0.5 and 1 kHz) and high (4 and 7 kHz) frequencies. At 4 kHz, with the 1.0 mm thick graft that was in contact with the bony tympanic rim, the impedance slightly decreased. While our earlier work with time-averaged holography allowed us to observe differences in the pattern of TM motion caused by application of cartilage to the TM, stroboscopic holography is more sensitive to TM motions and allowed us to quantify the magnitude and phase of motion of each point on the TM surface. Nonetheless, our results are similar to those of our earlier work: The placement of cartilage on the medial surface of TM reduces the motion of the TM that apposes the cartilage. These obvious local changes occur even though the cartilage had little effect on the sound-induced motion of the stapes. PMID:19909803

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.

Mechanical properties and structure-function relationships of human chondrocyte-seeded cartilage constructs after in vitro culture.

PubMed

Middendorf, Jill M; Griffin, Darvin J; Shortkroff, Sonya; Dugopolski, Caroline; Kennedy, Stephen; Siemiatkoski, Joseph; Cohen, Itai; Bonassar, Lawrence J

2017-10-01

Autologous Chondrocyte Implantation (ACI) is a widely recognized method for the repair of focal cartilage defects. Despite the accepted use, problems with this technique still exist, including graft hypertrophy, damage to surrounding tissue by sutures, uneven cell distribution, and delamination. Modified ACI techniques overcome these challenges by seeding autologous chondrocytes onto a 3D scaffold and securing the graft into the defect. Many studies on these tissue engineered grafts have identified the compressive properties, but few have examined frictional and shear properties as suggested by FDA guidance. This study is the first to perform three mechanical tests (compressive, frictional, and shear) on human tissue engineered cartilage. The objective was to understand the complex mechanical behavior, function, and changes that occur with time in these constructs grown in vitro using compression, friction, and shear tests. Safranin-O histology and a DMMB assay both revealed increased sulfated glycosaminoglycan (sGAG) content in the scaffolds with increased maturity. Similarly, immunohistochemistry revealed increased lubricin localization on the construct surface. Confined compression and friction tests both revealed improved properties with increased construct maturity. Compressive properties correlated with the sGAG content, while improved friction coefficients were attributed to increased lubricin localization on the construct surfaces. In contrast, shear properties did not improve with increased culture time. This study suggests the various mechanical and biological properties of tissue engineered cartilage improve at different rates, indicating thorough mechanical evaluation of tissue engineered cartilage is critical to understanding the performance of repaired cartilage. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:2298-2306, 2017. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

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.

Dual Contrast CT Method Enables Diagnostics of Cartilage Injuries and Degeneration Using a Single CT Image.

PubMed

Saukko, Annina E A; Honkanen, Juuso T J; Xu, Wujun; Väänänen, Sami P; Jurvelin, Jukka S; Lehto, Vesa-Pekka; Töyräs, Juha

2017-12-01

Cartilage injuries may be detected using contrast-enhanced computed tomography (CECT) by observing variations in distribution of anionic contrast agent within cartilage. Currently, clinical CECT enables detection of injuries and related post-traumatic degeneration based on two subsequent CT scans. The first scan allows segmentation of articular surfaces and lesions while the latter scan allows evaluation of tissue properties. Segmentation of articular surfaces from the latter scan is difficult since the contrast agent diffusion diminishes the image contrast at surfaces. We hypothesize that this can be overcome by mixing anionic contrast agent (ioxaglate) with bismuth oxide nanoparticles (BINPs) too large to diffuse into cartilage, inducing a high contrast at the surfaces. Here, a dual contrast method employing this mixture is evaluated by determining the depth-wise X-ray attenuation profiles in intact, enzymatically degraded, and mechanically injured osteochondral samples (n = 3 × 10) using a microCT immediately and at 45 min after immersion in contrast agent. BiNPs were unable to diffuse into cartilage, producing high contrast at articular surfaces. Ioxaglate enabled the detection of enzymatic and mechanical degeneration. In conclusion, the dual contrast method allowed detection of injuries and degeneration simultaneously with accurate cartilage segmentation using a single scan conducted at 45 min after contrast agent administration.

Thickness Distribution of Glenohumeral Joint Cartilage.

PubMed

Schleich, Christoph; Bittersohl, Bernd; Antoch, Gerald; Krauspe, Rüdiger; Zilkens, Christoph; Kircher, Jörn

2017-04-01

High-resolution 3-dimensional cartilage-specific magnetic resonance imaging (MRI) was performed at 3 T to test the following hypotheses: (1) there is a nonuniform cartilage thickness distribution both on the proximal humerus and on the glenoid surface and (2) the glenohumeral joint as a combined system is congruent with the level of the joint cartilage surface without substantial radial mismatch. Inclusion of 38 volunteers (19 females, mean age 24.34 ± 2.22 years; range 21-29 years) in a prospective study. Measurements of: cartilage thickness in 3 regions and 3 zones; radius of both circles (glenoid and humeral cartilage) for congruency calculation using 3-T MRI with 3-dimensional dual-echo steady-state sequence with water excitation. A homogenous mean cartilage thickness (1.2-1.5 mm) and slightly higher values for the glenoidal articulating surface radii both in the mid-paracoronar section (2.4 vs. 2.1 cm, P < 0.001) and in the mid-paraaxial section (2.4 vs. 2.1 cm, P < 0.001) compared with the humeral side were observed. The concept of a radial mismatch between the humeral head and the glenoid in healthy human subjects can be confirmed. This study provides normative data for the comparison of joint cartilage changes at the shoulder for future studies.

Thickness Distribution of Glenohumeral Joint Cartilage

PubMed Central

Schleich, Christoph; Bittersohl, Bernd; Antoch, Gerald; Krauspe, Rüdiger; Zilkens, Christoph; Kircher, Jörn

2016-01-01

High-resolution 3-dimensional cartilage-specific magnetic resonance imaging (MRI) was performed at 3 T to test the following hypotheses: (1) there is a nonuniform cartilage thickness distribution both on the proximal humerus and on the glenoid surface and (2) the glenohumeral joint as a combined system is congruent with the level of the joint cartilage surface without substantial radial mismatch. Inclusion of 38 volunteers (19 females, mean age 24.34 ± 2.22 years; range 21-29 years) in a prospective study. Measurements of: cartilage thickness in 3 regions and 3 zones; radius of both circles (glenoid and humeral cartilage) for congruency calculation using 3-T MRI with 3-dimensional dual-echo steady-state sequence with water excitation. A homogenous mean cartilage thickness (1.2-1.5 mm) and slightly higher values for the glenoidal articulating surface radii both in the mid-paracoronar section (2.4 vs. 2.1 cm, P < 0.001) and in the mid-paraaxial section (2.4 vs. 2.1 cm, P < 0.001) compared with the humeral side were observed. The concept of a radial mismatch between the humeral head and the glenoid in healthy human subjects can be confirmed. This study provides normative data for the comparison of joint cartilage changes at the shoulder for future studies. PMID:28345405

Enhanced chondrocyte culture and growth on biologically inspired nanofibrous cell culture dishes.

PubMed

Bhardwaj, Garima; Webster, Thomas J

2016-01-01

Chondral and osteochondral defects affect a large number of people in which treatment options are currently limited. Due to its ability to mimic the natural nanofibrous structure of cartilage, this current in vitro study aimed at introducing a new scaffold, called XanoMatrix™, for cartilage regeneration. In addition, this same scaffold is introduced here as a new substrate onto which to study chondrocyte functions. Current studies on chondrocyte functions are limited due to nonbiologically inspired cell culture substrates. With its polyethylene terephthalate and cellulose acetate composition, good mechanical properties and nanofibrous structure resembling an extracellular matrix, XanoMatrix offers an ideal surface for chondrocyte growth and proliferation. This current study demonstrated that the XanoMatrix scaffolds promote chondrocyte growth and proliferation as compared with the Corning and Falcon surfaces normally used for chondrocyte cell culture. The XanoMatrix scaffolds also have greater hydrophobicity, three-dimensional surface area, and greater tensile strength, making them ideal candidates for alternative treatment options for chondral and osteochondral defects as well as cell culture substrates to study chondrocyte functions.

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

Robust and general method for determining surface fluid flow boundary conditions in articular cartilage contact mechanics modeling.

PubMed

Pawaskar, Sainath Shrikant; Fisher, John; Jin, Zhongmin

2010-03-01

Contact detection in cartilage contact mechanics is an important feature of any analytical or computational modeling investigation when the biphasic nature of cartilage and the corresponding tribology are taken into account. The fluid flow boundary conditions will change based on whether the surface is in contact or not, which will affect the interstitial fluid pressurization. This in turn will increase or decrease the load sustained by the fluid phase, with a direct effect on friction, wear, and lubrication. In laboratory experiments or clinical hemiarthroplasty, when a rigid indenter or metallic prosthesis is used to apply load to the cartilage, there will not be any fluid flow normal to the surface in the contact region due to the impermeable nature of the indenter/prosthesis. In the natural joint, on the other hand, where two cartilage surfaces interact, flow will depend on the pressure difference across the interface. Furthermore, in both these cases, the fluid would flow freely in non-contacting regions. However, it should be pointed out that the contact area is generally unknown in advance in both cases and can only be determined as part of the solution. In the present finite element study, a general and robust algorithm was proposed to decide nodes in contact on the cartilage surface and, accordingly, impose the fluid flow boundary conditions. The algorithm was first tested for a rigid indenter against cartilage model. The algorithm worked well for two-dimensional four-noded and eight-noded axisymmetric element models as well as three-dimensional models. It was then extended to include two cartilages in contact. The results were in excellent agreement with the previous studies reported in the literature.

Research studies of aging changes of hyaline cartilage surface by using Raman-scattering spectroscopy

NASA Astrophysics Data System (ADS)

Timchenko, E. V.; Timchenko, P. E.; Dolgushkin, D. A.; Volova, L. T.; Lazarev, V. A.; Tyumchenkova, A. S.; Markova, M. D.

2017-08-01

The paper presents the results of a comparative analysis by the method of Raman spectroscopy of the joint hyaline cartilage of adults and children. Differences in the spectral characteristics of the surface of articular cartilage are shown. New optical coefficients have been introduced, which make it possible to evaluate the age-related changes in cartilaginous tissue.

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.

Near field effect on elasticity measurement for cartilage-bone structure using Lamb wave method.

PubMed

Xu, Hao; Chen, Shigao; An, Kai-Nan; Luo, Zong-Ping

2017-10-30

Cartilage elasticity changes with cartilage degeneration. Hence, cartilage elasticity detection might be an alternative to traditional imaging methods for the early diagnosis of osteoarthritis. Based on the wave propagation measurement, Shear wave elastography (SWE) become an emerging non-invasive elasticity detection method. The wave propagation model, which is affected by tissue shapes, is crucial for elasticity estimating in SWE. However, wave propagation model for cartilage was unclear. This study aimed to establish a wave propagation model for the cartilage-bone structure. We fabricated a cartilage-bone structure, and studied the elasticity measurement and wave propagation by experimental and numerical Lamb wave method (LWM). Results indicated the wave propagation model satisfied the lamb wave theory for two-layered structure. Moreover, a near field region, which affects wave speed measurements and whose occurrence can be prevented if the wave frequency is larger than one critical frequency, was observed. Our findings would provide a theoretical foundation for further application of LWM in elasticity measurement of cartilage in vivo. It can help the application of LWM to the diagnosis of osteoarthritis.

3.0T MR imaging of the ankle: Axial traction for morphological cartilage evaluation, quantitative T2 mapping and cartilage diffusion imaging-A preliminary study.

PubMed

Jungmann, Pia M; Baum, Thomas; Schaeffeler, Christoph; Sauerschnig, Martin; Brucker, Peter U; Mann, Alexander; Ganter, Carl; Bieri, Oliver; Rummeny, Ernst J; Woertler, Klaus; Bauer, Jan S

2015-08-01

To determine the impact of axial traction during high resolution 3.0T MR imaging of the ankle on morphological assessment of articular cartilage and quantitative cartilage imaging parameters. MR images of n=25 asymptomatic ankles were acquired with and without axial traction (6kg). Coronal and sagittal T1-weighted (w) turbo spin echo (TSE) sequences with a driven equilibrium pulse and sagittal fat-saturated intermediate-w (IMfs) TSE sequences were acquired for morphological evaluation on a four-point scale (1=best, 4=worst). For quantitative assessment of cartilage degradation segmentation was performed on 2D multislice-multiecho (MSME) SE T2, steady-state free-precession (SSFP; n=8) T2 and SSFP diffusion-weighted imaging (DWI; n=8) images. Wilcoxon-tests and paired t-tests were used for statistical analysis. With axial traction, joint space width increased significantly and delineation of cartilage surfaces was rated superior (P<0.05). Cartilage surfaces were best visualized on coronal T1-w images (P<0.05). Differences for cartilage matrix evaluation were smaller. Subchondral bone evaluation, motion artifacts and image quality were not significantly different between the acquisition methods (P>0.05). T2 values were lower at the tibia than at the talus (P<0.001). Reproducibility was better for images with axial traction. Axial traction increased the joint space width, allowed for better visualization of cartilage surfaces and improved compartment discrimination and reproducibility of quantitative cartilage parameters. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Biological aspects of early osteoarthritis.

PubMed

Madry, Henning; Luyten, Frank P; Facchini, Andrea

2012-03-01

Early OA primarily affects articular cartilage and involves the entire joint, including the subchondral bone, synovial membrane, menisci and periarticular structures. The aim of this review is to highlight the molecular basis and histopathological features of early OA. Selective review of literature. Risk factors for developing early OA include, but are not limited to, a genetic predisposition, mechanical factors such as axial malalignment, and aging. In early OA, the articular cartilage surface is progressively becoming discontinuous, showing fibrillation and vertical fissures that extend not deeper than into the mid-zone of the articular cartilage, reflective of OARSI grades 1.0-3.0. Early changes in the subchondral bone comprise a progressive increase in subchondral plate and subarticular spongiosa thickness. Early OA affects not only the articular cartilage and the subchondral bone but also other structures of the joint, such as the menisci, the synovial membrane, the joint capsule, ligaments, muscles and the infrapatellar fat pad. Genetic markers or marker combinations may become useful in the future to identify early OA and patients at risk. The high socioeconomic impact of OA suggests that a better insight into the mechanisms of early OA may be a key to develop more targeted reconstructive therapies at this first stage of the disease. Systematic review, Level II.

LOGISMOS—Layered Optimal Graph Image Segmentation of Multiple Objects and Surfaces: Cartilage Segmentation in the Knee Joint

PubMed Central

Zhang, Xiangmin; Williams, Rachel; Wu, Xiaodong; Anderson, Donald D.; Sonka, Milan

2011-01-01

A novel method for simultaneous segmentation of multiple interacting surfaces belonging to multiple interacting objects, called LOGISMOS (layered optimal graph image segmentation of multiple objects and surfaces), is reported. The approach is based on the algorithmic incorporation of multiple spatial inter-relationships in a single n-dimensional graph, followed by graph optimization that yields a globally optimal solution. The LOGISMOS method’s utility and performance are demonstrated on a bone and cartilage segmentation task in the human knee joint. Although trained on only a relatively small number of nine example images, this system achieved good performance. Judged by dice similarity coefficients (DSC) using a leave-one-out test, DSC values of 0.84 ± 0.04, 0.80 ± 0.04 and 0.80 ± 0.04 were obtained for the femoral, tibial, and patellar cartilage regions, respectively. These are excellent DSC values, considering the narrow-sheet character of the cartilage regions. Similarly, low signed mean cartilage thickness errors were obtained when compared to a manually-traced independent standard in 60 randomly selected 3-D MR image datasets from the Osteoarthritis Initiative database—0.11 ± 0.24, 0.05 ± 0.23, and 0.03 ± 0.17 mm for the femoral, tibial, and patellar cartilage thickness, respectively. The average signed surface positioning errors for the six detected surfaces ranged from 0.04 ± 0.12 mm to 0.16 ± 0.22 mm. The reported LOGISMOS framework provides robust and accurate segmentation of the knee joint bone and cartilage surfaces of the femur, tibia, and patella. As a general segmentation tool, the developed framework can be applied to a broad range of multiobject multisurface segmentation problems. PMID:20643602

Osteochondral integration of multiply incised pure cartilage allograft: repair method of focal chondral defects in a porcine model.

PubMed

Bardos, Tamas; Farkas, Boglarka; Mezes, Beata; Vancsodi, Jozsef; Kvell, Krisztian; Czompoly, Tamas; Nemeth, Peter; Bellyei, Arpad; Illes, Tamas

2009-11-01

A focal cartilage lesion has limited capacity to heal, and the repair modalities used at present are still unable to provide a universal solution. Pure cartilage graft implantation appears to be a simple option, but it has not been applied widely as cartilage will not reattach easily to the subchondral bone. We used a multiple-incision technique (processed chondrograft) to increase cartilage graft surface. We hypothesized that pure cartilage graft with augmented osteochondral fusion capacity may be used for cartilage repair and we compared this method with other repair techniques. Controlled laboratory study. Full-thickness focal cartilage defects were created on the medial femoral condyle of 9-month-old pigs; defects were repaired using various methods including bone marrow stimulation, autologous chondrocyte implantation, and processed chondrograft. After the repair, at weeks 6 and 24, macroscopic and histologic evaluation was carried out. Compared with other methods, processed chondrograft was found to be similarly effective in cartilage repair. Defects without repair and defects treated with bone marrow stimulation appeared slightly irregular with fibrocartilage filling. Autologous chondrocyte implantation produced hyalinelike cartilage, although its cellular organization was distinguishable from the surrounding articular cartilage. Processed chondrograft demonstrated good osteochondral integration, and the resulting tissue appeared to be hyaline cartilage. The applied cartilage surface processing method allows acceptable osteochondral integration, and the repair tissue appears to have good macroscopic and histologic characteristics. If further studies confirm its efficacy, this technique could be considered for human application in the future.

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.

Impact insertion of osteochondral grafts: Interference fit and central graft reduction affect biomechanics and cartilage damage.

PubMed

Su, Alvin W; Chen, Yunchan; Wailes, Dustin H; Wong, Van W; Cai, Shengqiang; Chen, Albert C; Bugbee, William D; Sah, Robert L

2018-01-01

An osteochondral graft (OCG) is an effective treatment for articular cartilage and osteochondral defects. Impact of an OCG during insertion into the osteochondral recipient site (OCR) can cause chondrocyte death and matrix damage. The aim of the present study was to analyze the effects of graft-host interference fit and a modified OCG geometry on OCG insertion biomechanics and cartilage damage. The effects of interference fit (radius of OCG - radius of OCR), loose (0.00 mm), moderate (0.05 mm), tight (0.10 mm), and of a tight fit with OCG geometry modification (central region of decreased radius), were analyzed for OCG cylinders and OCR blocks from adult bovine knee joints with an instrumented drop tower apparatus. An increasingly tight (OCG - OCR) interference fit led to increased taps for insertion, peak axial force, graft cartilage axial compression, cumulative and total energy delivery to cartilage, lower time of peak axial force, lesser graft advancement during each tap, higher total crack length in the cartilage surface, and lower chondrocyte viability. The modified OCG, with reduction of diameter in the central area, altered the biomechanical insertion variables and biological consequences to be similar to those of the moderate interference fit scenario. Micro-computed tomography confirmed structural interference between the OCR bone and both the proximal and distal bone segments of the OCGs, with the central regions being slightly separated for the modified OCGs. These results clarify OCG insertion biomechanics and mechanobiology, and introduce a simple modification of OCGs that facilitates insertion with reduced energy while maintaining a structural interference fit. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:377-386, 2018. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Stick-slip friction and wear of articular joints

PubMed Central

Lee, Dong Woog; Banquy, Xavier; Israelachvili, Jacob N.

2013-01-01

Stick-slip friction was observed in articular cartilage under certain loading and sliding conditions and systematically studied. Using the Surface Forces Apparatus, we show that stick-slip friction can induce permanent morphological changes (a change in the roughness indicative of wear/damage) in cartilage surfaces, even under mild loading and sliding conditions. The different load and speed regimes can be represented by friction maps—separating regimes of smooth and stick-slip sliding; damage generally occurs within the stick-slip regimes. Prolonged exposure of cartilage surfaces to stick-slip sliding resulted in a significant increase of surface roughness, indicative of severe morphological changes of the cartilage superficial zone. To further investigate the factors that are conducive to stick-slip and wear, we selectively digested essential components of cartilage: type II collagen, hyaluronic acid (HA), and glycosaminoglycans (GAGs). Compared with the normal cartilage, HA and GAG digestions modified the stick-slip behavior and increased surface roughness (wear) during sliding, whereas collagen digestion decreased the surface roughness. Importantly, friction forces increased up to 2, 10, and 5 times after HA, GAGs, and collagen digestion, respectively. Also, each digestion altered the friction map in different ways. Our results show that (i) wear is not directly related to the friction coefficient but (ii) more directly related to stick-slip sliding, even when present at small amplitudes, and that (iii) the different molecular components of joints work synergistically to prevent wear. Our results also suggest potential noninvasive diagnostic tools for sensing stick-slip in joints. PMID:23359687

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.

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

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.

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

Advanced morphological and biochemical magnetic resonance imaging of cartilage repair procedures in the knee joint at 3 Tesla.

PubMed

Welsch, Goetz H; Mamisch, Tallal C; Hughes, Timothy; Domayer, Stephan; Marlovits, Stefan; Trattnig, Siegfried

2008-09-01

Morphological and biochemical magnetic resonance imaging (MRI) is due to high field MR systems, advanced coil technology, and sophisticated sequence protocols capable of visualizing articular cartilage in vivo with high resolution in clinical applicable scan time. Several conventional two-dimensional (2D) and three-dimensional (3D) approaches show changes in cartilage structure. Furthermore newer isotropic 3D sequences show great promise in improving cartilage imaging and additionally in diagnosing surrounding pathologies within the knee joint. Functional MR approaches are additionally able to provide a specific measure of the composition of cartilage. Cartilage physiology and ultra-structure can be determined, changes in cartilage macromolecules can be detected, and cartilage repair tissue can thus be assessed and potentially differentiated. In cartilage defects and following nonsurgical and surgical cartilage repair, morphological MRI provides the basis for diagnosis and follow-up evaluation, whereas biochemical MRI provides a deeper insight into the composition of cartilage and cartilage repair tissue. A combination of both, together with clinical evaluation, may represent a desirable multimodal approach in the future, also available in routine clinical use.

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.

Osteochondral Biopsy Analysis Demonstrates That BST-CarGel Treatment Improves Structural and Cellular Characteristics of Cartilage Repair Tissue Compared With Microfracture

PubMed Central

Méthot, Stéphane; Changoor, Adele; Tran-Khanh, Nicolas; Hoemann, Caroline D.; Stanish, William D.; Restrepo, Alberto; Shive, Matthew S.; Buschmann, Michael D.

2016-01-01

Objective The efficacy and safety of BST-CarGel, a chitosan-based medical device for cartilage repair, was compared with microfracture alone at 1 year during a multicenter randomized controlled trial (RCT) in the knee. The quality of repair tissue of osteochondral biopsies collected from a subset of patients was compared using blinded histological assessments. Methods The international RCT evaluated repair tissue quantity and quality by 3-dimensional quantitative magnetic resonance imaging as co-primary endpoints at 12 months. At an average of 13 months posttreatment, 21/41 BST-CarGel and 17/39 microfracture patients underwent elective second look arthroscopies as a tertiary endpoint, during which ICRS (International Cartilage Repair Society) macroscopic scoring was carried out, and osteochondral biopsies were collected. Stained histological sections were evaluated by blinded readers using ICRS I and II histological scoring systems. Collagen organization was evaluated using a polarized light microscopy score. Results BST-CarGel treatment resulted in significantly better ICRS macroscopic scores (P = 0.0002) compared with microfracture alone, indicating better filling, integration, and tissue appearance. Histologically, BST-CarGel resulted in a significant improvement of structural parameters—Surface Architecture (P = 0.007) and Surface/Superficial Assessment (P = 0.042)—as well as cellular parameters—Cell Viability (P = 0.006) and Cell Distribution (P = 0.032). No histological parameters were significantly better for the microfracture group. BST-CarGel treatment also resulted in a more organized repair tissue with collagen stratification more similar to native hyaline cartilage, as measured by polarized light microscopy scoring (P = 0.0003). Conclusion Multiple and independent analyses in this biopsy substudy demonstrated that BST-CarGel treatment results in improved structural and cellular characteristics of repair tissue at 1 year posttreatment compared with microfracture alone, supporting previously reported results by quantitative magnetic resonance imaging. PMID:26958314

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.

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

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.

Chondrocytes and stem cells in 3D-bioprinted structures create human cartilage in vivo

PubMed Central

Amoroso, Matteo; Lindahl, Anders; Brantsing, Camilla; Rotter, Nicole; Gatenholm, Paul; Kölby, Lars

2017-01-01

Cartilage repair and replacement is a major challenge in plastic reconstructive surgery. The development of a process capable of creating a patient-specific cartilage framework would be a major breakthrough. Here, we described methods for creating human cartilage in vivo and quantitatively assessing the proliferative capacity and cartilage-formation ability in mono- and co-cultures of human chondrocytes and human mesenchymal stem cells in a three-dimensional (3D)-bioprinted hydrogel scaffold. The 3D-bioprinted constructs (5 × 5 × 1.2 mm) were produced using nanofibrillated cellulose and alginate in combination with human chondrocytes and human mesenchymal stem cells using a 3D-extrusion bioprinter. Immediately following bioprinting, the constructs were implanted subcutaneously on the back of 48 nude mice and explanted after 30 and 60 days, respectively, for morphological and immunohistochemical examination. During explantation, the constructs were easy to handle, and the majority had retained their macroscopic grid appearance. Constructs consisting of human nasal chondrocytes showed good proliferation ability, with 17.2% of the surface areas covered with proliferating chondrocytes after 60 days. In constructs comprising a mixture of chondrocytes and stem cells, an additional proliferative effect was observed involving chondrocyte production of glycosaminoglycans and type 2 collagen. This clinically highly relevant study revealed 3D bioprinting as a promising technology for the creation of human cartilage. PMID:29236765

Chondrocytes and stem cells in 3D-bioprinted structures create human cartilage in vivo.

PubMed

Apelgren, Peter; Amoroso, Matteo; Lindahl, Anders; Brantsing, Camilla; Rotter, Nicole; Gatenholm, Paul; Kölby, Lars

2017-01-01

Cartilage repair and replacement is a major challenge in plastic reconstructive surgery. The development of a process capable of creating a patient-specific cartilage framework would be a major breakthrough. Here, we described methods for creating human cartilage in vivo and quantitatively assessing the proliferative capacity and cartilage-formation ability in mono- and co-cultures of human chondrocytes and human mesenchymal stem cells in a three-dimensional (3D)-bioprinted hydrogel scaffold. The 3D-bioprinted constructs (5 × 5 × 1.2 mm) were produced using nanofibrillated cellulose and alginate in combination with human chondrocytes and human mesenchymal stem cells using a 3D-extrusion bioprinter. Immediately following bioprinting, the constructs were implanted subcutaneously on the back of 48 nude mice and explanted after 30 and 60 days, respectively, for morphological and immunohistochemical examination. During explantation, the constructs were easy to handle, and the majority had retained their macroscopic grid appearance. Constructs consisting of human nasal chondrocytes showed good proliferation ability, with 17.2% of the surface areas covered with proliferating chondrocytes after 60 days. In constructs comprising a mixture of chondrocytes and stem cells, an additional proliferative effect was observed involving chondrocyte production of glycosaminoglycans and type 2 collagen. This clinically highly relevant study revealed 3D bioprinting as a promising technology for the creation of human cartilage.

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.

A three-dimensional finite element model for biomechanical analysis of the hip.

PubMed

Chen, Guang-Xing; Yang, Liu; Li, Kai; He, Rui; Yang, Bin; Zhan, Yan; Wang, Zhi-Jun; Yu, Bing-Nin; Jian, Zhe

2013-11-01

The objective of this study was to construct a three-dimensional (3D) finite element model of the hip. The images of the hip were obtained from Chinese visible human dataset. The hip model includes acetabular bone, cartilage, labrum, and bone. The cartilage of femoral head was constructed using the AutoCAD and Solidworks software. The hip model was imported into ABAQUS analysis system. The contact surface of the hip joint was meshed. To verify the model, the single leg peak force was loaded, and contact area of the cartilage and labrum of the hip and pressure distribution in these structures were observed. The constructed 3D hip model reflected the real hip anatomy. Further, this model reflected biomechanical behavior similar to previous studies. In conclusion, this 3D finite element hip model avoids the disadvantages of other construction methods, such as imprecision of cartilage construction and the absence of labrum. Further, it provides basic data critical for accurately modeling normal and abnormal loads, and the effects of abnormal loads on the hip.

Chondrogenesis of infrapatellar fat pad derived adipose stem cells in 3D printed chitosan scaffold.

PubMed

Ye, Ken; Felimban, Raed; Traianedes, Kathy; Moulton, Simon E; Wallace, Gordon G; Chung, Johnson; Quigley, Anita; Choong, Peter F M; Myers, Damian E

2014-01-01

Infrapatellar fat pad adipose stem cells (IPFP-ASCs) have been shown to harbor chondrogenic potential. When combined with 3D polymeric structures, the stem cells provide a source of stem cells to engineer 3D tissues for cartilage repair. In this study, we have shown human IPFP-ASCs seeded onto 3D printed chitosan scaffolds can undergo chondrogenesis using TGFβ3 and BMP6. By week 4, a pearlescent, cartilage-like matrix had formed that penetrated the top layers of the chitosan scaffold forming a 'cap' on the scaffold. Chondrocytic morphology showed typical cells encased in extracellular matrix which stained positively with toluidine blue. Immunohistochemistry demonstrated positive staining for collagen type II and cartilage proteoglycans, as well as collagen type I. Real time PCR analysis showed up-regulation of collagen type II, aggrecan and SOX9 genes when IPFP-ASCs were stimulated by TGFβ3 and BMP6. Thus, IPFP-ASCs can successfully undergo chondrogenesis using TGFβ3 and BMP6 and the cartilage-like tissue that forms on the surface of 3D-printed chitosan scaffold may prove useful as an osteochondral graft.

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 of fibroblast growth factor 18 on exopolyphosphatase activity in the tissue. Polyphosphate also appears to act in a feedback loop to control exopolyphosphatase activity. Interestingly, polyphosphate also exhibits positive effects on cartilage matrix accumulation. The potential implication of polyphosphate in the maintenance of articular cartilage homeostasis is intriguing and must be investigated further.

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.

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.

In Vivo Patellar Tracking and Patellofemoral Cartilage Contacts during Dynamic Stair Ascending

PubMed Central

Suzuki, Takashi; Hosseini, Ali; Li, Jing-Sheng; Gill, Thomas J; Li, Guoan

2012-01-01

The knowledge of normal patellar tracking is essential for understanding of the knee joint function and for diagnosis of patellar instabilities. This paper investigated the patellar tracking and patellofemoral joint contact locations during a stair ascending activity using a validated dual-fluoroscopic imaging system. The results showed that the patellar flexion angle decreased from 41.9° to 7.5° with the knee extension during stair ascending. During first 80% of the activity, the patella shifted medially about 3.9 mm and then slightly shifted laterally during the last 20% of the ascending activity. Anterior translation of 13 mm of the patella was measured at the early 80% of the activity and then slightly moved posteriorly by about 2 mm at the last 20% of the activity. The path of the cartilage contact points was slightly lateral on the cartilage surfaces of patella and femur. On the patellar cartilage surface, the cartilage contact locations were about 2 mm laterally from heel strike to 60% of the stair ascending activity and moved laterally and reached 5.3 mm at full extension. However, the cartilage contact locations were relatively constant on the femoral cartilage surface (~5 mm lateral). The patellar tracking pattern was consistent with the patellofemoral cartilage contact location pattern. These data could provide baseline knowledge for understanding of normal physiology of the patellofemoral joint and can be used as a reference for clinical evaluation of patellofemoral disorder symptoms. PMID:22840488

Tissue-engineered trachea regeneration using decellularized trachea matrix treated with laser micropore technique.

PubMed

Xu, Yong; Li, Dan; Yin, Zongqi; He, Aijuan; Lin, Miaomiao; Jiang, Gening; Song, Xiao; Hu, Xuefei; Liu, Yi; Wang, Jinpeng; Wang, Xiaoyun; Duan, Liang; Zhou, Guangdong

2017-08-01

Tissue-engineered trachea provides a promising approach for reconstruction of long segmental tracheal defects. However, a lack of ideal biodegradable scaffolds greatly restricts its clinical translation. Decellularized trachea matrix (DTM) is considered a proper scaffold for trachea cartilage regeneration owing to natural tubular structure, cartilage matrix components, and biodegradability. However, cell residual and low porosity of DTM easily result in immunogenicity and incomplete cartilage regeneration. To address these problems, a laser micropore technique (LMT) was applied in the current study to modify trachea sample porosity to facilitate decellular treatment and cell ingrowth. Decellularization processing demonstrated that cells in LMT treated samples were more easily removed compared with untreated native trachea. Furthermore, after optimizing the protocols of LMT and decellular treatments, the LMT-treated DTM (LDTM) could retain their original tubular shape with only mild extracellular matrix damage. After seeding with chondrocytes and culture in vitro for 8 weeks, the cell-LDTM constructs formed tubular cartilage with relatively homogenous cell distribution in both micropores and bilateral surfaces. In vivo results further confirmed that the constructs could form mature tubular cartilage with increased DNA and cartilage matrix contents, as well as enhanced mechanical strength, compared with native trachea. Collectively, these results indicate that LDTM is an ideal scaffold for tubular cartilage regeneration and, thus, provides a promising strategy for functional reconstruction of trachea cartilage. Lacking ideal biodegradable scaffolds greatly restricts development of tissue-engineered trachea. Decellularized trachea matrix (DTM) is considered a proper scaffold for trachea cartilage regeneration. However, cell residual and low porosity of DTM easily result in immunogenicity and incomplete cartilage regeneration. By laser micropore technique (LMT), the current study efficiently enhanced the porosity and decellularized efficacy of DTM. The LMT-treated DTM basically retained the original tubular shape with mild matrix damage. After chondrocyte seeding followed by in vitro culture and in vivo implantation, the constructs formed mature tubular cartilage with matrix content and mechanical strength similar to native trachea. The current study provides an ideal scaffold and a promising strategy for cartilage regeneration and functional reconstruction of trachea. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

In-situ birth of MSCs multicellular spheroids in poly(L-glutamic acid)/chitosan scaffold for hyaline-like cartilage regeneration.

PubMed

Zhang, Kunxi; Yan, Shifeng; Li, Guifei; Cui, Lei; Yin, Jingbo

2015-12-01

The success of mesenchymal stem cells (MSCs) based articular cartilage tissue engineering is limited by the presence of fibrous tissue in generated cartilage, which is associated with the current scaffold strategy that promotes cellular adhesion and spreading. Here we design a non-fouling scaffold based on amide bonded poly(l-glutamic acid) (PLGA) and chitosan (CS) to drive adipose stem cells (ASCs) to aggregate to form multicellular spheroids with diameter of 80-110 μm in-situ. To illustrate the advantage of the present scaffolds, a cellular adhesive scaffold based on the same amide bonded PLGA and CS was created through a combination of air-drying and freeze-drying to limit the hydration effect while also achieving porous structure. Compared to ASCs spreading along the surface of pores within scaffold, the dense mass of aggregated ASCs in PLGA/CS scaffold exhibited enhanced chondrogenic differentiation capacity, as determined by up-regulated GAGs and COL II expression, and greatly decreased COL I deposition during in vitro chondrogenesis. Furthermore, after 12 weeks of implantation, neo-cartilages generated by ASCs adhered on scaffold significantly presented fibrous matrix which was characterized by high levels of COL I deposition. However, neo-cartilage at 12 weeks post-implantation generated by PLGA/CS scaffold carrying ASC spheroids possessed similar high level of GAGs and COL II and low level of COL I as that in normal cartilage. The in vitro and in vivo results indicated the present strategy could not only promote chondrogenesis of ASCs, but also facilitate hyaline-like cartilage regeneration with reduced fibrous tissue formation which may attenuate cartilage degradation in future long-term follow-up. Copyright © 2015 Elsevier Ltd. All rights reserved.

Acromegalic arthropathy in various stages of the disease: an MRI study.

PubMed

Claessen, K M J A; Canete, A Navas; de Bruin, P W; Pereira, A M; Kloppenburg, M; Kroon, H M; Biermasz, N R

2017-06-01

Arthropathy is a prevalent and invalidating complication of acromegaly with a characteristic radiographic phenotype. We aimed to further characterize cartilage and bone abnormalities associated with acromegalic arthropathy using magnetic resonance imaging (MRI). Twenty-six patients (23% women, mean age 56.8 ± 13.4 years), with active ( n  = 10) and controlled acromegaly ( n  = 16) underwent a 3.0 T MRI of the right knee. Osteophytes, cartilage defects, bone marrow lesions and subchondral cysts were assessed by the Knee Osteoarthritis Scoring System (KOSS) method. Cartilage thickness and cartilage T2 relaxation times, in which higher values reflect increased water content and/or structural changes, were measured. Twenty-five controls (52% women, mean age: 59.6 ± 8.0 years) with primary knee OA were included for comparison. Both in active and controlled acromegaly, structural OA defects were highly prevalent, with thickest cartilage and highest cartilage T2 relaxation times in the active patients. When compared to primary OA subjects, patients with acromegaly seem to have less cysts (12% vs 48%, P  = 0.001) and bone marrow lesions (15% vs 80%, P  = 0.006), but comparable prevalence of osteophytosis and cartilage defects. Patients with acromegaly had 31% thicker total joint cartilage ( P  < 0.001) with higher cartilage T2 relaxation times at all measured sites than primary OA subjects ( P  < 0.01). Patients with active acromegaly have a high prevalence of structural OA abnormalities in combination with thick joint cartilage. In addition, T2 relaxation times of cartilage are high in active patients, indicating unhealthy cartilage with increased water content, which is (partially) reversible by adequate treatment. Patients with acromegaly have a different distribution of structural OA abnormalities visualized by MRI than primary OA subjects, especially of cartilage defects. © 2017 European Society of Endocrinology.

Evaluation of the finite element software ABAQUS for biomechanical modelling of biphasic tissues.

PubMed

Wu, J Z; Herzog, W; Epstein, M

1998-02-01

The biphasic cartilage model proposed by Mow et al. (1980) has proven successful to capture the essential mechanical features of articular cartilage. In order to analyse the joint contact mechanics in real, anatomical joints, the cartilage model needs to be implemented into a suitable finite element code to approximate the irregular surface geometries of such joints. However, systematic and extensive evaluation of the capacity of commercial software for modelling the contact mechanics with biphasic cartilage layers has not been made. This research was aimed at evaluating the commercial finite element software ABAQUS for analysing biphasic soft tissues. The solutions obtained using ABAQUS were compared with those obtained using other finite element models and analytical solutions for three numerical tests: an unconfined indentation test, a test with the contact of a spherical cartilage surface with a rigid plate, and an axi-symmetric joint contact test. It was concluded that the biphasic cartilage model can be implemented into the commercial finite element software ABAQUS to analyse practical joint contact problems with biphasic articular cartilage layers.

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.

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

Oriented clonal cell dynamics enables accurate growth and shaping of vertebrate cartilage.

PubMed

Kaucka, Marketa; Zikmund, Tomas; Tesarova, Marketa; Gyllborg, Daniel; Hellander, Andreas; Jaros, Josef; Kaiser, Jozef; Petersen, Julian; Szarowska, Bara; Newton, Phillip T; Dyachuk, Vyacheslav; Li, Lei; Qian, Hong; Johansson, Anne-Sofie; Mishina, Yuji; Currie, Joshua D; Tanaka, Elly M; Erickson, Alek; Dudley, Andrew; Brismar, Hjalmar; Southam, Paul; Coen, Enrico; Chen, Min; Weinstein, Lee S; Hampl, Ales; Arenas, Ernest; Chagin, Andrei S; Fried, Kaj; Adameyko, Igor

2017-04-17

Cartilaginous structures are at the core of embryo growth and shaping before the bone forms. Here we report a novel principle of vertebrate cartilage growth that is based on introducing transversally-oriented clones into pre-existing cartilage. This mechanism of growth uncouples the lateral expansion of curved cartilaginous sheets from the control of cartilage thickness, a process which might be the evolutionary mechanism underlying adaptations of facial shape. In rod-shaped cartilage structures (Meckel, ribs and skeletal elements in developing limbs), the transverse integration of clonal columns determines the well-defined diameter and resulting rod-like morphology. We were able to alter cartilage shape by experimentally manipulating clonal geometries. Using in silico modeling, we discovered that anisotropic proliferation might explain cartilage bending and groove formation at the macro-scale.

Collagen type IX from human cartilage: a structural profile of intermolecular cross-linking sites.

PubMed Central

Diab, M; Wu, J J; Eyre, D R

1996-01-01

Type IX collagen, a quantitatively minor collagenous component of cartilage, is known to be associated with and covalently cross-linked to type II collagen fibrils in chick and bovine cartilage. Type IX collagen molecules have also been shown to form covalent cross-links with each other in bovine cartilage. In the present study we demonstrate by structural analysis and location of cross-linking sites that, in human cartilage, type IX collagen is covalently cross-linked to type II collagen and to other molecules of type IX collagen. We also present evidence that, if the proteoglycan form of type IX collagen is present in human cartilage, it can only be a minor component of the matrix, similar to findings with bovine cartilage. PMID:8660302

Novel electrospun nanofibers of modified gelatin-tyrosine in cartilage tissue engineering.

PubMed

Agheb, Maria; Dinari, Mohammad; Rafienia, Mohammad; Salehi, Hossein

2017-02-01

In natural cartilage tissues, chondrocytes are linked to extracellular matrix (ECM) through cell-surface binding proteins. Surface modification of gelatin can provide a new generation of biopolymers and fibrous scaffolds with chemical, mechanical, and biological properties. In this study tyrosine protein and 1,2,3-triazole ring were utilized to functionalize gelatin without Cu catalyst. Their molecular structure was characterized by Fourier transform infrared spectroscopy (FTIR) and nuclear magnetic resonance spectroscopy ( 1 HNMR). Chemical cross-linkers such as glutaraldehyde (GA) and 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC)/N-hydroxysulfosuccinimide (NHS) were used to electrospin the modified gelatin. The modification of gelatin and cross-linking effects were confirmed by scanning electron microscopy (SEM), contact angle measurement, and mechanical tests. MTT assay using chondrocyte cells showed cell viability of electrospun modified gelatin scaffolds. In vitro cell culture studies showed that electrospun engineered protein scaffolds would support the attachment and growth of cells. The results also showed that cross-linked nanofibers with EDC/NHS could be considered excellent matrices in cell adhesion and proliferation before electrospinning process and their potential substrate in tissue engineering applications, especially in the field of cartilage engineering. Copyright © 2016. Published by Elsevier B.V.

The electron microscope appearance of the subchondral bone plate in the human femoral head in osteoarthritis and osteoporosis

PubMed Central

LI, BAOHUA; MARSHALL, DEBORAH; ROE, MARTIN; ASPDEN, RICHARD M.

1999-01-01

The subchondral bone plate supports the articular cartilage in diarthrodial joints. It has a significant mechanical function in transmitting loads from the cartilage into the underlying cancellous bone and has been implicated in the destruction of cartilage in osteoarthritis (OA) and its sparing in osteoporosis (OP), but little is known of its composition, structure or material properties. This study investigated the microscopic appearance and mineral composition of the subchondral bone plate in femoral heads from patients with OA or OP to determine how these correspond to changes in composition and stiffness found in other studies. Freeze-fractured full-depth samples of the subchondral bone plate from the femoral heads of patients with osteoarthritis, osteoporosis or a matched control group were examined using back scattered and secondary emission scanning electron microscopy. Other samples were embedded and polished and examined using back-scattered electron microscopy and electron probe microanalysis. The appearances of the samples from the normal and osteoporotic patients were very similar, with the subchondral bone plate overlayed by a layer of calcified cartilage. Osteoporotic samples presented a more uniform fracture surface and the relative thicknesses of the layers appeared to be different. In contrast, the OA bone plate appeared to be porous and have a much more textured surface. There were occasional sites of microtrabecular bone formation between the trabeculae of the underlying cancellous bone, which were not seen in the other groups, and more numerous osteoclast resorption pits. The calcified cartilage layer was almost absent and the bone plate was apparently thickened. The appearance of the osteoarthritic subchondral bone plate was, therefore, considerably different from both the normal and the osteoporotic, strongly indicative of abnormal cellular activity. PMID:10473297

Collagen-PVA aligned nanofiber on collagen sponge as bi-layered scaffold for surface cartilage repair.

PubMed

Lin, Hsin-Yi; Tsai, Wen-Chi; Chang, Shih-Hsing

2017-05-01

Researchers have made bi-layered scaffolds but mostly for osteochondral repairs. The anatomic structure of human cartilage has different zones and that each has varying matrix morphology and mechanical properties is often overlooked. Two bi-layered collagen-based composites were made to replicate the superficial and transitional zones of an articular cartilage. Aligned and random collagen-PVA nanofibers were electrospun onto a freeze-dried collagen sponge to make the aligned and random composites, respectively. The morphology, swelling ratio, degradation and tensile properties of the two composites were examined. Primary porcine chondrocytes were cultured on the composites for three weeks and their proliferation and secretion of glycosaminoglycan (GAG) and type II collagen were measured. The influences of the cell culture on the tensile properties of the composites were studied. The nanofiber layer remained adhered to the sponge after three weeks of cell culture. Both composites lost 30-35% of their total weight in a saline buffer after three weeks. The tensile strength and Young's modulus of both composites increased after three weeks of chondrocyte culture (p < 0.05). The aligned composite with extracellular matrix deposition had a Young's modulus (0.35 MPa) similar to that of articular cartilage reported in literature (0.36-0.8 MPa). The chondrocytes on both aligned and random composites proliferated and secreted similar amounts of GAG and type II collagen. They were seen embedded in lacunae after three weeks. The aligned composite may be more suitable for articular cartilage repair because of the higher tensile strength from the aligned nanofibers on the surface that can better resist wear.

Two-photon excitation laser scanning microscopy of porcine nasal septal cartilage following Nd:YAG laser-mediated stress relaxation

NASA Astrophysics Data System (ADS)

Kim, Charlton C.; Wallace, Vincent P.; Rasouli, Alexandre; Coleno, Mariah L.; Dao, Xavier; Tromberg, Bruce J.; Wong, Brian J.

2000-05-01

Laser irradiation of hyaline cartilage result in stable shape changes due to temperature dependent stress relaxation. In this study, we determined the structural changes in chondrocytes within porcine nasal septal cartilage tissue over a 4-day period using a two-photon laser scanning microscope (TPM) following Nd:YAG laser irradiation (lambda equals 1.32 micrometer) using parameters that result in mechanical stress relaxation (6.0 W, 5.4 mm spot diameter). TPM excitation (780 nm) result in induction of fluorescence from endogenous agents such as NADH, NADPH, and flavoproteins in the 400 - 500 nm spectral region. During laser irradiation diffuse reflectance (from a probe HeNe laser, (lambda) equals 632.8 nm), surface temperature, and stress relaxation were measured dynamically. Each specimen received one, two, or three sequential laser exposures (average irradiation times of 5, 6, and 8 seconds). The cartilage reached a peak surface temperature of about 70 degrees Celsius during irradiation. Cartilage denatured in 50% EtOH (20 minutes) was used as a positive control. TPM was performed using a mode-locked 780 nm Titanium:Sapphire (Ti:Al203) beam with a, 63X, 1.2 N.A. water immersion objective (working distance of 200 mm) to detect the fluorescence emission from the chondrocytes. Images of chondrocytes were obtained at depths up to 150 microns (lateral resolution equals 35 micrometer X 35 micrometer). Images were obtained immediately following laser exposure, and also after 4 days in culture. In both cases, the irradiated and non-irradiated specimens do not show any discernible difference in general shape or auto fluorescence. In contrast, positive controls (immersed in 50% ethanol), show markedly increased fluorescence relative to both the native and irradiated specimens, in the cytoplasmic region.

Quasi-static elastography comparison of hyaline cartilage structures

NASA Astrophysics Data System (ADS)

McCredie, A. J.; Stride, E.; Saffari, N.

2009-11-01

Joint cartilage, a load bearing structure in mammals, has only limited ability for regeneration after damage. For tissue engineers to design functional constructs, better understanding of the properties of healthy tissue is required. Joint cartilage is a specialised structure of hyaline cartilage; a poroviscoelastic solid containing fibril matrix reinforcements. Healthy joint cartilage is layered, which is thought to be important for correct tissue function. However, the behaviour of each layer during loading is poorly understood. Ultrasound elastography provides access to depth-dependent information in real-time for a sample during loading. A 15 MHz focussed transducer provided details from scatterers within a small fixed region in each sample. Quasi-static loading was applied to cartilage samples while ultrasonic signals before and during compressions were recorded. Ultrasonic signals were processed to provide time-shift profiles using a sum-squared difference method and cross-correlation. Two structures of hyaline cartilage have been tested ultrasonically and mechanically to determine method suitability for monitoring internal deformation differences under load and the effect of the layers on the global mechanical material behaviour. Results show differences in both the global mechanical properties and the ultrasonically tested strain distributions between the two structures tested. It was concluded that these differences are caused primarily by the fibril orientations.

Analysis of Long Bone and Vertebral Failure Patterns.

DTIC Science & Technology

1982-09-30

processes further supported the findings of • :the scanning electron microscopy studies . In the impacted animals, the cartilage surface was eroded... cartilage matrix. In the six years post-impaction group, the articular cartilage had converted to fibrocartilage instead of normal hyaline cartilage . The...columns of four rhesus monkeys have been collected and are being processed for study with light microscopy and scanning electron microscopy. The baboon

The bovine patella as a model of early osteoarthritis.

PubMed

Hargrave-Thomas, E J; Thambyah, A; McGlashan, S R; Broom, N D

2013-12-01

The bovine patella model has been used extensively for studying important structure-function aspects of articular cartilage, including its degeneration. However, the degeneration seen in this model has, to our knowledge, never been adequately compared with human osteoarthritis (OA). In this study, bovine patellae displaying normal to severely degenerate states were compared with human tissue displaying intact cartilage to severe OA. Comparisons of normal and OA features were made with histological scoring, morphometric measurements, and qualitative observations. Differential interference contrast microscopy was used to image early OA changes in the articular cartilage matrix and to investigate whether this method provided comparable quality of visualisation of key structural features with standard histology. The intact bovine cartilage was found to be similar to healthy human cartilage and the degenerate bovine cartilage resembled the human OA tissues with regard to structural disruption, cellularity changes, and staining loss. The extent of degeneration in the bovine tissues matched the mild to moderate range of human OA tissues; however, no bovine samples exhibited late-stage OA. Additionally, in both bovine and human tissues, cartilage degeneration was accompanied by calcified cartilage thickening, tidemark duplication, and the advancement of the cement line by protrusions of bony spicules into the calcified cartilage. This comparison of degeneration in the bovine and human tissues suggests a common pathway for the progression of OA and thus the bovine patella is proposed to be an appropriate model for investigating the structural changes associated with early OA. © 2013 Anatomical Society.

Accuracy assessment of 3D bone reconstructions using CT: an intro comparison.

PubMed

Lalone, Emily A; Willing, Ryan T; Shannon, Hannah L; King, Graham J W; Johnson, James A

2015-08-01

Computed tomography provides high contrast imaging of the joint anatomy and is used routinely to reconstruct 3D models of the osseous and cartilage geometry (CT arthrography) for use in the design of orthopedic implants, for computer assisted surgeries and computational dynamic and structural analysis. The objective of this study was to assess the accuracy of bone and cartilage surface model reconstructions by comparing reconstructed geometries with bone digitizations obtained using an optical tracking system. Bone surface digitizations obtained in this study determined the ground truth measure for the underlying geometry. We evaluated the use of a commercially available reconstruction technique using clinical CT scanning protocols using the elbow joint as an example of a surface with complex geometry. To assess the accuracies of the reconstructed models (8 fresh frozen cadaveric specimens) against the ground truth bony digitization-as defined by this study-proximity mapping was used to calculate residual error. The overall mean error was less than 0.4 mm in the cortical region and 0.3 mm in the subchondral region of the bone. Similarly creating 3D cartilage surface models from CT scans using air contrast had a mean error of less than 0.3 mm. Results from this study indicate that clinical CT scanning protocols and commonly used and commercially available reconstruction algorithms can create models which accurately represent the true geometry. Copyright © 2015 IPEM. Published by Elsevier Ltd. All rights reserved.

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

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

Evaluation of structural and mechanical properties of electrospun nano-micro hybrid of poly hydroxybutyrate-chitosan/silk scaffold for cartilage tissue engineering

PubMed Central

Karbasi, Saeed; Fekrat, Farnoosh; Semnani, Daryoush; Razavi, Shahnaz; Zargar, Elham Naghash

2016-01-01

Background: One of the new methods of scaffold fabrication is a nano-micro hybrid structure in which the properties of the scaffold are improved by introducing nanometer and micrometer structures. This method could be suitable for scaffold designing if some features improve. Materials and Methods: In this study, electrospun nanofibers of 9% weight solution of poly (3-hydroxybutyrate) (P3HB) and a 15% weight of chitosan by trifluoroacetic acid were coated on both the surface of a silk knitted substrate in the optimum condition to improve the mechanical properties of scaffolds for cartilage tissue engineering application. These hybrid nano-micro fibrous scaffolds were characterized by structural and mechanical evaluation methods. Results: Scanning electron microscopy values and porosity analysis showed that average diameter of nanofibers was 584.94 nm in electrospinning part and general porosity was more than 80%. Fourier transform infrared spectroscopy results indicated the presence of all elements without pollution. The tensile test also stated that by electrospinning, as well as adding chitosan, both maximum strength and maximum elongation increased to 187 N and 10 mm. It means that the microfibrous part of scaffold could affect mechanical properties of nano part of the hybrid scaffold, significantly. Conclusions: It could be concluded that P3HB-chitosan/silk hybrid scaffolds can be a good candidate for cartilage tissue engineering. PMID:28028520

Evaluation of structural and mechanical properties of electrospun nano-micro hybrid of poly hydroxybutyrate-chitosan/silk scaffold for cartilage tissue engineering.

PubMed

Karbasi, Saeed; Fekrat, Farnoosh; Semnani, Daryoush; Razavi, Shahnaz; Zargar, Elham Naghash

2016-01-01

One of the new methods of scaffold fabrication is a nano-micro hybrid structure in which the properties of the scaffold are improved by introducing nanometer and micrometer structures. This method could be suitable for scaffold designing if some features improve. In this study, electrospun nanofibers of 9% weight solution of poly (3-hydroxybutyrate) (P3HB) and a 15% weight of chitosan by trifluoroacetic acid were coated on both the surface of a silk knitted substrate in the optimum condition to improve the mechanical properties of scaffolds for cartilage tissue engineering application. These hybrid nano-micro fibrous scaffolds were characterized by structural and mechanical evaluation methods. Scanning electron microscopy values and porosity analysis showed that average diameter of nanofibers was 584.94 nm in electrospinning part and general porosity was more than 80%. Fourier transform infrared spectroscopy results indicated the presence of all elements without pollution. The tensile test also stated that by electrospinning, as well as adding chitosan, both maximum strength and maximum elongation increased to 187 N and 10 mm. It means that the microfibrous part of scaffold could affect mechanical properties of nano part of the hybrid scaffold, significantly. It could be concluded that P3HB-chitosan/silk hybrid scaffolds can be a good candidate for cartilage tissue engineering.

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.

Gelatin Scaffolds with Controlled Pore Structure and Mechanical Property for Cartilage Tissue Engineering.

PubMed

Chen, Shangwu; Zhang, Qin; Nakamoto, Tomoko; Kawazoe, Naoki; Chen, Guoping

2016-03-01

Engineering of cartilage tissue in vitro using porous scaffolds and chondrocytes provides a promising approach for cartilage repair. However, nonuniform cell distribution and heterogeneous tissue formation together with weak mechanical property of in vitro engineered cartilage limit their clinical application. In this study, gelatin porous scaffolds with homogeneous and open pores were prepared using ice particulates and freeze-drying. The scaffolds were used to culture bovine articular chondrocytes to engineer cartilage tissue in vitro. The pore structure and mechanical property of gelatin scaffolds could be well controlled by using different ratios of ice particulates to gelatin solution and different concentrations of gelatin. Gelatin scaffolds prepared from ≥70% ice particulates enabled homogeneous seeding of bovine articular chondrocytes throughout the scaffolds and formation of homogeneous cartilage extracellular matrix. While soft scaffolds underwent cellular contraction, stiff scaffolds resisted cellular contraction and had significantly higher cell proliferation and synthesis of sulfated glycosaminoglycan. Compared with the gelatin scaffolds prepared without ice particulates, the gelatin scaffolds prepared with ice particulates facilitated formation of homogeneous cartilage tissue with significantly higher compressive modulus. The gelatin scaffolds with highly open pore structure and good mechanical property can be used to improve in vitro tissue-engineered cartilage.

[3-Tesla MRI vs. arthroscopy for diagnostics of degenerative knee cartilage diseases: preliminary clinical results].

PubMed

von Engelhardt, L V; Schmitz, A; Burian, B; Pennekamp, P H; Schild, H H; Kraft, C N; von Falkenhausen, M

2008-09-01

The literature contains only a few studies investigating the magnetic resonance imaging (MRI) diagnostics of degenerative cartilage diseases. Studies on MRI diagnostics of the cartilage using field strengths of 3-Tesla demonstrate promising results. To assess the value of 3-Tesla MRI for decision making regarding conservative or operative treatment possibilities, this study focused on patients with degenerative cartilage diseases. Thirty-two patients with chronic knee pain, a minimum age of 40 years, a negative history of trauma, and at least grade II degenerative cartilage disease were included. Cartilage abnormalities detected at preoperative 3-Tesla MRI (axial/koronar/sagittal PD-TSE-SPAIR, axial/sagittal 3D-T1-FFE, axial T2-FFE; Intera 3.0T, Philips Medical Systems) were classified (grades I-IV) and compared with arthroscopic findings. Thirty-six percent (70/192) of the examined cartilage surfaces demonstrated no agreement between MRI and arthroscopic grading. In most of these cases, grades II and III cartilage lesions were confounded with each other. Regarding the positive predictive values, the probability that a positive finding in MRI would be exactly confirmed by arthroscopy was 39-72%. In contrast, specificities and negative predictive values of different grades of cartilage diseases were 85-95%. Regarding the high specificities and negative predictive values, 3-Tesla MRI is a reliable method for excluding even slight cartilage degeneration. In summary, in degenerative cartilage diseases, 3-Tesla MRI is a supportive, noninvasive method for clinical decision making regarding conservative or operative treatment possibilities. However, the value of diagnostic arthroscopy for a definitive assessment of the articular surfaces and for therapeutic planning currently cannot be replaced by 3-Tesla MRI. This applies especially to treatment options in which a differentiation between grade II and III cartilage lesions is of interest.

Bioactive Nano-Fibrous Scaffolds for Bone and Cartilage Tissue Engineering

NASA Astrophysics Data System (ADS)

Feng, Kai

Scaffolds that can mimic the structural features of natural extracellular matrix and can deliver biomolecules in a controlled fashion may provide cells with a favorable microenvironment to facilitate tissue regeneration. Biodegradable nanofibrous scaffolds with interconnected pore network have previously been developed in our laboratory to mimic collagen matrix and advantageously support both bone and cartilage regeneration. This dissertation project aims to expand both the structural complexity and the biomolecule delivery capacity of such biomimetic scaffolds for tissue engineering. We first developed a nanofibrous scaffold that can release an antibiotic (doxycycline) with a tunable release rate and a tunable dosage, which was demonstrated to be able to inhibit bacterial growth over a prolonged time period. We then developed a nanofibrous tissue-engineciing scaffold that can release basic fibroblast growth factor (bFGF) in a spatially and temporally controlled fashion. In a mouse subcutaneous implantation model, the bFGF-releasing scaffold was shown to enhance cell penetration, tissue ingrowth and angiogenesis. It was also found that both the dose and the release rate of bFGF play roles in the biologic function of the scaffold. After that, we developed a nanofibrous PLLA scaffold that can release both bone morphogenetic protein 7 (BMP-7) and platelet-derived growth factor (PDGF) with distinct dosages and release kinetics. It was demonstrated that BMP-7 and PDGF could synergistically enhance bone regeneration using a mouse ectopic bone formation model and a rat periodontal fenestration defect regeneration model. The regeneration outcome was dependent on the dosage, the ratio and the release kinetics of the two growth factors. Last, we developed an anisotropic composite scaffold with an upper layer mimicking the superficial zone of cartilage and a lower layer mimicking the middle zone of cartilage. The thin superficial layer was fabricated using an electrospinning technique to support a more parallel ECM orientation to the cartilage surface. The lower layer was fabricated using a phase-separation technique to support a more isotropic ECM distribution. Human bone marrow-derived mesenchymal stem cells (hMSCs) were seeded on this complex scaffold and cultured under chondrogenic conditions. The results showed that the composite scaffold was indeed able to support anisotropic cartilage tissue structure formation.

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.

A novel nano-structured porous polycaprolactone scaffold improves hyaline cartilage repair in a rabbit model compared to a collagen type I/III scaffold: in vitro and in vivo studies.

PubMed

Christensen, Bjørn Borsøe; Foldager, Casper Bindzus; Hansen, Ole Møller; Kristiansen, Asger Albæk; Le, Dang Quang Svend; Nielsen, Agnete Desirée; Nygaard, Jens Vinge; Bünger, Cody Erik; Lind, Martin

2012-06-01

To develop a nano-structured porous polycaprolactone (NSP-PCL) scaffold and compare the articular cartilage repair potential with that of a commercially available collagen type I/III (Chondro-Gide) scaffold. By combining rapid prototyping and thermally induced phase separation, the NSP-PCL scaffold was produced for matrix-assisted autologous chondrocyte implantation. Lyophilizing a water-dioxane-PCL solution created micro and nano-pores. In vitro: The scaffolds were seeded with rabbit chondrocytes and cultured in hypoxia for 6 days. qRT-PCR was performed using primers for sox9, aggrecan, collagen type 1 and 2. In vivo: 15 New Zealand White Rabbits received bilateral osteochondral defects in the femoral intercondylar grooves. Autologous chondrocytes were harvested 4 weeks prior to surgery. There were 3 treatment groups: (1) NSP-PCL scaffold without cells. (2) The Chondro-Gide scaffold with autologous chondrocytes and (3) NSP-PCL scaffold with autologous chondrocytes. Observation period was 13 weeks. Histological evaluation was made using the O'Driscoll score. In vitro: The expressions of sox9 and aggrecan were higher in the NSP-PCL scaffold, while expression of collagen 1 was lower compared to the Chondro-Gide scaffold. In vivo: Both NSP-PCL scaffolds with and without cells scored significantly higher than the Chondro-Gide scaffold when looking at the structural integrity and the surface regularity of the repair tissue. No differences were found between the NSP-PCL scaffold with and without cells. The NSP-PCL scaffold demonstrated higher in vitro expression of chondrogenic markers and had higher in vivo histological scores compared to the Chondro-Gide scaffold. The improved chondrocytic differentiation can potentially produce more hyaline cartilage during clinical cartilage repair. It appears to be a suitable cell-free implant for hyaline cartilage repair and could provide a less costly and more effective treatment option than the Chondro-Gide scaffold with cells.

Image-guided smart laser system for precision implantation of cells in cartilage

NASA Astrophysics Data System (ADS)

Katta, Nitesh; Rector, John A.; Gardner, Michael R.; McElroy, Austin B.; Choy, Kevin C.; Crosby, Cody; Zoldan, Janet; Milner, Thomas E.

2017-03-01

State-of-the-art treatment for joint diseases like osteoarthritis focus on articular cartilage repair/regeneration by stem cell implantation therapy. However, the technique is limited by a lack of precision in the physician's imaging and cell deposition toolkit. We describe a novel combination of high-resolution, rapid scan-rate optical coherence tomography (OCT) alongside a short-pulsed nanosecond thulium (Tm) laser for precise cell seeding in cartilage. The superior beam quality of thulium lasers and wavelength of operation 1940 nm offers high volumetric tissue removal rates and minimizes the residual thermal footprint. OCT imaging enables targeted micro-well placement, precise cell deposition, and feature contrast. A bench-top system is constructed using a 15 W, 1940 nm, nanosecond-pulsed Tm fiber laser (500 μJ pulse energy, 100 ns pulse duration, 30kHz repetition rate) for removing tissue, and a swept source laser (1310 ± 70 nm, 100 kHz sweep rate) for OCT imaging, forming a combined Tm/OCT system - a "smart laser knife". OCT assists the smart laser knife user in characterizing cartilage to inform micro-well placement. The Tm laser creates micro-wells (2.35 mm diameter length, 1.5 mm width, 300 μm deep) and micro-incisions (1 mm wide, 200 μm deep) while OCT image-guidance assists and demonstrates this precision cutting and cell deposition with real-time feedback. To test micro-well creation and cell deposition protocol, gelatin phantoms are constructed mimicking cartilage optical properties and physiological structure. Cell viability is then assessed to illustrate the efficacy of the hydrogel deposition. Automated OCT feedback is demonstrated for cutting procedures to avoid important surface/subsurface structures. This bench-top smart laser knife system described here offers a new image-guided approach to precise stem cell seeding that can enhance the efficacy of articular cartilage repair.

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

Use of vascularised cartilage as an additional interposition in temporomandibular ankylosis surgery: Rationale, advantages and potential benefits.

PubMed

Jagannathan, Mukund; Devale, Maksud; Kesari, Prashantha; Karanth, Siddharth

2008-07-01

Surgery for the release of temporomandibular joint (TMJ) ankylosis is a commonly performed procedure. Various interposition materials have been tried with varying success rates. However, none of these procedures attempt to recreate the architecture of the joint as the glenoid surface is usually left raw. We aimed to use a vascularised cartilage flap and to line the raw surface of the bone to recreate the articular surface of the joint. There is a rich blood supply in the region of the helical root, based on branches from the Superficial Temporal Artery (STA), which enables the harvest of vascularised cartilage from the helical root for use in the temporomandibular joint. Two cases, one adult and the other a child, of unilateral ankylosis were operated upon using this additional technique. The adult patient had a bony segment excised along with a vascularised cartilage flap for lining the glenoid. The child was managed with an interposition graft of costochondral cartilage following the release of the ankylosis, in addition to the vascularised cartilage flap for lining the glenoid. The postoperative mouth opening was good in both the cases with significant reduction in pain. However, the long-term results of this procedure are yet to be ascertained. The vascularised cartilage flap as an additional interposition material in temporomandibular joint surgery enables early and painless mouth-opening with good short-term results. The potential applicability of this flap in various pathologies of the temporomandibular joint is enormous.

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

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.

Automatic segmentation of the glenohumeral cartilages from magnetic resonance images.

PubMed

Neubert, A; Yang, Z; Engstrom, C; Xia, Y; Strudwick, M W; Chandra, S S; Fripp, J; Crozier, S

2016-10-01

Magnetic resonance (MR) imaging plays a key role in investigating early degenerative disorders and traumatic injuries of the glenohumeral cartilages. Subtle morphometric and biochemical changes of potential relevance to clinical diagnosis, treatment planning, and evaluation can be assessed from measurements derived from in vivo MR segmentation of the cartilages. However, segmentation of the glenohumeral cartilages, using approaches spanning manual to automated methods, is technically challenging, due to their thin, curved structure and overlapping intensities of surrounding tissues. Automatic segmentation of the glenohumeral cartilages from MR imaging is not at the same level compared to the weight-bearing knee and hip joint cartilages despite the potential applications with respect to clinical investigation of shoulder disorders. In this work, the authors present a fully automated segmentation method for the glenohumeral cartilages using MR images of healthy shoulders. The method involves automated segmentation of the humerus and scapula bones using 3D active shape models, the extraction of the expected bone-cartilage interface, and cartilage segmentation using a graph-based method. The cartilage segmentation uses localization, patient specific tissue estimation, and a model of the cartilage thickness variation. The accuracy of this method was experimentally validated using a leave-one-out scheme on a database of MR images acquired from 44 asymptomatic subjects with a true fast imaging with steady state precession sequence on a 3 T scanner (Siemens Trio) using a dedicated shoulder coil. The automated results were compared to manual segmentations from two experts (an experienced radiographer and an experienced musculoskeletal anatomist) using the Dice similarity coefficient (DSC) and mean absolute surface distance (MASD) metrics. Accurate and precise bone segmentations were achieved with mean DSC of 0.98 and 0.93 for the humeral head and glenoid fossa, respectively. Mean DSC scores of 0.74 and 0.72 were obtained for the humeral and glenoid cartilage volumes, respectively. The manual interobserver reliability evaluated by DSC was 0.80 ± 0.03 and 0.76 ± 0.04 for the two cartilages, implying that the automated results were within an acceptable 10% difference. The MASD between the automatic and the corresponding manual cartilage segmentations was less than 0.4 mm (previous studies reported mean cartilage thickness of 1.3 mm). This work shows the feasibility of volumetric segmentation and separation of the glenohumeral cartilages from MR images. To their knowledge, this is the first fully automated algorithm for volumetric segmentation of the individual glenohumeral cartilages from MR images. The approach was validated against manual segmentations from experienced analysts. In future work, the approach will be validated on imaging datasets acquired with various MR contrasts in patients.

Automatic segmentation of the glenohumeral cartilages from magnetic resonance images

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

Neubert, A., E-mail: ales.neubert@csiro.au

Purpose: Magnetic resonance (MR) imaging plays a key role in investigating early degenerative disorders and traumatic injuries of the glenohumeral cartilages. Subtle morphometric and biochemical changes of potential relevance to clinical diagnosis, treatment planning, and evaluation can be assessed from measurements derived from in vivo MR segmentation of the cartilages. However, segmentation of the glenohumeral cartilages, using approaches spanning manual to automated methods, is technically challenging, due to their thin, curved structure and overlapping intensities of surrounding tissues. Automatic segmentation of the glenohumeral cartilages from MR imaging is not at the same level compared to the weight-bearing knee and hipmore » joint cartilages despite the potential applications with respect to clinical investigation of shoulder disorders. In this work, the authors present a fully automated segmentation method for the glenohumeral cartilages using MR images of healthy shoulders. Methods: The method involves automated segmentation of the humerus and scapula bones using 3D active shape models, the extraction of the expected bone–cartilage interface, and cartilage segmentation using a graph-based method. The cartilage segmentation uses localization, patient specific tissue estimation, and a model of the cartilage thickness variation. The accuracy of this method was experimentally validated using a leave-one-out scheme on a database of MR images acquired from 44 asymptomatic subjects with a true fast imaging with steady state precession sequence on a 3 T scanner (Siemens Trio) using a dedicated shoulder coil. The automated results were compared to manual segmentations from two experts (an experienced radiographer and an experienced musculoskeletal anatomist) using the Dice similarity coefficient (DSC) and mean absolute surface distance (MASD) metrics. Results: Accurate and precise bone segmentations were achieved with mean DSC of 0.98 and 0.93 for the humeral head and glenoid fossa, respectively. Mean DSC scores of 0.74 and 0.72 were obtained for the humeral and glenoid cartilage volumes, respectively. The manual interobserver reliability evaluated by DSC was 0.80 ± 0.03 and 0.76 ± 0.04 for the two cartilages, implying that the automated results were within an acceptable 10% difference. The MASD between the automatic and the corresponding manual cartilage segmentations was less than 0.4 mm (previous studies reported mean cartilage thickness of 1.3 mm). Conclusions: This work shows the feasibility of volumetric segmentation and separation of the glenohumeral cartilages from MR images. To their knowledge, this is the first fully automated algorithm for volumetric segmentation of the individual glenohumeral cartilages from MR images. The approach was validated against manual segmentations from experienced analysts. In future work, the approach will be validated on imaging datasets acquired with various MR contrasts in patients.« less

The Application of Sheet Technology in Cartilage Tissue Engineering.

PubMed

Ge, Yang; Gong, Yi Yi; Xu, Zhiwei; Lu, Yanan; Fu, Wei

2016-04-01

Cartilage tissue engineering started to act as a promising, even essential alternative method in the process of cartilage repair and regeneration, considering adult avascular structure has very limited self-renewal capacity of cartilage tissue in adults and a bottle-neck existed in conventional surgical treatment methods. Recent progressions in tissue engineering realized the development of more feasible strategies to treat cartilage disorders. Of these strategies, cell sheet technology has shown great clinical potentials in the regenerative areas such as cornea and esophagus and is increasingly considered as a potential way to reconstruct cartilage tissues for its non-use of scaffolds and no destruction of matrix secreted by cultured cells. Acellular matrix sheet technologies utilized in cartilage tissue engineering, with a sandwich model, can ingeniously overcome the drawbacks that occurred in a conventional acellular block, where cells are often blocked from migrating because of the non-nanoporous structure. Electrospun-based sheets with nanostructures that mimic the natural cartilage matrix offer a level of control as well as manipulation and make them appealing and widely used in cartilage tissue engineering. In this review, we focus on the utilization of these novel and promising sheet technologies to construct cartilage tissues with practical and beneficial functions.

Brief report: reconstruction of joint hyaline cartilage by autologous progenitor cells derived from ear elastic cartilage.

PubMed

Mizuno, Mitsuru; Kobayashi, Shinji; Takebe, Takanori; Kan, Hiroomi; Yabuki, Yuichiro; Matsuzaki, Takahisa; Yoshikawa, Hiroshi Y; Nakabayashi, Seiichiro; Ik, Lee Jeong; Maegawa, Jiro; Taniguchi, Hideki

2014-03-01

In healthy joints, hyaline cartilage covering the joint surfaces of bones provides cushioning due to its unique mechanical properties. However, because of its limited regenerative capacity, age- and sports-related injuries to this tissue may lead to degenerative arthropathies, prompting researchers to investigate a variety of cell sources. We recently succeeded in isolating human cartilage progenitor cells from ear elastic cartilage. Human cartilage progenitor cells have high chondrogenic and proliferative potential to form elastic cartilage with long-term tissue maintenance. However, it is unknown whether ear-derived cartilage progenitor cells can be used to reconstruct hyaline cartilage, which has different mechanical and histological properties from elastic cartilage. In our efforts to develop foundational technologies for joint hyaline cartilage repair and reconstruction, we conducted this study to obtain an answer to this question. We created an experimental canine model of knee joint cartilage damage, transplanted ear-derived autologous cartilage progenitor cells. The reconstructed cartilage was rich in proteoglycans and showed unique histological characteristics similar to joint hyaline cartilage. In addition, mechanical properties of the reconstructed tissues were higher than those of ear cartilage and equal to those of joint hyaline cartilage. This study suggested that joint hyaline cartilage was reconstructed from ear-derived cartilage progenitor cells. It also demonstrated that ear-derived cartilage progenitor cells, which can be harvested by a minimally invasive method, would be useful for reconstructing joint hyaline cartilage in patients with degenerative arthropathies. © AlphaMed Press.

Cartilage of the Intervertebral Disc Eng-Plate, A Histological, Histochemical, Fine Structure Study.

DTIC Science & Technology

1982-08-01

degeneration (Nachemson et al., 1970). These and related studies consider the end-plates to be composed of hyaline cartilage and thus homologues of articular...results of this study in rhesus indicate, that while present, the cartilage of the end-plate is quite different in structure and presumably...HZSTOLO6ZCAL,-ETCfU) I AUG 82 N 5 NUSSBAUM IUNCLASSIFDATRL8R-1222NL.rnximommmB~iIEND2 AFAMRL-TR-81 - 122 " CARTILAGE OF THE INTERVERTEBRAL DISC END-PLATE A

Oriented clonal cell dynamics enables accurate growth and shaping of vertebrate cartilage

PubMed Central

Kaucka, Marketa; Zikmund, Tomas; Tesarova, Marketa; Gyllborg, Daniel; Hellander, Andreas; Jaros, Josef; Kaiser, Jozef; Petersen, Julian; Szarowska, Bara; Newton, Phillip T; Dyachuk, Vyacheslav; Li, Lei; Qian, Hong; Johansson, Anne-Sofie; Mishina, Yuji; Currie, Joshua D; Tanaka, Elly M; Erickson, Alek; Dudley, Andrew; Brismar, Hjalmar; Southam, Paul; Coen, Enrico; Chen, Min; Weinstein, Lee S; Hampl, Ales; Arenas, Ernest; Chagin, Andrei S; Fried, Kaj; Adameyko, Igor

2017-01-01

Cartilaginous structures are at the core of embryo growth and shaping before the bone forms. Here we report a novel principle of vertebrate cartilage growth that is based on introducing transversally-oriented clones into pre-existing cartilage. This mechanism of growth uncouples the lateral expansion of curved cartilaginous sheets from the control of cartilage thickness, a process which might be the evolutionary mechanism underlying adaptations of facial shape. In rod-shaped cartilage structures (Meckel, ribs and skeletal elements in developing limbs), the transverse integration of clonal columns determines the well-defined diameter and resulting rod-like morphology. We were able to alter cartilage shape by experimentally manipulating clonal geometries. Using in silico modeling, we discovered that anisotropic proliferation might explain cartilage bending and groove formation at the macro-scale. DOI: http://dx.doi.org/10.7554/eLife.25902.001 PMID:28414273

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 investigations suggest that open wedge valgus HTO is a safe procedure for the lateral compartment to manage medial osteoarthritis of the knee with varus malalignment in the short term.

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

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.

Devitalisation of human cartilage by high hydrostatic pressure treatment: Subsequent cultivation of chondrocytes and mesenchymal stem cells on the devitalised tissue

PubMed Central

Hiemer, B.; Genz, B.; Jonitz-Heincke, A.; Pasold, J.; Wree, A.; Dommerich, S.; Bader, R.

2016-01-01

The regeneration of cartilage lesions still represents a major challenge. Cartilage has a tissue-specific architecture, complicating recreation by synthetic biomaterials. A novel approach for reconstruction is the use of devitalised cartilage. Treatment with high hydrostatic pressure (HHP) achieves devitalisation while biomechanical properties are remained. Therefore, in the present study, cartilage was devitalised using HHP treatment and the potential for revitalisation with chondrocytes and mesenchymal stem cells (MSCs) was investigated. The devitalisation of cartilage was performed by application of 480 MPa over 10 minutes. Effective cellular inactivation was demonstrated by the trypan blue exclusion test and DNA quantification. Histology and electron microscopy examinations showed undamaged cartilage structure after HHP treatment. For revitalisation chondrocytes and MSCs were cultured on devitalised cartilage without supplementation of chondrogenic growth factors. Both chondrocytes and MSCs significantly increased expression of cartilage-specific genes. ECM stainings showed neocartilage-like structure with positive AZAN staining as well as collagen type II and aggrecan deposition after three weeks of cultivation. Our results showed that HHP treatment caused devitalisation of cartilage tissue. ECM proteins were not influenced, thus, providing a scaffold for chondrogenic differentiation of MSCs and chondrocytes. Therefore, using HHP-treated tissue might be a promising approach for cartilage repair. PMID:27671122

On foundations of discrete element analysis of contact in diarthrodial joints.

PubMed

Volokh, K Y; Chao, E Y S; Armand, M

2007-06-01

Information about the stress distribution on contact surfaces of adjacent bones is indispensable for analysis of arthritis, bone fracture and remodeling. Numerical solution of the contact problem based on the classical approaches of solid mechanics is sophisticated and time-consuming. However, the solution can be essentially simplified on the following physical grounds. The bone contact surfaces are covered with a layer of articular cartilage, which is a soft tissue as compared to the hard bone. The latter allows ignoring the bone compliance in analysis of the contact problem, i.e. rigid bones are considered to interact through a compliant cartilage. Moreover, cartilage shear stresses and strains can be ignored because of the negligible friction between contacting cartilage layers. Thus, the cartilage can be approximated by a set of unilateral compressive springs normal to the bone surface. The forces in the springs can be computed from the equilibrium equations iteratively accounting for the changing contact area. This is the essence of the discrete element analysis (DEA). Despite the success in applications of DEA to various bone contact problems, its classical formulation required experimental validation because the springs approximating the cartilage were assumed linear while the real articular cartilage exhibited non-linear mechanical response in reported tests. Recent experimental results of Ateshian and his co-workers allow for revisiting the classical DEA formulation and establishing the limits of its applicability. In the present work, it is shown that the linear spring model is remarkably valid within a wide range of large deformations of the cartilage. It is also shown how to extend the classical DEA to the case of strong nonlinearity if necessary.

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

An in vitro study of cartilage-meniscus tribology to understand the changes caused by a meniscus implant.

PubMed

Majd, Sara Ehsani; Rizqy, Aditya Iman; Kaper, Hans J; Schmidt, Tannin A; Kuijer, Roel; Sharma, Prashant K

2017-07-01

Active lifestyles increase the risk of meniscal injury. A permanent meniscus implant of polycarbonate urethane (PCU) is a promising treatment to postpone/prevent total knee arthroplasty. Study of the changes in articular cartilage tribology in the presence of PCU is essential in developing the optimum meniscus implant. Therefore, a cartilage-meniscus reciprocating, sliding model was developed in vitro, mimicking the stance and swing phases of the gait cycle. The meniscus was further replaced with PCU and surface-modified PCUs (with C18 chains, mono-functional polydimethylsiloxane groups and mono-functional polytetrafluoroethylene groups) to study the changes. The coefficient of friction (COF) was calculated, and cartilage wear was determined and quantified histologically. The cartilage-meniscus sliding resulted in low COF during both stance and swing (0.01< COF <0.12) and low wear of cartilage (scores <1). The cartilage-PCU sliding, during stance, revealed similar low COFs. But during swing, the COFs were high (average ∼1, maximum 1.6), indicating a breakdown in interstitial fluid pressurization lubrication and non-effective activation of the boundary lubrication. This may lead to wear of cartilage in long term. However, under the tested conditions the wear of cartilage against PCUs was not higher than its wear against meniscus, and the cartilage was occasionally damaged. The COF decreased with increasing the contact pressure (as-per a power equation) up to 1MPa. The changes in the surface modification of PCU did not affect PCU's tribological performance. Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.

Impact of synovial fluid flow on temperature regulation in knee cartilage.

PubMed

Moghadam, Mohamadreza Nassajian; Abdel-Sayed, Philippe; Camine, Valérie Malfroy; Pioletti, Dominique P

2015-01-21

Several studies have reported an increase of temperature in cartilage submitted to cyclic sinusoidal loading. The temperature increase is in part due to the viscous behavior of this tissue, which partially dissipates the input mechanical energy into heat. While the synovial fluid flow within the intra-articular gap and inside the porous cartilage is supposed to play an important role in the regulation of the cartilage temperature, no specific study has evaluated this aspect. In the present numerical study, a poroelastic model of the knee cartilage is developed to evaluate first the temperature increase in the cartilage due to dissipation and second the impact of the synovial fluid flow in the cartilage heat transfer phenomenon. Our results showed that, the local temperature is effectively increased in knee cartilage due to its viscous behavior. The synovial fluid flow cannot significantly preventing this phenomenon. We explain this result by the low permeability of cartilage and the moderate fluid exchange at the surface of cartilage under deformation. Copyright © 2014 Elsevier Ltd. All rights reserved.

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.

Fat-suppressed three-dimensional spoiled gradient-echo MR imaging of hyaline cartilage defects in the knee: comparison with standard MR imaging and arthroscopy.

PubMed

Disler, D G; McCauley, T R; Kelman, C G; Fuchs, M D; Ratner, L M; Wirth, C R; Hospodar, P P

1996-07-01

The sensitivity of fat-suppressed three-dimensional spoiled gradient-echo (SPGR) images was compared with that of standard MR images for detecting hyaline cartilage defects of the knee, using arthroscopy as the standard of reference. We assessed 114 consecutive patients for hyaline cartilage defects of the knee with both standard MR imaging sequences and a sagittal fat-suppressed three-dimensional SPGR sequence. Of these patients, 48 with meniscal or ligament injury, or persistent symptoms, underwent subsequent arthroscopy. The standard MR images and SPGR images of these 48 patients were then retrospectively analyzed for articular defects in a blinded fashion by two independent observers. Sensitivity, specificity, and intraobserver and interobserver agreement were determined for the different imaging techniques. One fourth of the patients who went on to arthroscopy were shown to have isolated hyaline cartilage lesions that were clinically confused with meniscal tears and that were missed on the standard MR images. When looking at all surfaces combined for each reader, the SPGR imaging sequence had a significantly higher sensitivity than the standard MR imaging sequences for detecting hyaline cartilage defects (75-85% versus 29-38%, p < .001 for each comparison). When looking at individual surfaces for each reader, significant differences in sensitivity were shown for each surface except the trochlear and lateral tibial surfaces. We found no difference in specificity (97% versus 97%, p > .99). We also found that combined evaluation of standard MR and SPGR images gave no added diagnostic advantage (sensitivity, 86%; specificity, 97%; p > .42). Except for the lateral tibial surface, the study achieved excellent reproducibility among readings and between readers. Fat-suppressed three-dimensional SPGR imaging is more sensitive than standard MR imaging for the detection of hyaline cartilage defects of the knee.

Effect of traction on wrist joint space and cartilage visibility with and without MR arthrography

PubMed Central

Griffith, James F; Tang, W K; Ng, Alex W H; Yeung, David K W

2017-01-01

Objective: To compare the effect of traction during non-arthrographic and arthrographic MR examination of the wrist with regard to joint space width, joint fluid dispersion and cartilage surface visibility. Methods: Prospective 3-T MRI study of 100 wrists in 96 patients. The first 50 wrists underwent MR arthrography first without traction and then with traction. The following 50 wrists underwent standard MR first without traction and then with traction. On these examinations, two radiologists independently measured (i) joint space width, semi-quantitatively graded (ii) joint fluid dispersion between opposing cartilage surfaces and (iii) articular cartilage surface visibility. The three parameters were compared between the two groups. Results: Traction led to an increase in joint space width at nearly all joints in all patients (p < 0.05), although more so in the arthrography (∆ = 0.08–0.79 mm, all p < 0.05) than in the non-arthrography (∆ = 0.001–0.61 mm, all p < 0.05) group. Joint fluid dispersion and cartilage surface visibility improved after traction in nearly all joints (p < 0.05) in all patients and more so in the arthographic than in the non-arthrography group. Conclusion: Traction did significantly improve cartilage surface visibility for standard MRI of the wrist although the effect was not as great as that seen with MR arthography or MR arthrography with traction. Advances in knowledge: This is the first study to show the beneficial effect of traction during standard non-arthrography MRI of the wrist and compare the effect of traction between non-arthrographic and arthrographic MRI of the wrist. PMID:28181830

3D Human cartilage surface characterization by optical coherence tomography.

PubMed

Brill, Nicolai; Riedel, Jörn; Schmitt, Robert; Tingart, Markus; Truhn, Daniel; Pufe, Thomas; Jahr, Holger; Nebelung, Sven

2015-10-07

Early diagnosis and treatment of cartilage degeneration is of high clinical interest. Loss of surface integrity is considered one of the earliest and most reliable signs of degeneration, but cannot currently be evaluated objectively. Optical Coherence Tomography (OCT) is an arthroscopically available light-based non-destructive real-time imaging technology that allows imaging at micrometre resolutions to millimetre depths. As OCT-based surface evaluation standards remain to be defined, the present study investigated the diagnostic potential of 3D surface profile parameters in the comprehensive evaluation of cartilage degeneration. To this end, 45 cartilage samples of different degenerative grades were obtained from total knee replacements (2 males, 10 females; mean age 63.8 years), cut to standard size and imaged using a spectral-domain OCT device (Thorlabs, Germany). 3D OCT datasets of 8  ×  8, 4  ×  4 and 1  ×  1 mm (width  ×  length) were obtained and pre-processed (image adjustments, morphological filtering). Subsequent automated surface identification algorithms were used to obtain the 3D primary profiles, which were then filtered and processed using established algorithms employing ISO standards. The 3D surface profile thus obtained was used to calculate a set of 21 3D surface profile parameters, i.e. height (e.g. Sa), functional (e.g. Sk), hybrid (e.g. Sdq) and segmentation-related parameters (e.g. Spd). Samples underwent reference histological assessment according to the Degenerative Joint Disease classification. Statistical analyses included calculation of Spearman's rho and assessment of inter-group differences using the Kruskal Wallis test. Overall, the majority of 3D surface profile parameters revealed significant degeneration-dependent differences and correlations with the exception of severe end-stage degeneration and were of distinct diagnostic value in the assessment of surface integrity. None of the 3D surface profile parameters investigated were capable of reliably differentiating healthy from early-degenerative cartilage, while scan area sizes considerably affected parameter values. In conclusion, cartilage surface integrity may be adequately assessed by 3D surface profile parameters, which should be used in combination for the comprehensive and thorough evaluation and overall improved diagnostic performance. OCT- and image-based surface assessment could become a valuable adjunct tool to standard arthroscopy.

3D Human cartilage surface characterization by optical coherence tomography

NASA Astrophysics Data System (ADS)

Brill, Nicolai; Riedel, Jörn; Schmitt, Robert; Tingart, Markus; Truhn, Daniel; Pufe, Thomas; Jahr, Holger; Nebelung, Sven

2015-10-01

Early diagnosis and treatment of cartilage degeneration is of high clinical interest. Loss of surface integrity is considered one of the earliest and most reliable signs of degeneration, but cannot currently be evaluated objectively. Optical Coherence Tomography (OCT) is an arthroscopically available light-based non-destructive real-time imaging technology that allows imaging at micrometre resolutions to millimetre depths. As OCT-based surface evaluation standards remain to be defined, the present study investigated the diagnostic potential of 3D surface profile parameters in the comprehensive evaluation of cartilage degeneration. To this end, 45 cartilage samples of different degenerative grades were obtained from total knee replacements (2 males, 10 females; mean age 63.8 years), cut to standard size and imaged using a spectral-domain OCT device (Thorlabs, Germany). 3D OCT datasets of 8  ×  8, 4  ×  4 and 1  ×  1 mm (width  ×  length) were obtained and pre-processed (image adjustments, morphological filtering). Subsequent automated surface identification algorithms were used to obtain the 3D primary profiles, which were then filtered and processed using established algorithms employing ISO standards. The 3D surface profile thus obtained was used to calculate a set of 21 3D surface profile parameters, i.e. height (e.g. Sa), functional (e.g. Sk), hybrid (e.g. Sdq) and segmentation-related parameters (e.g. Spd). Samples underwent reference histological assessment according to the Degenerative Joint Disease classification. Statistical analyses included calculation of Spearman’s rho and assessment of inter-group differences using the Kruskal Wallis test. Overall, the majority of 3D surface profile parameters revealed significant degeneration-dependent differences and correlations with the exception of severe end-stage degeneration and were of distinct diagnostic value in the assessment of surface integrity. None of the 3D surface profile parameters investigated were capable of reliably differentiating healthy from early-degenerative cartilage, while scan area sizes considerably affected parameter values. In conclusion, cartilage surface integrity may be adequately assessed by 3D surface profile parameters, which should be used in combination for the comprehensive and thorough evaluation and overall improved diagnostic performance. OCT- and image-based surface assessment could become a valuable adjunct tool to standard arthroscopy.

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

Surface characteristics of bioactive Ti fabricated by chemical treatment for cartilaginous-integration.

PubMed

Miyajima, Hiroyuki; Ozer, Fusun; Imazato, Satoshi; Mante, Francis K

2017-09-01

Artificial hip joints are generally expected to fail due to wear after approximately 15years and then have to be replaced by revision surgery. If articular cartilage can be integrated onto the articular surfaces of artificial joints in the same way as osseo-integration of titanium dental implants, the wear of joint implants may be reduced or prevented. However, very few studies have focused on the relationship between Ti surface and cartilage. To explore the possibility of cartilaginous-integration, we fabricated chemically treated Ti surfaces with H 2 O 2 /HCl, collagen type II and SBF, respectively. Then, we evaluated surface characteristics of the prepared Ti samples and assessed the cartilage formation by culturing chondrocytes on the Ti samples. When oxidized Ti was immersed in SBF for 7days, apatite was formed on the Ti surface. The surface characteristics of Ti indicated that the wettability was increased by all chemical treatments compared to untreated Ti, and that H 2 O 2 /HCl treated surface had significantly higher roughness compared to the other three groups. Chondrocytes produced significantly more cartilage matrix on all chemically treated Ti surfaces compared to untreated Ti. Thus, to realize cartilaginous-integration and to prevent wear of the implants in joints, application of bioactive Ti formed by chemical treatment would be a promising and effective strategy to improve durability of joint replacement. Copyright © 2017 Elsevier B.V. All rights reserved.

Ex vivo culture platform for assessment of cartilage repair treatment strategies.

PubMed

Schwab, Andrea; Meeuwsen, Annick; Ehlicke, Franziska; Hansmann, Jan; Mulder, Lars; Smits, Anthal; Walles, Heike; Kock, Linda

2017-01-01

There is a great need for valuable ex vivo models that allow for assessment of cartilage repair strategies to reduce the high number of animal experiments. In this paper we present three studies with our novel ex vivo osteochondral culture platform. It consists of two separated media compartments for cartilage and bone, which better represents the in vivo situation and enables supply of factors specific to the different needs of bone and cartilage. We investigated whether separation of the cartilage and bone compartments and/or culture media results in the maintenance of viability, structural and functional properties of cartilage tissue. Next, we evaluated for how long we can preserve cartilage matrix stability of osteochondral explants during long-term culture over 84 days. Finally, we determined the optimal defect size that does not show spontaneous self-healing in this culture system. It was demonstrated that separated compartments for cartilage and bone in combination with tissue-specific medium allow for long-term culture of osteochondral explants while maintaining cartilage viability, matrix tissue content, structure and mechanical properties for at least 56 days. Furthermore, we could create critical size cartilage defects of different sizes in the model. The osteochondral model represents a valuable preclinical ex vivo tool for studying clinically relevant cartilage therapies, such as cartilage biomaterials, for their regenerative potential, for evaluation of drug and cell therapies, or to study mechanisms of cartilage regeneration. It will undoubtedly reduce the number of animals needed for in vivo testing.

The effect of high-energy extracorporeal shock waves on hyaline cartilage of adult rats in vivo.

PubMed

Mayer-Wagner, Susanne; Ernst, Judith; Maier, Markus; Chiquet, Matthias; Joos, Helga; Müller, Peter E; Jansson, Volkmar; Sievers, Birte; Hausdorf, Jörg

2010-08-01

The aim of this study was to determine if extracorporeal shock wave therapy (ESWT) in vivo affects the structural integrity of articular cartilage. A single bout of ESWT (1500 shock waves of 0.5 mJ/mm(2)) was applied to femoral heads of 18 adult Sprague-Dawley rats. Two sham-treated animals served as controls. Cartilage of each femoral head was harvested at 1, 4, or 10 weeks after ESWT (n = 6 per treatment group) and scored on safranin-O-stained sections. Expression of tenascin-C and chitinase 3-like protein 1 (Chi3L1) was analyzed by immunohistochemistry. Quantitative real-time polymerase chain reaction (PCR) was used to examine collagen (II)alpha(1) (COL2A1) expression and chondrocyte morphology was investigated by transmission electron microscopy no changes in Mankin scores were observed after ESWT. Positive immunostaining for tenascin-C and Chi3L1 was found up to 10 weeks after ESWT in experimental but not in control cartilage. COL2A1 mRNA was increased in samples 1 and 4 weeks after ESWT. Alterations found on the ultrastructural level showed expansion of the rough-surfaced endoplasmatic reticulum, detachment of the cell membrane and necrotic chondrocytes. Extracorporeal shock waves caused alterations of hyaline cartilage on a molecular and ultrastructural level that were distinctly different from control. Similar changes were described before in the very early phase of osteoarthritis (OA). High-energy ESWT might therefore cause degenerative changes in hyaline cartilage as they are found in initial OA. Copyright 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Relationships Between Quantitative Pulse-Echo Ultrasound Parameters from the Superficial Zone of the Human Articular Cartilage and Changes in Surface Roughness, Collagen Content or Collagen Orientation Caused by Early Degeneration.

PubMed

Kiyan, Wataru; Ito, Akira; Nakagawa, Yasuaki; Mukai, Shogo; Mori, Koji; Arai, Tatsuo; Uchino, Eiichiro; Okuno, Yasushi; Kuroki, Hiroshi

2017-08-01

We aimed to quantitatively investigate the relationship between amplitude-based pulse-echo ultrasound parameters and early degeneration of the knee articular cartilage. Twenty samples from six human femoral condyles judged as grade 0 or 1 according to International Cartilage Repair Society grading were assessed using a 15-MHz pulsed-ultrasound 3-D scanning system ex vivo. Surface roughness (R q ), average collagen content (A 1 ) and collagen orientation (A 12 ) in the superficial zone of the cartilage were measured via laser microscopy and Fourier transform infrared imaging spectroscopy. Multiple regression analysis with a linear mixed-effects model (LMM) revealed that a time-domain reflection coefficient at the cartilage surface (R c ) had a significant coefficient of determination with R q and A 12 (R LMMm 2 =0.79); however, R c did not correlate with A 1 . Concerning the collagen characteristic in the superficial zone, R c was found to be a sensitive indicator reflecting collagen disorganization, not collagen content, for the early degeneration samples. Copyright © 2017 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Repair of articular osteochondral defects of the knee joint using a composite lamellar scaffold.

PubMed

Lv, Y M; Yu, Q S

2015-04-01

The major problem with repair of an articular cartilage injury is the extensive difference in the structure and function of regenerated, compared with normal cartilage. Our work investigates the feasibility of repairing articular osteochondral defects in the canine knee joint using a composite lamellar scaffold of nano-ß-tricalcium phosphate (ß-TCP)/collagen (col) I and II with bone marrow stromal stem cells (BMSCs) and assesses its biological compatibility. The bone-cartilage scaffold was prepared as a laminated composite, using hydroxyapatite nanoparticles (nano-HAP)/collagen I/copolymer of polylactic acid-hydroxyacetic acid as the bony scaffold, and sodium hyaluronate/poly(lactic-co-glycolic acid) as the cartilaginous scaffold. Ten-to 12-month-old hybrid canines were randomly divided into an experimental group and a control group. BMSCs were obtained from the iliac crest of each animal, and only those of the third generation were used in experiments. An articular osteochondral defect was created in the right knee of dogs in both groups. Those in the experimental group were treated by implanting the composites consisting of the lamellar scaffold of ß-TCP/col I/col II/BMSCs. Those in the control group were left untreated. After 12 weeks of implantation, defects in the experimental group were filled with white semi-translucent tissue, protruding slightly over the peripheral cartilage surface. After 24 weeks, the defect space in the experimental group was filled with new cartilage tissues, finely integrated into surrounding normal cartilage. The lamellar scaffold of ß-TCP/col I/col II was gradually degraded and absorbed, while new cartilage tissue formed. In the control group, the defects were not repaired. This method can be used as a suitable scaffold material for the tissue-engineered repair of articular cartilage defects. Cite this article: Bone Joint Res 2015;4:56-64. ©2015 The British Editorial Society of Bone & Joint Surgery.

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.

The bovine patella as a model of early osteoarthritis

PubMed Central

Hargrave-Thomas, E J; Thambyah, A; McGlashan, S R; Broom, N D

2013-01-01

The bovine patella model has been used extensively for studying important structure–function aspects of articular cartilage, including its degeneration. However, the degeneration seen in this model has, to our knowledge, never been adequately compared with human osteoarthritis (OA). In this study, bovine patellae displaying normal to severely degenerate states were compared with human tissue displaying intact cartilage to severe OA. Comparisons of normal and OA features were made with histological scoring, morphometric measurements, and qualitative observations. Differential interference contrast microscopy was used to image early OA changes in the articular cartilage matrix and to investigate whether this method provided comparable quality of visualisation of key structural features with standard histology. The intact bovine cartilage was found to be similar to healthy human cartilage and the degenerate bovine cartilage resembled the human OA tissues with regard to structural disruption, cellularity changes, and staining loss. The extent of degeneration in the bovine tissues matched the mild to moderate range of human OA tissues; however, no bovine samples exhibited late-stage OA. Additionally, in both bovine and human tissues, cartilage degeneration was accompanied by calcified cartilage thickening, tidemark duplication, and the advancement of the cement line by protrusions of bony spicules into the calcified cartilage. This comparison of degeneration in the bovine and human tissues suggests a common pathway for the progression of OA and thus the bovine patella is proposed to be an appropriate model for investigating the structural changes associated with early OA. PMID:24111904

Assessment of Biomarkers Associated with Joint Injury and Subsequent Post-Traumatic Arthritis

DTIC Science & Technology

2016-12-01

patella and patellar cartilage (Geomagic Studio, Research Triangle Park, NC). Changes in cartilage thickness between post -operative and 18-month...defined as the distance to a test surface ( post -fx bone surface) that was either outside (positive) or inside (negative) of the reference surface (pre-fx...of the Orthopaedic Research Society, San Diego, CA. (poster presentation) "Assessment of Biomarkers Associated with Joint Injury and Subsequent Post

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.

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

A pseudo-elastic effective material property representation of the costal cartilage for use in finite element models of the whole human body.

PubMed

Forman, Jason L; de Dios, Eduardo del Pozo; Kent, Richard W

2010-12-01

Injury-predictive finite element (FE) models of the chest must reproduce the structural coupling behavior of the costal cartilage accurately. Gross heterogeneities (the perichondrium and calcifications) may cause models developed based on local material properties to erroneously predict the structural behavior of cartilage segments. This study sought to determine the pseudo-elastic effective material properties required to reproduce the structural behavior of the costal cartilage under loading similar to what might occur in a frontal automobile collision. Twenty-eight segments of cadaveric costal cartilage were subjected to cantilever-like, dynamic loading. Three limited-mesh FE models were then developed for each specimen, having element sizes of 10 mm (typical of current whole-body FE models), 3 mm, and 2 mm. The cartilage was represented as a homogeneous, isotropic, linear elastic material. The elastic moduli of the cartilage models were optimized to fit the anterior-posterior (x-axis) force versus displacement responses observed in the experiments. For a subset of specimens, additional model validation tests were performed under a second boundary condition. The pseudo-elastic effective moduli ranged from 4.8 to 49 MPa, with an average and standard deviation of 22 ± 13.6 MPa. The models were limited in their ability to reproduce the lateral (y-axis) force responses observed in the experiments. The prediction of the x-axis and y-axis forces in the second boundary condition varied. Neither the effective moduli nor the model fit were significantly affected (Student's t-test, p < 0.05) by the model mesh density. The average pseudo-elastic effective moduli were significantly (p < 0.05) greater than local costal cartilage modulus values reported in the literature. These results are consistent with the presence of stiffening heterogeneities within the costal cartilage structure. These effective modulus values may provide guidance for the representation of the costal cartilage in whole-body FE models where these heterogeneities cannot be modeled distinctly.

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 part, its poor regenerative abilities. Tissue engineering approaches should thus not only reproduce the correct tissue mechanics but also its pronounced sturdiness to guarantee a similar longevity. Copyright © 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

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.

Genipin crosslinking decreases the mechanical wear and biochemical degradation of impacted cartilage in vitro.

PubMed

Bonitsky, Craig M; McGann, Megan E; Selep, Michael J; Ovaert, Timothy C; Trippel, Stephen B; Wagner, Diane R

2017-03-01

High energy trauma to cartilage causes surface fissures and microstructural damage, but the degree to which this damage renders the tissue more susceptible to wear and contributes to the progression of post-traumatic osteoarthritis (PTOA) is unknown. Additionally, no treatments are currently available to strengthen cartilage after joint trauma and to protect the tissue from subsequent degradation and wear. The purposes of this study were to investigate the role of mechanical damage in the degradation and wear of cartilage, to evaluate the effects of impact and subsequent genipin crosslinking on the changes in the viscoelastic parameters of articular cartilage, and to test the hypothesis that genipin crosslinking is an effective treatment to enhance the resistance to biochemical degradation and mechanical wear. Results demonstrate that cartilage stiffness decreases after impact loading, likely due to the formation of fissures and microarchitectural damage, and is partially or fully restored by crosslinking. The wear resistance of impacted articular cartilage was diminished compared to undamaged cartilage, suggesting that mechanical damage that is directly induced by the impact may contribute to the progression of PTOA. However, the decrease in wear resistance was completely reversed by the crosslinking treatments. Additionally, the crosslinking treatments improved the resistance to collagenase digestion at the impact-damaged articular surface. These results highlight the potential therapeutic value of collagen crosslinking via genipin in the prevention of cartilage degeneration after traumatic injury. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:558-565, 2017. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

[The initial (I and II) and advanced (III and IV) stages of juvenile patellar chondromalacia. Its diagnosis by magnetic resonance using a 1.5-T magnet with FLASH sequences].

PubMed

Macarini, L; Rizzo, A; Martino, F; Zaccheo, N; Angelelli, G; Rotondo, A

1998-06-01

Juvenile patellar chondromalacia is a common orthopedic disorder which can mimic other conditions; early diagnosis is mandatory to prevent its evolution into osteoarthrosis. In the early stages of patellar chondromalacia (I and II), the lesions originate in the deep cartilage layer and the joint surface is not affected. Arthroscopy can demonstrate joint surface changes only and give indirect information about deeper lesions. We investigated the yield of 2D FLASH MRI with 30 degrees flip angle and a dedicated coil in the diagnosis of patellar chondromalacia, especially in its early stages. Eighteen patients (mean age: 21 years) with clinically suspected patellar chondromalacia were examined with MRI; 13 of them were also submitted to arthroscopy. A 1.5 T unit with a transmit-and-receive extremity coil was used. We acquired T1 SE sequences (TR/TE: 500-700/15/20) and 2D T2* FLASH sequence (TR/TE/FA: 500-800/18/30 degrees). The field of view was 160-180 mm and the matrix 192 x 256, with 2-3 NEX. The images were obtained on the axial plane. The lesions were classified in 4 stages according to Shahriaree classification. Agreement between MR and arthroscopic findings was good in both early and advanced lesions in 12/13 cases. Early lesions appeared as hyperintense focal thickening of the hyaline cartilage (stage I) or as small cystic lesions within the cartilage and no articular surface involvement (stage II). The medial patellar facet was the most frequent site. Advanced lesions appeared as articular surface ulcerations, thinning and cartilage hypointensity (stage III); stage IV lesions presented as complete erosions of the hyaline cartilage and hypointense underlying bone. 2D FLASH MRI with 30 degrees flip angle can show the differences in water content in the cartilage and thus permit to detect early chondromalacia lesions in the deep cartilage.

Thermometric determination of cartilage matrix temperatures during thermal chondroplasty: comparison of bipolar and monopolar radiofrequency devices.

PubMed

Edwards, Ryland B; Lu, Yan; Rodriguez, Edwin; Markel, Mark D

2002-04-01

To compare cartilage matrix temperatures between monopolar radiofrequency energy (mRFE) and bipolar RFE (bRFE) at 3 depths under the articular surface during thermal chondroplasty. We hypothesized that cartilage temperatures would be higher at all cartilage depths for the bRFE device than for the mRFE device. Randomized trial using bovine cartilage. Sixty osteochondral sections from the femoropatellar joint of 15 adult cattle were used for this study. Using a custom jig, fluoroptic thermometry probes were placed at one of the following depths under the articular surface: 200 microm, 500 microm, or 2,000 microm. RF treatment was performed either with fluid flow (F) (120 mL/min) or without fluid flow (NF) (n = 5/depth/RFE device/flow; total specimens, 60). Irrigation fluid temperature was room temperature (22 degrees C). Thermometry data were acquired at 4 Hz for 5 seconds with the RF probe off, for 20 seconds with the RF probe on, and then for 15 seconds with the RF probe off. During RF treatment, a 0.79-cm2 area (1.0-cm diameter) of the articular surface centered over the thermometry probe was treated in a paintbrush manner in noncontact (bRFE) or light contact (mRFE). Thermal chondroplasty with bRFE resulted in higher cartilage matrix temperatures compared with mRFE for all depths and regardless of fluid flow. Bipolar RFE resulted in temperatures of 95 degrees C to 100 degrees C at 200 microm and 500 microm under the surface, with temperatures of 75 degrees C to 78 degrees C at 2,000 microm. Fluid flow during bRFE application had no effect at 200 microm. Monopolar RFE resulted in temperatures of 61 degrees C to 68 degrees C at 200 microm, 54 degrees C to 70 degrees C at 500 microm under the surface, and 28 degrees C to 30 degrees C at 2,000 microm below the surface. A significant effect of fluid flow during mRFE application occurred at 200 microm (NF, 61 degrees C; F, 63 degrees C) and 500 microm (NF, 53 degrees C; F, 68 degrees C). In this study, we found significant differences between bRFE and a temperature-controlled mRFE device with regard to depth of thermal heating of cartilage in vitro. Bipolar RFE resulted in matrix temperatures high enough (>70 degrees C) to kill cells as deep as 2,000 microm under the articular surface. Fluid flow during thermal chondroplasty had the effect of significantly increasing cartilage matrix temperatures at 200 and 500 microm with the mRFE device. During thermal chondroplasty, bRFE creates greater matrix temperature elevations at equivalent depths and treatment duration than does mRFE. Excessive temperatures generated deep within the cartilage matrix could cause full-thickness chondrocyte death, in vivo.

Assessment of Biomarkers Associated with Joint Injury and Subsequent Post-Traumatic Arthritis

DTIC Science & Technology

2016-12-01

models of the patella and patellar cartilage (Geomagic Studio, Research Triangle Park, NC). Changes in cartilage thickness between post -operative... quantitative scales, and "Assessment of Biomarkers Associated with Joint Injury and Subsequent Post -Traumatic Arthritis" Start date: 9/30/2012 PIs...Geomagic®). Positive and negative deviations of the bone surface were measured, and defined as the distance to a test surface ( post -fx bone surface

Development and characterization of decellularized human nasoseptal cartilage matrix for use in tissue engineering.

PubMed

Graham, M Elise; Gratzer, Paul F; Bezuhly, Michael; Hong, Paul

2016-10-01

Reconstruction of cartilage defects in the head and neck can require harvesting of autologous cartilage grafts, which can be associated with donor site morbidity. To overcome this limitation, tissue-engineering approaches may be used to generate cartilage grafts. The objective of this study was to decellularize and characterize human nasoseptal cartilage with the aim of generating a biological scaffold for cartilage tissue engineering. Laboratory study using nasoseptal cartilage. Remnant human nasoseptal cartilage specimens were collected and subjected to a novel decellularization treatment. The decellularization process involved several cycles of enzymatic detergent treatments. For characterization, decellularized and fresh (control) specimens underwent histological, biochemical, and mechanical analyses. Scanning electron microscopy and biocompatibility assay were also performed. The decellularization process had minimal effect on glycosaminoglycan content of the cartilage extracellular matrix. Deoxyribonucleic acid (DNA) analysis revealed the near-complete removal of genomic DNA from decellularized tissues. The effectiveness of the decellularization process was also confirmed on histological and scanning electron microscopic analyses. Mechanical testing results showed that the structural integrity of the decellularized tissue was maintained, and biocompatibility was confirmed. Overall, the current decellularization treatment resulted in significant reduction of genetic/cellular material with preservation of the underlying extracellular matrix structure. This decellularized material may serve as a potential scaffold for cartilage tissue engineering. N/A. Laryngoscope, 126:2226-2231, 2016. © 2016 The American Laryngological, Rhinological and Otological Society, Inc.

Cationic Contrast Agent Diffusion Differs Between Cartilage and Meniscus.

PubMed

Honkanen, Juuso T J; Turunen, Mikael J; Freedman, Jonathan D; Saarakkala, Simo; Grinstaff, Mark W; Ylärinne, Janne H; Jurvelin, Jukka S; Töyräs, Juha

2016-10-01

Contrast enhanced computed tomography (CECT) is a non-destructive imaging technique used for the assessment of composition and structure of articular cartilage and meniscus. Due to structural and compositional differences between these tissues, diffusion and distribution of contrast agents may differ in cartilage and meniscus. The aim of this study is to determine the diffusion kinematics of a novel iodine based cationic contrast agent (CA(2+)) in cartilage and meniscus. Cylindrical cartilage and meniscus samples (d = 6 mm, h ≈ 2 mm) were harvested from healthy bovine knee joints (n = 10), immersed in isotonic cationic contrast agent (20 mgI/mL), and imaged using a micro-CT scanner at 26 time points up to 48 h. Subsequently, normalized X-ray attenuation and contrast agent diffusion flux, as well as water, collagen and proteoglycan (PG) contents in the tissues were determined. The contrast agent distributions within cartilage and meniscus were different. In addition, the normalized attenuation and diffusion flux were higher (p < 0.05) in cartilage. Based on these results, diffusion kinematics vary between cartilage and meniscus. These tissue specific variations can affect the interpretation of CECT images and should be considered when cartilage and meniscus are assessed simultaneously.

Structure‐function relationships at the human spinal disc‐vertebra interface

PubMed Central

Berg‐Johansen, Britta; Fields, Aaron J.; Liebenberg, Ellen C.; Li, Alfred

2017-01-01

ABSTRACT Damage at the intervertebral disc‐vertebra interface associates with back pain and disc herniation. However, the structural and biomechanical properties of the disc‐vertebra interface remain underexplored. We sought to measure mechanical properties and failure mechanisms, quantify architectural features, and assess structure‐function relationships at this vulnerable location. Vertebra‐disc‐vertebra specimens from human cadaver thoracic spines were scanned with micro‐computed tomography (μCT), surface speckle‐coated, and loaded to failure in uniaxial tension. Digital image correlation (DIC) was used to calculate local surface strains. Failure surfaces were scanned using scanning electron microscopy (SEM), and adjacent sagittal slices were analyzed with histology and SEM. Seventy‐one percent of specimens failed initially at the cartilage endplate‐bone interface of the inner annulus region. Histology and SEM both indicated a lack of structural integration between the cartilage endplate (CEP) and bone. The interface failure strength was increased in samples with higher trabecular bone volume fraction in the vertebral endplates. Furthermore, failure strength decreased with degeneration, and in discs with thicker CEPs. Our findings indicate that poor structural connectivity between the CEP and vertebra may explain the structural weakness at this region, and provide insight into structural features that may contribute to risk for disc‐vertebra interface injury. The disc‐vertebra interface is the site of failure in the majority of herniation injuries. Here we show new structure‐function relationships at this interface that may motivate the development of diagnostics, prevention strategies, and treatments to improve the prognosis for many low back pain patients with disc‐vertebra interface injuries. © 2017 The Authors. Journal of Orthopaedic Research® Published by Wiley Periodicals, Inc. on behalf of Orthopaedic Research Society. J Orthop Res 36:192–201, 2018. PMID:28590060

Regional differences of tibial and femoral cartilage in the chondrocyte gene expression, immunhistochemistry and composite in different stages of osteoarthritis.

PubMed

Lahm, A; Dabravolski, D; Spank, H; Merk, H; Esser, J; Kasch, R

2017-04-01

The function of articular cartilage as an avascular tissue is mainly served by collagen type II and proteoglycan molecules. Within this matrix homeostasis between production and breakdown of the matrix is exceptionally sensitive. The current study was conducted to identify regional differences in specific alterations in cartilage composition during the osteoarthritic process of the human knee joint. Therefor the changes in the expression of the key molecules of the extracellular matrix were measured in dependence of the anatomical side (femoral vs tibial) and associated with immunohistochemistry and quantitative measurement. 60 serial osteochondral femoral condyle and the tibial plateau samples of patients undergoing implantation of total knee endoprosthesis of areas showing mild (Group A, macroscopically ICRS grade 1b) respectively advanced (Group B, macroscopically ICRS grade 3a/3b) (30 each) osteoarthritis according to the histological-histochemical grading system (HHGS) were compared with 20 healthy biopsies with immunohistochemistry and histology. We quantified our results on the gene expression of collagen type I and II and aggrecan with the help of real-time (RT)-PCR. Proteoglycan content was measured colorometrically. In group A slightly increased colour intensity was found for collagen II in deeper layers, suggesting a persisting but initially still intact repair process. But especially on the medial tibia plateau the initial Col II increase in gene expression is followed by a decrease leading to the lowest over all Col II expression on the medial plateau, here especially in the central part. There in late stage diseases the collagen type I expression was also more pronounced. Markedly decreased safranin O staining intensity was observed in the radial zone and less reduced intensity in the transitional zone with loss of zonal anatomy in 40% of the specimens in group A and all specimens in group B. Correlation between colorometrically analysed proteoglycan GAG content and aggrecan Real Time PCR is mainly weak. Tibial and femoral cartilage in contrast to patellar cartilage both are preferential exposed to compressive stresses, but presence of menisci affects the load distribution at the tibial side, which creates varying conditions for the different cartilage surfaces in the knee. As directly measured Poissońs ratio in tibial cartilage is higher but Younǵs modulus is lower than in femoral cartilage, different resulting feedback amplification loops interact with proceeding cartilage damage. The initial loss of aggrecan may support Matrix metalloproteinases (Mmps) in the access to the collagen network and the considerably differing mechanical properties at both joint surfaces result in varying increased synthesis and release of matrix degrading enzymes. The present study has identified a selection of events which reflect the response of cartilage structure and composite, chondrocytes itself and their productivity to changes in mechanical stress depending on the anatomical site. Copyright © 2017 Elsevier Ltd. All rights reserved.

Quantitative detection of cartilage surfaces and ligament geometry of the wrist using an imaging cryomicrotome system.

PubMed

Dvinskikh, N A; Blankevoort, L; Foumani, M; Spaan, J A E; Streekstra, G J

2010-03-22

Biomechanical models may aid in improving diagnosis and treatment of wrist joint disorders. As input, geometrical information is required for model development. Previous studies acquired some elements of the average wrist joint geometry. However, there is a close geometric functional match between articulating surfaces and ligament geometry. Therefore, biomechanical models need to be fed with the geometric data of individual joints. This study is aimed at acquiring geometric data of cartilage surfaces and ligaments from individual wrist joints by using a cryomicrotome imaging system and the evaluation of inter- and intra-observer variability of the data. The 3D geometry of 30 cartilage surfaces and 15 ligaments in three cadaver wrists was manually detected and quantitatively reconstructed. The inter- and intra-observer variability of the cartilage surface detection was 0.14 and 0.19 mm, respectively. For the position of the radius attachment of the dorsal radiocarpal ligament (DRC), the observer variations were 0.12 and 0.65 mm, for intra-/inter-observer, respectively. For the DRC attachment on the triquetrum, the observer variations were 0.22 and 1.19 mm. Anatomic reconstruction from 3D cryomicrotome images offer a method to obtain unique geometry data of the entire wrist joint for modeling purposes. Copyright (c) 2009 Elsevier Ltd. All rights reserved.

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

Quantitative analysis of collagen network structure and fibril dimensions in cartilage repair with autologous chondrocyte transplantation.

PubMed

Långsjö, Teemu K; Vasara, Anna I; Hyttinen, Mika M; Lammi, Mikko J; Kaukinen, Antti; Helminen, Heikki J; Kiviranta, Ilkka

2010-01-01

The aim of this study was to undertake a stereological analysis to quantify the dimensions of the collagen network in the repair tissue of porcine joints after they had been subjected to autologous chondrocyte transplantation (ACT). ACT was used to repair cartilage lesions in knee joints of pigs. Electron-microscopic stereology, immunostaining for type II collagen, and quantitative polarized-light microscopy were utilized to study the collagen fibrils in the repair tissue 3 and 12 months after the operation. The collagen volume density (V(V)) was lower in the repair tissue than in normal cartilage at 3 months (20.4 vs. 23.7%) after the operation. The collagen surface density (S(V), 1.5·10(-2) vs. 3.1·10(-2) nm(2)/nm(3)) and V(V) increased with time in the repair tissue (20.4 vs. 44.7%). Quantitative polarized-light microscopy detected a higher degree of collagen parallelism in the repair tissue at 3 months after the operation (55.7 vs. 49.7%). In contrast, 1 year after the operation, fibril parallelism was lower in the repair tissue than in the control cartilage (47.5 vs. 69.8%). Following ACT, V(V) and S(V) increased in the repair tissue with time, reflecting maturation of the tissue. One year after the operation, there was a lower level of fibril organization in the repair tissue than in the control cartilage. Thus, the newly synthesized collagen fibrils in the repair tissue appeared to form a denser network than in the control cartilage, but the fibrils remained more randomly oriented. Copyright © 2010 S. Karger AG, Basel.

Volumetric quantitative characterization of human patellar cartilage with topological and geometrical features on phase-contrast X-ray computed tomography.

PubMed

Nagarajan, Mahesh B; Coan, Paola; Huber, Markus B; Diemoz, Paul C; Wismüller, Axel

2015-11-01

Phase-contrast X-ray computed tomography (PCI-CT) has attracted significant interest in recent years for its ability to provide significantly improved image contrast in low absorbing materials such as soft biological tissue. In the research context of cartilage imaging, previous studies have demonstrated the ability of PCI-CT to visualize structural details of human patellar cartilage matrix and capture changes to chondrocyte organization induced by osteoarthritis. This study evaluates the use of geometrical and topological features for volumetric characterization of such chondrocyte patterns in the presence (or absence) of osteoarthritic damage. Geometrical features derived from the scaling index method (SIM) and topological features derived from Minkowski Functionals were extracted from 1392 volumes of interest (VOI) annotated on PCI-CT images of ex vivo human patellar cartilage specimens. These features were subsequently used in a machine learning task with support vector regression to classify VOIs as healthy or osteoarthritic; classification performance was evaluated using the area under the receiver operating characteristic curve (AUC). Our results show that the classification performance of SIM-derived geometrical features (AUC: 0.90 ± 0.09) is significantly better than Minkowski Functionals volume (AUC: 0.54 ± 0.02), surface (AUC: 0.72 ± 0.06), mean breadth (AUC: 0.74 ± 0.06) and Euler characteristic (AUC: 0.78 ± 0.04) (p < 10(-4)). These results suggest that such geometrical features can provide a detailed characterization of the chondrocyte organization in the cartilage matrix in an automated manner, while also enabling classification of cartilage as healthy or osteoarthritic with high accuracy. Such features could potentially serve as diagnostic imaging markers for evaluating osteoarthritis progression and its response to different therapeutic intervention strategies.

Analysis of human knee osteoarthritic cartilage using polarization sensitive second harmonic generation microscopy

NASA Astrophysics Data System (ADS)

Kumar, Rajesh; Grønhaug, Kirsten M.; Romijn, Elisabeth I.; Drogset, Jon O.; Lilledahl, Magnus B.

2014-05-01

Osteoarthritis is one of the most prevalent joint diseases in the world. Although the cause of osteoarthritis is not exactly clear, the disease results in a degradation of the quality of the articular cartilage including collagen and other extracellular matrix components. We have investigated alterations in the structure of collagen fibers in the cartilage tissue of the human knee using mulitphoton microscopy. Due to inherent high nonlinear susceptibility, ordered collagen fibers present in the cartilage tissue matrix produces strong second harmonic generation (SHG) signals. Significant morphological differences are found in different Osteoarthritic grades of cartilage by SHG microscopy. Based on the polarization analysis of the SHG signal, we find that a few locations of hyaline cartilage (mainly type II collagen) is being replaced by fibrocartilage (mainly type I cartilage), in agreement with earlier literature. To locate the different types and quantify the alteration in the structure of collagen fiber, we employ polarization-SHG microscopic analysis, also referred to as _-tensor imaging. The image analysis of p-SHG image obtained by excitation polarization measurements would represent different tissue constituents with different numerical values at pixel level resolution.

From gristle to chondrocyte transplantation: treatment of cartilage injuries

PubMed Central

Lindahl, Anders

2015-01-01

This review addresses the progress in cartilage repair technology over the decades with an emphasis on cartilage regeneration with cell therapy. The most abundant cartilage is the hyaline cartilage that covers the surface of our joints and, due to avascularity, this tissue is unable to repair itself. The cartilage degeneration seen in osteoarthritis causes patient suffering and is a huge burden to society. The surgical approach to cartilage repair was non-existing until the 1950s when new surgical techniques emerged. The use of cultured cells for cell therapy started as experimental studies in the 1970s that developed over the years to a clinical application in 1994 with the introduction of the autologous chondrocyte transplantation technique (ACT). The technology is now spread worldwide and has been further refined by combining arthroscopic techniques with cells cultured on matrix (MACI technology). The non-regenerating hypothesis of cartilage has been revisited and we are now able to demonstrate cell divisions and presence of stem-cell niches in the joint. Furthermore, cartilage derived from human embryonic stem cells and induced pluripotent stem cells could be the base for new broader cell treatments for cartilage injuries and the future technology base for prevention and cure of osteoarthritis. PMID:26416680

Polymer Formulations for Cartilage Repair

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

Gutowska, Anna; Jasionowski, Marek; Morris, J. E.

2001-05-15

Regeneration of destroyed articular cartilage can be induced by transplantation of cartilage cells into a defect. The best results are obtained with the use of autologus cells. However, obtaining large amounts of autologus cartilage cells causes a problem of creating a large cartilage defect in a donor site. Techniques are currently being developed to harvest a small number of cells and propagate them in vitro. It is a challenging task, however, due to the fact that ordinarily, in a cell culture on flat surfaces, chondrocytes do not maintain their in vivo phenotype and irreversibly diminish or cease the synthesis ofmore » aggregating proteoglycans. Therefore, the research is continuing to develop culture conditions for chondrocytes with the preserved phenotype.« less

Polarization-sensitive optical coherence tomography-based imaging, parameterization, and quantification of human cartilage degeneration

NASA Astrophysics Data System (ADS)

Brill, Nicolai; Wirtz, Mathias; Merhof, Dorit; Tingart, Markus; Jahr, Holger; Truhn, Daniel; Schmitt, Robert; Nebelung, Sven

2016-07-01

Polarization-sensitive optical coherence tomography (PS-OCT) is a light-based, high-resolution, real-time, noninvasive, and nondestructive imaging modality yielding quasimicroscopic cross-sectional images of cartilage. As yet, comprehensive parameterization and quantification of birefringence and tissue properties have not been performed on human cartilage. PS-OCT and algorithm-based image analysis were used to objectively grade human cartilage degeneration in terms of surface irregularity, tissue homogeneity, signal attenuation, as well as birefringence coefficient and band width, height, depth, and number. Degeneration-dependent changes were noted for the former three parameters exclusively, thereby questioning the diagnostic value of PS-OCT in the assessment of human cartilage degeneration.

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.

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.

Allogeneic Mesenchymal Stem Cells in Combination with Hyaluronic Acid for the Treatment of Osteoarthritis in Rabbits.

PubMed

Chiang, En-Rung; Ma, Hsiao-Li; Wang, Jung-Pan; Liu, Chien-Lin; Chen, Tain-Hsiung; Hung, Shih-Chieh

2016-01-01

Mesenchymal stem cell (MSC)-based therapies may aid in the repair of articular cartilage defects. The purpose of this study was to investigate the effects of intraarticular injection of allogeneic MSCs in an in vivo anterior cruciate ligament transection (ACLT) model of osteoarthritis in rabbits. Allogeneic bone marrow-derived MSCs were isolated and cultured under hypoxia (1% O2). After 8 weeks following ACLT, MSCs suspended in hyaluronic acid (HA) were injected into the knees, and the contralateral knees were injected with HA alone. Additional controls consisted of a sham operation group as well as an untreated osteoarthritis group. The tissues were analyzed by macroscopic examination as well as histologic and immunohistochemical methods at 6 and 12 weeks post-transplantation. At 6 and 12 weeks, the joint surface showed less cartilage loss and surface abrasion after MSC injection as compared to the tissues receiving HA injection alone. Significantly better histological scores and cartilage content were observed with the MSC transplantation. Furthermore, engraftment of allogenic MSCs were evident in surface cartilage. Thus, injection of the allogeneic MSCs reduced the progression of osteoarthritis in vivo.

Surface smoothness: cartilage biomarkers for knee OA beyond the radiologist

NASA Astrophysics Data System (ADS)

Tummala, Sudhakar; Dam, Erik B.

2010-03-01

Fully automatic imaging biomarkers may allow quantification of patho-physiological processes that a radiologist would not be able to assess reliably. This can introduce new insight but is problematic to validate due to lack of meaningful ground truth expert measurements. Rather than quantification accuracy, such novel markers must therefore be validated against clinically meaningful end-goals such as the ability to allow correct diagnosis. We present a method for automatic cartilage surface smoothness quantification in the knee joint. The quantification is based on a curvature flow method used on tibial and femoral cartilage compartments resulting from an automatic segmentation scheme. These smoothness estimates are validated for their ability to diagnose osteoarthritis and compared to smoothness estimates based on manual expert segmentations and to conventional cartilage volume quantification. We demonstrate that the fully automatic markers eliminate the time required for radiologist annotations, and in addition provide a diagnostic marker superior to the evaluated semi-manual markers.

Repair of massively defected hemi-joints using demineralized osteoarticular allografts with protected cartilage.

PubMed

Li, Siming; Yang, Xiaohong; Tang, Shenghui; Zhang, Xunmeng; Feng, Zhencheng; Cui, Shuliang

2015-08-01

Surgical replacement of massively defected joints necessarily relies on osteochondral grafts effective to both of bone and cartilage. Demineralized bone matrix (DBM) retains the osteoconductivity but destroys viable chondrocytes in the cartilage portion essential for successful restoration of defected joints. This study prepared osteochondral grafts of DBM with protected cartilage. Protected cartilage portions was characterized by cellular and molecular biology and the grafts were allogenically used for grafting. Protected cartilage showed similar histomorphological structure and protected proteins estimated by total proteins and cartilage specific proteins as in those of fresh controls when DBMs were generated in bone portions. Such grafts were successfully used for simultaneously repair of bone and cartilage in massively defected osteoarticular joints within 16 weeks post-surgery. These results present an allograft with clinical potential for simultaneous restoration of bone and cartilage in defected joints.

Injection of Compressed Diced Cartilage in the Correction of Secondary and Primary Rhinoplasty: A New Technique with 12 Years' Experience.

PubMed

Erol, O Onur

2017-11-01

There are instances where small or large pockets are filled with diced cartilage in the nose, without use of wrapping materials. For this purpose, 1-cc commercial syringes were used. The obtained results were partial and incomplete. For better and improved results, the author designed new syringes, with two different sizes, which compress the diced cartilage for injection. The author presents his experience accrued over the past 12 years with 2366 primary, 749 secondary, 67 cleft lip and nose, and a total of 3182 rhinoplasties, using his new syringe design, which compresses diced cartilage and injects the diced cartilages as a conglutinate mass, simulating carved costal cartilage, but a malleable one. In 3125 patients, the take of cartilage graft was complete (98.2 percent) and a smooth surface was obtained, giving them a natural appearance. In 21 patients (0.65 percent), there was partial resorption of cartilage. Correction was performed with touch-up surgery by reinjection of a small amount of diced cartilage. In 36 patients (1.13 percent), there was overcorrection that, 1 year later, was treated by simple rasping. Compared with diced cartilage wrapped with Surgicel or fascia, the amount of injected cartilage graft is predictable because it consists purely of cartilage. The injected diced cartilage, because it is compressed and becomes a conglutinated mass, resembles a wood chip and simulates carved cartilage. It is superior to carved cartilage in that it is moldable, time saving, and gives a good result with no late show or warping. The injection takes only a few minutes.

Decellularization of Human Nasal Septal Cartilage for the Novel Filler Material of Vocal Fold Augmentation.

PubMed

Kang, Dae-Woon; Shin, Sung-Chan; Jang, Jeon-Yeob; Park, Hee-Young; Lee, Jin-Choon; Wang, Soo-Geun; Lee, Byung-Joo

2017-01-01

The clinical application of allogenic and/or xenogenic cartilage for vocal fold augmentation requires to remove the antigenic cellular component. The objective of this study was to assess the effect of cartilage decellularization and determine the change in immunogenicity after detergent treatment in human nasal septal cartilage flakes made by the freezing and grinding method. Human nasal septal cartilages were obtained from surgical cases. The harvested cartilages were treated by the freezing and grinding technique. The obtained cartilage flakes were treated with 1% Triton X-100 or 2% sodium dodecyl sulfate (SDS) for decellularization of the cartilage flakes. Hematoxylin and eosin stain (H&E stain), surface electric microscopy, immunohistochemical stain for major histocompatibility complex I and II, and ELISA for DNA contents were performed to assess the effect of cartilage decellularization after detergent treatment. A total of 10 nasal septal cartilages were obtained from surgical cases. After detergent treatment, the average size of the cartilage flakes was significantly decreased. With H&E staining, the cell nuclei of decellularized cartilage flakes were not observed. The expression of major histocompatibility complex (MHC)-I and II antigens was not identified in the decellularized cartilage flakes after treatment with detergent. DNA content was removed almost entirely from the decellularized cartilage flakes. Treatment with 2% SDS or 1% Triton X-100 for 1 hour appears to be a promising method for decellularization of human nasal septal cartilage for vocal fold augmentation. Copyright © 2017 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

Knee cartilage extraction and bone-cartilage interface analysis from 3D MRI data sets

NASA Astrophysics Data System (ADS)

Tamez-Pena, Jose G.; Barbu-McInnis, Monica; Totterman, Saara

2004-05-01

This works presents a robust methodology for the analysis of the knee joint cartilage and the knee bone-cartilage interface from fused MRI sets. The proposed approach starts by fusing a set of two 3D MR images the knee. Although the proposed method is not pulse sequence dependent, the first sequence should be programmed to achieve good contrast between bone and cartilage. The recommended second pulse sequence is one that maximizes the contrast between cartilage and surrounding soft tissues. Once both pulse sequences are fused, the proposed bone-cartilage analysis is done in four major steps. First, an unsupervised segmentation algorithm is used to extract the femur, the tibia, and the patella. Second, a knowledge based feature extraction algorithm is used to extract the femoral, tibia and patellar cartilages. Third, a trained user corrects cartilage miss-classifications done by the automated extracted cartilage. Finally, the final segmentation is the revisited using an unsupervised MAP voxel relaxation algorithm. This final segmentation has the property that includes the extracted bone tissue as well as all the cartilage tissue. This is an improvement over previous approaches where only the cartilage was segmented. Furthermore, this approach yields very reproducible segmentation results in a set of scan-rescan experiments. When these segmentations were coupled with a partial volume compensated surface extraction algorithm the volume, area, thickness measurements shows precisions around 2.6%

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.

Biodynamic Performance of Hyaluronic Acid versus Synovial fluid of the Knee for Osteoarthritic Therapy

PubMed Central

Corvelli, Michael; Che, Bernadette; Saeui, Christopher; Singh, Anirudha; Elisseeff, Jennifer

2015-01-01

Hyaluronic acid (HA), a natural biomaterial present in healthy joints but depleted in osteoarthritis (OA), has been employed clinically to provide symptomatic relief of joint pain. Joint movement combined with a reduced joint lubrication in osteoarthritic knees can result in increased wear and tear, chondrocyte apoptosis, and inflammation, leading to cascading cartilage deterioration. Therefore, development of an appropriate cartilage model and evaluation for its friction properties with potential lubricants in different conditions is necessary, which can closely resemble a mechanically induced OA cartilage. Additionally, the comparison of different models with and without endogenous lubricating surface zone proteins, such as PRG4 promotes a well-rounded understanding of cartilage lubrication. In this study, we present our findings on the lubricating effects of HA on different articular cartilage model surfaces in comparison to synovial fluid, a physiological lubricating biomaterial. The mechanical testings data demonstrated that HA reduced average static and kinetic friction coefficient values of the cartilage samples by 75% and 70%, respectively. Furthermore, HA mimicked the friction characteristics of freshly harvested natural synovial fluid throughout all tested and modeled OA conditions with no statistically significant difference. These characteristics led us to exclusively identify HA as an effective boundary layer lubricant in the technology that we develop to treat OA [Singh et al. 2104]. PMID:25858258

Peptide-Based Materials for Cartilage Tissue Regeneration.

PubMed

Hastar, Nurcan; Arslan, Elif; Guler, Mustafa O; Tekinay, Ayse B

2017-01-01

Cartilaginous tissue requires structural and metabolic support after traumatic or chronic injuries because of its limited capacity for regeneration. However, current techniques for cartilage regeneration are either invasive or ineffective for long-term repair. Developing alternative approaches to regenerate cartilage tissue is needed. Therefore, versatile scaffolds formed by biomaterials are promising tools for cartilage regeneration. Bioactive scaffolds further enhance the utility in a broad range of applications including the treatment of major cartilage defects. This chapter provides an overview of cartilage tissue, tissue defects, and the methods used for regeneration, with emphasis on peptide scaffold materials that can be used to supplement or replace current medical treatment options.

A reassessment of cervical surface anatomy via CT scan in an adult population.

PubMed

Shen, Xin-Hua; Xue, Hua-Dan; Chen, Yu; Wang, Man; Mirjalili, S Ali; Zhang, Zhu-Hua; Ma, Chao

2017-04-01

Surface landmarks in the neck are important for orientations of cervical glands, arteries, veins, nerves, and vertebrae. Recent research suggests some orientations are not correct. What are the cervical landmark orientations in the Chinese population? In this study, two essential cervical anatomy planes, the thyroid cartilage and C7 planes, were assessed in living adult Chinese subjects using computed tomography (CT), and the hyoid, carotid bifurcation, cricoid cartilage, thyroid arteries, and vertebral artery were simultaneously positioned. After excluding patients with distorting pathology, a total of 108 cervical CT scans were examined. The thyroid cartilage plane commonly passed through the C5 (in males) or C4 (in females) vertebral level. The carotid artery bifurcated most commonly at C3 (left) or C4 (right), more than 10 mm above the thyroid cartilage plane bilaterally in most cases. Orientation of the carotid bifurcation according to the body or greater horn of the hyoid was more accurate. The superior thyroid artery was found a finger-breadth below the thyroid cartilage plane, and the inferior thyroid artery in the C7 plane. The inferior border of the cricoid cartilage was most often at C7 (in males) or C6 (in females). The vertebral artery entered the C6 transverse foramen in more than 80% of scans. This reassessment of cervical surface anatomy using modern imaging tools in vivo provides both qualitative and quantitative information for surgeons in clinical practice. Clin. Anat. 30:330-335, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Articular disc and eminence modeling after experimental relocation of the glenoid fossa in growing rabbits.

PubMed

Pirttiniemi, P; Kantomaa, T; Tuominen, M; Salo, L

1994-02-01

The articular surface of the glenoid fossa shows some analogy to the mandibular condyle, since the surface is covered by secondary cartilage, which makes the process more elastic than purely bony structures. The condylar cartilage has been shown to be responsive to alterations in load pressures, and this secondary type of cartilage is also able to increase its proliferative activity to a limited extent when the load pressure is altered. The aim here was to measure changes in proliferative activity and type II collagen secretion in the articular surface of the glenoid fossa after steady experimental posterior relocation of the fossa in the rabbit without actively interfering with normal masticatory action. The shape of the articular disc and interrelations of the joint components were measured macroscopically. Twenty-four five-day-old rabbits underwent gluing of the interparietal, temporoparietal, and lambdoidal sutures. Three experimental and 3 control rabbits were injected with tritiated thymidine at 10, 15, 20, and 30 days and were killed after 2 h for histological, autoradiographic, and immunohistochemical examination. The total number of labeled cells in the proliferative layer near the articular eminence was higher in the experimental group, the difference being greatest in the 15- and 20-day-old rabbits. Immunohistochemical examination revealed less staining for type II collagen on the postero-inferior side of the eminence in the experimental group. The articular disc was flattened in the experimental group, and the elastic tissue bundle connecting the articular eminence and the anterior border of the disc was significantly narrower and longer.

Direct sectioning of unembedded cartilage: a simple method for microscopical and histochemical studies on chondrocytes and extracellular matrix.

PubMed

Stockert, J C; Del Castillo, P

1990-01-01

On account of the rigidity and compact structure of the hyaline cartilage, unfixed or formaldehyde fixed samples of this tissue can be directly sectioned by using a conventional ultramicrotome and a glass knife. This simple method allows to obtain microscopical sections from unembedded cartilage blocks, which show a well preserved histological structure and are very suitable to carry out morphological and histochemical studies on chondrocytes and cartilaginous matrix.

Redifferentiation of in vitro expanded adult articular chondrocytes by combining the hanging-drop cultivation method with hypoxic environment.

PubMed

Martinez, Inigo; Elvenes, Jan; Olsen, Randi; Bertheussen, Kjell; Johansen, Oddmund

2008-01-01

The main purpose of this work has been to establish a new culturing technique to improve the chondrogenic commitment of isolated adult human chondrocytes, with the aim of being used during cell-based therapies or tissue engineering strategies. By using a rather novel technique to generate scaffold-free three-dimensional (3D) structures from in vitro expanded chondrocytes, we have explored the effects of different culture environments on cartilage formation. Three-dimensional chondrospheroids were developed by applying the hanging-drop technique. Cartilage tissue formation was attempted after combining critical factors such as serum-containing or serum-free media and atmospheric (20%) or low (2.5%) oxygen tensions. The quality of the formed microtissues was analyzed by histology, immunohistochemistry, electron microscopy, and real-time PCR, and directly compared with native adult cartilage. Our results revealed highly organized, 3D tissue-like structures developed by the hanging-drop method. All culture conditions allowed formation of 3D spheroids; however, cartilage generated under low oxygen tension had a bigger size, enhanced matrix deposition, and higher quality of cartilage formation. Real-time PCR demonstrated enhanced expression of cartilage-specific genes such us collagen type II and aggrecan in 3D cultures when compared to monolayers. Cartilage-specific matrix proteins and genes expressed in hanging-drop-developed spheroids were comparable to the expression obtained by applying the pellet culture system. In summary, our results indicate that a combination of 3D cultures of chondrocytes in hanging drops and a low oxygen environment represent an easy and convenient way to generate cartilage-like microstructures. We also show that a new specially tailored serum-free medium is suitable for in vitro cartilage tissue formation. This new methodology opens up the possibility of using autogenously produced solid 3D structures with redifferentiated chondrocytes as an attractive alternative to the currently used autologous chondrocyte transplantation for cartilage repair.

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.

Characterisation of mineralisation of bone and cartilage: X-ray diffraction and Ca and Sr K α X-ray fluorescence microscopy

NASA Astrophysics Data System (ADS)

Bradley, D. A.; Muthuvelu, P.; Ellis, R. E.; Green, E. M.; Attenburrow, D.; Barrett, R.; Arkill, K.; Colridge, D. B.; Winlove, C. P.

2007-10-01

Bone is a dynamic structure, constantly remodelling in response to changing mechanical and environmental factors. This is particularly evident in the mineral component encrusting the collagenous framework. The mineral is principally in the form of calcium apatite, but calcium can exchange with strontium, both during the cellular processes of mineralisation and resorption and by passive exchange with the deposited crystals. Mineralisation is generally characterized by densitometry, but because of the differences in absorption cross sections of calcium and strontium it can be misleading in studies of composition. In this work we have used X-ray diffraction to identify calcium and strontium apatite and X-ray fluorescence to quantify strontium and calcium distribution. With the beam characteristics available from synchrotron radiation, this has enabled us to obtain microscopic resolution on thin sections of bone and cartilage from the equine metacarpophalangeal joint. Two issues have been investigated; the first is the distribution of mineral in the bone-cartilage interface and within individual trabeculae. In trabecular bone the ratio of strontium to calcium concentration was typically 0.0035 ± 0.0020, and higher by a factor of ∼3 at the periphery than in the centre of a trabeculum (possibly reflecting the more rapid turnover of mineral in the surface layer). In the dense subchondral bone the ratio was similar, approximately doubling in the calcified cartilage. The second objective was to explore the changes in mineralisation associated with development of osteoarthrosis. We analysed lesions showing cartilage thinning and changes in the trabecular organization and density of the underlying bone. At the centre of the lesion the ratio of strontium to calcium was much lower than that in normal tissue, although the calcified cartilage still showed a higher ratio than the underlying bone. In the superficially normal tissue around the lesion the calcified cartilage returned to a normal ratio much more rapidly than the underlying bone. These data demonstrate the complex relationship between changes in cartilage and the underlying bone.

[The influences of the stress distribution on the condylar cartilage surface by Herbst appliance under various bite reconstruction--a three dimensional finite element analysis].

PubMed

Hu, L; Zhao, Z; Song, J; Fan, Y; Jiang, W; Chen, J

2001-02-01

The distribution of stress on the surface of condylar cartilage was investigated. Three-dimensional model of the 'Temporomandibular joint mandible Herbst appliance system' was set up by SUPER SAP software (version 9.3). On this model, various bite reconstruction was simulated according to specified advanced displacement and vertical bite opening. The distribution of maximum and minimum principal stress on the surface of condylar cartilage were computerized and analyzed. When Herbst appliance drove the mandible forward, the anterior condyle surface was compressed while the posterior surface was drawn. The trend of stress on the same point on the condyle surface was consistent in various reconstruction conditions, but the trend of stress on various point were different in same reconstruction conditions. All five groups of bite reconstruction (3-7 mm advancement, 4-2 mm vertical bite opening of the mandible) designed by this study can be selected in clinic according to the patient's capability of adaptation, the extent of malocclusion and the potential and direction of growth.

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.

Transplantation of rib cartilage reshaped with 1.56 μm laser radiation in rabbits

NASA Astrophysics Data System (ADS)

Sobol, E.; Baum, O.; Alexandrovskaya, Yu.; Shekhter, A.; Selezneva, L.; Svistuskin, V.

2017-02-01

As cartilage is an ideal natural material for transplantation, its use in the ENT surgery is limited by a difficulty to get proper shape of cartilage implants. Aim of the work is to make ring-shaped cartilage implants, to check their stability after laser reshaping and to perform transplantation into rabbits in vivo. We experimented with costal cartilages of 1-2 mm in thickness obtained from 3rd and 4rd ribs of a rabbit. 1.56 μm laser (Arcuo Medical Inc.) was used for cartilage reshaping. The laser settings were established taking into account anisotropy of cartilage structure for different orientation of the implants. The reshaped cartilage implants were surgically sewn to rib cartilages of the other rabbits. The rabbits were slaughtered in 3.5-4 months after surgery. The results have shown that (1) all reshaped implants kept circular form, and (2) the implants were adhered to the native rabbit cartilage sites (3) pronounced signs of regeneration in the intermediate zones were observed. The prospects of the cartilage implants use in larynx stenosis surgery are discussed.

Autofluorescence lifetime metrology for label-free detection of cartilage matrix degradation

NASA Astrophysics Data System (ADS)

Nickdel, Mohammad B.; Lagarto, João. L.; Kelly, Douglas J.; Manning, Hugh B.; Yamamoto, Kazuhiro; Talbot, Clifford B.; Dunsby, Christopher; French, Paul; Itoh, Yoshifumi

2014-03-01

Degradation of articular cartilage extracellular matrix (ECM) by proteolytic enzyme is the hallmark of arthritis that leads to joint destruction. Detection of early biochemical changes in cartilage before irreversible structural damages become apparent is highly desirable. Here we report that the autofluorescence decay profile of cartilage is significantly affected by proteolytic degradation of cartilage ECM and can be characterised by measurements of the autofluorescence lifetime (AFL). A multidimensional fluorometer utilizing ultraviolet excitation at 355 nm or 375 nm coupled to a fibreoptic probe was developed for single point time-resolved AFL measurements of porcine articular cartilage explants treated with different proteinases. Degradation of cartilage matrix components by treating with bacterial collagenase, matrix metalloproteinase 1, or trypsin resulted in significant reduction of AFL of the cartilage in both a dose and time dependent manner. Differences in cartilage AFL were also confirmed by fluorescence lifetime imaging microscopy (FLIM). Our data suggest that AFL of cartilage tissue is a potential non-invasive readout to monitor cartilage matrix integrity that may be utilized for diagnosis of arthritis as well as monitoring the efficacy of anti-arthritic therapeutic agents.

In Vivo Efficacy of Fresh vs. Frozen Osteochondral Allografts in the Goat at 6 Months is Associated with PRG4 Secretion

PubMed Central

Pallante-Kichura, Andrea L.; Chen, Albert C.; Temple-Wong, Michele M.; Bugbee, William D.; Sah, Robert L.

2014-01-01

The long-term efficacy of osteochondral allografts is due to the presence of viable chondrocytes within graft cartilage. Chondrocytes in osteochondral allografts, especially those at the articular surface that normally produce the lubricant proteoglycan-4 (PRG4), are susceptible to storage-associated death. The hypothesis of this study was that the loss of chondrocytes within osteochondral grafts leads to decreased PRG4 secretion, after graft storage and subsequent implant. The objectives were to determine the effect of osteochondral allograft treatment (FROZEN vs. FRESH) on secretion of functional PRG4 after (i) storage, and (ii) 6months in vivo in adult goats. FROZEN allograft storage reduced PRG4 secretion from cartilage by ~85% compared to FRESH allograft storage. After 6months in vivo, the PRG4-secreting function of osteochondral allografts was diminished with prior FROZEN storage by ~81% versus FRESH allografts and by ~84% versus non-operated control cartilage. Concomitantly, cellularity at the articular surface in FROZEN allografts was ~96% lower than FRESH allografts and non-operated cartilage. Thus, the PRG4-secreting function of allografts appears to be maintained in vivo based on its state after storage. PRG4 secretion may be not only a useful marker of allograft performance, but also a biological process protecting the articular surface of grafts following cartilage repair. PMID:23362152

In vitro physical stimulation of tissue-engineered and native cartilage.

PubMed

Li, Kelvin W; Klein, Travis J; Chawla, Kanika; Nugent, Gayle E; Bae, Won C; Sah, Robert L

2004-01-01

Because of the limited availability of donor cartilage for resurfacing defects in articular surfaces, there is tremendous interest in the in vitro bioengineering of cartilage replacements for clinical applications. However, attaining mechanical properties in engineered cartilaginous constructs that approach those of native cartilage has not been previously achieved when constructs are cultured under free-swelling conditions. One approach toward stimulating the development of constructs that are mechanically more robust is to expose them to physical environments that are similar, in certain ways, to those encountered by native cartilage. This is a strategy motivated by observations in numerous short-term experiments that certain mechanical signals are potent stimulators of cartilage metabolism. On the other hand, excess mechanical loading can have a deleterious effect on cartilage. Culture conditions that include a physical stimulation component are made possible by the use of specialized bioreactors. This chapter addresses some of the issues involved in using bioreactors as integral components of cartilage tissue engineering and in studying the physical regulation of cartilage. We first consider the generation of cartilaginous constructs in vitro. Next we describe the rationale and design of bioreactors that can impart either mechanical deformation or fluid-induced mechanical signals.

Hyaline cartilage degenerates after autologous osteochondral transplantation.

PubMed

Tibesku, C O; Szuwart, T; Kleffner, T O; Schlegel, P M; Jahn, U R; Van Aken, H; Fuchs, S

2004-11-01

Autologous osteochondral grafting is a well-established clinical procedure to treat focal cartilage defects in patients, although basic research on this topic remains sparse. The aim of the current study was to evaluate (1) histological changes of transplanted hyaline cartilage of osteochondral grafts and (2) the tissue that connects the transplanted cartilage with the adjacent cartilage in a sheep model. Both knee joints of four sheep were opened surgically and osteochondral grafts were harvested and simultaneously transplanted to the contralateral femoral condyle. The animals were sacrificed after three months and the received knee joints were evaluated histologically. Histological evaluation showed a complete ingrowth of the osseous part of the osteochondral grafts. A healing or ingrowth at the level of the cartilage could not be observed. Histological evaluation of the transplanted grafts according to Mankin revealed significantly more and more severe signs of degeneration than the adjacent cartilage, such as cloning of chondrocytes and irregularities of the articular surface. We found no connecting tissue between the transplanted and the adjacent cartilage and histological signs of degeneration of the transplanted hyaline cartilage. In the light of these findings, long-term results of autologous osteochondral grafts in human beings have to be followed critically.

From gristle to chondrocyte transplantation: treatment of cartilage injuries.

PubMed

Lindahl, Anders

2015-10-19

This review addresses the progress in cartilage repair technology over the decades with an emphasis on cartilage regeneration with cell therapy. The most abundant cartilage is the hyaline cartilage that covers the surface of our joints and, due to avascularity, this tissue is unable to repair itself. The cartilage degeneration seen in osteoarthritis causes patient suffering and is a huge burden to society. The surgical approach to cartilage repair was non-existing until the 1950s when new surgical techniques emerged. The use of cultured cells for cell therapy started as experimental studies in the 1970s that developed over the years to a clinical application in 1994 with the introduction of the autologous chondrocyte transplantation technique (ACT). The technology is now spread worldwide and has been further refined by combining arthroscopic techniques with cells cultured on matrix (MACI technology). The non-regenerating hypothesis of cartilage has been revisited and we are now able to demonstrate cell divisions and presence of stem-cell niches in the joint. Furthermore, cartilage derived from human embryonic stem cells and induced pluripotent stem cells could be the base for new broader cell treatments for cartilage injuries and the future technology base for prevention and cure of osteoarthritis. © 2015 The Author(s).

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.

Cell Culture in Microgravity: Opening the Door to Space Cell Biology

NASA Technical Reports Server (NTRS)

Pellis, Neal R.; Dawson, David L. (Technical Monitor)

1999-01-01

Adaptational response of human cell populations to microgravity is investigated using simulation, short-term Shuttle experiments, and long-term microgravity. Simulation consists of a clinostatically-rotated cell culture system. The system is a horizontally-rotated cylinder completely filled with culture medium. Low speed rotation results in continuous-fall of the cells through the fluid medium. In this setting, cells: 1) aggregate, 2) propagate in three dimensions, 3) synthesize matrix, 4) differentiate, and 5) form sinusoids that facilitate mass transfer. Space cell culture is conducted in flight bioreactors and in static incubators. Cells grown in microgravity are: bovine cartilage, promyelocytic leukemia, kidney proximal tubule cells, adrenal medulla, breast and colon cancer, and endothelium. Cells were cultured in space to test specific hypotheses. Cartilage cells were used to determine structural differences in cartilage grown in space compared to ground-based bioreactors. Results from a 130-day experiment on Mir revealed that cartilage grown in space was substantially more compressible due to insufficient glycosaminoglycan in the matrix. Interestingly, earth-grown cartilage conformed better to the dimensions of the scaffolding material, while the Mir specimens were spherical. The other cell populations are currently being analyzed for cell surface properties, gene expression, and differentiation. Results suggest that some cells spontaneously differentiate in microgravity. Additionally, vast changes in gene expression may occur in response to microgravity. In conclusion, the transition to microgravity may constitute a physical perturbation in cells resulting in unique gene expressions, the consequences of which may be useful in tissue engineering, disease modeling, and space cell biology.

Current concepts of etiology and treatment of chondromalacia patellae.

PubMed

Bentley, G; Dowd, G

1984-10-01

Chondromalacia patellae is a distinct clinical entity characterized by retropatellar pain that is associated with recognizable changes in the articular cartilage of the posterior surface of the patella. Several factors may be involved in the etiology, such as severe patella alta, trauma, and, in rare cases, abnormal patellar tracking. Clinical symptoms and signs are reliable in only 50% of cases, but measurable quadriceps wasting, palpable patellofemoral crepitus, and effusion are strongly suggestive. Diagnosis must be confirmed by arthroscopy or direct examination of the posterior surface of the patella. Radiologic measurements of patellofemoral relations are of limited value in diagnosis. The initial pathologic finding is usually surface cartilage breakdown. Radioisotope studies show cartilage cell replication which suggests a healing capacity in early cases following treatment that alters the load through the affected cartilage. There is no evidence of progression to patellofemoral osteoarthritis, which is probably a different entity. The treatment should be conservative where possible with isometric quadriceps exercises and simple anti-inflammatory drugs such as aspirin. Operative treatment is indicated for patients with persistent pain and macroscopic involvement of more than half a centimeter of the articular cartilage surface. The simplest effective procedure that avoids quadriceps dysfunction and fibrosis is a distal patellar tendon medial realignment with lateral release and medial reefing of the quadriceps expansion. Patellectomy is indicated in more extensive involvement of the patella of 2 or more centimeters in diameter, but this must be performed only when the patient has excellent quadriceps function before surgery and is motivated to exercise after surgery.

Study of cartilage and bone layers of the bearing surface of the equine metacarpophalangeal joint relative to different timescales of maturation.

PubMed

van der Harst, M R; van de Lest, C H A; Degroot, J; Kiers, G H; Brama, P A J; van Weeren, P R

2005-05-01

A detailed and comprehensive insight into the normal maturation process of the different tissues that make up functional units of the locomotor system such as joints is necessary to understand the influence of early training on musculoskeletal tissues. To study simultaneously the maturation process in the entire composite structure that makes up the bearing surface of a joint (cartilage, subchondral and trabecular bone) in terms of biochemical changes in the tissues of juvenile horses at 2 differently loaded sites of the metacarpophalangeal joint, compared to a group of mature horses. In all the structures described above developmental changes may follow a different timescale. Age-related changes in biochemical characteristics of the collagen part of the extracellular matrix (hydroxylysine, hydroxyproline, hydroxypyridinum crosslinks) of articular cartilage and of the underlying subchondral and trabecular bone were determined in a group of juvenile horses (n = 13) (Group 1, age 6 months-4 years) and compared to a group of mature horses (n = 30) (Group 2, >4 years). In both bony layers, bone mineral density, ash content and levels of individual minerals were determined. In cartilage, subchondral bone and trabecular bone, virtually all collagen parameters in juvenile horses were already at a similar (stable) level as in mature horses. In both bony layers, bone mineral density, ash- and calcium content were also stable in the mature horses, but continued to increase in the juvenile group. For magnesium there was a decrease in the juvenile animals, followed by a steady state in the mature horses. In horses age 6 months-4 years, the collagen network of all 3 layers within the joint has already attained a mature biochemical composition, but the mineral composition of both subchondral and trabecular bone continues to develop until approximately age 4 years. The disparity in maturation of the various extracellular matrix components of a joint can be assumed to have consequences for the capacity to sustain load and should hence be taken into account when training or racing young animals.

Engineering ear-shaped cartilage using electrospun fibrous membranes of gelatin/polycaprolactone.

PubMed

Xue, Jixin; Feng, Bei; Zheng, Rui; Lu, Yang; Zhou, Guangdong; Liu, Wei; Cao, Yilin; Zhang, Yanzhong; Zhang, Wen Jie

2013-04-01

Tissue engineering approach continuously requires for emerging strategies to improve the efficacy in repairing and regeneration of tissue defects. Previously, we developed a sandwich model strategy for cartilage engineering, using the combination of acellular cartilage sheets (ACSs) and chondrocytes. However, the process for the preparation of ACSs is complicated, and it is also difficult to obtain large ACSs. The aim of this study was to engineer cartilage with precise three-dimensional (3-D) structures by applying electrospun fibrous membranes of gelatin/polycaprolactone (GT/PCL). We first prepared the electrospun GT/PCL membranes into rounded shape, and then seeded chondrocytes in the sandwich model. After in vitro and in vivo cultivation, the newly formed cartilage-like tissues were harvested. Macroscopic observations and histological analysis confirmed that the engineering of cartilage using the electrospun GT/PCL membranes was feasible. An ear-shaped cartilage was then constructed in the sandwich model, with the help of an ear-shaped titanium alloy mold. After 2 weeks of culture in vitro and 6 weeks of subcutaneous incubation in vivo, the ear-shaped cartilage largely maintained their original shape, with a shape similarity up to 91.41% of the titanium mold. In addition, the engineered cartilage showed good elasticity and impressive mechanical strength. These results demonstrated that the engineering of 3-D cartilage in a sandwich model using electrospun fibrous membranes was a facile and effective approach, which has the potential to be applied for the engineering of other tissues with complicated 3-D structures. Copyright © 2012 Elsevier Ltd. All rights reserved.

Knee Joint Kinematics during Walking Influences the Spatial Cartilage Thickness Distribution in the Knee

PubMed Central

Koo, Seungbum; Rylander, Jonathan H.; Andriacchi, Thomas P.

2010-01-01

The regional adaptation of knee cartilage morphology to the kinematics of walking has been suggested as an important factor in the evaluation of the consequences of alteration in normal gait leading to osteoarthritis. The purpose of this study was to investigate the association of spatial cartilage thickness distributions of the femur and tibia in the knee to the knee kinematics during walking. Gait data and knee MR images were obtained from 17 healthy volunteers (age 33.2±9.8 years). Cartilage thickness maps were created for the femoral and tibial cartilage. Locations of thickest cartilage in the medial and lateral compartments in the femur and tibia were identified using a numerical method. The flexion-extension (FE) angle associated with the cartilage contact regions on the femur, and the anterior-posterior (AP) translation and internal-external (IE) rotation associated with the cartilage contact regions on the tibia at the heel strike of walking were tested for correlation with the locations of thickest cartilage. The locations of the thickest cartilage had relatively large variation (SD 8.9°) and was significantly associated with the FE angle at heel strike only in the medial femoral condyle (R2=0.41, p<0.01). The natural knee kinematics and contact surface shapes seem to affect the functional adaptation of knee articular cartilage morphology. The sensitivity of cartilage morphology to kinematics at the knee during walking suggests that regional cartilage thickness variations are influenced by both loading and the number of loading cycles. Thus walking is an important consideration in the analysis of the morphological variations of articular cartilage, since it is the dominant cyclic activity of daily living. The sensitivity of cartilage morphology to gait kinematics is also important in understanding the etiology and pathomechanics of osteoarthritis. PMID:21371712

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.

Effects of growth factors and glucosamine on porcine mandibular condylar cartilage cells and hyaline cartilage cells for tissue engineering applications.

PubMed

Wang, Limin; Detamore, Michael S

2009-01-01

Temporomandibular joint (TMJ) condylar cartilage is a distinct cartilage that has both fibrocartilaginous and hyaline-like character, with a thin proliferative zone that separates the fibrocartilaginous fibrous zone at the surface from the hyaline-like mature and hypertrophic zones below. In this study, we compared the effects of insulin-like growth factor-I (IGF-I), basic fibroblast growth factor (bFGF), transforming growth factor beta1 (TGF-beta1), and glucosamine sulphate on porcine TMJ condylar cartilage and ankle cartilage cells in monolayer culture. In general, TMJ condylar cartilage cells proliferated faster than ankle cartilage cells, while ankle cells produced significantly greater amounts of glycosaminoglycans (GAGs) and collagen than TMJ condylar cartilage cells. IGF-I and bFGF were potent stimulators of TMJ cell proliferation, while no signals statistically outperformed controls for ankle cell proliferation. IGF-I was the most effective signal for GAG production with ankle cells, and the most potent upregulator of collagen synthesis for both cell types. Glucosamine sulphate promoted cell proliferation and biosynthesis at specific concentrations and outperformed growth factors in certain instances. In conclusion, hyaline cartilage cells had lower cell numbers and superior biosynthesis compared to TMJ condylar cartilage cells, and we have found IGF-I at 100 ng/mL and glucosamine sulphate at 100 microg/mL to be the most effective signals for these cells under the prescribed conditions.

Technical Report: Correlation Between the Repair of Cartilage and Subchondral Bone in an Osteochondral Defect Using Bilayered, Biodegradable Hydrogel Composites.

PubMed

Lu, Steven; Lam, Johnny; Trachtenberg, Jordan E; Lee, Esther J; Seyednejad, Hajar; van den Beucken, Jeroen J J P; Tabata, Yasuhiko; Kasper, F Kurtis; Scott, David W; Wong, Mark E; Jansen, John A; Mikos, Antonios G

2015-12-01

The present work investigated correlations between cartilage and subchondral bone repair, facilitated by a growth factor-delivering scaffold, in a rabbit osteochondral defect model. Histological scoring indices and microcomputed tomography morphological parameters were used to evaluate cartilage and bone repair, respectively, at 6 and 12 weeks. Correlation analysis revealed significant associations between specific cartilage indices and subchondral bone parameters that varied with location in the defect (cortical vs. trabecular region), time point (6 vs. 12 weeks), and experimental group (insulin-like growth factor-1 only, bone morphogenetic protein-2 only, or both growth factors). In particular, significant correlations consistently existed between cartilage surface regularity and bone quantity parameters. Overall, correlation analysis between cartilage and bone repair provided a fuller understanding of osteochondral repair and can help drive informed studies for future osteochondral regeneration strategies.

Three-dimensional polycaprolactone-hydroxyapatite scaffolds combined with bone marrow cells for cartilage tissue engineering.

PubMed

Wei, Bo; Yao, Qingqiang; Guo, Yang; Mao, Fengyong; Liu, Shuai; Xu, Yan; Wang, Liming

2015-08-01

The goal of this study was to investigate the chondrogenic potential of three-dimensional polycaprolactone-hydroxyapatite (PCL-HA) scaffolds loaded with bone marrow cells in vitro and the effect of PCL-HA scaffolds on osteochondral repair in vivo. Here, bone marrow was added to the prepared PCL-HA scaffolds and cultured in chondrogenic medium for 10 weeks. Osteochondral defects were created in the trochlear groove of 29 knees in 17 New Zealand white rabbits, which were then divided into four groups that underwent: implantation of PCL-HA scaffolds (left knee, n = 17; Group 1), microfracture (right knee, n = 6; Group 2), autologous osteochondral transplantation (right knee, n = 6; Group 3), and no treatment (right knee, n = 5; Control). Extracellular matrix produced by bone marrow cells covered the surface and filled the pores of PCL-HA scaffolds after 10 weeks in culture. Moreover, many cell-laden cartilage lacunae were observed, and cartilage matrix was concentrated in the PCL-HA scaffolds. After a 12-week repair period, Group 1 showed excellent vertical and lateral integration with host bone, but incomplete cartilage regeneration and matrix accumulation. An uneven surface of regenerated cartilage and reduced distribution of cartilage matrix were observed in Group 2. In addition, abnormal bone growth and unstable integration between repaired and host tissues were detected. For Group 3, the integration between transplanted and host cartilage was interrupted. Our findings indicate that the PCL-HA scaffolds loaded with bone marrow cells improved chondrogenesis in vitro and implantation of PCL-HA scaffolds for osteochondral repairenhanced integration with host bone. However, cartilage regeneration remained unsatisfactory. The addition of trophic factors or the use of precultured cell-PCL-HA constructs for accelerated osteochondral repair requires further investigation. © The Author(s) 2015.

Anatomically shaped tissue-engineered cartilage with tunable and inducible anticytokine delivery for biological joint resurfacing

PubMed Central

Moutos, Franklin T.; Glass, Katherine A.; Compton, Sarah A.; Ross, Alison K.; Gersbach, Charles A.; Estes, Bradley T.

2016-01-01

Biological resurfacing of entire articular surfaces represents an important but challenging strategy for treatment of cartilage degeneration that occurs in osteoarthritis. Not only does this approach require anatomically sized and functional engineered cartilage, but the inflammatory environment within an arthritic joint may also inhibit chondrogenesis and induce degradation of native and engineered cartilage. The goal of this study was to use adult stem cells to engineer anatomically shaped, functional cartilage constructs capable of tunable and inducible expression of antiinflammatory molecules, specifically IL-1 receptor antagonist (IL-1Ra). Large (22-mm-diameter) hemispherical scaffolds were fabricated from 3D woven poly(ε-caprolactone) (PCL) fibers into two different configurations and seeded with human adipose-derived stem cells (ASCs). Doxycycline (dox)-inducible lentiviral vectors containing eGFP or IL-1Ra transgenes were immobilized to the PCL to transduce ASCs upon seeding, and constructs were cultured in chondrogenic conditions for 28 d. Constructs showed biomimetic cartilage properties and uniform tissue growth while maintaining their anatomic shape throughout culture. IL-1Ra–expressing constructs produced nearly 1 µg/mL of IL-1Ra upon controlled induction with dox. Treatment with IL-1 significantly increased matrix metalloprotease activity in the conditioned media of eGFP-expressing constructs but not in IL-1Ra–expressing constructs. Our findings show that advanced textile manufacturing combined with scaffold-mediated gene delivery can be used to tissue engineer large anatomically shaped cartilage constructs that possess controlled delivery of anticytokine therapy. Importantly, these cartilage constructs have the potential to provide mechanical functionality immediately upon implantation, as they will need to replace a majority, if not the entire joint surface to restore function. PMID:27432980

Effect of low-dose irradiation on structural and mechanical properties of hyaline cartilage-like fibrocartilage.

PubMed

Öncan, Tevfik; Demirağ, Burak; Ermutlu, Cenk; Yalçinkaya, Ulviye; Özkan, Lütfü

2013-01-01

The aim of this study was to analyze the effect of low-dose irradiation on fibrous cartilage and to obtain a hyaline cartilage-like fibrocartilage (HCLF) with similar structural and mechanical properties to hyaline cartilage. An osteochondral defect was created in 40 knees of 20 rabbits. At the 7th postoperative day, a single knee of each rabbit was irradiated with a total dose of 5.0 Gy in 1.0 Gy fractions for 5 days (radiotherapy group), while the other knee was not irradiated (control group). Rabbits were then divided into four groups of 5 rabbits each. The first three groups were sacrificed at the 4th, 8th and the 12th postoperative weeks and cartilage defects were macroscopically and microscopically evaluated. The remaining group of 5 rabbits was sacrificed at the 12th week and biomechanical compression tests were performed on the cartilage defects. There was no significant biomechanical difference between the radiotherapy and the control group (p=0.686). There was no significant macroscopic and microscopic difference between groups (p=0.300). Chondrocyte clustering was observed in the irradiated group. Low-dose irradiation does not affect the mechanical properties of HCLF in vivo. However, structural changes such as chondrocyte clustering were observed.

[Orthotopic cartilage transplantation. Morphologic, angiography and histochemical studies of the vitality of free septum transplants].

PubMed

Gubisch, W; Donath, K

1999-11-01

Orthotopic cartilage transplantation is a technique frequently used in modern septal surgery. The prerequisite for a stable long-term result is viability of the transplanted cartilage. Therefore, we studied the healing process histologically, angiographically, and histochemically. We found a characteristic picture. Due to chondronal structure of the cartilage, the healing process varied in time and location. Reintegration took place by chondroneogenesis, commencing at the inner perichondrium. Reintegration depended directly on the distance of the cartilage cells to the surrounding vessels. Histochemically, we found an intact respiratory chain in the mitochondria and thus, we were able to demonstrate the preservation of viability in orthotopic transplanted cartilage.

Laser-induced regeneration of cartilage

NASA Astrophysics Data System (ADS)

Sobol, Emil; Shekhter, Anatoly; Guller, Anna; Baum, Olga; Baskov, Andrey

2011-08-01

Laser radiation provides a means to control the fields of temperature and thermo mechanical stress, mass transfer, and modification of fine structure of the cartilage matrix. The aim of this outlook paper is to review physical and biological aspects of laser-induced regeneration of cartilage and to discuss the possibilities and prospects of its clinical applications. The problems and the pathways of tissue regeneration, the types and features of cartilage will be introduced first. Then we will review various actual and prospective approaches for cartilage repair; consider possible mechanisms of laser-induced regeneration. Finally, we present the results in laser regeneration of joints and spine disks cartilages and discuss some future applications of lasers in regenerative medicine.

Magnetic resonance imaging can accurately assess the long-term progression of knee structural changes in experimental dog osteoarthritis.

PubMed

Boileau, C; Martel-Pelletier, J; Abram, F; Raynauld, J-P; Troncy, E; D'Anjou, M-A; Moreau, M; Pelletier, J-P

2008-07-01

Osteoarthritis (OA) structural changes take place over decades in humans. MRI can provide precise and reliable information on the joint structure and changes over time. In this study, we investigated the reliability of quantitative MRI in assessing knee OA structural changes in the experimental anterior cruciate ligament (ACL) dog model of OA. OA was surgically induced by transection of the ACL of the right knee in five dogs. High resolution three dimensional MRI using a 1.5 T magnet was performed at baseline, 4, 8 and 26 weeks post surgery. Cartilage volume/thickness, cartilage defects, trochlear osteophyte formation and subchondral bone lesion (hypersignal) were assessed on MRI images. Animals were killed 26 weeks post surgery and macroscopic evaluation was performed. There was a progressive and significant increase over time in the loss of knee cartilage volume, the cartilage defect and subchondral bone hypersignal. The trochlear osteophyte size also progressed over time. The greatest cartilage loss at 26 weeks was found on the tibial plateaus and in the medial compartment. There was a highly significant correlation between total knee cartilage volume loss or defect and subchondral bone hypersignal, and also a good correlation between the macroscopic and the MRI findings. This study demonstrated that MRI is a useful technology to provide a non-invasive and reliable assessment of the joint structural changes during the development of OA in the ACL dog model. The combination of this OA model with MRI evaluation provides a promising tool for the evaluation of new disease-modifying osteoarthritis drugs (DMOADs).

Focal cartilage defect compromises fluid-pressure dependent load support in the knee joint.

PubMed

Dabiri, Yaghoub; Li, LePing

2015-06-01

A focal cartilage defect involves tissue loss or rupture. Altered mechanics in the affected joint may play an essential role in the onset and progression of osteoarthritis. The objective of the present study was to determine the compromised load support in the human knee joint during defect progression from the cartilage surface to the cartilage-bone interface. Ten normal and defect cases were simulated with a previously tested 3D finite element model of the knee. The focal defects were considered in both condyles within high load-bearing regions. Fluid pressurization, anisotropic fibril-reinforcement, and depth-dependent mechanical properties were considered for the articular cartilages and menisci. The results showed that a small cartilage defect could cause 25% reduction in the load support of the knee joint due to a reduced capacity of fluid pressurization in the defect cartilage. A partial-thickness defect could cause a fluid pressure decrease or increase in the remaining underlying cartilage depending on the defect depth. A cartilage defect also increased the shear strain at the cartilage-bone interface, which was more significant with a full-thickness defect. The effect of cartilage defect on the fluid pressurization also depended on the defect sites and contact conditions. In conclusion, a focal cartilage defect causes a fluid-pressure dependent load reallocation and a compromised load support in the joint, which depend on the defect depth, site, and contact condition. Copyright © 2015 John Wiley & Sons, Ltd.

Calcified cartilage or bone? Collagens in the tessellated endoskeletons of cartilaginous fish (sharks and rays).

PubMed

Seidel, Ronald; Blumer, Michael; Pechriggl, Elisabeth-Judith; Lyons, Kady; Hall, Brian K; Fratzl, Peter; Weaver, James C; Dean, Mason N

2017-10-01

The primary skeletal tissue in elasmobranchs -sharks, rays and relatives- is cartilage, forming both embryonic and adult endoskeletons. Only the skeletal surface calcifies, exhibiting mineralized tiles (tesserae) sandwiched between a cartilage core and overlying fibrous perichondrium. These two tissues are based on different collagens (Coll II and I, respectively), fueling a long-standing debate as to whether tesserae are more like calcified cartilage or bone (Coll 1-based) in their matrix composition. We demonstrate that stingray (Urobatis halleri) tesserae are bipartite, having an upper Coll I-based 'cap' that merges into a lower Coll II-based 'body' zone, although tesserae are surrounded by cartilage. We identify a 'supratesseral' unmineralized cartilage layer, between tesserae and perichondrium, distinguished from the cartilage core in containing Coll I and X (a common marker for mammalian mineralization), in addition to Coll II. Chondrocytes within tesserae appear intact and sit in lacunae filled with Coll II-based matrix, suggesting tesserae originate in cartilage, despite comprising a diversity of collagens. Intertesseral joints are also complex in their collagenous composition, being similar to supratesseral cartilage closer to the perichondrium, but containing unidentified fibrils nearer the cartilage core. Our results indicate a unique potential for tessellated cartilage in skeletal biology research, since it lacks features believed diagnostic for vertebrate cartilage mineralization (e.g. hypertrophic and apoptotic chondrocytes), while offering morphologies amenable for investigating the regulation of complex mineralized ultrastructure and tissues patterned on multiple collagens. Copyright © 2017 Elsevier Inc. All rights reserved.

The cranial cartilages of teleosts and their classification.

PubMed

Benjamin, M

1990-04-01

The structure and distribution of cartilages has been studied in 45 species from 24 families. The resulting data have been used as a basis for establishing a new classification. A cartilage is regarded as 'cell-rich' if its cells or their lacunae occupy more than half of the tissue volume. Five classes of cell-rich cartilage are recognised (a) hyaline-cell cartilage (common in the lips of bottom-dwelling cyprinids) and its subtypes fibro/hyaline-cell cartilage, elastic/hyaline-cell cartilage and lipo/hyaline-cell cartilage, (b) Schaffer's Zellknorpel, typified by the cartilage in the gill filaments of most teleosts examined, (c) elastic/cell-rich cartilage, such as that which supports the barbels and oral valves of catfish, e.g. Corydoras metae, (d) fibro/cell-rich cartilage, as in the submaxillary meniscus of Sphaerichthys osphromenoides, (e) cell-rich hyaline and (f) matrix-rich hyaline cartilage--both of which are common in the neurocranium and gill arches of most teleosts. The range of cartilages seen, and the predominant cartilage type, is recorded for each species and a list is provided of the tissues that most typify different organs or regions of the head. As a preliminary pointer to developmental relationships between the cartilages, note was taken of gradual transitions between one cartilage and another. It is suggested that hyaline-cell cartilage occupies a key position in teleosts as the most labile of the supporting tissues and is highly characteristic of Cypriniformes. The cartilage that best resembles mammalian hyaline cartilage (matrix-rich hyaline cartilage) has a very conservative distribution in different skeletal elements and the least number of associations with other tissues. It is well represented in Siluriformes.

Magnetic Resonance Imaging of Cartilage Repair

PubMed Central

Trattnig, Siegfried; Winalski, Carl S.; Marlovits, Stephan; Jurvelin, Jukka S.; Welsch, Goetz H.; Potter, Hollis G.

2011-01-01

Articular cartilage lesions are a common pathology of the knee joint, and many patients may benefit from cartilage repair surgeries that offer the chance to avoid the development of osteoarthritis or delay its progression. Cartilage repair surgery, no matter the technique, requires a noninvasive, standardized, and high-quality longitudinal method to assess the structure of the repair tissue. This goal is best fulfilled by magnetic resonance imaging (MRI). The present article provides an overview of the current state of the art of MRI of cartilage repair. In the first 2 sections, preclinical and clinical MRI of cartilage repair tissue are described with a focus on morphological depiction of cartilage and the use of functional (biochemical) MR methodologies for the visualization of the ultrastructure of cartilage repair. In the third section, a short overview is provided on the regulatory issues of the United States Food and Drug Administration (FDA) and the European Medicines Agency (EMEA) regarding MR follow-up studies of patients after cartilage repair surgeries. PMID:26069565

Structural and Anatomic Restoration of the Anterior Cruciate Ligament Is Associated With Less Cartilage Damage 1 Year After Surgery: Healing Ligament Properties Affect Cartilage Damage

PubMed Central

Kiapour, Ata M.; Fleming, Braden C.; Murray, Martha M.

2017-01-01

Background: Abnormal joint motion has been linked to joint arthrosis after anterior cruciate ligament (ACL) reconstruction. However, the relationships between the graft properties (ie, structural and anatomic) and extent of posttraumatic osteoarthritis are not well defined. Hypotheses: (1) The structural (tensile) and anatomic (area and alignment) properties of the reconstructed graft or repaired ACL correlate with the total cartilage lesion area 1 year after ACL surgery, and (2) side-to-side differences in anterior-posterior (AP) knee laxity correlate with the total cartilage lesion area 1 year postoperatively. Study Design: Controlled laboratory study. Methods: Sixteen minipigs underwent unilateral ACL transection and were randomly treated with ACL reconstruction or bridge-enhanced ACL repair. The tensile properties, cross-sectional area, and multiplanar alignment of the healing ACL or graft, AP knee laxity, and cartilage lesion areas were assessed 1 year after surgery. Results: In the reconstructed group, the normalized graft yield and maximum failure loads, cross-sectional area, sagittal and coronal elevation angles, and side-to-side differences in AP knee laxity at 60° of flexion were associated with the total cartilage lesion area 1 year after surgery (R 2 > 0.5, P < .04). In the repaired group, normalized ACL yield load, linear stiffness, cross-sectional area, and the sagittal and coronal elevation angles were associated with the total cartilage lesion area (R 2 > 0.5, P < .05). Smaller cartilage lesion areas were observed in the surgically treated knees when the structural and anatomic properties of the ligament or graft and AP laxity values were closer to those of the contralateral ACL-intact knee. Reconstructed grafts had a significantly larger normalized cross-sectional area and sagittal elevation angle (more vertical) when compared with repaired ACLs (P < .02). Conclusion: The tensile properties, cross-sectional area, and multiplanar alignment of the healing ACLs or grafts and AP knee laxity in reconstructed knees were associated with the extent of tibiofemoral cartilage damage after ACL surgery. Clinical Relevance: These data highlight the need for novel ACL injury treatments that can restore the structural and anatomic properties of the torn ACL to those of the native ACL in an effort to minimize the risk of early-onset posttraumatic osteoarthritis. PMID:28875154

Cartilage Health in Knees Treated with Metal Resurfacing Implants or Untreated Focal Cartilage Lesions: A Preclinical Study in Sheep.

PubMed

Martinez-Carranza, Nicolas; Hultenby, Kjell; Lagerstedt, Anne Sofie; Schupbach, Peter; Berg, Hans E

2017-07-01

Background Full-depth cartilage lesions do not heal and the long-term clinical outcome is uncertain. In the symptomatic middle-aged (35-60 years) patient, treatment with metal implants has been proposed. However, the cartilage health surrounding these implants has not been thoroughly studied. Our objective was to evaluate the health of cartilage opposing and adjacent to metal resurfacing implants. Methods The medial femoral condyle was operated in 9 sheep bilaterally. A metallic resurfacing metallic implant was immediately inserted into an artificially created 7.5 mm defect while on the contralateral knee the defect was left untreated. Euthanasia was performed at 6 months. Six animals, of similar age and study duration, from a previous study were used for comparison in the evaluation of cartilage health adjacent to the implant. Cartilage damage to joint surfaces within the knee, cartilage repair of the defect, and cartilage adjacent to the implant was evaluated macroscopically and microscopically. Results Six animals available for evaluation of cartilage health within the knee showed a varying degree of cartilage damage with no statistical difference between defects treated with implants or left untreated ( P = 0.51; 95% CI -3.7 to 6.5). The cartilage adjacent to the implant (score 0-14; where 14 indicates no damage) remained healthy in these 6 animals showing promising results (averaged 10.5; range 9-11.5, SD 0.95). Cartilage defects did not heal in any case. Conclusion Treatment of a critical size focal lesion with a metal implant is a viable alternative treatment.

Current state of cartilage tissue engineering

PubMed Central

Tuli, Richard; Li, Wan-Ju; Tuan, Rocky S

2003-01-01

Damage to cartilage is of great clinical consequence given the tissue's limited intrinsic potential for healing. Current treatments for cartilage repair are less than satisfactory, and rarely restore full function or return the tissue to its native normal state. The rapidly emerging field of tissue engineering holds great promise for the generation of functional cartilage tissue substitutes. The general approach involves a biocompatible, structurally and mechanically sound scaffold, with an appropriate cell source, which is loaded with bioactive molecules that promote cellular differentiation and/or maturation. This review highlights aspects of current progress in cartilage tissue engineering. PMID:12932283

Investigation of Essential Element Distribution in the Equine Metacarpophalangeal Joint using a Synchrotron Radiation Micro X-Ray Fluorescence Technique

NASA Astrophysics Data System (ADS)

Kaabar, Wejdan; Gundogdu, O.; Tzaphlidou, M.; Janousch, M.; Attenburrow, D.; Bradley, D. A.

2008-05-01

In articular cartilage, Ca, P, K and S are among some of the well known co-factors of the metalloproteinases enzymatic family, the latter playing a pivotal role in the growth and degeneration of the collagenous bone-cartilage interface of articulating joints. Current study forms part of a larger investigation concerning the distribution of these and other key elements in such media. For the purpose of evaluating these low atomic number elements (Z⩽20), use was made of the capabilities of the LUCIA Station, located at the synchrotron facility of the Paul Scherrer Institute (PSI). Using an incident radiation energy of 4.06 keV, a synchrotron radiation micro x-ray fluorescence (SR-μXRF) technique was applied in examining the distribution of the essential elements Ca, P, K and S in the bone-cartilage interface of both healthy and diseased (osteoarthritic) areas of an equine metacarpophalangeal joint. The SR-μXRF mappings and line profile patterns have revealed remarkable changes in both the pattern and absolute distributions of these elements, agreeing with the findings of others. The elemental presence shown in the individual area scans encompassing the lesion each reflect the visibly abraded outer surface of the cartilage and change in shape of the bone surface. One of the area scans for the bone-cartilage interface shows a marked change in both the pattern and absolute elemental presence for all three elements compared to that observed at two other scan sites. The observation of change in bone cartilage composition around the surface of the articulating joint is thought to be novel, the variation being almost certainly due to the differing weight-bearing role of the subchondral bone at each location.

Investigation of Essential Element Distribution in the Equine Metacarpophalangeal Joint using a Synchrotron Radiation Micro X-Ray Fluorescence Technique

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

Kaabar, Wejdan; Gundogdu, O.; Attenburrow, D.

2008-05-20

In articular cartilage, Ca, P, K and S are among some of the well known co-factors of the metalloproteinases enzymatic family, the latter playing a pivotal role in the growth and degeneration of the collagenous bone-cartilage interface of articulating joints. Current study forms part of a larger investigation concerning the distribution of these and other key elements in such media. For the purpose of evaluating these low atomic number elements (Z{<=}20), use was made of the capabilities of the LUCIA Station, located at the synchrotron facility of the Paul Scherrer Institute (PSI). Using an incident radiation energy of 4.06 keV,more » a synchrotron radiation micro x-ray fluorescence (SR-{mu}XRF) technique was applied in examining the distribution of the essential elements Ca, P, K and S in the bone-cartilage interface of both healthy and diseased (osteoarthritic) areas of an equine metacarpophalangeal joint. The SR-{mu}XRF mappings and line profile patterns have revealed remarkable changes in both the pattern and absolute distributions of these elements, agreeing with the findings of others. The elemental presence shown in the individual area scans encompassing the lesion each reflect the visibly abraded outer surface of the cartilage and change in shape of the bone surface. One of the area scans for the bone-cartilage interface shows a marked change in both the pattern and absolute elemental presence for all three elements compared to that observed at two other scan sites. The observation of change in bone cartilage composition around the surface of the articulating joint is thought to be novel, the variation being almost certainly due to the differing weight-bearing role of the subchondral bone at each locati0008.« less

Semi-Quantitative Imaging Biomarkers of Knee Osteoarthritis Progression: Data from the FNIH OA Biomarkers Consortium

PubMed Central

Collins, Jamie E.; Losina, Elena; Nevitt, Michael C.; Roemer, Frank W.; Guermazi, Ali; Lynch, John A.; Katz, Jeffrey N.; Kwoh, C. Kent; Kraus, Virginia B.; Hunter, David J.

2017-01-01

Objective To determine the association between changes in semi-quantitative knee MRI biomarkers over 24 months and radiographic and pain progression over 48 months in knees with mild to moderate osteoarthritis. Methods We undertook a nested case-control study as part of the Osteoarthritis Biomarkers Consortium Project. We built multivariable logistic regression models to examine the association between change over 24 months in semi-quantitative MR imaging markers and knee OA radiographic and pain progression. MRIs were read according to the MRI Osteoarthritis Knee Score (MOAKS) scoring system. We focused on changes in cartilage, osteophytes, meniscus, bone marrow lesions, Hoffa-synovitis, and synovitis-effusion. Results The most parsimonious model included changes in cartilage thickness and surface area, synovitis-effusion, Hoffa-synovitis, and meniscal morphology (C-statistic =0.740). Subjects with worsening cartilage thickness in 3+ subregions vs. no worsening had 2.8-fold (95% CI: 1.3 – 5.9) greater odds of being a case while subjects with worsening in cartilage surface area in 3+ subregions vs. no worsening had 2.4-fold (95% CI: 1.3 – 4.4) greater odds of being a case. Having worsening in any region in meniscal morphology was associated with a 2.2-fold (95%CI: 1.3 – 3.8) greater odds of being a case. Worsening synovitis-effusion (OR=2.7) and Hoffa-synovitis (OR=2.0) were also associated with greater odds of being a case. Conclusion Twenty-four-month change in cartilage thickness, cartilage surface area, synovitis-effusion, Hoffa-synovitis, and meniscal morphology were independently associated with OA progression, suggesting that they may serve as efficacy biomarkers in clinical trials of disease modifying interventions for knee OA. PMID:27111771

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.

Microstructural changes in cartilage and bone related to repetitive overloading in an equine athlete model

PubMed Central

Turley, Sean M; Thambyah, Ashvin; Riggs, Christopher M; Firth, Elwyn C; Broom, Neil D

2014-01-01

The palmar aspect of the third metacarpal (MC3) condyle of equine athletes is known to be subjected to repetitive overloading that can lead to the accumulation of joint tissue damage, degeneration, and stress fractures, some of which result in catastrophic failure. However, there is still a need to understand at a detailed microstructural level how this damage progresses in the context of the wider joint tissue complex, i.e. the articular surface, the hyaline and calcified cartilage, and the subchondral bone. MC3 bones from non-fractured joints were obtained from the right forelimbs of 16 Thoroughbred racehorses varying in age between 3 and 8 years, with documented histories of active race training. Detailed microstructural analysis of two clinically important sites, the parasagittal grooves and the mid-condylar regions, identified extensive levels of microdamage in the calcified cartilage and subchondral bone concealed beneath outwardly intact hyaline cartilage. The study shows a progression in microdamage severity, commencing with mild hard-tissue microcracking in younger animals and escalating to severe subchondral bone collapse and lesion formation in the hyaline cartilage with increasing age and thus athletic activity. The presence of a clearly distinguishable fibrous tissue layer at the articular surface immediately above sites of severe subchondral collapse suggested a limited reparative response in the hyaline cartilage. PMID:24689513

Detectable reporter gene expression following transduction of adenovirus and adeno-associated virus serotype 2 vectors within full-thickness osteoarthritic and unaffected canine cartilage in vitro and unaffected guinea pig cartilage in vivo.

PubMed

Santangelo, Kelly S; Baker, Sarah A; Nuovo, Gerard; Dyce, Jonathan; Bartlett, Jeffrey S; Bertone, Alicia L

2010-02-01

This study quantified and compared the transduction efficiencies of adenoviral (Ad), Arg-Gly-Asp (RGD)-modified Ad, adeno-associated viral serotype 2 (AAV2), and self-complementary AAV2 (scAAV2) vectors within full-thickness osteoarthritic (OA) and unaffected canine cartilage explants in vitro. Intraarticular administration of Ad and scAAV2 vectors was performed to determine the ability of these vectors to transduce unaffected guinea pig cartilage in vivo. Following explant exposure to vector treatment or control, the onset and surface distribution of reporter gene expression was monitored daily with fluorescent microscopy. At termination, explants were divided: one half was digested for analysis using flow cytometry; the remaining portion was used for histology and immunohistochemistry (IHC). Intact articular joints were collected for real-time RT-PCR and IHC to detect reporter gene expression following injection of selected vectors. Ad vector transduced focal areas along the perimeters of explants; the remaining vectors transduced chondrocytes across 100% of the surface. Greater mean transduction efficiencies were found with both AAV2 vectors as compared to the Ad vector (p < or = 0.026). Ad and Ad-RGD vectors transduced only superficial chondrocytes of OA and unaffected cartilage. Uniform reporter gene expression from AAV2 and scAAV2 was detected in the tangential and transitional zones of OA cartilage, but not deeper zones. AAV2 and scAAV2 vectors achieved partial and full-thickness transduction of unaffected cartilage. In vivo work revealed that scAAV2 vector, but not Ad vector, transduced deeper zones of cartilage and menisci. This study demonstrates that AAV2 and scAAV2 are reliable vectors for use in cartilage in vitro and in vivo. (c) 2009 Orthopaedic Research Society.

In Vitro Analysis of Cartilage Regeneration Using a Collagen Type I Hydrogel (CaReS) in the Bovine Cartilage Punch Model.

PubMed

Horbert, Victoria; Xin, Long; Foehr, Peter; Brinkmann, Olaf; Bungartz, Matthias; Burgkart, Rainer H; Graeve, T; Kinne, Raimund W

2018-02-01

Objective Limitations of matrix-assisted autologous chondrocyte implantation to regenerate functional hyaline cartilage demand a better understanding of the underlying cellular/molecular processes. Thus, the regenerative capacity of a clinically approved hydrogel collagen type I implant was tested in a standardized bovine cartilage punch model. Methods Cartilage rings (outer diameter 6 mm; inner defect diameter 2 mm) were prepared from the bovine trochlear groove. Collagen implants (± bovine chondrocytes) were placed inside the cartilage rings and cultured up to 12 weeks. Cartilage-implant constructs were analyzed by histology (hematoxylin/eosin; safranin O), immunohistology (aggrecan, collagens 1 and 2), and for protein content, RNA expression, and implant push-out force. Results Cartilage-implant constructs revealed vital morphology, preserved matrix integrity throughout culture, progressive, but slight proteoglycan loss from the "host" cartilage or its surface and decreasing proteoglycan release into the culture supernatant. In contrast, collagen 2 and 1 content of cartilage and cartilage-implant interface was approximately constant over time. Cell-free and cell-loaded implants showed (1) cell migration onto/into the implant, (2) progressive deposition of aggrecan and constant levels of collagens 1 and 2, (3) progressively increased mRNA levels for aggrecan and collagen 2, and (4) significantly augmented push-out forces over time. Cell-loaded implants displayed a significantly earlier and more long-lasting deposition of aggrecan, as well as tendentially higher push-out forces. Conclusion Preserved tissue integrity and progressively increasing cartilage differentiation and push-out forces for up to 12 weeks of cultivation suggest initial cartilage regeneration and lateral bonding of the implant in this in vitro model for cartilage replacement materials.

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.

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.

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.

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.

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.

Superolateral Hoffa's fat pad (SHFP) oedema and patellar cartilage volume loss: quantitative analysis using longitudinal data from the Foundation for the National Institute of Health (FNIH) Osteoarthritis Biomarkers Consortium.

PubMed

Haj-Mirzaian, Arya; Guermazi, Ali; Hafezi-Nejad, Nima; Sereni, Christopher; Hakky, Michael; Hunter, David J; Zikria, Bashir; Roemer, Frank W; Demehri, Shadpour

2018-04-12

To determine the association of superolateral Hoffa's fat pad (SHFP) oedema and patellofemoral joint structural damage in participants of Foundation for the National Institute of Health Osteoarthritis Biomarkers Consortium study. Baseline and 24-month MRIs of 600 subjects were assessed. The presence of SHFP oedema (using 0-3 grading scale) and patellar morphology metrics were determined using baseline MRI. Quantitative patellar cartilage volume and semi-quantitative MRI osteoarthritis knee score (MOAKS) variables were extracted. The associations between SHFP oedema and patellar cartilage damage, bone marrow lesion (BML), osteophyte and morphology were evaluated in cross-sectional model. In longitudinal analysis, the associations between oedema and cartilage volume loss (defined using reliable change index) and MOAKS worsening were evaluated. In cross-sectional evaluations, the presence of SHFP oedema was associated with simultaneous lateral patellar cartilage/BML defects and inferior-medial patellar osteophyte size. A significant positive correlation between the degree of patella alta and SHFP oedema was detected (r = 0.259, p < 0.001). The presence of oedema was associated with 24-month cartilage volume loss (odds ratio (OR) 2.11, 95% confidence interval 1.46-3.06) and medial patellar BML size (OR 1.92 (1.15-3.21)) and number (OR 2.50 (1.29-4.88)) worsening. The optimal cut-off value for the grade of baseline SHFP oedema regarding both presence and worsening of patellar structural damage was ≥ 1 (presence of any SHFP hyperintensity). The presence of SHFP oedema could be considered as a predictor of future patellar cartilage loss and BML worsening, and an indicator of simultaneous cartilage, BML and osteophyte defects. • SHFP oedema was associated with simultaneous lateral patellar OA-related structural damage. • SHFP oedema was associated with longitudinal patellar cartilage loss over 24 months. • SHFP oedema could be considered as indicator and predictor of patellar OA.

Research trends in biomimetic medical materials for tissue engineering: 3D bioprinting, surface modification, nano/micro-technology and clinical aspects in tissue engineering of cartilage and bone.

PubMed

Chen, Cen; Bang, Sumi; Cho, Younghak; Lee, Sahnghoon; Lee, Inseop; Zhang, ShengMin; Noh, Insup

2016-01-01

This review discusses about biomimetic medical materials for tissue engineering of bone and cartilage, after previous scientific commentary of the invitation-based, Korea-China joint symposium on biomimetic medical materials, which was held in Seoul, Korea, from October 22 to 26, 2015. The contents of this review were evolved from the presentations of that symposium. Four topics of biomimetic medical materials were discussed from different research groups here: 1) 3D bioprinting medical materials, 2) nano/micro-technology, 3) surface modification of biomaterials for their interactions with cells and 4) clinical aspects of biomaterials for cartilage focusing on cells, scaffolds and cytokines.

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. Current scaffolds often focus on providing sufficient mechanical support or bio-mimetic structure to promote cartilage repair. Thus, silk has been adopted and investigated broadly. However, inflammation is one of the most important factors in OA. But few scaffolds for cartilage repair reported anti-inflammation property. Meanwhile, chondroitin sulfate (CS) is a glycosaminoglycan present in the natural cartilage ECM, and has exhibited a number of useful biological properties including anti-inflammatory activity. Thus, we designed this silk-CS scaffold and proved that this scaffold exhibited good anti-inflammatory effects both in vitro and in vivo, promoted the repair of articular cartilage defect in animal model. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Risk Factors and Predictors of Significant Chondral Surface Change From Primary to Revision Anterior Cruciate Ligament Reconstruction: A MOON and MARS Cohort Study.

PubMed

Magnussen, Robert A; Borchers, James R; Pedroza, Angela D; Huston, Laura J; Haas, Amanda K; Spindler, Kurt P; Wright, Rick W; Kaeding, Christopher C; Allen, Christina R; Anderson, Allen F; Cooper, Daniel E; DeBerardino, Thomas M; Dunn, Warren R; Lantz, Brett A; Mann, Barton; Stuart, Michael J; Albright, John P; Amendola, Annunziato; Andrish, Jack T; Annunziata, Christopher C; Arciero, Robert A; Bach, Bernard R; Baker, Champ L; Bartolozzi, Arthur R; Baumgarten, Keith M; Bechler, Jeffery R; Berg, Jeffrey H; Bernas, Geoffrey A; Brockmeier, Stephen F; Brophy, Robert H; Bush-Joseph, Charles A; Butler, J Brad; Campbell, John D; Carey, James L; Carpenter, James E; Cole, Brian J; Cooper, Jonathan M; Cox, Charles L; Creighton, R Alexander; Dahm, Diane L; David, Tal S; Flanigan, David C; Frederick, Robert W; Ganley, Theodore J; Garofoli, Elizabeth A; Gatt, Charles J; Gecha, Steven R; Giffin, James Robert; Hame, Sharon L; Hannafin, Jo A; Harner, Christopher D; Harris, Norman Lindsay; Hechtman, Keith S; Hershman, Elliott B; Hoellrich, Rudolf G; Hosea, Timothy M; Johnson, David C; Johnson, Timothy S; Jones, Morgan H; Kamath, Ganesh V; Klootwyk, Thomas E; Levy, Bruce A; Ma, C Benjamin; Maiers, G Peter; Marx, Robert G; Matava, Matthew J; Mathien, Gregory M; McAllister, David R; McCarty, Eric C; McCormack, Robert G; Miller, Bruce S; Nissen, Carl W; O'Neill, Daniel F; Owens, Brett D; Parker, Richard D; Purnell, Mark L; Ramappa, Arun J; Rauh, Michael A; Rettig, Arthur C; Sekiya, Jon K; Shea, Kevin G; Sherman, Orrin H; Slauterbeck, James R; Smith, Matthew V; Spang, Jeffrey T; Svoboda, Steven J; Taft, Timothy N; Tenuta, Joachim J; Tingstad, Edwin M; Vidal, Armando F; Viskontas, Darius G; White, Richard A; Williams, James S; Wolcott, Michelle L; Wolf, Brian R; York, James J

2018-03-01

Articular cartilage health is an important issue following anterior cruciate ligament (ACL) injury and primary ACL reconstruction. Factors present at the time of primary ACL reconstruction may influence the subsequent progression of articular cartilage damage. Larger meniscus resection at primary ACL reconstruction, increased patient age, and increased body mass index (BMI) are associated with increased odds of worsened articular cartilage damage at the time of revision ACL reconstruction. Case-control study; Level of evidence, 3. Subjects who had primary and revision data in the databases of the Multicenter Orthopaedics Outcomes Network (MOON) and Multicenter ACL Revision Study (MARS) were included. Reviewed data included chondral surface status at the time of primary and revision surgery, meniscus status at the time of primary reconstruction, primary reconstruction graft type, time from primary to revision ACL surgery, as well as demographics and Marx activity score at the time of revision. Significant progression of articular cartilage damage was defined in each compartment according to progression on the modified Outerbridge scale (increase ≥1 grade) or >25% enlargement in any area of damage. Logistic regression identified predictors of significant chondral surface change in each compartment from primary to revision surgery. A total of 134 patients were included, with a median age of 19.5 years at revision surgery. Progression of articular cartilage damage was noted in 34 patients (25.4%) in the lateral compartment, 32 (23.9%) in the medial compartment, and 31 (23.1%) in the patellofemoral compartment. For the lateral compartment, patients who had >33% of the lateral meniscus excised at primary reconstruction had 16.9-times greater odds of progression of articular cartilage injury than those with an intact lateral meniscus ( P < .001). For the medial compartment, patients who had <33% of the medial meniscus excised at the time of the primary reconstruction had 4.8-times greater odds of progression of articular cartilage injury than those with an intact medial meniscus ( P = .02). Odds of significant chondral surface change increased by 5% in the lateral compartment and 6% in the medial compartment for each increased year of age ( P ≤ .02). For the patellofemoral compartment, the use of allograft in primary reconstruction was associated with a 15-fold increased odds of progression of articular cartilage damage relative to a patellar tendon autograft ( P < .001). Each 1-unit increase in BMI at the time of revision surgery was associated with a 10% increase in the odds of progression of articular cartilage damage ( P = .046) in the patellofemoral compartment. Excision of the medial and lateral meniscus at primary ACL reconstruction increases the odds of articular cartilage damage in the corresponding compartment at the time of revision ACL reconstruction. Increased age is a risk factor for deterioration of articular cartilage in both tibiofemoral compartments, while increased BMI and the use of allograft for primary ACL reconstruction are associated with an increased risk of progression in the patellofemoral compartment.

Recent advances in hydrogels for cartilage tissue engineering.

PubMed

Vega, S L; Kwon, M Y; Burdick, J A

2017-01-30

Articular cartilage is a load-bearing tissue that lines the surface of bones in diarthrodial joints. Unfortunately, this avascular tissue has a limited capacity for intrinsic repair. Treatment options for articular cartilage defects include microfracture and arthroplasty; however, these strategies fail to generate tissue that adequately restores damaged cartilage. Limitations of current treatments for cartilage defects have prompted the field of cartilage tissue engineering, which seeks to integrate engineering and biological principles to promote the growth of new cartilage to replace damaged tissue. To date, a wide range of scaffolds and cell sources have emerged with a focus on recapitulating the microenvironments present during development or in adult tissue, in order to induce the formation of cartilaginous constructs with biochemical and mechanical properties of native tissue. Hydrogels have emerged as a promising scaffold due to the wide range of possible properties and the ability to entrap cells within the material. Towards improving cartilage repair, hydrogel design has advanced in recent years to improve their utility. Some of these advances include the development of improved network crosslinking (e.g. double-networks), new techniques to process hydrogels (e.g. 3D printing) and better incorporation of biological signals (e.g. controlled release). This review summarises these innovative approaches to engineer hydrogels towards cartilage repair, with an eye towards eventual clinical translation.

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 results in immediate loss of biomechanical function. In conjunction with delayed superficial sGAG loss, these changes may predispose the articular surface to further softening and tissue damage, thus increasing the risk of development of secondary osteoarthritis.« less

A Model to Study Articular Cartilage Mechanical and Biological Responses to Sliding Loads.

PubMed

Schätti, Oliver R; Gallo, Luigi M; Torzilli, Peter A

2016-08-01

In physiological conditions, joint function involves continuously moving contact areas over the tissue surface. Such moving contacts play an important role for the durability of the tissue. It is known that in pathological joints these motion paths and contact mechanics change. Nevertheless, limited information exists on the impact of such physiological and pathophysiological dynamic loads on cartilage mechanics and its subsequent biological response. We designed and validated a mechanical device capable of applying simultaneous compression and sliding forces onto cartilage explants to simulate moving joint contact. Tests with varying axial loads (1-4 kg) and sliding speeds (1-20 mm/s) were performed on mature viable bovine femoral condyles to investigate cartilage mechanobiological responses. High loads and slow sliding speeds resulted in highest cartilage deformations. Contact stress and effective cartilage moduli increased with increasing load and increasing speed. In a pilot study, changes in gene expression of extracellular matrix proteins were correlated with strain, contact stress and dynamic effective modulus. This study describes a mechanical test system to study the cartilage response to reciprocating sliding motion and will be helpful in identifying mechanical and biological mechanisms leading to the initiation and development of cartilage degeneration.

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.

The effects of monosodium urate monohydrate crystals on chondrocyte viability and function: implications for development of cartilage damage in gout.

PubMed

Chhana, Ashika; Callon, Karen E; Pool, Bregina; Naot, Dorit; Gamble, Gregory D; Dray, Michael; Pitto, Rocco; Bentley, Jarome; McQueen, Fiona M; Cornish, Jillian; Dalbeth, Nicola

2013-12-01

Cartilage damage is frequently observed in advanced destructive gout. The aim of our study was to investigate the effects of monosodium urate monohydrate (MSU) crystals on chondrocyte viability and function. The alamarBlue assay and flow cytometry were used to assess the viability of primary human chondrocytes and cartilage explants following culture with MSU crystals. The number of dead chondrocytes in cartilage explants cultured with MSU crystals was quantified. Real-time PCR was used to determine changes in the relative mRNA expression levels of chondrocytic genes. The histological appearance of cartilage in joints affected by gout was also examined. MSU crystals rapidly reduced primary human chondrocyte and cartilage explant viability in a dose-dependent manner (p < 0.01 for both). Cartilage explants cultured with MSU crystals had a greater percentage of dead chondrocytes at the articular surface compared to untreated cartilage (p = 0.004). Relative mRNA expression of type II collagen and the cartilage matrix proteins aggrecan and versican was decreased in chondrocytes following culture with MSU crystals (p < 0.05 for all). However, expression of the degradative enzymes ADAMTS4 and ADAMTS5 was increased (p < 0.05 for both). In joints affected by gout, normal cartilage architecture was lost, with empty chondrocyte lacunae observed. MSU crystals have profound inhibitory effects on chondrocyte viability and function. Interactions between MSU crystals and chondrocytes may contribute to cartilage damage in gout through reduction of chondrocyte viability and promotion of a catabolic state.

A modular approach to creating large engineered cartilage surfaces.

PubMed

Ford, Audrey C; Chui, Wan Fung; Zeng, Anne Y; Nandy, Aditya; Liebenberg, Ellen; Carraro, Carlo; Kazakia, Galateia; Alliston, Tamara; O'Connell, Grace D

2018-01-23

Native articular cartilage has limited capacity to repair itself from focal defects or osteoarthritis. Tissue engineering has provided a promising biological treatment strategy that is currently being evaluated in clinical trials. However, current approaches in translating these techniques to developing large engineered tissues remains a significant challenge. In this study, we present a method for developing large-scale engineered cartilage surfaces through modular fabrication. Modular Engineered Tissue Surfaces (METS) uses the well-known, but largely under-utilized self-adhesion properties of de novo tissue to create large scaffolds with nutrient channels. Compressive mechanical properties were evaluated throughout METS specimens, and the tensile mechanical strength of the bonds between attached constructs was evaluated over time. Raman spectroscopy, biochemical assays, and histology were performed to investigate matrix distribution. Results showed that by Day 14, stable connections had formed between the constructs in the METS samples. By Day 21, bonds were robust enough to form a rigid sheet and continued to increase in size and strength over time. Compressive mechanical properties and glycosaminoglycan (GAG) content of METS and individual constructs increased significantly over time. The METS technique builds on established tissue engineering accomplishments of developing constructs with GAG composition and compressive properties approaching native cartilage. This study demonstrated that modular fabrication is a viable technique for creating large-scale engineered cartilage, which can be broadly applied to many tissue engineering applications and construct geometries. Copyright © 2017 Elsevier Ltd. All rights reserved.

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.

Articulation of Native Cartilage Against Different Femoral Component Materials. Oxidized Zirconium Damages Cartilage Less Than Cobalt-Chrome.

PubMed

Vanlommel, Jan; De Corte, Ronny; Luyckx, Jean Philippe; Anderson, Melissa; Labey, Luc; Bellemans, Johan

2017-01-01

Oxidized zirconium (OxZr) is produced by thermally driven oxidization creating an oxidized surface with the properties of a ceramic at the top of the Zr metal substrate. OxZr is much harder and has a lower coefficient of friction than cobalt-chrome (CoCr), both leading to better wear characteristics. We evaluated and compared damage to the cartilage of porcine patella plugs, articulating against OxZr vs CoCr. Our hypothesis was that, owing to its better wear properties, OxZr would damage cartilage less than CoCr. If this is true, OxZr might be a better material for the femoral component during total knee arthroplasty if the patella is not resurfaced. Twenty-one plugs from porcine patellae were prepared and tested in a reciprocating pin-on-disk machine while lubricated with bovine serum and under a constant load. Three different configurations were tested: cartilage-cartilage as the control group, cartilage-OxZr, and cartilage-CoCr. Macroscopic appearance, cartilage thickness, and the modified Mankin score were evaluated after 400,000 wear cycles. The control group showed statistically significant less damage than plugs articulating against both other materials. Cartilage plugs articulating against OxZr were statistically significantly less damaged than those articulating against CoCr. Although replacing cartilage by an implant always leads to deterioration of the cartilage counterface, OxZr results in less damage than CoCr. The use of OxZr might thus be preferable to CoCr in case of total knee arthroplasty without patella resurfacing. Copyright © 2016 Elsevier Inc. All rights reserved.

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.

Correction of lobule-type microtia: I. The first stage of costal cartilage grafting.

PubMed

Yotsuyanagi, Takatoshi; Yamashita, Ken; Yamauchi, Makoto; Sugai, Asuka; Kayama, Musashi; Gonda, Ayako; Kita, Arisa

2014-01-01

Recently, auriculoplasty with costal cartilage grafting has been successfully used for correcting microtia and creating a clearly refined contour and a natural appearance of the ear. However, several important problems remain unsolved in these techniques. The authors describe an improved technique for harvesting costal cartilage with minimal morbidity and a new procedure for fabricating a cartilage frame that ensures a refined shape and rigid structure of the constructed ear. Costal cartilage is harvested directly with a chisel. This technique enables some of the cartilage at the chest wall to remain intact. The base frame is fabricated by two cartilage blocks partly overlapped on the area of the antihelix. The thickness in the overlapping area emphasizes the contour between the antihelix and the helical crus. To prevent absorption of the cartilage, helical and antihelical parts are created using the outer rigid layer of the harvested cartilage and are covered as much as possible by perichondrium. A total of 137 ears in 121 patients were corrected with the authors' technique and followed up for at least 3 years. Almost all of the patients could walk within 2 days after the operation. The structure and contour of the constructed ear were well maintained. Attention should be given not only to successful outcomes of construction of the ear but also to minimal morbidity for the patients. Our technique made it possible to construct a cosmetically refined ear that could be maintained for a long period and minimize the pain and deformity of the donor's chest.

Generation of scaffoldless hyaline cartilaginous tissue from human iPSCs.

PubMed

Yamashita, Akihiro; Morioka, Miho; Yahara, Yasuhito; Okada, Minoru; Kobayashi, Tomohito; Kuriyama, Shinichi; Matsuda, Shuichi; Tsumaki, Noriyuki

2015-03-10

Defects in articular cartilage ultimately result in loss of joint function. Repairing cartilage defects requires cell sources. We developed an approach to generate scaffoldless hyaline cartilage from human induced pluripotent stem cells (hiPSCs). We initially generated an hiPSC line that specifically expressed GFP in cartilage when teratoma was formed. We optimized the culture conditions and found BMP2, transforming growth factor β1 (TGF-β1), and GDF5 critical for GFP expression and thus chondrogenic differentiation of the hiPSCs. The subsequent use of scaffoldless suspension culture contributed to purification, producing homogenous cartilaginous particles. Subcutaneous transplantation of the hiPSC-derived particles generated hyaline cartilage that expressed type II collagen, but not type I collagen, in immunodeficiency mice. Transplantation of the particles into joint surface defects in immunodeficiency rats and immunosuppressed mini-pigs indicated that neocartilage survived and had potential for integration into native cartilage. The immunodeficiency mice and rats suffered from neither tumors nor ectopic tissue formation. The hiPSC-derived cartilaginous particles constitute a viable cell source for regenerating cartilage defects. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Generation of Scaffoldless Hyaline Cartilaginous Tissue from Human iPSCs

PubMed Central

Yamashita, Akihiro; Morioka, Miho; Yahara, Yasuhito; Okada, Minoru; Kobayashi, Tomohito; Kuriyama, Shinichi; Matsuda, Shuichi; Tsumaki, Noriyuki

2015-01-01

Summary Defects in articular cartilage ultimately result in loss of joint function. Repairing cartilage defects requires cell sources. We developed an approach to generate scaffoldless hyaline cartilage from human induced pluripotent stem cells (hiPSCs). We initially generated an hiPSC line that specifically expressed GFP in cartilage when teratoma was formed. We optimized the culture conditions and found BMP2, transforming growth factor β1 (TGF-β1), and GDF5 critical for GFP expression and thus chondrogenic differentiation of the hiPSCs. The subsequent use of scaffoldless suspension culture contributed to purification, producing homogenous cartilaginous particles. Subcutaneous transplantation of the hiPSC-derived particles generated hyaline cartilage that expressed type II collagen, but not type I collagen, in immunodeficiency mice. Transplantation of the particles into joint surface defects in immunodeficiency rats and immunosuppressed mini-pigs indicated that neocartilage survived and had potential for integration into native cartilage. The immunodeficiency mice and rats suffered from neither tumors nor ectopic tissue formation. The hiPSC-derived cartilaginous particles constitute a viable cell source for regenerating cartilage defects. PMID:25733017

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 μCT assessments. Copyright © 2017 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Cartilage grafting in nasal reconstruction.

PubMed

Immerman, Sara; White, W Matthew; Constantinides, Minas

2011-02-01

Nasal reconstruction after resection for cutaneous malignancies poses a unique challenge to facial plastic surgeons. The nose, a unique 3-D structure, not only must remain functional but also be aesthetically pleasing to patients. A complete understanding of all the layers of the nose and knowledge of available cartilage grafting material is necessary. Autogenous material, namely septal, auricular, and costal cartilage, is the most favored material in a free cartilage graft or a composite cartilage graft. All types of material have advantages and disadvantages that should guide the most appropriate selection to maximize the functional and cosmetic outcomes for patients. Copyright © 2011 Elsevier Inc. All rights reserved.

Characterisation of lubricin in synovial fluid from horses with osteoarthritis.

PubMed

Svala, E; Jin, C; Rüetschi, U; Ekman, S; Lindahl, A; Karlsson, N G; Skiöldebrand, E

2017-01-01

The glycoprotein lubricin contributes to the boundary lubrication of the articular cartilage surface. The early events of osteoarthritis involve the superficial layer where lubricin is synthesised. To characterise the glycosylation profile of lubricin in synovial fluid from horses with osteoarthritis and study secretion and degradation of lubricin in an in vitro inflammation cartilage model. In vitro study. Synovial fluid samples collected from horses with joints with normal articular cartilage and structural osteoarthritic lesions; with and without osteochondral fragments, were analysed for the lubricin glycosylation profiles. Articular cartilage explants were stimulated with or without interleukin-1β for 25 days. Media samples collected at 3-day intervals were analysed by quantitative proteomics, western blot and enzyme-linked immunosorbent assay. O-glycosylation profiles in synovial fluid revealed both Core 1 and 2 O-glycans, with Core 1 O-glycans predominating. Synovial fluid from normal joints (49.5 ± 1.9%) contained significantly lower amounts of monosialylated Core 1 O-glycans compared with joints with osteoarthritis (53.8 ± 7.8%, P = 0.03) or joints with osteochondral fragments (57.3 ± 8.8%, P = 0.001). Additionally, synovial fluid from normal joints (26.7 ± 6.7%) showed higher amounts of disialylated Core 1 O-glycan than from joints with osteochondral fragments (21.2 ± 4.9%, P = 0.03). A C-terminal proteolytic cleavage site in lubricin was found in synovial fluid from normal and osteochondral fragment joints and in media from interleukin-1β stimulated and unstimulated articular cartilage explants. This is the first demonstration of a change in the glycosylation profile of lubricin in synovial fluid from diseased equine joints compared with that from normal joints. We demonstrate an identical proteolytic cleavage site of lubricin both in vitro and in vivo. The reduced sialation of lubricin in synovial fluid from diseased joints may affect the boundary lubricating ability of the superficial layer of articular cartilage and could be one of the early events in the progression of osteoarthritis. © 2015 EVJ Ltd.

Characteristics and time-dependence of cut marks and blunt force fractures on costal cartilages: an experimental study.

PubMed

Spagnoli, Laura; Amadasi, Alberto; Frustaci, Michela; Mazzarelli, Debora; Porta, Davide; Cattaneo, Cristina

2016-03-01

The distinction between cut marks and blunt force injuries on costal cartilages is a crucial issue in the forensic field. Moreover, a correct distinction may further be complicated by decomposition, so the need arises to investigate the distinctive features of lesions on cartilage and their changes over time. This study aimed to assess the stereomicroscopic features of cut marks (performed with six different knives) and blunt fractures (performed with a hammer and by means of manual bending) on 48 fragments of human costal cartilages. Moreover, in order to simulate decomposition, the cut and fractured surfaces were checked with stereomicroscopy and through casts after 1 and 2 days, 1 week, and 1, 2 and 4 months of drying in ambient air. In fresh samples, for single and unique cuts, striations were observed in between 44 and 88% of cases when non-serrated blades were used, and between 77 and 88% for serrated blades; in the case of "repeated" (back and forth movement) cuts, striations were detected in between 56 and 89% of cases for non-serrated blades, and between 66 and 100% for serrated blades. After only 1 week of decomposition the detection rates fell to percentages of between 28 and 39% for serrated blades and between 17 and 33% for non-serrated blades. Blunt force injuries showed non-specific characteristics, which, if properly assessed, may lead to a reliable distinction between different cut marks in fresh samples. The most evident alterations of the structure of the cartilage occurred in the first week of decomposition in ambient air. After one week of drying, the characteristics of cut marks were almost undetectable, thereby making it extremely challenging to distinguish between cut marks, blunt force fractures and taphonomic effects. The study represents a contribution to the correct assessment and distinction of cut marks and blunt force injuries on cartilages, providing a glimpse on the modifications such lesions may undergo with decomposition.

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.

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.

Microscopic and histochemical manifestations of hyaline cartilage dynamics.

PubMed

Malinin, G I; Malinin, T I

1999-01-01

Structure and function of hyaline cartilages has been the focus of many correlative studies for over a hundred years. Much of what is known regarding dynamics and function of cartilage constituents has been derived or inferred from biochemical and electron microscopic investigations. Here we show that in conjunction with ultrastructural, and high-magnification transmission light and polarization microscopy, the well-developed histochemical methods are indispensable for the analysis of cartilage dynamics. Microscopically demonstrable aspects of cartilage dynamics include, but are not limited to, formation of the intracellular liquid crystals, phase transitions of the extracellular matrix and tubular connections between chondrocytes. The role of the interchondrocytic liquid crystals is considered in terms of the tensegrity hypothesis and non-apoptotic cell death. Phase transitions of the extracellular matrix are discussed in terms of self-alignment of chondrons, matrix guidance pathways and cartilage growth in the absence of mitosis. The possible role of nonenzymatic glycation reactions in cartilage dynamics is also reviewed.

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

Advancing osteochondral tissue engineering: bone morphogenetic protein, transforming growth factor, and fibroblast growth factor signaling drive ordered differentiation of periosteal cells resulting in stable cartilage and bone formation in vivo.

PubMed

Mendes, L F; Katagiri, H; Tam, W L; Chai, Y C; Geris, L; Roberts, S J; Luyten, F P

2018-02-21

Chondrogenic mesenchymal stem cells (MSCs) have not yet been used to address the clinical demands of large osteochondral joint surface defects. In this study, self-assembling tissue intermediates (TIs) derived from human periosteum-derived stem/progenitor cells (hPDCs) were generated and validated for stable cartilage formation in vivo using two different animal models. hPDCs were aggregated and cultured in the presence of a novel growth factor (GF) cocktail comprising of transforming growth factor (TGF)-β1, bone morphogenetic protein (BMP)2, growth differentiation factor (GDF)5, BMP6, and fibroblast growth factor (FGF)2. Quantitative polymerase chain reaction (PCR) and immunohistochemistry were used to study in vitro differentiation. Aggregates were then implanted ectopically in nude mice and orthotopically in critical-size osteochondral defects in nude rats and evaluated by microcomputed tomography (µCT) and immunohistochemistry. Gene expression analysis after 28 days of in vitro culture revealed the expression of early and late chondrogenic markers and a significant upregulation of NOGGIN as compared to human articular chondrocytes (hACs). Histological examination revealed a bilayered structure comprising of chondrocytes at different stages of maturity. Ectopically, TIs generated both bone and mineralized cartilage at 8 weeks after implantation. Osteochondral defects treated with TIs displayed glycosaminoglycan (GAG) production, type-II collagen, and lubricin expression. Immunostaining for human nuclei protein suggested that hPDCs contributed to both subchondral bone and articular cartilage repair. Our data indicate that in vitro derived osteochondral-like tissues can be generated from hPDCs, which are capable of producing bone and cartilage ectopically and behave orthotopically as osteochondral units.

Cartilage.

ERIC Educational Resources Information Center

Caplan, Arnold I.

1984-01-01

Cartilage is a fundamental biological material that helps to shape the body and then helps to support it. Its fundamental properties of strength and resilience are explained in terms of the tissue's molecular structure. (JN)

Development of Scaffold-Free Elastic Cartilaginous Constructs with Structural Similarities to Auricular Cartilage

PubMed Central

Giardini-Rosa, Renata; Joazeiro, Paulo P.; Thomas, Kathryn; Collavino, Kristina; Weber, Joanna

2014-01-01

External ear reconstruction with autologous cartilage still remains one of the most difficult problems in the fields of plastic and reconstructive surgery. As the absence of tissue vascularization limits the ability to stimulate new tissue growth, relatively few surgical approaches are currently available (alloplastic implants or sculpted autologous cartilage grafts) to repair or reconstruct the auricle (or pinna) as a result of traumatic loss or congenital absence (e.g., microtia). Alternatively, tissue engineering can offer the potential to grow autogenous cartilage suitable for implantation. While tissue-engineered auricle cartilage constructs can be created, a substantial number of cells are required to generate sufficient quantities of tissue for reconstruction. Similarly, as routine cell expansion can elicit negative effects on chondrocyte function, we have developed an approach to generate large-sized engineered auricle constructs (≥3 cm2) directly from a small population of donor cells (20,000–40,000 cells/construct). Using rabbit donor cells, the developed bioreactor-cultivated constructs adopted structural-like characteristics similar to native auricular cartilage, including the development of distinct cartilaginous and perichondrium-like regions. Both alterations in media composition and seeding density had profound effects on the formation of engineered elastic tissue constructs in terms of cellularity, extracellular matrix accumulation, and tissue structure. Higher seeding densities and media containing sodium bicarbonate produced tissue constructs that were closer to the native tissue in terms of structure and composition. Future studies will be aimed at improving the accumulation of specific tissue constituents and determining the clinical effectiveness of this approach using a reconstructive animal model. PMID:24124666

Development of scaffold-free elastic cartilaginous constructs with structural similarities to auricular cartilage.

PubMed

Giardini-Rosa, Renata; Joazeiro, Paulo P; Thomas, Kathryn; Collavino, Kristina; Weber, Joanna; Waldman, Stephen D

2014-03-01

External ear reconstruction with autologous cartilage still remains one of the most difficult problems in the fields of plastic and reconstructive surgery. As the absence of tissue vascularization limits the ability to stimulate new tissue growth, relatively few surgical approaches are currently available (alloplastic implants or sculpted autologous cartilage grafts) to repair or reconstruct the auricle (or pinna) as a result of traumatic loss or congenital absence (e.g., microtia). Alternatively, tissue engineering can offer the potential to grow autogenous cartilage suitable for implantation. While tissue-engineered auricle cartilage constructs can be created, a substantial number of cells are required to generate sufficient quantities of tissue for reconstruction. Similarly, as routine cell expansion can elicit negative effects on chondrocyte function, we have developed an approach to generate large-sized engineered auricle constructs (≥3 cm(2)) directly from a small population of donor cells (20,000-40,000 cells/construct). Using rabbit donor cells, the developed bioreactor-cultivated constructs adopted structural-like characteristics similar to native auricular cartilage, including the development of distinct cartilaginous and perichondrium-like regions. Both alterations in media composition and seeding density had profound effects on the formation of engineered elastic tissue constructs in terms of cellularity, extracellular matrix accumulation, and tissue structure. Higher seeding densities and media containing sodium bicarbonate produced tissue constructs that were closer to the native tissue in terms of structure and composition. Future studies will be aimed at improving the accumulation of specific tissue constituents and determining the clinical effectiveness of this approach using a reconstructive animal model.

The cranial cartilages of teleosts and their classification.

PubMed Central

Benjamin, M

1990-01-01

The structure and distribution of cartilages has been studied in 45 species from 24 families. The resulting data have been used as a basis for establishing a new classification. A cartilage is regarded as 'cell-rich' if its cells or their lacunae occupy more than half of the tissue volume. Five classes of cell-rich cartilage are recognised (a) hyaline-cell cartilage (common in the lips of bottom-dwelling cyprinids) and its subtypes fibro/hyaline-cell cartilage, elastic/hyaline-cell cartilage and lipo/hyaline-cell cartilage, (b) Schaffer's Zellknorpel, typified by the cartilage in the gill filaments of most teleosts examined, (c) elastic/cell-rich cartilage, such as that which supports the barbels and oral valves of catfish, e.g. Corydoras metae, (d) fibro/cell-rich cartilage, as in the submaxillary meniscus of Sphaerichthys osphromenoides, (e) cell-rich hyaline and (f) matrix-rich hyaline cartilage--both of which are common in the neurocranium and gill arches of most teleosts. The range of cartilages seen, and the predominant cartilage type, is recorded for each species and a list is provided of the tissues that most typify different organs or regions of the head. As a preliminary pointer to developmental relationships between the cartilages, note was taken of gradual transitions between one cartilage and another. It is suggested that hyaline-cell cartilage occupies a key position in teleosts as the most labile of the supporting tissues and is highly characteristic of Cypriniformes. The cartilage that best resembles mammalian hyaline cartilage (matrix-rich hyaline cartilage) has a very conservative distribution in different skeletal elements and the least number of associations with other tissues. It is well represented in Siluriformes. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 8 Fig. 9 Fig. 10 Fig. 11 Fig. 12 Fig. 15 Fig. 16 Fig. 17 Fig. 18 Fig. 19 Fig. 20 Fig. 24 Fig. 25 Fig. 26 Fig. 27 PMID:2384333

Treatment of Osteochondral Defects in the Rabbit's Knee Joint by Implantation of Allogeneic Mesenchymal Stem Cells in Fibrin Clots

PubMed Central

Berninger, Markus T.; Wexel, Gabriele; Rummeny, Ernst J.; Imhoff, Andreas B.; Anton, Martina

2013-01-01

The treatment of osteochondral articular defects has been challenging physicians for many years. The better understanding of interactions of articular cartilage and subchondral bone in recent years led to increased attention to restoration of the entire osteochondral unit. In comparison to chondral lesions the regeneration of osteochondral defects is much more complex and a far greater surgical and therapeutic challenge. The damaged tissue does not only include the superficial cartilage layer but also the subchondral bone. For deep, osteochondral damage, as it occurs for example with osteochondrosis dissecans, the full thickness of the defect needs to be replaced to restore the joint surface 1. Eligible therapeutic procedures have to consider these two different tissues with their different intrinsic healing potential 2. In the last decades, several surgical treatment options have emerged and have already been clinically established 3-6. Autologous or allogeneic osteochondral transplants consist of articular cartilage and subchondral bone and allow the replacement of the entire osteochondral unit. The defects are filled with cylindrical osteochondral grafts that aim to provide a congruent hyaline cartilage covered surface 3,7,8. Disadvantages are the limited amount of available grafts, donor site morbidity (for autologous transplants) and the incongruence of the surface; thereby the application of this method is especially limited for large defects. New approaches in the field of tissue engineering opened up promising possibilities for regenerative osteochondral therapy. The implantation of autologous chondrocytes marked the first cell based biological approach for the treatment of full-thickness cartilage lesions and is now worldwide established with good clinical results even 10 to 20 years after implantation 9,10. However, to date, this technique is not suitable for the treatment of all types of lesions such as deep defects involving the subchondral bone 11. The sandwich-technique combines bone grafting with current approaches in Tissue Engineering 5,6. This combination seems to be able to overcome the limitations seen in osteochondral grafts alone. After autologous bone grafting to the subchondral defect area, a membrane seeded with autologous chondrocytes is sutured above and facilitates to match the topology of the graft with the injured site. Of course, the previous bone reconstruction needs additional surgical time and often even an additional surgery. Moreover, to date, long-term data is missing 12. Tissue Engineering without additional bone grafting aims to restore the complex structure and properties of native articular cartilage by chondrogenic and osteogenic potential of the transplanted cells. However, again, it is usually only the cartilage tissue that is more or less regenerated. Additional osteochondral damage needs a specific further treatment. In order to achieve a regeneration of the multilayered structure of osteochondral defects, three-dimensional tissue engineered products seeded with autologous/allogeneic cells might provide a good regeneration capacity 11. Beside autologous chondrocytes, mesenchymal stem cells (MSC) seem to be an attractive alternative for the development of a full-thickness cartilage tissue. In numerous preclinical in vitro and in vivo studies, mesenchymal stem cells have displayed excellent tissue regeneration potential 13,14. The important advantage of mesenchymal stem cells especially for the treatment of osteochondral defects is that they have the capacity to differentiate in osteocytes as well as chondrocytes. Therefore, they potentially allow a multilayered regeneration of the defect. In recent years, several scaffolds with osteochondral regenerative potential have therefore been developed and evaluated with promising preliminary results 1,15-18. Furthermore, fibrin glue as a cell carrier became one of the preferred techniques in experimental cartilage repair and has already successfully been used in several animal studies 19-21 and even first human trials 22. The following protocol will demonstrate an experimental technique for isolating mesenchymal stem cells from a rabbit's bone marrow, for subsequent proliferation in cell culture and for preparing a standardized in vitro-model for fibrin-cell-clots. Finally, a technique for the implantation of pre-established fibrin-cell-clots into artificial osteochondral defects of the rabbit's knee joint will be described. PMID:23728213

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

Xiphoid Process-Derived Chondrocytes: A Novel Cell Source for Elastic Cartilage Regeneration

PubMed Central

Nam, Seungwoo; Cho, Wheemoon; Cho, Hyunji; Lee, Jungsun

2014-01-01

Reconstruction of elastic cartilage requires a source of chondrocytes that display a reliable differentiation tendency. Predetermined tissue progenitor cells are ideal candidates for meeting this need; however, it is difficult to obtain donor elastic cartilage tissue because most elastic cartilage serves important functions or forms external structures, making these tissues indispensable. We found vestigial cartilage tissue in xiphoid processes and characterized it as hyaline cartilage in the proximal region and elastic cartilage in the distal region. Xiphoid process-derived chondrocytes (XCs) showed superb in vitro expansion ability based on colony-forming unit fibroblast assays, cell yield, and cumulative cell growth. On induction of differentiation into mesenchymal lineages, XCs showed a strong tendency toward chondrogenic differentiation. An examination of the tissue-specific regeneration capacity of XCs in a subcutaneous-transplantation model and autologous chondrocyte implantation model confirmed reliable regeneration of elastic cartilage regardless of the implantation environment. On the basis of these observations, we conclude that xiphoid process cartilage, the only elastic cartilage tissue source that can be obtained without destroying external shape or function, is a source of elastic chondrocytes that show superb in vitro expansion and reliable differentiation capacity. These findings indicate that XCs could be a valuable cell source for reconstruction of elastic cartilage. PMID:25205841

Processed xenogenic cartilage as innovative biomatrix for cartilage tissue engineering: effects on chondrocyte differentiation and function.

PubMed

Schwarz, Silke; Elsaesser, Alexander F; Koerber, Ludwig; Goldberg-Bockhorn, Eva; Seitz, Andreas M; Bermueller, Christian; Dürselen, Lutz; Ignatius, Anita; Breiter, Roman; Rotter, Nicole

2015-12-01

One key point in the development of new bioimplant matrices for the reconstruction and replacement of cartilage defects is to provide an adequate microenvironment to ensure chondrocyte migration and de novo synthesis of cartilage-specific extracellular matrix (ECM). A recently developed decellularization and sterilization process maintains the three-dimensional (3D) collagen structure of native septal cartilage while increasing matrix porosity, which is considered to be crucial for cartilage tissue engineering. Human primary nasal septal chondrocytes were amplified in monolayer culture and 3D-cultured on processed porcine nasal septal cartilage scaffolds. The influence of chondrogenic growth factors on neosynthesis of ECM proteins was examined at the protein and gene expression levels. Seeding experiments demonstrated that processed xenogenic cartilage matrices provide excellent environmental properties for human nasal septal chondrocytes with respect to cell adhesion, migration into the matrix and neosynthesis of cartilage-specific ECM proteins, such as collagen type II and aggrecan. Matrix biomechanical stability indicated that the constructs retrieve full stability and function during 3D culture for up to 42 days, proportional to collagen type II and GAG production. Thus, processed xenogenic cartilage offers a suitable environment for human nasal chondrocytes and has promising potential for cartilage tissue engineering in the head and neck region. Copyright © 2012 John Wiley & Sons, Ltd.

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.

Bone cysts after osteochondral allograft repair of cartilage defects in goats suggest abnormal interaction between subchondral bone and overlying synovial joint tissues.

PubMed

Pallante-Kichura, Andrea L; Cory, Esther; Bugbee, William D; Sah, Robert L

2013-11-01

The efficacy of osteochondral allografts (OCAs) may be affected by osseous support of the articular cartilage, and thus affected by bone healing and remodeling in the OCA and surrounding host. Bone cysts, and their communication pathways, may be present in various locations after OCA insertion and reflect distinct pathogenic mechanisms. Previously, we analyzed the effect of OCA storage (FRESH, 4°C/14d, 4°C/28d, FROZEN) on cartilage quality in fifteen adult goats after 12months in vivo. The objectives of this study were to further analyze OCAs and contralateral non-operated (Non-Op) CONTROLS from the medial femoral condyle to (1) determine the effect of OCA storage on local subchondral bone (ScB) and trabecular bone (TB) structure, (2) characterize the location and structure of bone cysts and channels, and (3) assess the relationship between cartilage and bone properties. (1) Overall bone structure after OCAs was altered compared to Non-Op, with OCA samples displaying bone cysts, ScB channels, and ScB roughening. ScB BV/TV in FROZEN OCAs was lower than Non-Op and other OCAs. TB BV/TV in FRESH, 4°C/14d, and 4°C/28d OCAs did not vary compared to Non-Op, but BS/TV was lower. (2) OCAs contained "basal" cysts, localized to deeper regions, some "subchondral" cysts, localized near the bone-cartilage interface, and some ScB channels. TB surrounding basal cysts exhibited higher BV/TV than Non-Op. (3) Basal cysts occurred (a) in isolation, (b) with subchondral cysts and ScB channels, (c) with ScB channels, or (d) with subchondral cysts, ScB channels, and ScB erosion. Deterioration of cartilage gross morphology was strongly associated with abnormal μCT bone structure. Evidence of cartilage-bone communication following OCA repair may favor fluid intrusion as a mechanism for subchondral cyst formation, while bone resorption at the graft-host interface without affecting overall bone and cartilage structure may favor bony contusion mechanism for basal cyst formation. These findings suggest that cysts occurring after OCAs may result from aberrant mechanobiology due to (1) altered compartmentalization that normally separates overlying cartilage and subchondral bone, either from distinct ScB channels or more general ScB plate deterioration, and (2) bone resorption at the basal graft-host interface. © 2013.

Bone Cysts After Osteochondral Allograft Repair of Cartilage Defects in Goats Suggest Abnormal Interaction Between Subchondral Bone and Overlying Synovial Joint Tissues

PubMed Central

Pallante-Kichura, Andrea L.; Cory, Esther; Bugbee, William D.; Sah, Robert L.

2013-01-01

The efficacy of osteochondral allografts (OCA) may be affected by osseous support of the articular cartilage, and thus affected by bone healing and remodeling in the OCA and surrounding host. Bone cysts, and their communication pathways, may be present in various locations after OCA insertion and reflect distinct pathogenic mechanisms. Previously, we analyzed the effect of OCA storage (FRESH, 4°C/14d, 4°C/28d, FROZEN) on cartilage quality in fifteen adult goats after 12 months in vivo. The objectives of this study were to further analyze OCA and contralateral non-operated (Non-Op) CONTROLS from the medial femoral condyle to (1) determine the effect of OCA storage on local subchondral (ScB) and trabecular (TB) bone structure, (2) characterize the location and structure of bone cysts and channels, and (3) assess the relationship between cartilage and bone properties. (1) Overall bone structure after OCA was altered compared to Non-Op, with OCA samples displaying bone cysts, ScB channels, and ScB roughening. ScB BV/TV in FROZEN OCA was lower than Non-Op and other OCA. TB BV/TV in FRESH, 4°C/14d, and 4°C/28d OCA did not vary compared to Non-Op, but BS/TV was lower. (2) OCA contained “basal” cysts, localized to deeper regions, some “subchondral” cysts, localized near the bone-cartilage interface, and some ScB channels. TB surrounding basal cysts exhibited higher BV/TV than Non-Op. (3) Basal cysts occurred (a) in isolation, (b) with subchondral cysts and ScB channels, (c) with ScB channels, or (d) with subchondral cysts, ScB channels, and ScB erosion. Deterioration of cartilage gross morphology was strongly associated with abnormal μCT bone structure. Evidence of cartilage-bone communication following OCA repair may favor fluid intrusion as a mechanism for subchondral cyst formation, while bone resorption at the graft-host interface without affecting overall bone and cartilage structure may favor bony contusion mechanism for basal cyst formation. These findings suggest that cysts occurring after OCA may result from aberrant mechanobiology due to (1) altered compartmentalization that normally separates overlying cartilage and subchondral bone, either from distinct ScB channels or more general ScB plate deterioration, and (2) bone resorption at the basal graft-host interface. PMID:23958821

Radiostereometric analysis of hemiarthroplasties of the hip--a highly precise method for measurements of cartilage wear.

PubMed

Figved, W; Dahl, J; Snorrason, F; Frihagen, F; Röhrl, S; Madsen, J E; Nordsletten, L

2012-01-01

Cartilage wear is a feature of osteoarthritis and rheumatoid arthritis. Precise measurements of wear have been difficult. Cartilage wear caused by an artificial articulating joint surface is a well-known feature of hemiarthroplasties. The aim of this study was to demonstrate that radiostereometric analysis (RSA) may be used for three-dimensional measurements of cartilage wear in hemiarthroplasties of the hip. We performed a phantom model study to assess the feasibility of a subsequent clinical trial. We showed that the motion of the prosthetic head relative to the pelvis was not influenced by the orientation of the prosthetic head. Twenty-two patients were randomised to treatment with a cemented or an uncemented hemiarthroplasty for an acute femoral neck fracture. Migration of the prosthetic head into the acetabulum was measured using RSA. A mean migration of the prosthetic head into the acetabulum of 0.62 mm was found at 3 months [95% confidence interval (CI): 0.27-0.97] and a further migration of -0.07 mm at 12 months (95% CI: -0.16-0.32). There were no differences between the groups in prosthetic migration or functional outcome. Between three and 12 months, there was no detectable cartilage wear during the first postoperative year. Whether the migration during the first 3 months represents a period of bedding in due to a harder opposite surface remains to be shown. RSA may be used for measurement of cartilage wear in hemiarthroplasties of the hip. This study demonstrates a highly precise method for measurements of cartilage wear. Copyright © 2011 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Combinatory approach for developing silk fibroin scaffolds for cartilage regeneration.

PubMed

Ribeiro, Viviana P; da Silva Morais, Alain; Maia, F Raquel; Canadas, Raphael F; Costa, João B; Oliveira, Ana L; Oliveira, Joaquim M; Reis, Rui L

2018-05-01

Several processing technologies and engineering strategies have been combined to create scaffolds with superior performance for efficient tissue regeneration. Cartilage tissue is a good example of that, presenting limited self-healing capacity together with a high elasticity and load-bearing properties. In this work, novel porous silk fibroin (SF) scaffolds derived from horseradish peroxidase (HRP)-mediated crosslinking of highly concentrated aqueous SF solution (16 wt%) in combination with salt-leaching and freeze-drying methodologies were developed for articular cartilage tissue engineering (TE) applications. The HRP-crosslinked SF scaffolds presented high porosity (89.3 ± 0.6%), wide pore distribution and high interconnectivity (95.9 ± 0.8%). Moreover, a large swelling capacity and favorable degradation rate were observed up to 30 days, maintaining the porous-like structure and β-sheet conformational integrity obtained with salt-leaching and freeze-drying processing. The in vitro studies supported human adipose-derived stem cells (hASCs) adhesion, proliferation, and high glycosaminoglycans (GAGs) synthesis under chondrogenic culture conditions. Furthermore, the chondrogenic differentiation of hASCs was assessed by the expression of chondrogenic-related markers (collagen type II, Sox-9 and Aggrecan) and deposition of cartilage-specific extracellular matrix for up to 28 days. The cartilage engineered constructs also presented structural integrity as their mechanical properties were improved after chondrogenic culturing. Subcutaneous implantation of the scaffolds in CD-1 mice demonstrated no necrosis or calcification, and deeply tissue ingrowth. Collectively, the structural properties and biological performance of these porous HRP-crosslinked SF scaffolds make them promising candidates for cartilage regeneration. In cartilage tissue engineering (TE), several processing technologies have been combined to create scaffolds for efficient tissue repair. In our study, we propose novel silk fibroin (SF) scaffolds derived from enzymatically crosslinked SF hydrogels processed by salt-leaching and freeze-drying technologies, for articular cartilage applications. Though these scaffolds, we were able to combine the elastic properties of hydrogel-based systems, with the stability, resilience and controlled porosity of scaffolds processed via salt-leaching and freeze-drying technologies. SF protein has been extensively explored for TE applications, as a result of its mechanical strength, elasticity, biocompatibility, and biodegradability. Thus, the structural, mechanical and biological performance of the proposed scaffolds potentiates their use as three-dimensional matrices for cartilage regeneration. Copyright © 2018 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Automatic segmentation of the bone and extraction of the bone cartilage interface from magnetic resonance images of the knee

NASA Astrophysics Data System (ADS)

Fripp, Jurgen; Crozier, Stuart; Warfield, Simon K.; Ourselin, Sébastien

2007-03-01

The accurate segmentation of the articular cartilages from magnetic resonance (MR) images of the knee is important for clinical studies and drug trials into conditions like osteoarthritis. Currently, segmentations are obtained using time-consuming manual or semi-automatic algorithms which have high inter- and intra-observer variabilities. This paper presents an important step towards obtaining automatic and accurate segmentations of the cartilages, namely an approach to automatically segment the bones and extract the bone-cartilage interfaces (BCI) in the knee. The segmentation is performed using three-dimensional active shape models, which are initialized using an affine registration to an atlas. The BCI are then extracted using image information and prior knowledge about the likelihood of each point belonging to the interface. The accuracy and robustness of the approach was experimentally validated using an MR database of fat suppressed spoiled gradient recall images. The (femur, tibia, patella) bone segmentation had a median Dice similarity coefficient of (0.96, 0.96, 0.89) and an average point-to-surface error of 0.16 mm on the BCI. The extracted BCI had a median surface overlap of 0.94 with the real interface, demonstrating its usefulness for subsequent cartilage segmentation or quantitative analysis.

Studies of cartilaginous tissue using Raman spectroscopy method

NASA Astrophysics Data System (ADS)

Timchenko, Pavel E.; Timchenko, Elena V.; Volova, Larisa T.; Dolgyshkin, Dmitry A.; Markova, Maria D.; Kylabyhova, A. Y.; Kornilin, Dmitriy V.

2016-10-01

The work presents the results of studies of samples of human articular surface of the knee joint, obtained by Raman spectroscopy implementedduring endoprosthesis replacement surgery . The main spectral characteristics of articular surface areas with varying degrees of cartilage damage were detected at 956 cm-1, 1066 cm-1 wavenumbers, corresponding to phosphate and carbonate, and at 1660 cm-1, 1271 cm-1 wavenumbers, corresponding to amide I and amide III. Criteria allowing to identify the degree of articular hyaline cartilage damage were introduced.

Improved quality of cartilage repair by bone marrow mesenchymal stem cells for treatment of an osteochondral defect in a cynomolgus macaque model

PubMed Central

Araki, Susumu; Imai, Shinji; Ishigaki, Hirohito; Mimura, Tomohiro; Nishizawa, Kazuya; Ueba, Hiroaki; Kumagai, Kousuke; Kubo, Mitsuhiko; Mori, Kanji; Ogasawara, Kazumasa; Matsusue, Yoshitaka

2015-01-01

Background and purpose Integration of repaired cartilage with surrounding native cartilage is a major challenge for successful tissue-engineering strategies of cartilage repair. We investigated whether incorporation of mesenchymal stem cells (MSCs) into the collagen scaffold improves integration and repair of cartilage defects in a cynomolgus macaque model. Methods Cynomolgus macaque bone marrow-derived MSCs were isolated and incorporated into type-I collagen gel. Full-thickness osteochondral defects (3 mm in diameter, 5 mm in depth) were created in the patellar groove of 36 knees of 18 macaques and were either left untreated (null group, n = 12), had collagen gel alone inserted (gel group, n = 12), or had collagen gel incorporating MSCs inserted (MSC group, n = 12). After 6, 12, and 24 weeks, the cartilage integration and tissue response were evaluated macroscopically and histologically (4 null, 4 gel, and 4 MSC knees at each time point). Results The gel group showed most cartilage-rich reparative tissue covering the defect, owing to formation of excessive cartilage extruding though the insufficient subchondral bone. Despite the fact that a lower amount of new cartilage was produced, the MSC group had better-quality cartilage with regular surface, seamless integration with neighboring naïve cartilage, and reconstruction of trabecular subchondral bone. Interpretation Even with intensive investigation, MSC-based cell therapy has not yet been established in experimental cartilage repair. Our model using cynomolgus macaques had optimized conditions, and the method using MSCs is superior to other experimental settings, allowing the possibility that the procedure might be introduced to future clinical practice. PMID:25175660

One-Step Cartilage Repair Technique as a Next Generation of Cell Therapy for Cartilage Defects: Biological Characteristics, Preclinical Application, Surgical Techniques, and Clinical Developments.

PubMed

Zhang, Chi; Cai, You-Zhi; Lin, Xiang-Jin

2016-07-01

To provide a comprehensive overview of the basic science rationale, surgical technique, and clinical outcomes of 1-step cartilage repair technique used as a treatment strategy for cartilage defects. A systematic review was performed in the main medical databases to evaluate the several studies concerning 1-step procedures for cartilage repair. The characteristics of cell-seed scaffolds, behavior of cells seeded into scaffolds, and surgical techniques were also discussed. Clinical outcomes and quality of repaired tissue were assessed using several standardized outcome assessment tools, magnetic resonance imaging scans, and biopsy histology. One-step cartilage repair could be divided into 2 types: chondrocyte-matrix complex (CMC) and autologous matrix-induced chondrogenesis (AMIC), both of which allow a simplified surgical approach. Studies with Level IV evidence have shown that 1-step cartilage repair techniques could significantly relieve symptoms and improve functional assessment (P < .05, compared with preoperative evaluation) at short-term follow-up. Furthermore, magnetic resonance imaging showed that 76% cases in all included case series showed at least 75% defect coverage in each lesion, and 3 studies clearly showed hyaline-like cartilage tissue in biopsy tissues by second-look arthroscopy. The 1-step cartilage repair technique, with its potential for effective, homogeneous distribution of chondrocytes and multipotent stem cells on the surface of the cartilage defect, is able to regenerate hyaline-like cartilage tissue, and it could be applied to cartilage repair by arthroscopy. Level IV, systematic review of Level II and IV studies. Copyright © 2016 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

A novel therapeutic strategy for cartilage diseases based on lipid nanoparticle-RNAi delivery system.

PubMed

Wang, Shaowei; Wei, Xiaochun; Sun, Xiaojuan; Chen, Chongwei; Zhou, Jingming; Zhang, Ge; Wu, Heng; Guo, Baosheng; Wei, Lei

2018-01-01

Cartilage degeneration affects millions of people but preventing its degeneration is a big challenge. Although RNA interference (RNAi) has been used in human trials via silencing specific genes, the cartilage RNAi has not been possible to date because the cartilage is an avascular and very dense tissue with very low permeability. The objective of this study was to develop and validate a novel lipid nanoparticle (LNP)-siRNA delivery system that can prevent cartilage degeneration by knocking down specific genes. LNP transfection efficiency was evaluated in vitro and ex vivo. Indian Hedgehog ( Ihh ) has been correlated with cartilage degeneration. The in vivo effects of LNP-Ihh siRNA complexes on cartilage degeneration were evaluated in a rat model of surgery-induced osteoarthritis (OA). In vitro, 100% of chondrocytes were transfected with siRNA in the LNP-siRNA group. In accordance with the cell culture results, red positive signals could be detected even in the deep layer of cartilage tissue cultures treated by LNP-beacon. In vivo data showed that LNP is specific for cartilage, since positive signals were detected by fluorescence molecular tomography and confocal microscopy in joint cartilage injected with LNP-beacon, but not on the surface of the synovium. In the rat model of OA, intraarticular injection of LNP-Ihh siRNA attenuated OA progression, and PCR results showed LNP-Ihh siRNA exerted a positive impact on anabolic metabolism and negative impact on catabolic metabolism. This study demonstrates that our LNP-RNAi delivery system has a significantly chondroprotective effect that attenuates cartilage degeneration and holds great promise as a powerful tool for treatment of cartilage diseases by knocking down specific genes.

A novel therapeutic strategy for cartilage diseases based on lipid nanoparticle-RNAi delivery system

PubMed Central

Wang, Shaowei; Wei, Xiaochun; Sun, Xiaojuan; Chen, Chongwei; Zhou, Jingming; Zhang, Ge; Wu, Heng; Guo, Baosheng

2018-01-01

Background Cartilage degeneration affects millions of people but preventing its degeneration is a big challenge. Although RNA interference (RNAi) has been used in human trials via silencing specific genes, the cartilage RNAi has not been possible to date because the cartilage is an avascular and very dense tissue with very low permeability. Purpose The objective of this study was to develop and validate a novel lipid nanoparticle (LNP)-siRNA delivery system that can prevent cartilage degeneration by knocking down specific genes. Methods LNP transfection efficiency was evaluated in vitro and ex vivo. Indian Hedgehog (Ihh) has been correlated with cartilage degeneration. The in vivo effects of LNP-Ihh siRNA complexes on cartilage degeneration were evaluated in a rat model of surgery-induced osteoarthritis (OA). Results In vitro, 100% of chondrocytes were transfected with siRNA in the LNP-siRNA group. In accordance with the cell culture results, red positive signals could be detected even in the deep layer of cartilage tissue cultures treated by LNP-beacon. In vivo data showed that LNP is specific for cartilage, since positive signals were detected by fluorescence molecular tomography and confocal microscopy in joint cartilage injected with LNP-beacon, but not on the surface of the synovium. In the rat model of OA, intraarticular injection of LNP-Ihh siRNA attenuated OA progression, and PCR results showed LNP-Ihh siRNA exerted a positive impact on anabolic metabolism and negative impact on catabolic metabolism. Conclusion This study demonstrates that our LNP-RNAi delivery system has a significantly chondroprotective effect that attenuates cartilage degeneration and holds great promise as a powerful tool for treatment of cartilage diseases by knocking down specific genes. PMID:29440889

An Immunohistochemical Study of Matrix Proteins in the Craniofacial Cartilage in Midterm Human Fetuses

PubMed Central

Shibata, S.; Sakamoto, Y.; Baba, O.; Qin, C.; Murakami, G.; Cho, B.H.

2013-01-01

Immunohistochemical localization of collagen types I, II, and X, aggrecan, versican, dentin matrix protein (DMP)-1, martix extracellular phosphoprotein (MEPE) were performed for Meckel’s cartilage, cranial base cartilage, and mandibular condylar cartilage in human midterm fetuses; staining patterns within the condylar cartilage were compared to those within other cartilaginous structures. Mandibular condylar cartilage contained aggrecan; it also had more type I collagen and a thicker hypertrophic cell layer than the other two types of cartilage; these three characteristics are similar to those of the secondary cartilage of rodents. MEPE immunoreactivity was first evident in the cartilage matrix of all types of cartilage in the human fetuses and in Meckel’s cartilage of mice and rats. MEPE immunoreactivity was enhanced in the deep layer of the hypertrophic cell layer and in the cartilaginous core of the bone trabeculae in the primary spongiosa. These results indicated that MEPE is a component of cartilage matrix and may be involved in cartilage mineralization. DMP-1 immunoreactivity first became evident in human bone lacunae walls and canaliculi; this pattern of expression was comparable to the pattern seen in rodents. In addition, chondroid bone was evident in the mandibular (glenoid) fossa of the temporal bone, and it had aggrecan, collagen types I and X, MEPE, and DMP-1 immunoreactivity; these findings indicated that chondroid bone in this region has phenotypic expression indicative of both hypertrophic chondrocytes and osteocytes. PMID:24441192

Autologous chondrocyte implantation in knee joint: MR imaging and histologic features at 1-year follow-up.

PubMed

Tins, Bernhard J; McCall, Iain W; Takahashi, Tomoki; Cassar-Pullicino, Victor; Roberts, Sally; Ashton, Brian; Richardson, James

2005-02-01

To evaluate magnetic resonance (MR) imaging features of autologous chondrocyte implantation (ACI) grafts and compare these with graft histologic features 1 year after ACI for treatment of femoral condylar defects. This study was approved by the regional ethics committee, and all patients gave informed consent. Forty-one patients (mean age, 35 years; 30 men, 11 women) underwent ACI for treatment of femoral condylar defects. One year later, knee joint MR imaging and graft biopsy were performed. Graft biopsy results were categorized into those showing hyaline, mixed fibrohyaline cartilage, fibrocartilage, and fibrous tissue. Standard T1-, T2-, T2*-, and intermediate-weighted sequences were performed, as well as three-dimensional (3D) fast low-angle shot (FLASH) and double-echo steady-state sequences for cartilage assessment. ACI grafts were assessed for signal intensity (with FLASH sequence), thickness, overgrowth, surface smoothness, integration to adjacent cartilage and underlying bone, bone marrow edema underneath graft, and contour of bone underneath graft. MR images were assessed by two observers, first independently and then in consensus. MR imaging findings were correlated with histologic findings. All 41 grafts were present at 1-year follow-up. The graft consisted of hyaline cartilage in four, mixed fibrohyaline cartilage in 10, fibrocartilage in 25, and fibrous tissue in two cases. Graft signal intensity was virtually always lower than adjacent normal cartilage signal intensity, and there was no relationship between graft signal intensity and histologic appearance (P = .34). Graft thickness (P = .83), overgrowth (P = .69), surface smoothness (P = .28), and integration with adjacent cartilage and underlying bone (P = .90); edema in bone marrow underneath graft (P = .63); and bone contour underneath graft (P = .94) at MR imaging had no correlation with graft histologic appearance. Graft overgrowth (n = 16; 39%) and edema-like signal in bone marrow underneath graft (n = 23; 56%) were common. The origin of graft overgrowth remains unclear. With the methods presented here, MR imaging findings cannot predict ACI graft histologic features, and graft histologic appearance determined at biopsy was not related to graft signal intensity, graft thickness, overgrowth, surface smoothness, integration with adjacent cartilage or underlying bone, signal intensity change in underlying bone marrow, or underlying bone contour. Overgrowth and bone marrow changes underneath the graft were common. (c) RSNA, 2004.

Skeletal morphology and development of the olfactory region of Spea (Anura: Scaphiopodidae)

PubMed Central

Pugener, L A; Maglia, A M

2007-01-01

The nasal capsules of anurans are formed by an intricate set of sac-like cavities that house the olfactory organ and constitute the beginning of the respiratory system. In tadpoles, nasal capsules do not have a respiratory function, but each is composed of a single soft tissue cavity lined with olfactory epithelium. Our study has revealed that in Spea the nasal cartilages and septomaxillae are de novo adult structures that form dorsal to the larval skeleton of the ethmoid region. The only element of the adult nasal capsule that is partially derived from the larval skeleton is the solum nasi. Development of the nasal skeleton begins at about Gosner Stage 31, with chondrification of the septum nasi and lamina orbitonasalis. The alary cartilage and superior prenasal cartilage are the first of the anterior nasal cartilages to chondrify at Gosner Stage 37. By Gosner Stages 40/41, the ethmoid region is composed of the larval structures ventrally and the adult structures dorsally. By Stage 44, the larval structures have eroded. The adult nasal capsule is characterized by: (1) a septum nasi that projects ventrally beyond the plane of the nasal floor; (2) a paranasal commissure that forms the ventral margin of the fenestra nasolateralis; and (3) a large skeletal support for the eminentia olfactoria formed by the nasal floor and vomer. The timing of chondrification of the anterior nasal cartilages and the development of the postnasal wall, inferior prenasal cartilage, fenestra nasolateralis, and paranasal commissure are discussed and compared with those of other anuran species. This study also includes a discussion of the morphology of the skeletal support for the eminentia olfactoria, a structure best developed in distinctly ground-dwelling frogs such as spadefoot toads. Finally, we propose a more precise restriction of the terminology that is used to designate the posterior structures of the olfactory region of anurans. PMID:18045351

Comprehensive analysis of translational osteochondral repair: Focus on the histological assessment.

PubMed

Orth, Patrick; Peifer, Carolin; Goebel, Lars; Cucchiarini, Magali; Madry, Henning

2015-10-01

Articular cartilage guarantees for an optimal functioning of diarthrodial joints by providing a gliding surface for smooth articulation, weight distribution, and shock absorbing while the subchondral bone plays a crucial role in its biomechanical and nutritive support. Both tissues together form the osteochondral unit. The structural assessment of the osteochondral unit is now considered the key standard procedure for evaluating articular cartilage repair in translational animal models. The aim of this review is to give a detailed overview of the different methods for a comprehensive evaluation of osteochondral repair. The main focus is on the histological assessment as the gold standard, together with immunohistochemistry, and polarized light microscopy. Additionally, standards of macroscopic, non-destructive imaging such as high resolution MRI and micro-CT, biochemical, and molecular biological evaluations are addressed. Potential pitfalls of analysis are outlined. A second focus is to suggest recommendations for osteochondral evaluation. Copyright © 2015 Elsevier GmbH. All rights reserved.

Correction of the lobule.

PubMed

Siegert, Ralf

2004-11-01

Many techniques have been described for the correction of protruding ears. Most of them concentrate on correcting the form and position of auricular cartilage. The lobule is a soft tissue structure. Skin resections of its posterior surface have been propagated for the correction of its position; however, these cause tension on the wound and might increase the already relatively high risk for the development of keloids. We have modified the technique for correcting the protruding lobule for its exact positioning and minimizing the risk for relapse and keloids. Starting from the incision performed for the anthelix plasty, a subcutaneous pocket is prepared between the anterior and posterior sides of the lobule. Afterwards, the subcutaneous layer of the postlobular skin is adjusted and fixed to the cartilage of the conchal cavum with a special mattress suture. This technique is a refinement of otoplasty for bat ears. It is indicated for precise modification of form and position of protruding lobules.

Cellular preservation of musculoskeletal specializations in the Cretaceous bird Confuciusornis

PubMed Central

Jiang, Baoyu; Zhao, Tao; Regnault, Sophie; Edwards, Nicholas P.; Kohn, Simon C.; Li, Zhiheng; Wogelius, Roy A.; Benton, Michael J.; Hutchinson, John R.

2017-01-01

The hindlimb of theropod dinosaurs changed appreciably in the lineage leading to extant birds, becoming more ‘crouched' in association with changes to body shape and gait dynamics. This postural evolution included anatomical changes of the foot and ankle, altering the moment arms and control of the muscles that manipulated the tarsometatarsus and digits, but the timing of these changes is unknown. Here, we report cellular-level preservation of tendon- and cartilage-like tissues from the lower hindlimb of Early Cretaceous Confuciusornis. The digital flexor tendons passed through cartilages, cartilaginous cristae and ridges on the plantar side of the distal tibiotarsus and proximal tarsometatarsus, as in extant birds. In particular, fibrocartilaginous and cartilaginous structures on the plantar surface of the ankle joint of Confuciusornis may indicate a more crouched hindlimb posture. Recognition of these specialized soft tissues in Confuciusornis is enabled by our combination of imaging and chemical analyses applied to an exceptionally preserved fossil. PMID:28327586

The rapid manufacture of uniform composite multicellular-biomaterial micropellets, their assembly into macroscopic organized tissues, and potential applications in cartilage tissue engineering.

PubMed

Babur, Betul Kul; Kabiri, Mahboubeh; Klein, Travis Jacob; Lott, William B; Doran, Michael Robert

2015-01-01

We and others have published on the rapid manufacture of micropellet tissues, typically formed from 100-500 cells each. The micropellet geometry enhances cellular biological properties, and in many cases the micropellets can subsequently be utilized as building blocks to assemble complex macrotissues. Generally, micropellets are formed from cells alone, however when replicating matrix-rich tissues such as cartilage it would be ideal if matrix or biomaterials supplements could be incorporated directly into the micropellet during the manufacturing process. Herein we describe a method to efficiently incorporate donor cartilage matrix into tissue engineered cartilage micropellets. We lyophilized bovine cartilage matrix, and then shattered it into microscopic pieces having average dimensions < 10 μm diameter; we termed this microscopic donor matrix "cartilage dust (CD)". Using a microwell platform, we show that ~0.83 μg CD can be rapidly and efficiently incorporated into single multicellular aggregates formed from 180 bone marrow mesenchymal stem/stromal cells (MSC) each. The microwell platform enabled the rapid manufacture of thousands of replica composite micropellets, with each micropellet having a material/CD core and a cellular surface. This micropellet organization enabled the rapid bulking up of the micropellet core matrix content, and left an adhesive cellular outer surface. This morphological organization enabled the ready assembly of the composite micropellets into macroscopic tissues. Generically, this is a versatile method that enables the rapid and uniform integration of biomaterials into multicellular micropellets that can then be used as tissue building blocks. In this study, the addition of CD resulted in an approximate 8-fold volume increase in the micropellets, with the donor matrix functioning to contribute to an increase in total cartilage matrix content. Composite micropellets were readily assembled into macroscopic cartilage tissues; the incorporation of CD enhanced tissue size and matrix content, but did not enhance chondrogenic gene expression.

The Rapid Manufacture of Uniform Composite Multicellular-Biomaterial Micropellets, Their Assembly into Macroscopic Organized Tissues, and Potential Applications in Cartilage Tissue Engineering

PubMed Central

Kul Babur, Betul; Kabiri, Mahboubeh; Klein, Travis Jacob; Lott, William B.; Doran, Michael Robert

2015-01-01

We and others have published on the rapid manufacture of micropellet tissues, typically formed from 100–500 cells each. The micropellet geometry enhances cellular biological properties, and in many cases the micropellets can subsequently be utilized as building blocks to assemble complex macrotissues. Generally, micropellets are formed from cells alone, however when replicating matrix-rich tissues such as cartilage it would be ideal if matrix or biomaterials supplements could be incorporated directly into the micropellet during the manufacturing process. Herein we describe a method to efficiently incorporate donor cartilage matrix into tissue engineered cartilage micropellets. We lyophilized bovine cartilage matrix, and then shattered it into microscopic pieces having average dimensions < 10 μm diameter; we termed this microscopic donor matrix “cartilage dust (CD)”. Using a microwell platform, we show that ~0.83 μg CD can be rapidly and efficiently incorporated into single multicellular aggregates formed from 180 bone marrow mesenchymal stem/stromal cells (MSC) each. The microwell platform enabled the rapid manufacture of thousands of replica composite micropellets, with each micropellet having a material/CD core and a cellular surface. This micropellet organization enabled the rapid bulking up of the micropellet core matrix content, and left an adhesive cellular outer surface. This morphological organization enabled the ready assembly of the composite micropellets into macroscopic tissues. Generically, this is a versatile method that enables the rapid and uniform integration of biomaterials into multicellular micropellets that can then be used as tissue building blocks. In this study, the addition of CD resulted in an approximate 8-fold volume increase in the micropellets, with the donor matrix functioning to contribute to an increase in total cartilage matrix content. Composite micropellets were readily assembled into macroscopic cartilage tissues; the incorporation of CD enhanced tissue size and matrix content, but did not enhance chondrogenic gene expression. PMID:26020956

New cell engineering approaches for cartilage regenerative medicine.

PubMed

Cucchiarini, Magali

2017-01-01

Articular cartilage injuries have an inadequate aptitude to reproduce the original structure and functions of this highly specialized tissue. As most of the currently available options also do not lead to the restoration of the original hyaline cartilage, novel treatments are critically needed to address this global problems in the clinics. Gene therapy combined with tissue engineering approaches offers effective tools capable of enhancing cartilage repair experimentally, especially those based on the controlled delivery of the highly effective, clinically adapted recombinant adeno-associated viral (rAAV) vectors. This work presents an overview of the most recent evidence showing the benefits of using rAAV vectors and biocompatible materials for the elaboration of adapted treatments against cartilage injuries.

Morphogenesis of the second pharyngeal arch cartilage (Reichert's cartilage) in human embryos

PubMed Central

Rodríguez-Vázquez, J F; Mérida-Velasco, J R; Verdugo-López, S; Sánchez-Montesinos, I; Mérida-Velasco, J A

2006-01-01

This study was performed on 50 human embryos and fetuses between 7 and 17 weeks of development. Reichert's cartilage is formed in the second pharyngeal arch in two segments. The longer cranial or styloid segment is continuous with the otic capsule; its inferior end is angulated and is situated very close to the oropharynx. The smaller caudal segment is in contact with the body and greater horn of the hyoid cartilaginous structure. No cartilage forms between these segments. The persistent angulation of the inferior end of the cranial or styloid segment of Reichert's cartilage and its important neurovascular relationships may help explain the symptomatology of Eagle's syndrome. PMID:16441562

A role for FoxN3 in the development of cranial cartilages and muscles in Xenopus laevis (Amphibia: Anura: Pipidae) with special emphasis on the novel rostral cartilages

PubMed Central

Schmidt, Jennifer; Schuff, Maximilian; Olsson, Lennart

2011-01-01

The origin of morphological novelties is a controversial topic in evolutionary developmental biology. The heads of anuran larvae have several unique structures, including the supra- and infrarostral cartilages, the specialised structure of the gill basket (used for filtration), and novel cranial muscle arrangements. FoxN3, a member of the forkhead/winged helix family of transcription factors, has been implicated as important for normal craniofacial development in the pipid anuran Xenopus laevis. We have investigated the effects of functional knockdown of FoxN3 (using antisense oligonucleotide morpholino) on the development of the larval head skeleton and the associated cranial muscles in X. laevis. Our data complement earlier studies and provide a more complete account of the requirement of FoxN3 in chondrocranium development. In addition, we analyse the effects of FoxN3 knockdown on cranial muscle development. We show that FoxN3 knockdown primarily affects the novel skeletal structures unique to anuran larvae, i.e. the rostralia or the fine structure of the gill apparatus. The articulation between the infrarostral and Meckel's cartilage is malformed and the filigreed processes of the gill basket do not develop. Because these features do not develop after FoxN3 knockdown, the head morphology resembles that in the less specialised larvae of salamanders. Furthermore, the development of all cartilages derived from the neural crest is delayed and cranial muscle fibre development incomplete. The cartilage precursors initially condense in their proper position but later differentiate incompletely; several visceral arch muscles start to differentiate at their origin but fail to extend toward their insertion. Our findings indicate that FoxN3 is essential for the development of novel cartilages such as the infrarostral and other cranial tissues derived from the neural crest and, indirectly, also for muscle morphogenesis. PMID:21050205

miR-322 stabilizes MEK1 expression to inhibit RAF/MEK/ERK pathway activation in cartilage.

PubMed

Bluhm, Björn; Ehlen, Harald W A; Holzer, Tatjana; Georgieva, Veronika S; Heilig, Juliane; Pitzler, Lena; Etich, Julia; Bortecen, Toman; Frie, Christian; Probst, Kristina; Niehoff, Anja; Belluoccio, Daniele; Van den Bergen, Jocelyn; Brachvogel, Bent

2017-10-01

Cartilage originates from mesenchymal cell condensations that differentiate into chondrocytes of transient growth plate cartilage or permanent cartilage of the articular joint surface and trachea. MicroRNAs fine-tune the activation of entire signaling networks and thereby modulate complex cellular responses, but so far only limited data are available on miRNAs that regulate cartilage development. Here, we characterize a miRNA that promotes the biosynthesis of a key component in the RAF/MEK/ERK pathway in cartilage. Specifically, by transcriptome profiling we identified miR-322 to be upregulated during chondrocyte differentiation. Among the various miR-322 target genes in the RAF/MEK/ERK pathway, only Mek1 was identified as a regulated target in chondrocytes. Surprisingly, an increased concentration of miR-322 stabilizes Mek1 mRNA to raise protein levels and dampen ERK1/2 phosphorylation, while cartilage-specific inactivation of miR322 in mice linked the loss of miR-322 to decreased MEK1 levels and to increased RAF/MEK/ERK pathway activation. Such mice died perinatally due to tracheal growth restriction and respiratory failure. Hence, a single miRNA can stimulate the production of an inhibitory component of a central signaling pathway to impair cartilage development. © 2017. Published by The Company of Biologists Ltd.

Electric field theory based approach to search-direction line definition in image segmentation: application to optimal femur-tibia cartilage segmentation in knee-joint 3-D MR

NASA Astrophysics Data System (ADS)

Yin, Y.; Sonka, M.

2010-03-01

A novel method is presented for definition of search lines in a variety of surface segmentation approaches. The method is inspired by properties of electric field direction lines and is applicable to general-purpose n-D shapebased image segmentation tasks. Its utility is demonstrated in graph construction and optimal segmentation of multiple mutually interacting objects. The properties of the electric field-based graph construction guarantee that inter-object graph connecting lines are non-intersecting and inherently covering the entire object-interaction space. When applied to inter-object cross-surface mapping, our approach generates one-to-one and all-to-all vertex correspondent pairs between the regions of mutual interaction. We demonstrate the benefits of the electric field approach in several examples ranging from relatively simple single-surface segmentation to complex multiobject multi-surface segmentation of femur-tibia cartilage. The performance of our approach is demonstrated in 60 MR images from the Osteoarthritis Initiative (OAI), in which our approach achieved a very good performance as judged by surface positioning errors (average of 0.29 and 0.59 mm for signed and unsigned cartilage positioning errors, respectively).

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.

A tribological and biomimetic study of potential bone joint repair materials

NASA Astrophysics Data System (ADS)

Ribeiro, Rahul

This research investigates materials for bone-joint failure repair using tribological and biomimicking approaches. The materials investigated represent three different repairing strategies. Refractory metals with and without treatment are candidates for total joint replacements due to their mechanical strength, high corrosion resistance and biocompatibility. A composite of biodegradable polytrimethylene carbonate, hydroxyl apatite, and nanotubes was investigated for application as a tissue engineering scaffold. Non-biodegradable polymer polyimide combined with various concentrations of nanotubes was investigated as a cartilage replacement material. A series of experimental approaches were used in this research. These include analysis of material surfaces and debris using high-resolution techniques and tribological experiments, as well as evaluation of nanomechanical properties. Specifically, the surface structure and wear mechanisms were investigated using a scanning electron microscope and an atomic force microscope. Debris morphology and structure was investigated using a transmission electron microscope. The debris composition was analyzed using an X-ray diffractometer. Nanoindentation was incorporated to investigate the surface nanomechanical properties. Polytrimythelene carbonate combined with hydroxyapatite and nanotubes exhibited a friction coefficient lower than UHMWPE. The nanoindentation response mimicked cartilage more closely than UHMWPE. A composite formed with PI and nanotubes showed a varying friction coefficient and varying nanoindentation response with variation in nanotube concentration. Low friction coefficients corresponded with low modulus values. A theory was proposed to explain this behavior based on surface interactions between nanotubes and between nanotubes and PI. A model was developed to simulate the modulus as a function of nanotube concentration. The boronized refractory metals exhibited brittleness and cracking. Higher friction coefficients were associated with the formation of amorphous debris. The friction coefficient for boronized Cr (˜0.06) under simulated body fluid conditions was in the range found in natural joints.

Measuring the nose in septorhinoplasty patients: ultrasonographic standard values and clinical correlations.

PubMed

Stenner, Markus; Koopmann, Mario; Rudack, Claudia

2017-02-01

Although septorhinoplasty is the most commonly performed operation in plastic surgery, and the surgical plan as well as its outcome is directly related to the configuration of the anatomical structures in the nose, these are not routinely assessed preoperatively. The aim of our study was to evaluate the nasal soft tissue and cartilaginous structures by means of high-resolution ultrasonography to set up clinical correlations and standard values. We examined 44 patients before septorhinoplasty by high-resolution ultrasonography in noncontact mode. All pictures were quantitatively evaluated by measuring 13 lengths and 4 ratios. All patients underwent a rhinomanometry measuring the nasal air flow. Besides others, men as well as older patients have a significantly thicker alar cartilage. Patients with thinner alar cartilages have a significantly smaller interdomal distance as well as significantly thinner upper lateral cartilages. The soft tissue above the bony dorsum was significantly thicker in older patients. Younger patients have significantly thicker soft tissue in relation to their cartilage. Patients with thicker soft tissue and thinner cartilage have a smaller tip. The interdomal distance and the thickness of the cartilaginous septum significantly correlated with the nasal air flow. We set up standard values of nasal structures in septorhinoplasty patients which can be used as reference values. By judging cartilage and soft tissue characteristics preoperatively, relevant factors for distinct procedures could be analyzed and the surgical steps can be better planned. Visualization by ultrasonography enables the surgeon to achieve treatment goals in a more predictable fashion.

Saddle-nose deformity repair with microplate-adapted costal cartilage.

PubMed

Eren, Fikret; Öksüz, Sinan; Melikoğlu, Cenk; Karagöz, Hüseyin; Ülkür, Ersin

2014-08-01

Nasal deformities affecting the bone and lower two-thirds of the nose due to the loss of septal height and tip support are defined as "saddle-nose" deformity. Reconstruction of a saddle-nose deformity essentially necessitates structural grafting. This article presents an alternative approach for correction of saddle-nose deformity using a microplate and costal cartilage. The results are compared with those of the previously applied costal cartilage repair methods. Between 2004 and 2013, 16 patients were treated with costal cartilage autografts. Of these 16 patients, 7 were treated with a microplate and costal cartilage autograft combination, 4 were treated with a costal cartilage autograft and Kirschner (K)-wire, and 5 were treated with onlay costal cartilage grafts. The mean follow-up periods were 16 months for group treated with microplate-adapted autologous costal cartilage, 12 months for the group treated with K-wire and autologous costal cartilage, and 16 months for the group treated with onlay costal cartilage. The patients treated with K-wire inserted cartilages and the patients treated onlay dorsal costal cartilages encountered complications such as extrusion of the wire and warping, respectively. The seven patients treated with microplate and dorsal onlay costal cartilage graft did not experience any infection, warping, or extrusion complication. The warping tendency of the costal cartilage autograft can be efficiently prevented without a prominent complication risk by using microplate-adapted costal cartilage grafts. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Physicochemical Properties of Cartilage in the Light of Ion Exchange Theory

PubMed Central

Maroudas, Alice

1968-01-01

Ion exchange theory has been applied to articular cartilage. Relationships were derived between permeability, diffusivity, electrical conductivity, and streaming potential. Systematic measurements were undertaken on these properties. Experimental techniques are described and data tabulated. Theoretical correlations were found to hold within the experimental error. The concentration of fixed negatively-charged groups in cartilage was shown to be the most important parameter. Fixed charge density was found to increase with distance from the articular surface and this variation was reflected in the other properties. PMID:5699797

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 48 weeks showed columnar orientation. The control side showed no changes over the shaved off articular surface in all the rabbits. One rabbit at 4 weeks had a dislocation of the patella on the control side. None of the rabbits developed any infection or wound dehiscence. Conclusion: Autologous periosteal graft transplantation can be a promising substitute for articular cartilaginous defects. PMID:19838382

Microdrilled cartilage defects treated with thrombin-solidified chitosan/blood implant regenerate a more hyaline, stable, and structurally integrated osteochondral unit compared to drilled controls.

PubMed

Marchand, Catherine; Chen, Gaoping; Tran-Khanh, Nicolas; Sun, Jun; Chen, Hongmei; Buschmann, Michael D; Hoemann, Caroline D

2012-03-01

This study analyzed the long-term cartilage and subchondral bone repair of microdrilled defects treated with chitosan glycerol-phosphate/blood implant, using thrombin (Factor IIa) to accelerate in situ solidification. We also evaluated the cartilage repair response to six smaller microdrill holes compared with two larger holes. Bilateral knee trochlear cartilage defects were created in n=8 skeletally mature rabbits, drilled with six proximal 0.5 mm and two distal 0.9 mm holes, then covered with in situ-solidified IIa-implants (treated) or with IIa-alone (control). After 6.5 months of repair, cartilage repair tissues were analyzed by histological scoring and histomorphometry for hyaline matrix characteristics and osseous integration. Subchondral repair bone was analyzed by 3D microcomputed tomography and compared to acute defects (n=6) and intact trochlea (n=8). Implant-treated cartilage repair tissues had higher structural integrity through the entire defect (p=0.02), twofold higher percent staining for glycosaminoglycan (p=0.0004), and ~24% more collagen type II staining over the smaller drill holes (p=0.008) compared with controls. Otherwise, hole diameter had no specific effect on cartilage repair. The subchondral bone plate was partially restored in treated and control defects but less dense than intact trochlea, with evidence of incomplete regeneration of the calcified cartilage layer. More residual drill holes (p=0.054) were detected in control versus treated defects, and control defects with more than 40% residual holes presented abnormally thicker trabeculae compared with treated defects. Low osteoclast numbers after 6.5 months repair suggested that bone was no longer remodeling. The subchondral bone plate surrounding the defects exhibited a significant thickening compared with age-matched intact trochlea. These data suggest that debridement and drilling can lead to long-term subchondral bone changes outside the cartilage defect. Compared with drilled controls, chitosan implants solidified with thrombin elicited a more hyaline and structurally integrated osteochondral unit, features needed for long-term durability.

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

[Evaluation of cartilage defects in the knee: validity of clinical, magnetic-resonance-imaging and radiological findings compared with arthroscopy].

PubMed

Spahn, G; Wittig, R; Kahl, E; Klinger, H M; Mückley, T; Hofmann, G O

2007-05-01

The study was aimed to evaluate the validity of clinical, radiological and MRI examination for cartilage defects of the knee compared with arthroscopic finding. Seven-hundred seventy-two patients who were suffering from knee pain over more than 3 months were evaluated clinical (grinding-sign) and with radiography and magnetic resonance imaging (MRI) and subsequent arthroscopy. The grinding sign had a sensitivity of 0.39. The association of a positive grinding test with high grade cartilage defects was significant (p<0.000). In 97.4% an intact chondral surface correlated with a normal radiological finding. Subchondral sclerosis, exophytes and a joint space narrowing was significantly associated with high grade cartilage defects (p<0.000). The accuracy of MRI was 59.5%. The MRI resulted in an overestimation in 36.6% and an underestimation in 3.9%. False-positive results were significant more often assessed in low-grade cartilage defects (p<0.000). Clinical signs, x-ray imaging and MRI correlate with arthroscopic findings in cases of deep cartilage lesions. In intact or low-grade degenerated cartilage often results an overestimating of these findings.

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.

Evolutionary Transformation of the Palmaris Longus Muscle in Flying Squirrels (Pteromyini: Sciuridae): An Anatomical Consideration of the Origin of the Uniquely Specialized Styliform Cartilage.

PubMed

Kawashima, Tomokazu; Thorington, Richard W; Bohaska, Paula W; Sato, Fumi

2017-02-01

A long-standing issue in squirrel evolution and development is the origin of the styliform cartilage of flying squirrels, which extends laterally from the carpus to support the gliding membrane (patagium). Because the styliform cartilage is one of the uniquely specialized structures permitting gliding locomotion, the knowledge of its origin and surrounding transformation is key for understanding their aerodynamic evolution. The developmental study that would definitely answer this question would be difficult due to the rarity of embryological material. Instead, anatomical examinations have suggested two major hypotheses on the homology of the styliform cartilage: the pisiform bone of other mammals, or an additional carpal structure, such as the ulnar sesamoid of some of the other mammals or the hypothenar cartilage of the non-gliding squirrels. To test these hypotheses, a detailed examination of the anatomy of the carpus of gliding and non-gliding squirrels, and the colugo were undertaken. Based on physical and virtual dissections of the carpus, this study showed that both the pisiform bone and styliform cartilage were present in flying squirrels. This finding is further supported by demonstration that a "true Palmaris longus," with innervation typical for this muscle, inserts on the styliform cartilage. Taken together, our osteological, muscular, and neurological results suggest that the styliform cartilage was transformed in flying squirrels from an initially superficial and ulnar-derived anlagen into its current form. Anat Rec, 300:340-352, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Co-expression of DKK-1 and Sclerostin in Subchondral Bone of the Proximal Femoral Heads from Osteoarthritic Hips.

PubMed

Zarei, Allahdad; Hulley, Philippa A; Sabokbar, Afsie; Javaid, M Kassim

2017-06-01

Osteoarthritis (OA) is a progressively degenerative joint disease influenced by structural and metabolic factors. There is growing evidence that subchondral bone is involved in both symptomatic and structural progression in OA. The Wnt pathway has been implicated in the progression of OA but the expression and function of the Wnt inhibitors, Dikkopf (DKK-1) and sclerostin (SOST), are unclear. We examined the regional distribution of DKK-1 and SOST in subchondral bone of the femoral head using resection specimens following arthroplasty in patients presenting with end-stage OA. Cylindrical cores for immunohistochemistry were taken through midpoint of full thickness cartilage defect, partial cartilage defect, through base of osteophyte and through macroscopically normal cartilage. Subchondral bone was thickest in cores taken from regions with full cartilage defect and thinnest in cores taken from osteophyte regions. In subchondral bone, expression of both DKK-1 and SOST was observed exclusively in osteocytes. Expression was highest in subchondral bone in cores taken from regions with partial but not full thickness cartilage defects. DKK-1 but not SOST was expressed by chondrocytes in cores with macroscopically normal cartilage. The current study describes the regional cellular distribution of SOST and DKK-1 in hip OA. Expression was highest in the osteocytes in bone underlying partial thickness cartilage defects. It is however not clear if this is a cause or a consequence of alterations in the overlying cartilage. However, it is suggestive of an active remodeling process which might be targeted by disease-modifying agents.

Effects of aluminum trichloride on the cartilage stimulatory growth factors in rats.

PubMed

Zhang, Fan; Sun, Xudong; Yu, Hongyan; Yang, Xu; Song, Miao; Han, Yanfei; Li, Yanfei; Zhu, Yanzhu

2017-02-01

Aluminum (Al) is considered to be a potentially toxic metal and inhibits cartilage formation. Transforming growth factor β1 (TGF-β1) and bone morphogenetic protein 2 (BMP-2) are cartilage stimulatory growth factors, which play important roles in regulating the cartilage formation. To investigate the effects of aluminum trichloride (AlCl 3 ) on the regulation of cartilage formation. Eighty Wistar rats were orally exposed to 0 (control group), 0.4 g/L (low-dose group), 0.8 g/L (mid-dose group) and 1.6 g/L (high-dose group) AlCl 3 for 120 days, respectively. The rats body weight were decreased, the cartilage histological structure were disrupted, the cartilage and serum contents of Al and the serum level of C-telopeptide of type II collagen were all increased, the serum level of type II collagen (Col II) and alkaline phosphatase (ALP), and the mRNA expressions of TGF-β1, BMP-2, ALP and Col II were all decreased in the AlCl 3 -treated groups compared with those in control group. These results indicate that AlCl 3 inhibits the cartilage formation through inhibition of the cartilage stimulatory growth factors expressions.

Longitudinal analysis of cartilage T2 relaxation times and joint degeneration in African American and Caucasian American women over an observation period of 6 years - data from the Osteoarthritis Initiative.

PubMed

Kretzschmar, M; Heilmeier, U; Yu, A; Joseph, G B; Liu, F; Solka, M; McCulloch, C E; Nevitt, M C; Link, T M

2016-08-01

To investigate the change in cartilage T2 values and structural degeneration in knee joints over 72 months in women of African American (AA) vs Caucasian American (CA) ethnicity. Knee 3T magnetic resonance imaging (MRIs) from baseline, 24, 48 and 72 months visits of 100 AA and 100 CA women from the Osteoarthritis Initiative (OAI) were assessed for cartilage T2 values and whole-organ magnetic resonance imaging (WORMS) score. Subjects were pair-matched by age, body mass index (BMI), Kellgren-Lawrence (KL) score, clinical site and subcohort within the OAI. We compared the rate of change in whole knee cartilage T2 values and WORMS cartilage, bone marrow edema pattern (BMEP) and meniscus scores between the two ethnic groups using mixed random effects models. At 24 and 48 months 60 subjects and at 72 months 45 subjects per group were available for analysis resulting in 38 complete pairs with data of all time points. Compared to CA, cartilage T2 values in AA increased at a significantly faster rate at baseline (AA: 0.45 ms/y, CA: 0.35 ms/y, P = 0.029) and averaged over 6 years (AA: 0.36 ms/y, CA: 0.27 ms/y, P = 0.039) with changes in both groups reaching a plateau by 48 months. Cartilage, meniscus and BMEP scores tended to increase in both groups during follow up, but rates of change did not differ by ethnicity. Cartilage T2 values increased faster over 72 months in AA than CA, however changes in WORMS cartilage, meniscus and BMEP scores did not differ. T2 values may be able to distinguish ethnicity-related differences of cartilage degeneration at an early stage before differences in structural joint degeneration appear. Copyright © 2016 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Rib Diced Cartilage-Fascia Grafting in Dorsal Nasal Reconstruction: A Randomized Clinical Trial of Wrapping With Rectus Muscle Fascia vs Deep Temporal Fascia.

PubMed

As'adi, Kamran; Salehi, Seyed Hamid; Shoar, Saeed

2014-08-01

Rib cartilage is an abundant source for cartilage grafts when significant dorsal nasal augmentation or structural support is indicated. Diced cartilage wrapped in fascia was developed to counteract warping, visibility, and displacement of rib cartilage as a dorsal solid graft. The technique for wrapping diced cartilage has evolved during the past several years. The authors compared 2 distinct fascial sleeves for wrapping rib diced cartilage in the treatment of patients who required major dorsal nasal augmentation. Thirty-six patients who planned to undergo major dorsal nasal reconstruction with diced costal rib cartilage were assigned randomly to 1 of 2 groups: the intervention group, which received grafts wrapped with rectus muscle fascia from the rib cartilage harvesting site, or the control group, which received deep temporal fascia harvested separately. Outcomes were compared between the groups. Patients in the intervention group had significantly shorter operating times, significantly higher average satisfaction scores, and significantly shorter postoperative hospital stays than did patients in the control group. Harvesting rectus muscle fascia for wrapping diced rib cartilage is a feasible and reliable technique in dorsal nasal reconstruction surgery. It is associated with favorable outcomes and a high level of patient satisfaction. 4. © 2014 The American Society for Aesthetic Plastic Surgery, Inc.

Chondroitin sulfate immobilization at the surface of electrospun nanofiber meshes for cartilage tissue regeneration approaches

NASA Astrophysics Data System (ADS)

Piai, Juliana Francis; da Silva, Marta Alves; Martins, Albino; Torres, Ana Bela; Faria, Susana; Reis, Rui L.; Muniz, Edvani Curti; Neves, Nuno M.

2017-05-01

Aiming at improving the biocompatibility of biomaterial scaffolds, surface modification presents a way to preserve their mechanical properties and to improve the surface bioactivity. In this work, chondroitin sulfate (CS) was immobilized at the surface of electrospun poly(caprolactone) nanofiber meshes (PCL NFMs), previously functionalized by UV/O3 exposure and aminolysis. Contact angle, SEM, optical profilometry, FTIR, X-ray photoelectron spectroscopy techniques confirmed the success of CS-immobilization in PCL NFMs. Furthermore, CS-immobilized PCL NFMs showed lower roughness and higher hydrophilicity than the samples without CS. Human articular chondrocytes (hACs) were cultured on electrospun PCL NFMs with or without CS immobilization. It was observed that hACs proliferated through the entire time course of the experiment in both types of nanofibrous scaffolds, as well as for the production of glycosaminoglycans. Quantitative-PCR results demonstrated over-expression of cartilage-related genes such as Aggrecan, Collagen type II, COMP and Sox9 on both types of nanofibrous scaffolds. Morphological observations from SEM and LSCM revealed that hACs maintained their characteristic round shape and cellular agglomeration exclusively on PCL NFMs with CS immobilization. In conclusion, CS immobilization at the surface of PCL NFMs was achieved successfully and provides a valid platform enabling further surface functionalization methods in scaffolds to be developed for cartilage tissue engineering.

Correction of cleft lip nose deformity with rib cartilage.

PubMed

Hafezi, Farhad; Naghibzadeh, Bijan; Ashtiani, Abbas Kazemi; Mousavi, S Jaber; Nouhi, Amir Hossein; Naghibzadeh, Ghazal

2013-07-01

Correction of cleft lip nasal deformities (CLND) is often unsatisfactory because of problems resulting from cartilage weakness and strong soft tissue forces. Therefore, strong cartilaginous support, such as rib cartilage, is mandatory. The authors describe placement of rib cartilage grafts to create a more symmetric and aesthetically acceptable repair of CLND with improved nasal air flow. Two groups of patients, including those with unilateral and bilateral CLND, underwent operations with different sources of autologous cartilage. Group 1 received grafts from the septum and ear, whereas group 2 received grafts from the septum and ribs. Results were evaluated by 2 independent physicians who rated improvement between pre- and postoperative photographs. There were significant differences in postoperative improvement between patients who received septal/ear cartilage grafts and those who received septal/rib cartilage grafts in both unilateral and bilateral cases (P = .028 and P = .043, respectively). The authors' results demonstrate that rib cartilage has a positive effect on the aesthetic outcome of CLND operations and provides a strong support structure for correcting this deformity with minimal postoperative complications.

Cartilage fragments from osteoarthritic knee promote chondrogenesis of mesenchymal stem cells without exogenous growth factor induction.

PubMed

Chen, Chia-Chun; Liao, Cheng-Hao; Wang, Yao-Horng; Hsu, Yuan-Ming; Huang, Shih-Horng; Chang, Chih-Hung; Fang, Hsu-Wei

2012-03-01

Extracellular matrix (ECM) is thought to participate significantly in guiding the differentiation process of mesenchymal stem cells (MSCs). In this study, we hypothesized that cartilage fragments from osteoarthritic knee could promote chondrogenesis of MSCs. Nonworn parts of cartilage tissues were obtained during total knee arthroplasty (TKA) surgery. Cartilage fragments and MSCs were wrapped into fibrin glue; and the constructs were implanted subcutaneously into nude mice. Histological analysis showed neocartilage-like structure with positive Alcian blue staining in the cartilage fragment-fibrin-MSC constructs. However, constructs with only MSCs in fibrin showed condensed appearance like MSCs in the pellet culture. Gene expression of type II collagen in the constructs with 60 mg cartilage fragments were significantly elevated after 4 weeks of implantation. Conversely, the constructs without cartilage fragments failed to express type II collagen, which indicated MSCs did not differentiate into a chondrogenic lineage. In conclusion, we demonstrated the effect of cartilage fragments from osteoarthritic knee in promoting chondrogenic differentiation of MSCs. This may be a favorable strategy for MSC chondrogenesis without exogenous growth factor induction. Copyright © 2011 Orthopaedic Research Society.

Nanodrugs to target articular cartilage: An emerging platform for osteoarthritis therapy.

PubMed

Bottini, Massimo; Bhattacharya, Kunal; Fadeel, Bengt; Magrini, Andrea; Bottini, Nunzio; Rosato, Nicola

2016-02-01

Cartilage undergoes drastic structural changes during the development of osteoarthritis and cannot heal itself due to a defective chondrocyte response. Thus, much effort has been invested in the development of disease modifying drugs able to block key mediators within the cartilage matrix and biochemical pathways inside chondrocytes. However, the delivery of therapeutic agents into cartilage is ineffective. This has led to the use of cartilage-targeted nanodrugs to accumulate therapeutic agents into specific cartilage sub-compartments. This review will describe the nanodrugs targeted to specific components of cartilage matrix to generate drug reservoirs within the cartilage. The nanodrugs used as chondrocyte-specific gene delivery systems are also described. Although the use of cartilage-targeted nanodrugs in osteoarthritis is still in its infancy, these studies lay the foundation for the development of novel approaches for preventing the progression of cartilage breakdown and improving the quality of life of patients with osteoarthritis. Osteoarthritis is a degeneration of joint cartilage, which affects a large number of aging people. Current therapy for disease modification is often suboptimal. Recent research in nanomedicine has led to the design and use of nanodrugs with the aim to help reverse the disease process. In this comprehensive review, the authors described and discussed various nanodrugs in the hope that newer drugs could be discovered in the future. Copyright © 2015 Elsevier Inc. All rights reserved.

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 joint from 74.6% to 88.9%, with only a small reduction in specificity. The greatest improvement in sensitivity with use of the T2 maps was in the identification of early cartilage degeneration. © RSNA, 2013.

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-pathology. Our data suggest that MC1-signaling protects against cartilage degradation and subchondral bone sclerosis in OA indicating a beneficial role of the POMC system in joint pathophysiology.

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-pathology. Our data suggest that MC1-signaling protects against cartilage degradation and subchondral bone sclerosis in OA indicating a beneficial role of the POMC system in joint pathophysiology. PMID:25191747

Efficacy of platelet-rich fibrin matrix on viability of diced cartilage grafts in a rabbit model.

PubMed

Güler, İsmail; Billur, Deniz; Aydin, Sevim; Kocatürk, Sinan

2015-03-01

The objective of this study was to compare the viability of cartilage grafts embedded in platelet-rich fibrin matrix (PRFM) wrapped with no material (bare diced cartilage grafts), oxidized methylcellulose (Surgicel), or acellular dermal tissue (AlloDerm). Experimental study. In this study, six New Zealand rabbits were used. Cartilage grafts including perichondrium were excised from each ear and diced into 2-mm-by 2-mm pieces. There were four comparison groups: 1) group A, diced cartilage (not wrapped with any material); 2) group B, diced cartilage wrapped with AlloDerm; 3) group C, diced cartilage grafts wrapped with Surgicel; and 4) group D, diced cartilage wrapped with PRFM. Four cartilage grafts were implanted under the skin at the back of each rabbit. All rabbits were sacrificed at the end of 10 weeks. The cartilages were stained with hematoxylin-eosin, Masson's Trichrome, and Orcein. After that, they were evaluated for the viability of chondrocytes, collagen content, fibrillar structure of matrix, and changes in peripheral tissues. When the viability of chondrocytes, the content of fiber in matrix, and changes in peripheral tissues were compared, the cartilage embedded in the PRFM group was statistically significantly higher than in the other groups (P < 0.05). We concluded that PRFM has significant advantages in ensuring the chondrocyte viability of diced cartilage grafts. It is also biocompatible, with relatively lesser inflammation and fibrosis. © 2014 The American Laryngological, Rhinological and Otological Society, Inc.

Quantification of collagen distributions in rat hyaline and fibro cartilages based on second harmonic generation imaging

NASA Astrophysics Data System (ADS)

Zhu, Xiaoqin; Liao, Chenxi; Wang, Zhenyu; Zhuo, Shuangmu; Liu, Wenge; Chen, Jianxin

2016-10-01

Hyaline cartilage is a semitransparent tissue composed of proteoglycan and thicker type II collagen fibers, while fibro cartilage large bundles of type I collagen besides other territorial matrix and chondrocytes. It is reported that the meniscus (fibro cartilage) has a greater capacity to regenerate and close a wound compared to articular cartilage (hyaline cartilage). And fibro cartilage often replaces the type II collagen-rich hyaline following trauma, leading to scar tissue that is composed of rigid type I collagen. The visualization and quantification of the collagen fibrillar meshwork is important for understanding the role of fibril reorganization during the healing process and how different types of cartilage contribute to wound closure. In this study, second harmonic generation (SHG) microscope was applied to image the articular and meniscus cartilage, and textural analysis were developed to quantify the collagen distribution. High-resolution images were achieved based on the SHG signal from collagen within fresh specimens, and detailed observations of tissue morphology and microstructural distribution were obtained without shrinkage or distortion. Textural analysis of SHG images was performed to confirm that collagen in fibrocartilage showed significantly coarser compared to collagen in hyaline cartilage (p < 0.01). Our results show that each type of cartilage has different structural features, which may significantly contribute to pathology when damaged. Our findings demonstrate that SHG microscopy holds potential as a clinically relevant diagnostic tool for imaging degenerative tissues or assessing wound repair following cartilage injury.

Association Between Infrapatellar Fat Pad Volume and Knee Structural Changes in Patients with Knee Osteoarthritis.

PubMed

Cai, Jingyu; Xu, Jianhua; Wang, Kang; Zheng, Shuang; He, Fan; Huan, Shuting; Xu, Shengqing; Zhang, Hui; Laslett, Laura; Ding, Changhai

2015-10-01

The function of the infrapatellar fat pad (IPFP) in knee osteoarthritis (OA) remains uncertain. This study aimed to examine cross-sectional associations between IPFP volume and knee structures in patients with knee OA. The study included 174 patients with clinical knee OA (mean age, 55.5 yrs). Fat-suppressed 3-D T1-weighted spoiled gradient recall magnetic resonance imaging (MRI) was used to measure the IPFP and cartilage volume. T2-weighted fast spin echo MRI was used to assess cartilage defects and bone marrow lesions (BML). Radiographic knee osteophytes and joint space narrowing (JSN) were assessed using the Osteoarthritis Research Society International atlas. After adjustment for potential confounders, greater IPFP volume was associated with greater tibial and patellar cartilage volume (all p < 0.05), and fewer cartilage defects at all sites (OR 0.88-0.91, all p < 0.05). IPFP volume was associated with presence of BML at lateral tibial and medial femoral sites (OR 0.88-0.91, all p < 0.05) and osteophytes at lateral tibiofemoral compartment (OR 0.88, p < 0.05). IPFP volume was not significantly associated with JSN. Greater IPFP volume was associated with greater knee cartilage volume and fewer structural abnormalities, suggesting a protective role of IPFP size in knee OA.

Ultra-low friction between boundary layers of hyaluronan-phosphatidylcholine complexes.

PubMed

Zhu, Linyi; Seror, Jasmine; Day, Anthony J; Kampf, Nir; Klein, Jacob

2017-09-01

The boundary layers coating articular cartilage in synovial joints constitute unique biomaterials, providing lubricity at levels unmatched by any human-made materials. The underlying molecular mechanism of this lubricity, essential to joint function, is not well understood. Here we study the interactions between surfaces bearing attached hyaluronan (hyaluronic acid, or HA) to which different phosphatidylcholine (PC) lipids had been added, in the form of small unilamellar vesicles (SUVs or liposomes), using a surface force balance, to shed light on possible cartilage boundary lubrication by such complexes. Surface-attached HA was complexed with different PC lipids (hydrogenated soy PC (HSPC), 1,2-dimyristoyl-sn-glycero-3-PC (DMPC) and 1-palmitoyl-2-oleoyl-sn-glycero-3-PC (POPC)), followed by rinsing. Atomic force microscopy (AFM) and cryo-scanning electron microscopy (Cryo-SEM) were used to image the HA-PC surface complexes following addition of the SUVs. HA-HSPC complexes provide very efficient lubrication, with friction coefficients as low as μ∼0.001 at physiological pressures P≈150atm, while HA-DMPC and HA-POPC complexes are efficient only at low P (up to 10-20atm). The friction reduction in all cases is attributed to hydration lubrication by highly-hydrated phosphocholine groups exposed by the PC-HA complexes. The greater robustness at high P of the HSPC (C 16(15%) ,C 18(85%) ) complexes relative to the DMPC ((C 14 ) 2 ) or POPC (C 16 , C 18:1 ) complexes is attributed to the stronger van der Waals attraction between the HSPC acyl tails, relative to the shorter or un-saturated tails of the other two lipids. Our results shed light on possible lubrication mechanisms at the articular cartilage surface in joints. Can designed biomaterials emulate the unique lubrication ability of articular cartilage, and thus provide potential alleviation to friction-related joint diseases? This is the motivation behind the present study. The principles of cartilage lubrication have attracted considerable attention for decades, and several models have been proposed to elucidate it, however, the mechanism of this ultralow friction is still not clear. In this paper we explore the recent suggestion that its efficient lubrication arises from boundary layers of hyaluronan-lipid complexes at its surface, in particular exploring a range of different phosphatidylcholines (PCs) mimicking the wide range of PCs in synovial joints. The present study suggests a synergistic lubricating behavior of the different lipids in living joints, and potential treatment directions using such biomaterial complexes for widespread cartilage-friction-related diseases such as osteoarthritis. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Laser-induced micropore formation and modification of cartilage structure in osteoarthritis healing

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

Sobol, Emil; Baum, Olga; Shekhter, Anatoly

Pores are vital for functioning of avascular tissues. Laser-induced pores play an important role in the process of cartilage regeneration. The aim of any treatment for osteoarthritis is to repair hyaline-type cartilage. The aims of this study are to answer two questions: (1) How do laser-assisted pores affect the cartilaginous cells to synthesize hyaline cartilage (HC)? and (2) How can the size distribution of pores arising in the course of laser radiation be controlled? We have shown that in cartilage, the pores arise predominately near chondrocytes, which promote nutrition of cells and signal molecular transfer that activates regeneration of cartilage.more » In vivo laser treatment of damaged cartilage of miniature pig joints provides cellular transformation and formation of HC. We propose a simple model of pore formation in biopolymers that paves the way for going beyond the trial-anderror approach when choosing an optimal laser treatment regime. Our findings support the approach toward laser healing of osteoarthritis.« less

Laser-induced micropore formation and modification of cartilage structure in osteoarthritis healing.

PubMed

Sobol, Emil; Baum, Olga; Shekhter, Anatoly; Wachsmann-Hogiu, Sebastian; Shnirelman, Alexander; Alexandrovskaya, Yulia; Sadovskyy, Ivan; Vinokur, Valerii

2017-09-01

Pores are vital for functioning of avascular tissues. Laser-induced pores play an important role in the process of cartilage regeneration. The aim of any treatment for osteoarthritis is to repair hyaline-type cartilage. The aims of this study are to answer two questions: (1) How do laser-assisted pores affect the cartilaginous cells to synthesize hyaline cartilage (HC)? and (2) How can the size distribution of pores arising in the course of laser radiation be controlled? We have shown that in cartilage, the pores arise predominately near chondrocytes, which promote nutrition of cells and signal molecular transfer that activates regeneration of cartilage. In vivo laser treatment of damaged cartilage of miniature pig joints provides cellular transformation and formation of HC. We propose a simple model of pore formation in biopolymers that paves the way for going beyond the trial-and-error approach when choosing an optimal laser treatment regime. Our findings support the approach toward laser healing of osteoarthritis.

Laser-induced micropore formation and modification of cartilage structure in osteoarthritis healing

NASA Astrophysics Data System (ADS)

Sobol, Emil; Baum, Olga; Shekhter, Anatoly; Wachsmann-Hogiu, Sebastian; Shnirelman, Alexander; Alexandrovskaya, Yulia; Sadovskyy, Ivan; Vinokur, Valerii

2017-09-01

Pores are vital for functioning of avascular tissues. Laser-induced pores play an important role in the process of cartilage regeneration. The aim of any treatment for osteoarthritis is to repair hyaline-type cartilage. The aims of this study are to answer two questions: (1) How do laser-assisted pores affect the cartilaginous cells to synthesize hyaline cartilage (HC)? and (2) How can the size distribution of pores arising in the course of laser radiation be controlled? We have shown that in cartilage, the pores arise predominately near chondrocytes, which promote nutrition of cells and signal molecular transfer that activates regeneration of cartilage. In vivo laser treatment of damaged cartilage of miniature pig joints provides cellular transformation and formation of HC. We propose a simple model of pore formation in biopolymers that paves the way for going beyond the trial-and-error approach when choosing an optimal laser treatment regime. Our findings support the approach toward laser healing of osteoarthritis.

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

Dingman, R.O.; Grabb, W.C.

Use of preserved cartilage homografts in restoring contour to defects of the supporting structures of the face is described and illustrated. Adequate sterilization of contaminated cartilage is effected by Co/sup 60/ gamma irradiation for 15 hr using 3,000,000 rep. The cartilage is then stored in saline at room temperature. No pathologic organisms were cultured from a series of 70 cases in which Co/sup 60/sterilized cartilage was used. Experiments in dogs, with direct measurement and inspection of 38 grafts implanted in the rectus sheath and on the pericranium, 2-12 months after transplantation, revealed that canine costal cartilage sterilized in merthiosaline gavemore » 33.3% complete and 33.3% partial absorption, while irradiated cartilage stored in saline gave 27.8% complete and 5.5% partial absorption. Clinical evaluation of 30 patients examined from 7 months to 31/2 yr postoperatively revealed evidence of absorption only in two grafts. Techniques of preparing, sterilizing by irradiation, and storing of human costal cartilage are described. (TCO)« less

Dietary 2-oxoglutarate mitigates gastrectomy-evoked structural changes in cartilage of female rats

PubMed Central

Tomaszewska, Ewa; Kurlak, Paulina; Pierzynowski, Stefan G

2015-01-01

Gastrectomy (Gx) leads to osteopenia/osteoporosis in humans and animals. However, little is known about the influence of Gx on the cartilage in this regard. Recent studies have demonstrated a protective effect of 2-oxoglutaric acid (2-Ox) on bone and cartilage. Hence, the purpose of this study was to investigate whether 2-Ox can mitigate eventual Gx-induced cartilage impairment. Twenty female Sprague-Dawley rats were subjected to Gx and randomly divided into two groups: Gx + 2-Ox and Gx. Another 20 rats were sham-operated (ShO) and randomly divided into two groups: ShO + 2-Ox and ShO. The daily dose of 2-Ox administered to the rats in the drinking water was 0.43 g per 100 g rat. After eight weeks, rats were euthanized and femora and tibiae were collected. Histology and histomorphometry analyses of the articular cartilage and the growth plate were done. Gx resulted in a 32% (±44.5 femur, ±35.8 tibia) decrease in overall thickness of articular cartilage in both bones (femur: ShO 279.1 ± 48.5 vs. Gx 190.2 ± 38.4 µm, tibia: ShO 222.9 ± 50.3 µm vs. Gx 151.3 ± 52.6 µm) (in some zones up to 58 ± 28.0%), and in the growth plate up to 20% (±22.4) (femur: ShO 243.0 ± 34.0 vs. Gx 207.0 ± 33.7 µm, tibia: ShO 220.0 ± 24.6 µm vs. Gx 171.1 ± 16.1 µm). Gx altered the spatial distribution of thick and thin collagen fibers, and chondrocyte shape and size. 2-Ox administration prevented the reduction in both cartilages thickness (Gx + 2-Ox: articular cartilage 265.2 ± 53.8 µm, 235.6 ± 42.7 µm, growth plate 236.7 ± 39.2 µm, 191.3 ± 16.5 µm in femur and tibia, respectively), and abolished the spatial changes in collagen distribution and structure induced by Gx. Gx affects cartilage structure and thickness, however, 2-Ox administration mitigates these effects and showed protective and stimulatory properties. Our observations suggest that dietary 2-Ox can be used to offset some of the changes in hyaline cartilage, in particular articular cartilage, following bariatric surgeries. PMID:26202375

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.

Angiogenic response in the chick chorioallantoic membrane model to laser-irradiated cartilage

NASA Astrophysics Data System (ADS)

Karamzadeh, Amir M.; Wong, Brian J.; Milner, Thomas E.; Wilson, Marie; Liaw, Lih-Huei L.; Nelson, J. Stuart

1999-06-01

Laser radiation can be used to reshape cartilage grafts via thermally mediated stress relaxation. While several studies have addressed the biophysical changes accompanying reshaping, cartilage viability following laser irradiation has not been extensively investigated. The objective of this study was to determine the extent of angioinvasion of irradiated cartilage explant placed onto the chick chorioallantoic membrane (CAM) model. Angioinvasion of the tissue matrix does not occur in viable cartilage tissue, whereas denatured tissue is readily vasculairzed and/or resorbed in vivo. Porcine septal cartilage specimens were removed from freshly sacrificed animals and divided into three protocols (n=10 each group) consisting of an untreated control, cartilage boiled in saline solution for one hour, and a laser irradiated group (Nd:YAG, λ=1.32 μm, 30.8 W/cm2, irradiation time = 10 sec). Following laser irradiation, tissue specimens were washed in antibiotic solution sand cut into small cubes (~1.5 mm3). The cartilage specimens were placed onto the surface of twenty CAMs, six of which, survived the entire 14 days incubation period. After incubation, the membranes and specimens were fixed in situ with formaldehyde, an then photographed using a dissection microscope. Cartilage specimens were prepared for histologic evaluation and stained with hematoxylin and eosin. Examination with a dissecting microscope showed no obvious vascular invasion of the cartilage or loss of gross tissue integrity in both the control and laser treated groups. In contrast, boiled specimens appeared to be partially or completely resorbed by the surrounding CAM vascular network. These gross findings were also confirmed by histological examination. In summary, our preliminary studies suggest that cartilage specimens treated using the present laser parameters remain resistant to angioinvasion or metabolism by the CAM, whereas boiled tissue undergoes resorption. Clinically, uncontrolled heating may result in total resorption of cartilage with catastrophic sequelae such as infection, necrosis, and total graft resorption. This study underscores the importance of preserving cartilage viability during laser surgical procedures relying on a photothermal mechanism.

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.

[Histologic assessment of tissue healing of hyaline cartilage by use of semiquantitative evaluation scale].

PubMed

Vukasović, Andreja; Ivković, Alan; Jezek, Davor; Cerovecki, Ivan; Vnuk, Drazen; Kreszinger, Mario; Hudetz, Damir; Pećina, Marko

2011-01-01

Articular cartilage is an avascular and aneural tissue lacking lymph drainage, hence its inability of spontaneous repair following injury. Thus, it offers an interesting model for scientific research. A number of methods have been suggested to enhance cartilage repair, but none has yet produced significant success. The possible application of the aforementioned methods has brought about the necessity to evaluate their results. The objective of this study was to analyze results of a study of the effects of the use of TGF-beta gene transduced bone marrow clot on articular cartilage defects using ICRS visual histological assessment scale. The research was conducted on 28 skeletally mature sheep that were randomly assigned to four groups and surgically inflicted femoral chondral defects. The articular surfaces were then treated with TGF-beta1 gene transduced bone marrow clot (TGF group), GFP transduced bone marrow clot (GFP group), untransduced bone marrow clot (BM group) or left untreated (NC group). The analysis was performed by visual examination of cartilage samples and results were obtained using ICRS visual histological assessment scale. The results were subsequently subjected to statistical assessment using Kruskal-Wallis and Mann-Whitney tests. Kruskal-Wallis test yielded statistically significant difference with respect to cell distribution. Mann-Whitney test showed statistically significant difference between TGF and NC groups (P = 0.002), as well as between BM and NC groups (P = 0.002 with Bonferroni correction). Twenty-six of the twenty-eight samples were subjected to histologic and subsequent statistical analysis; two were discarded due to faulty histology technique. Our results indicated a level of certainty as to the positive effect of TGF-beta1 gene transduced bone marrow clot in restoration of articular cartilage defects. However, additional research is necessary in the field. One of the significant drawbacks on histologic assessment of cartilage samples were the errors in histologic preparation, for which some samples had to be discarded and significantly impaired the analytical quality of the others. Defects of structures surrounding the articular cartilage, e.g., subchondral bone or connective tissue, might also impair the quality of histologic analysis. Additional analyses, i.e. polarizing microscopy should be performed to determine the degree of integration of the newly formed tissue with the surrounding cartilage. The semiquantitative ICRS scale, although of great practical value, has limitations as to the objectivity of the assessment, taking into account the analytical ability of the evaluator, as well as the accuracy of semiquantitative analysis in comparison to the methods of quantitative analysis. Overall results of histologic analysis indicated that the application of TGF-beta1 gene transduced bone marrow clot could have measurable clinical effects on articular cartilage repair. The ICRS visual histological assessment scale is a valuable analytical method for cartilage repair evaluation. In this respect, further analyses of the method value would be of great importance.

Nanoparticles for diagnostics and laser medical treatment of cartilage in orthopaedics

NASA Astrophysics Data System (ADS)

Baum, O. I.; Soshnikova, Yu. M.; Omelchenko, A. I.; Sobol, Emil

2013-02-01

Laser reconstruction of intervertebral disc (LRD) is a new technique which uses local, non-destructive laser irradiation for the controlled activation of regenerative processes in a targeted zone of damaged disc cartilage. Despite pronounced advancements of LRD, existing treatments may be substantially improved if laser radiation is absorbed near diseased and/or damaged regions in cartilage so that required thermomechanical stress and strain at chondrocytes may be generated and non-specific injury reduced or eliminated. The aims of the work are to study possibility to use nanoparticles (NPs) to provide spatial specificity for laser regeneration of cartilage. Two types of porcine joint cartilage have been impregnated with magnetite NPs: 1) fresh cartilage; 2) mechanically damaged cartilage. NPs distribution was studied using transition electron microscopy, dynamic light scattering and analytical ultracentrifugation techniques. Laser radiation and magnetic field have been applied to accelerate NPs impregnation. It was shown that NPs penetrate by diffusion into the mechanically damaged cartilage, but do not infiltrate healthy cartilage. Temperature dynamics in cartilage impregnated with NPs have been theoretically calculated and measurements using an IR thermo vision system have been performed. Laser-induced alterations of cartilage structure and cellular surviving have been studied for cartilage impregnated with NPs using histological and histochemical techniques. Results of our study suggest that magnetite NPs might be used to provide spatial specificity of laser regeneration. When damaged, the regions of cartilage impreganted with NPs have higher absorption of laser radiation than that for healthy areas. Regions containing NPs form target sites that can be used to generate laser-induced thermo mechanical stress leading to regeneration of cartilage of hyaline type.

The interaction between physical activity and amount of baseline knee cartilage.

PubMed

Teichtahl, Andrew J; Wang, Yuanyuan; Heritier, Stephane; Wluka, Anita E; Strauss, Boyd J; Proietto, Joseph; Dixon, John B; Jones, Graeme; Cicuttini, Flavia M

2016-07-01

Conflicting reports of the effect of physical activity on knee cartilage may be due to the heterogeneity of populations examined and, in particular, the underlying health of the knee joint. This study examined the influence of recreational and occupational physical activity on cartilage volume loss. A total of 250 participants with no significant musculoskeletal disease were recruited. A gender-specific median cartilage volume split was used to define people in the lowest and highest 50% of baseline cartilage volume. Baseline recreational and occupational activity was examined by questionnaire, while cartilage volume was assessed by MRI at baseline and 2.4 years later. Significant interactions were demonstrable between physical activity and cartilage volume loss based on stratification of baseline cartilage volume (all P ⩽ 0.03). There was a dose-response relationship between frequently performed baseline occupational activities and medial cartilage volume loss in both the low (B = 0.2% per annum, 95% CI: 0.0, 0.04% per annum) and high (B = -0.2% per annum, 95% CI: -0.4, 0.0% per annum) baseline cartilage volume groups (P = 0.001 for interaction). Individuals with low baseline cartilage volume who were active in their occupation and/or recreational activity had greater medial cartilage volume loss than their more inactive counterparts (2.4% per annum vs 1.5% per annum, P = 0.02). Whereas people with less baseline cartilage volume are more at risk of structural knee damage with either heavy occupational or recreational workloads or both, individuals with high baseline cartilage volume may advantageously modify their risk for knee OA by participating in more frequent occupational physical activities. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

The Roles of Mechanical Stresses in the Pathogenesis of Osteoarthritis

PubMed Central

Anderson, Donald D.; Brown, Thomas D.; Tochigi, Yuki; Martin, James A.

2013-01-01

Excessive joint surface loadings, either single (acute impact event) or repetitive (cumulative contact stress), can cause the clinical syndrome of osteoarthritis (OA). Despite advances in treatment of injured joints, the risk of OA following joint injuries has not decreased in the past 50 years. Cumulative excessive articular surface contact stress that leads to OA results from posttraumatic joint incongruity and instability, and joint dysplasia, but may also cause OA in patients without known joint abnormalities. In vitro investigations show that excessive articular cartilage loading triggers release of reactive oxygen species (ROS) from mitochondria, and that these ROS cause chondrocyte death and matrix degradation. Preventing release of ROS or inhibiting their effects preserves chondrocytes and their matrix. Fibronectin fragments released from articular cartilage subjected to excessive loads also stimulate matrix degradation; inhibition of molecular pathways initiated by these fragments prevents this effect. Additionally, injured chondrocytes release alarmins that activate chondroprogentior cells in vitro that propogate and migrate to regions of damaged cartilage. These cells also release chemokines and cytokines that may contribute to inflammation that causes progressive cartilage loss. Distraction and motion of osteoarthritic human ankles can promote joint remodeling, decrease pain, and improve joint function in patients with end-stage posttraumatic OA. These advances in understanding of how altering mechanical stresses can lead to remodeling of osteoarthritic joints and how excessive stress causes loss of articular cartilage, including identification of mechanically induced mediators of cartilage loss, provide the basis for new biologic and mechanical approaches to the prevention and treatment of OA. PMID:25067995

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

Preparation and characterization of collagen/PLA, chitosan/PLA, and collagen/chitosan/PLA hybrid scaffolds for cartilage tissue engineering.

PubMed

Haaparanta, Anne-Marie; Järvinen, Elina; Cengiz, Ibrahim Fatih; Ellä, Ville; Kokkonen, Harri T; Kiviranta, Ilkka; Kellomäki, Minna

2014-04-01

In this study, three-dimensional (3D) porous scaffolds were developed for the repair of articular cartilage defects. Novel collagen/polylactide (PLA), chitosan/PLA, and collagen/chitosan/PLA hybrid scaffolds were fabricated by combining freeze-dried natural components and synthetic PLA mesh, where the 3D PLA mesh gives mechanical strength, and the natural polymers, collagen and/or chitosan, mimic the natural cartilage tissue environment of chondrocytes. In total, eight scaffold types were studied: four hybrid structures containing collagen and/or chitosan with PLA, and four parallel plain scaffolds with only collagen and/or chitosan. The potential of these types of scaffolds for cartilage tissue engineering applications were determined by the analysis of the microstructure, water uptake, mechanical strength, and the viability and attachment of adult bovine chondrocytes to the scaffolds. The manufacturing method used was found to be applicable for the manufacturing of hybrid scaffolds with highly porous 3D structures. All the hybrid scaffolds showed a highly porous structure with open pores throughout the scaffold. Collagen was found to bind water inside the structure in all collagen-containing scaffolds better than the chitosan-containing scaffolds, and the plain collagen scaffolds had the highest water absorption. The stiffness of the scaffold was improved by the hybrid structure compared to plain scaffolds. The cell viability and attachment was good in all scaffolds, however, the collagen hybrid scaffolds showed the best penetration of cells into the scaffold. Our results show that from the studied scaffolds the collagen/PLA hybrids are the most promising scaffolds from this group for cartilage tissue engineering.

Synovium-derived stem cells: a tissue-specific stem cell for cartilage engineering and regeneration.

PubMed

Jones, Brendan A; Pei, Ming

2012-08-01

Articular cartilage is difficult to heal once injury or disease occurs. Autologous chondrocyte transplantation is a biological treatment with good prognosis, but donor site morbidity and limited cell source are disadvantages. Currently, mesenchymal stem cells (MSCs) are a promising approach for cartilage regeneration. Despite there being various sources, the best candidate for cartilage regeneration is the one with the greatest chondrogenic potential and the least hypertrophic differentiation. These properties are able to insure that the regenerated tissue is hyaline cartilage of high quality. This review article will summarize relevant literature to justify synovium-derived stem cells (SDSCs) as a tissue-specific stem cell for chondrogenesis by comparing synovium and cartilage with respect to anatomical location and functional structure, comparing the growth characterization and chondrogenic capacity of SDSCs and MSCs, evaluating the application of SDSCs in regenerative medicine and diseases, and discussing potential future directions.

Papain-induced changes in rabbit cartilage; alterations in the chemical structure of the cartilage matrix.

PubMed

TSALTAS, T T

1958-10-01

Some biochemical aspects of the collapse of the rabbit ears produced by the intravenous injection of papain have been studied. A marked depletion of chondromucoprotein (M.C.S.) and a reduction of the S(35) content of cartilage matrix were found to coincide with the gross and histologic changes in the cartilage. At the same time there was a marked increase in the amount of S(35) in the serum and an increase of S(35) and glucuronic acid excreted in the urine. Alteration in the composition of the M.C.S. remaining in the cartilage of the papain-injected animals was detected. The findings indicate that the collapse of the rabbit ears is due to loss of chondromucoprotein from cartilage and reduction of chondroitin sulfate in the chondromucoprotein that remains. All these changes were reversed in recovery.

Synergistic Interactions of a Synthetic Lubricin-Mimetic with Fibronectin for Enhanced Wear Protection

PubMed Central

Andresen Eguiluz, Roberto C.; Cook, Sierra G.; Tan, Mingchee; Brown, Cory N.; Pacifici, Noah J.; Samak, Mihir S.; Bonassar, Lawrence J.; Putnam, David; Gourdon, Delphine

2017-01-01

Lubricin (LUB), a major mucinous glycoprotein of mammalian synovial fluids, is believed to provide excellent lubrication to cartilage surfaces. Consequently, when joint disease or replacement leads to increased friction and surface damage in the joint, robust synthetic LUB alternatives that could be used therapeutically to improve lubrication and surface protection are needed. Here, we report the characterization of a lubricating multiblock bottlebrush polymer whose architecture was inspired by LUB, and we investigate the role of fibronectin (FN), a glycoprotein found in the superficial zone of cartilage, in mediating the tribological properties of the polymer upon shear between mica surfaces. Our surface forces apparatus (SFA) normal force measurements indicate that the lubricin-mimetic (mimLUB) could be kept anchored between mica surfaces, even under high contact pressures, when an intermediate layer of FN was present. Additional SFA friction measurements show that FN would also extend the wearless friction regime of the polymer up to pressures of 3.4 MPa while ensuring stable friction coefficients (μ ≈ 0.28). These results demonstrate synergistic interactions between mimLUB and FN in assisting the lubrication and wear protection of ideal (mica) substrates upon shear. Collectively, these findings suggest that our proposed mimLUB might be a promising alternative to LUB, as similar mechanisms could potentially facilitate the interaction between the polymer and cartilage surfaces in articular joints and prosthetic implants in vivo. PMID:28702455

Tissue Mechanics and Its Relationship to Athletic Injury Prevention.

ERIC Educational Resources Information Center

Alexander, Marion J. L.

Three types of dense fibrous connective tissue are described: articular cartilage; tendon; and ligament; and the characteristics of each are related to its function. Articular cartilage is the smooth covering over the surface of bone at joints, and is comprised of up to 80 percent water. This smooth covering serves to decrease the friction between…

Joint surface modeling with thin-plate splines.

PubMed

Boyd, S K; Ronsky, J L; Lichti, D D; Salkauskas, K; Chapman, M A; Salkauskas, D

1999-10-01

Mathematical joint surface models based on experimentally determined data points can be used to investigate joint characteristics such as curvature, congruency, cartilage thickness, joint contact areas, as well as to provide geometric information well suited for finite element analysis. Commonly, surface modeling methods are based on B-splines, which involve tensor products. These methods have had success; however, they are limited due to the complex organizational aspect of working with surface patches, and modeling unordered, scattered experimental data points. An alternative method for mathematical joint surface modeling is presented based on the thin-plate spline (TPS). It has the advantage that it does not involve surface patches, and can model scattered data points without experimental data preparation. An analytical surface was developed and modeled with the TPS to quantify its interpolating and smoothing characteristics. Some limitations of the TPS include discontinuity of curvature at exactly the experimental surface data points, and numerical problems dealing with data sets in excess of 2000 points. However, suggestions for overcoming these limitations are presented. Testing the TPS with real experimental data, the patellofemoral joint of a cat was measured with multistation digital photogrammetry and modeled using the TPS to determine cartilage thicknesses and surface curvature. The cartilage thickness distribution ranged between 100 to 550 microns on the patella, and 100 to 300 microns on the femur. It was found that the TPS was an effective tool for modeling joint surfaces because no preparation of the experimental data points was necessary, and the resulting unique function representing the entire surface does not involve surface patches. A detailed algorithm is presented for implementation of the TPS.

Structural Associations of Symptomatic Knee Osteoarthritis

PubMed Central

Stoppiello, Laura A; Mapp, Paul I; Wilson, Deborah; Hill, Roger; Scammell, Brigitte E; Walsh, David A

2014-01-01

Objective Structural changes of osteoarthritis (OA) may occur in the absence of pain. In this study, we aimed to identify histopathologic features that are associated with symptomatic knee OA. Methods Medial tibial plateaus and synovium samples were obtained at the time of total knee replacement (TKR) surgery for OA (advanced OA group) or were obtained postmortem from subjects who had not sought medical attention for knee pain during the last year of life (non-OA control group). To identify features of OA, we compared the patients with advanced OA with the age-matched non-OA controls (n = 26 per group). To identify OA features associated with symptoms, we compared two additional groups of subjects who were matched for severity of chondropathy (n = 29 per group): patients undergoing TKR for symptomatic OA (symptomatic chondropathy group) and postmortem subjects with similar severity of chondropathy who were asymptomatic during the last year of life (asymptomatic chondropathy group). The histologic features of the samples were graded, and immunoreactivities for macrophages (CD68) and nerve growth factor (NGF) in the synovium were quantified. The cellular localization of synovial NGF was determined by double immunofluorescence analysis. Results Advanced OA cases displayed more severe changes in the synovium (synovitis, increased synovial NGF, and CD68-immunoreactive macrophages) and cartilage (loss of cartilage surface integrity, loss of proteoglycan, tidemark breaching, and alterations in chondrocyte morphology) than did the non-OA controls. Synovial NGF was localized predominantly to fibroblasts and to some macrophages. The symptomatic chondropathy group displayed greater levels of synovitis, synovial NGF, and loss of cartilage integrity, in addition to alterations in chondrocyte morphology, than did the asymptomatic chondropathy group (P < 0.05 for each comparison). Conclusion Synovitis, increased synovial NGF, alterations in chondrocyte morphology, and loss of cartilage integrity are features of knee OA that may be associated with symptoms. PMID:25049144

Osteoarthritis-derived chondrocytes are a potential source of multipotent progenitor cells for cartilage tissue engineering

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

Oda, Tomoyuki; Sakai, Tadahiro; Hiraiwa, Hideki

The natural healing capacity of damaged articular cartilage is poor, rendering joint surface injuries a prime target for regenerative medicine. While autologous chondrocyte or mesenchymal stem cell (MSC) implantation can be applied to repair cartilage defects in young patients, no appropriate long-lasting treatment alternative is available for elderly patients with osteoarthritis (OA). Multipotent progenitor cells are reported to present in adult human articular cartilage, with a preponderance in OA cartilage. These facts led us to hypothesize the possible use of osteoarthritis-derived chondrocytes as a cell source for cartilage tissue engineering. We therefore analyzed chondrocyte- and stem cell-related markers, cell growthmore » rate, and multipotency in OA chondrocytes (OACs) and bone marrow-derived MSCs, along with normal articular chondrocytes (ACs) as a control. OACs demonstrated similar phenotype and proliferation rate to MSCs. Furthermore, OACs exhibited multilineage differentiation ability with a greater chondrogenic differentiation ability than MSCs, which was equivalent to ACs. We conclude that chondrogenic capacity is not significantly affected by OA, and OACs could be a potential source of multipotent progenitor cells for cartilage tissue engineering. - Highlights: • Osteoarthritis chondrocytes (OACs) have multilineage differentiation capacity. • Articular chondrocytes (ACs) and OACs have similar gene expression profiles. • OACs have high chondrogenic potential. • OACs could be a cell resource for cartilage tissue engineering.« less

Priming Adipose-Derived Mesenchymal Stem Cells with Hyaluronan Alters Growth Kinetics and Increases Attachment to Articular Cartilage

PubMed Central

Succar, Peter; Medynskyj, Michael; Breen, Edmond J.; Batterham, Tony; Molloy, Mark P.; Herbert, Benjamin R.

2016-01-01

Background. Biological therapeutics such as adipose-derived mesenchymal stem cell (MSC) therapy are gaining acceptance for knee-osteoarthritis (OA) treatment. Reports of OA-patients show reductions in cartilage defects and regeneration of hyaline-like-cartilage with MSC-therapy. Suspending MSCs in hyaluronan commonly occurs in animals and humans, usually without supporting data. Objective. To elucidate the effects of different concentrations of hyaluronan on MSC growth kinetics. Methods. Using a range of hyaluronan concentrations, we measured MSC adherence and proliferation on culture plastic surfaces and a novel cartilage-adhesion assay. We employed time-course and dispersion imaging to assess MSC binding to cartilage. Cytokine profiling was also conducted on the MSC-secretome. Results. Hyaluronan had dose-dependent effects on growth kinetics of MSCs at concentrations of entanglement point (1 mg/mL). At higher concentrations, viscosity effects outweighed benefits of additional hyaluronan. The cartilage-adhesion assay highlighted for the first time that hyaluronan-primed MSCs increased cell attachment to cartilage whilst the presence of hyaluronan did not. Our time-course suggested patients undergoing MSC-therapy for OA could benefit from joint-immobilisation for up to 8 hours. Hyaluronan also greatly affected dispersion of MSCs on cartilage. Conclusion. Our results should be considered in future trials with MSC-therapy using hyaluronan as a vehicle, for the treatment of OA. PMID:26981136

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.

Arthroscopic Anatomy of the Ankle Joint.

PubMed

Ray, Ronald G

2016-10-01

There are a number of variations in the intra-articular anatomy of the ankle which should not be considered pathological under all circumstances. The anteromedial corner of the tibial plafond (between the anterior edge of the tibial plafond and the medial malleolus) can have a notch, void of cartilage and bone. This area can appear degenerative arthroscopically; it is actually a normal variant of the articular surface. The anterior inferior tibiofibular ligament (AITF) can possess a lower, accessory band which can impinge on the anterolateral edge of the talar dome. In some cases it can cause irritation along this area of the talus laterally. If it is creating local irritation it can be removed since it does not provide any additional stabilization to the syndesmosis. There is a beveled region at the anterior leading edge of the lateral and dorsal surfaces of the talus laterally. This triangular region is void of cartilage and subchondral bone. The lack of talar structure in this region allows the lower portion of the AITF ligament to move over the talus during end range dorsiflexion of the ankle, preventing impingement. The variation in talar anatomy for this area should not be considered pathological. Copyright © 2016 Elsevier Inc. All rights reserved.

Biologic resurfacing of the patella: current status.

PubMed

Scapinelli, Raphaele; Aglietti, Paolo; Baldovin, Marino; Giron, Francesco; Teitge, Robert

2002-07-01

The techniques of biologic resurfacing of the patella, like other joint surfaces, are still evolving. Currently none of them is free from criticism. In this regard it is our hope that progress in the basic science will offer in the near future new and more optimistic therapeutic possibilities (i.e., the restoration of a reparative cartilage that is structurally and functionally comparable to the native one). The greater expectancies come perhaps from the present experimental investigations about the combined use of tissue-engineered implants embedded with staminal cells and growth factors. Many problems remain to be solved, however, before reliable applicability in humans. From a general point of view, stem cells obtained from various sources (e.g., adult bone marrow, umbilical cord) offer the same finalities as the embryonic stem cells, without the ethical obstacles related to the latter. Therefore, it may be that restoration of part or all of the articular surface of a joint will be possible by way of these mesenchymal progenitors that have the ability to differentiate into the chondrogenic and osteogenic lines, which is required for the restoration of the various layers of a normal articular cartilage and subchondral bone.

Ex vivo investigations of laser auricular cartilage reshaping with carbon dioxide spray cooling in a rabbit model

PubMed Central

Wu, Edward C.; Sun, Victor; Manuel, Cyrus T.; Protsenko, Dmitriy E.; Jia, Wangcun; Nelson, J. Stuart; Wong, Brian J. F.

2014-01-01

Laser cartilage reshaping (LCR) with cryogen spray cooling is a promising modality for producing cartilage shape change while reducing cutaneous thermal injury. However, LCR in thicker tissues, such as auricular cartilage, requires higher laser power, thus increasing cooling requirements. To eliminate the risks of freeze injury characteristic of high cryogen spray pulse rates, a carbon dioxide (CO2) spray, which evaporates rapidly from the skin, has been proposed as the cooling medium. This study aims to identify parameter sets which produce clinically significant reshaping while producing minimal skin thermal injury in LCR with CO2 spray cooling in ex vivo rabbit auricular cartilage. Excised whole rabbit ears were mechanically deformed around a cylindrical jig and irradiated with a 1.45-μm wavelength diode laser (fluence 12–14 J/cm2 per pulse, four to six pulse cycles per irradiation site, five to six irradiation sites per row for four rows on each sample) with concomitant application of CO2 spray (pulse duration 33–85 ms) to the skin surface. Bend angle measurements were performed before and after irradiation, and the change quantified. Surface temperature distributions were measured during irradiation/cooling. Maximum skin surface temperature ranged between 49.0 to 97.6 °C following four heating/cooling cycles. Significant reshaping was achieved with all laser dosimetry values with a 50–70 °C difference noted between controls (no cooling) and irradiated ears. Increasing cooling pulse duration yielded progressively improved gross skin protection during irradiation. CO2 spray cooling may potentially serve as an alternative to traditional cryogen spray cooling in LCR and may be the preferred cooling medium for thicker tissues. Future studies evaluating preclinical efficacy in an in vivo rabbit model are in progress. PMID:23307439

Ex vivo investigations of laser auricular cartilage reshaping with carbon dioxide spray cooling in a rabbit model.

PubMed

Wu, Edward C; Sun, Victor; Manuel, Cyrus T; Protsenko, Dmitriy E; Jia, Wangcun; Nelson, J Stuart; Wong, Brian J F

2013-11-01

Laser cartilage reshaping (LCR) with cryogen spray cooling is a promising modality for producing cartilage shape change while reducing cutaneous thermal injury. However, LCR in thicker tissues, such as auricular cartilage, requires higher laser power, thus increasing cooling requirements. To eliminate the risks of freeze injury characteristic of high cryogen spray pulse rates, a carbon dioxide (CO2) spray, which evaporates rapidly from the skin, has been proposed as the cooling medium. This study aims to identify parameter sets which produce clinically significant reshaping while producing minimal skin thermal injury in LCR with CO2 spray cooling in ex vivo rabbit auricular cartilage. Excised whole rabbit ears were mechanically deformed around a cylindrical jig and irradiated with a 1.45-μm wavelength diode laser (fluence 12-14 J/cm(2) per pulse, four to six pulse cycles per irradiation site, five to six irradiation sites per row for four rows on each sample) with concomitant application of CO2 spray (pulse duration 33-85 ms) to the skin surface. Bend angle measurements were performed before and after irradiation, and the change quantified. Surface temperature distributions were measured during irradiation/cooling. Maximum skin surface temperature ranged between 49.0 to 97.6 °C following four heating/cooling cycles. Significant reshaping was achieved with all laser dosimetry values with a 50-70 °C difference noted between controls (no cooling) and irradiated ears. Increasing cooling pulse duration yielded progressively improved gross skin protection during irradiation. CO2 spray cooling may potentially serve as an alternative to traditional cryogen spray cooling in LCR and may be the preferred cooling medium for thicker tissues. Future studies evaluating preclinical efficacy in an in vivo rabbit model are in progress.

Substrate porosity enhances chondrocyte attachment, spreading, and cartilage tissue formation in vitro.

PubMed

Spiteri, C G; Pilliar, R M; Kandel, R A

2006-09-15

Tissue engineering is being explored as a new approach to treat damaged cartilage. As the biomaterial used may influence tissue formation, the effects of substrate geometry on chondrocyte behavior in vitro were examined. Articular chondrocytes were isolated and cultured on the surface of smooth, rough, porous-coated, and fully porous Ti-6Al-4V substrates. The percentage of chondrocytes that attached to each substrate at 24 h was determined. After 24 and 72 h, chondrocytes were visualized by scanning electron microscopy and cell areas were measured. Collagen and proteoglycan accumulation within the first 24 h was determined by incorporation with [3H]-proline and [35S]-SO4, respectively. Chondrocyte attachment as well as matrix accumulation was enhanced as substrate surface area increased. Cell areas on the fully porous substrate were over four times greater than on any other substrate by 72 h in culture. After 8 weeks in culture, a continuous layer of cartilaginous tissue formed only on the surface of the fully porous substrate. This suggests that fully porous Ti-6Al-4V substrates provide the conditions that favor cartilage tissue formation by influencing cell attachment and extent of cell spreading. Understanding how substrate porosity influences chondrocyte behavior may help identify methods to further enhance cartilage tissue formation in vitro. 2006 Wiley Periodicals, Inc. J Biomed Mater Res, 2006.

Topographical investigation of changes in depth-wise proteoglycan distribution in rabbit femoral articular cartilage at 4 weeks after transection of the anterior cruciate ligament.

PubMed

Arokoski, Mikko E A; Tiitu, Virpi; Jurvelin, Jukka S; Korhonen, Rami K; Fick, James M

2015-09-01

In this study, we explore topographical changes in proteoglycan distribution from femoral condylar cartilage in early osteoarthritis, acquired from both the lateral and medial condyles of anterior cruciate ligament transected (ACLT) and contralateral (CNTRL) rabbit knee joints, at 4 weeks post operation. Four sites across the cartilage surface in a parasagittal plane were defined across tissue sections taken from femoral condyles, and proteoglycan (PG) content was quantified using digital densitometry. The greatest depth-wise change in PG content due to an ACLT (compared to the CNTRL group) was observed anteriorly (site C) from the most weight-bearing location within the lateral compartment. In the medial compartment, the greatest change was observed in the most weight-bearing location (site B). The depth-wise changes in PG content were observed up to 48% and 28% depth from the tissue surface at these aforementioned sites, respectively (p < 0.05). The smallest depth-wise change in PG content was observed posteriorly (site A) from the most weight-bearing location within both femoral condyles (up to 20% and up to 5% depth from the tissue surface at lateral and medial compartments, respectively). This study gives further insight into how early cartilage deterioration progresses across the parasagittal plane of the femoral condyle. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

What is the effect of physical activity on the knee joint? A systematic review.

PubMed

Urquhart, Donna M; Tobing, Jephtah F L; Hanna, Fahad S; Berry, Patricia; Wluka, Anita E; Ding, Changhai; Cicuttini, Flavia M

2011-03-01

Although several studies have examined the relationship between physical activity and knee osteoarthritis, the effect of physical activity on knee joint health is unclear. The aim of this systematic review was to examine the relationships between physical activity and individual joint structures at the knee. Computer-aided searches were conducted up until November 2008, and the reference lists of key articles were examined. The methodological quality of selected studies was assessed based on established criteria, and a best-evidence synthesis was used to summarize the results. We found that the relationships between physical activity and individual joint structures at the knee differ. There was strong evidence for a positive association between physical activity and tibiofemoral osteophytes. However, we also found strong evidence for the absence of a relationship between physical activity and joint space narrowing, a surrogate method of assessing cartilage. Moreover, there was limited evidence from magnetic resonance imaging studies for a positive relationship between physical activity and cartilage volume and strong evidence for an inverse relationship between physical activity and cartilage defects. This systematic review found that knee structures are affected differently by physical activity. Although physical activity is associated with an increase in radiographic osteophytes, there was no related increase in joint space narrowing, rather emerging evidence of an associated increase in cartilage volume and decrease in cartilage defects on magnetic resonance imaging. Given that optimizing cartilage health is important in preventing osteoarthritis, these findings indicate that physical activity is beneficial, rather than detrimental, to joint health.

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.

Visualization of small lesions in rat cartilage by means of laboratory-based x-ray phase contrast imaging

NASA Astrophysics Data System (ADS)

Marenzana, Massimo; Hagen, Charlotte K.; Das Neves Borges, Patricia; Endrizzi, Marco; Szafraniec, Magdalena B.; Ignatyev, Konstantin; Olivo, Alessandro

2012-12-01

Being able to quantitatively assess articular cartilage in three-dimensions (3D) in small rodent animal models, with a simple laboratory set-up, would prove extremely important for the development of pre-clinical research focusing on cartilage pathologies such as osteoarthritis (OA). These models are becoming essential tools for the development of new drugs for OA, a disease affecting up to 1/3 of the population older than 50 years for which there is no cure except prosthetic surgery. However, due to limitations in imaging technology, high-throughput 3D structural imaging has not been achievable in small rodent models, thereby limiting their translational potential and their efficiency as research tools. We show that a simple laboratory system based on coded-aperture x-ray phase contrast imaging (CAXPCi) can correctly visualize the cartilage layer in slices of an excised rat tibia imaged both in air and in saline solution. Moreover, we show that small, surgically induced lesions are also correctly detected by the CAXPCi system, and we support this finding with histopathology examination. Following these successful proof-of-concept results in rat cartilage, we expect that an upgrade of the system to higher resolutions (currently underway) will enable extending the method to the imaging of mouse cartilage as well. From a technological standpoint, by showing the capability of the system to detect cartilage also in water, we demonstrate phase sensitivity comparable to other lab-based phase methods (e.g. grating interferometry). In conclusion, CAXPCi holds a strong potential for being adopted as a routine laboratory tool for non-destructive, high throughput assessment of 3D structural changes in murine articular cartilage, with a possible impact in the field similar to the revolution that conventional microCT brought into bone research.

High-throughput bone and cartilage micropellet manufacture, followed by assembly of micropellets into biphasic osteochondral tissue.

PubMed

Babur, Betul Kul; Futrega, Kathryn; Lott, William B; Klein, Travis Jacob; Cooper-White, Justin; Doran, Michael Robert

2015-09-01

Engineered biphasic osteochondral tissues may have utility in cartilage defect repair. As bone-marrow-derived mesenchymal stem/stromal cells (MSC) have the capacity to make both bone-like and cartilage-like tissues, they are an ideal cell population for use in the manufacture of osteochondral tissues. Effective differentiation of MSC to bone-like and cartilage-like tissues requires two unique medium formulations and this presents a challenge both in achieving initial MSC differentiation and in maintaining tissue stability when the unified osteochondral tissue is subsequently cultured in a single medium formulation. In this proof-of-principle study, we used an in-house fabricated microwell platform to manufacture thousands of micropellets formed from 166 MSC each. We then characterized the development of bone-like and cartilage-like tissue formation in the micropellets maintained for 8-14 days in sequential combinations of osteogenic or chondrogenic induction medium. When bone-like or cartilage-like micropellets were induced for only 8 days, they displayed significant phenotypic changes when the osteogenic or chondrogenic induction medium, respectively, was swapped. Based on these data, we developed an extended 14-day protocol for the pre-culture of bone-like and cartilage-like micropellets in their respective induction medium. Unified osteochondral tissues were formed by layering 12,000 osteogenic micropellets and 12,000 chondrogenic micropellets into a biphasic structure and then further culture in chondrogenic induction medium. The assembled tissue was cultured for a further 8 days and characterized via histology. The micropellets had amalgamated into a continuous structure with distinctive bone-like and cartilage-like regions. This proof-of-concept study demonstrates the feasibility of micropellet assembly for the formation of osteochondral-like tissues for possible use in osteochondral defect repair.

Patellofemoral Instability in Children: Correlation Between Risk Factors, Injury Patterns, and Severity of Cartilage Damage.

PubMed

Kim, Hee Kyung; Shiraj, Sahar; Kang, Chang Ho; Anton, Christopher; Kim, Dong Hoon; Horn, Paul S

2016-06-01

The purpose of this study was to compare MRI findings between groups with and without patellofemoral instability and to correlate the MRI findings with the severity of patellar cartilage damage. Fifty-three children with patellofemoral instability and 53 age- and sex-matched children without patellofemoral instability (15.9 ± 2.4 years) were included. Knee MRI with T2-weighted mapping was performed. On MR images, femoral trochlear dysplasia, patellofemoral malalignment, medial retinaculum injury, and bone marrow edema were documented. The degree of patellar cartilage damage was evaluated on MR images by use of a morphologic grading scale (0-4) and on T2 maps with mean T2 values at the medial, central, and lateral facets. MRI findings were compared between the two groups. In cases of patellofemoral instability, MRI findings were correlated with the severity of cartilage damage at each region. Trochlear structure and alignment were significantly different between the two groups (Wilcoxon p < 0.0001). In patellofemoral instability, a high-riding patella was associated with central patellar cartilage damage with a higher morphologic grade and T2 value (Spearman p < 0.05). The severity of medial retinacular injury and presence of bone marrow edema at either the medial patella or the lateral femoral condyle were associated with a higher grade of medial patellar cartilage damage (Wilcoxon p < 0.05). None of the other findings correlated with the severity of patellar cartilage damage. Patients with patellofemoral instability have significantly different trochlear structure and alignment than those who do not, and these differences are known risk factors for patellofemoral instability. However, the only risk factors or injury patterns that directly correlated with the severity of patellar cartilage damage were patella alta, medial stabilizer injury, and bone marrow edema.

Association Between Pain at Sites Outside the Knee and Knee Cartilage Volume Loss in Elderly People Without Knee Osteoarthritis: A Prospective Study.

PubMed

Pan, Feng; Laslett, Laura; Tian, Jing; Cicuttini, Flavia; Winzenberg, Tania; Ding, Changhai; Jones, Graeme

2017-05-01

Pain is common in the elderly. Knee pain may predict knee cartilage loss, but whether generalized pain is associated with knee cartilage loss is unclear. This study, therefore, aimed to determine whether pain at multiple sites predicts knee cartilage volume loss among community-dwelling older adults, and, if so, to explore potential mechanisms. Data from the prospective Tasmanian Older Adult Cohort study was utilized (n = 394, mean age 63 years, range 52-79 years). Experience of pain at multiple sites was assessed using a questionnaire at baseline. T1-weighted fat-saturated magnetic resonance imaging of the right knee was performed to assess the cartilage volume at baseline and after 2.6 years. Linear regression modeling was used with adjustment for potential confounders. The median number of painful sites was 3 (range 0-7). There was a dose-response relationship between the number of painful sites and knee cartilage volume loss in the lateral and total tibiofemoral compartments (lateral β = -0.28% per annum; total β = -0.25% per annum, both P for trend < 0.05), but not in the medial compartment. These associations were stronger in participants without radiographic knee osteoarthritis (OA) (P < 0.05) and independent of age, sex, body mass index, physical activity, pain medication, and knee structural abnormalities. The number of painful sites independently predicts knee cartilage volume loss, especially in people without knee OA, suggesting that widespread pain may be an early marker of more rapid knee cartilage loss in those without radiographic knee OA. The underlying mechanism is unclear, but it is independent of anthropometrics, physical activity, and knee structural abnormalities. © 2016, American College of Rheumatology.

Avidin as a Model for Charge Driven Transport into Cartilage and Drug Delivery for treating Early Stage Post-traumatic Osteoarthritis

PubMed Central

Bajpayee, Ambika G.; Wong, Cliff R.; Bawendi, Moungi G.; Frank, Eliot H.; Grodzinsky, Alan J.

2013-01-01

Local drug delivery into cartilage remains a challenge due to its dense extracellular matrix of negatively charged proteoglycans enmeshed within a collagen fibril network. The high negative fixed charge density of cartilage offers the unique opportunity to utilize electrostatic interactions to augment transport, binding and retention of drug carriers. With the goal of developing particle-based drug delivery mechanisms for treating post-traumatic osteoarthritis, our objectives were, first, to determine the size range of a variety of solutes that could penetrate and diffuse through normal cartilage and enzymatically treated cartilage to mimic early stages of OA, and second, to investigate the effects of electrostatic interactions on particle partitioning, uptake and binding within cartilage using the highly positively charged protein, Avidin, as a model. Results showed that solutes having a hydrodynamic diameter ≤ 10 nm can penetrate into the full thickness of cartilage explants while larger sized solutes were trapped in the tissue’s superficial zone. Avidin had a 400-fold higher uptake than its neutral same-sized counterpart, NeutrAvidin, and >90% of the absorbed Avidin remained within cartilage explants for at least 15 days. We report reversible, weak binding (KD ~150 μM) of Avidin to intratissue sites in cartilage. The large effective binding site density (NT ~ 2920 μM) within cartilage matrix facilitates Avidin’s retention, making its structure suitable for particle based drug delivery into cartilage. PMID:24120044

Development of a 3D cell printed structure as an alternative to autologs cartilage for auricular reconstruction.

PubMed

Park, Ju Young; Choi, Yeong-Jin; Shim, Jin-Hyung; Park, Jeong Hun; Cho, Dong-Woo

2017-07-01

Surgical technique using autologs cartilage is considered as the best treatment for cartilage tissue reconstruction, although the burdens of donor site morbidity and surgical complications still remain. The purpose of this study is to apply three-dimensional (3D) cell printing to fabricate a tissue-engineered graft, and evaluate its effects on cartilage reconstruction. A multihead tissue/organ building system is used to print cell-printed scaffold (CPS), then assessed the effect of the CPS on cartilage regeneration in a rabbit ear. The cell viability and functionality of chondrocytes were significantly higher in CPS than in cell-seeded scaffold (CSS) and cell-seeded hybrid scaffold (CSHS) in vitro. CPS was then implanted into a rabbit ear that had an 8 mm-diameter cartilage defect; at 3 months after implantation the CPS had fostered complete cartilage regeneration whereas CSS and autologs cartilage (AC) fostered only incomplete healing. This result demonstrates that cell printing technology can provide an appropriate environment in which encapsulated chondrocytes can survive and differentiate into cartilage tissue in vivo. Moreover, the effects of CPS on cartilage regeneration were even better than those of AC. Therefore, we confirmed the feasibility of CPS as an alternative to AC for auricular reconstruction. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 1016-1028, 2017. © 2016 Wiley Periodicals, Inc.

A composite scaffold of MSC affinity peptide-modified demineralized bone matrix particles and chitosan hydrogel for cartilage regeneration

NASA Astrophysics Data System (ADS)

Meng, Qingyang; Man, Zhentao; Dai, Linghui; Huang, Hongjie; Zhang, Xin; Hu, Xiaoqing; Shao, Zhenxing; Zhu, Jingxian; Zhang, Jiying; Fu, Xin; Duan, Xiaoning; Ao, Yingfang

2015-12-01

Articular cartilage injury is still a significant challenge because of the poor intrinsic healing potential of cartilage. Stem cell-based tissue engineering is a promising technique for cartilage repair. As cartilage defects are usually irregular in clinical settings, scaffolds with moldability that can fill any shape of cartilage defects and closely integrate with the host cartilage are desirable. In this study, we constructed a composite scaffold combining mesenchymal stem cells (MSCs) E7 affinity peptide-modified demineralized bone matrix (DBM) particles and chitosan (CS) hydrogel for cartilage engineering. This solid-supported composite scaffold exhibited appropriate porosity, which provided a 3D microenvironment that supports cell adhesion and proliferation. Cell proliferation and DNA content analysis indicated that the DBM-E7/CS scaffold promoted better rat bone marrow-derived MSCs (BMMSCs) survival than the CS or DBM/CS groups. Meanwhile, the DBM-E7/CS scaffold increased matrix production and improved chondrogenic differentiation ability of BMMSCs in vitro. Furthermore, after implantation in vivo for four weeks, compared to those in control groups, the regenerated issue in the DBM-E7/CS group exhibited translucent and superior cartilage-like structures, as indicated by gross observation, histological examination, and assessment of matrix staining. Overall, the functional composite scaffold of DBM-E7/CS is a promising option for repairing irregularly shaped cartilage defects.

Production of three-dimensional tissue-engineered cartilage through mutual fusion of chondrocyte pellets.

PubMed

Hoshi, K; Fujihara, Y; Mori, Y; Asawa, Y; Kanazawa, S; Nishizawa, S; Misawa, M; Numano, T; Inoue, H; Sakamoto, T; Watanabe, M; Komura, M; Takato, T

2016-09-01

In this study, the mutual fusion of chondrocyte pellets was promoted in order to produce large-sized tissue-engineered cartilage with a three-dimensional (3D) shape. Five pellets of human auricular chondrocytes were first prepared, which were then incubated in an agarose mold. After 3 weeks of culture in matrix production-promoting medium under 5.78g/cm(2) compression, the tissue-engineered cartilage showed a sufficient mechanical strength. To confirm the usefulness of these methods, a transplantation experiment was performed using beagles. Tissue-engineered cartilage prepared with 50 pellets of beagle chondrocytes was transplanted subcutaneously into the cell-donor dog for 2 months. The tissue-engineered cartilage of the beagles maintained a rod-like shape, even after harvest. Histology showed fair cartilage regeneration. Furthermore, 20 pellets were made and placed on a beta-tricalcium phosphate prism, and this was then incubated within the agarose mold for 3 weeks. The construct was transplanted into a bone/cartilage defect in the cell-donor beagle. After 2 months, bone and cartilage regeneration was identified on micro-computed tomography and magnetic resonance imaging. This approach involving the fusion of small pellets into a large structure enabled the production of 3D tissue-engineered cartilage that was close to physiological cartilage tissue in property, without conventional polyper scaffolds. Copyright © 2016. Published by Elsevier Ltd.

Bone sialoprotein in laboratory diagnostic work-up of osteoarthritis.

PubMed

Lis, Kinga

2008-01-01

Changes in osteoarthritis joint appear in the articular cartilage, synovium and in subchondral bone. It is necessary to find, apart from markers of cartilage destruction, a sensitive and specific biochemical marker which would reflect the metabolism as well as degradation of subchondral bone. Bone sialoprotein is mostly synthesized in osseous tissue found directly under the surface of joint cartilage. As a result, it is being increasingly perceived as a valuable marker of the metabolism rate of this layer of bone. Bone sialoprotein seems to be of use as a marker for subchondral bone degradation rate in laboratory diagnostic work-up of osteoarthritis.

Solid freeform-fabricated scaffolds designed to carry multicellular mesenchymal stem cell spheroids for cartilage regeneration.

PubMed

Huang, G S; Tseng, C S; Linju Yen, B; Dai, L G; Hsieh, P S; Hsu, S-h

2013-10-13

Three-dimensional (3D) cellular spheroids have recently emerged as a new trend to replace suspended single cells in modern cell-based therapies because of their greater regeneration capacities in vitro. They may lose the 3D structure during a change of microenvironment, which poses challenges to their translation in vivo. Besides, the conventional microporous scaffolds may have difficulty in accommodating these relatively large spheroids. Here we revealed a novel design of microenvironment for delivering and sustaining the 3D spheroids. Biodegradable scaffolds with macroporosity to accommodate mesenchymal stem cell (MSC) spheroids were made by solid freeform fabrication (SFF) from the solution of poly(D,L-lactide-co-glycolide). Their internal surface was modified with chitosan following air plasma treatment in order to preserve the morphology of the spheroids. It was demonstrated that human MSC spheroids loaded in SFF scaffolds produced a significantly larger amount of cartilage-associated extracellular matrix in vitro and in NOD/SCID mice compared to single cells in the same scaffolds. Implantation of MSC spheroid-loaded scaffolds into the chondral defects of rabbit knees showed superior cartilage regeneration. This study establishes new perspectives in designing the spheroid-sustaining microenvironment within a tissue engineering scaffold for in vivo applications.

Validation of tool mark analysis of cut costal cartilage.

PubMed

Love, Jennifer C; Derrick, Sharon M; Wiersema, Jason M; Peters, Charles

2012-03-01

This study was designed to establish the potential error rate associated with the generally accepted method of tool mark analysis of cut marks in costal cartilage. Three knives with different blade types were used to make experimental cut marks in costal cartilage of pigs. Each cut surface was cast, and each cast was examined by three analysts working independently. The presence of striations, regularity of striations, and presence of a primary and secondary striation pattern were recorded for each cast. The distance between each striation was measured. The results showed that striations were not consistently impressed on the cut surface by the blade's cutting edge. Also, blade type classification by the presence or absence of striations led to a 65% misclassification rate. Use of the classification tree and cross-validation methods and inclusion of the mean interstriation distance decreased the error rate to c. 50%. © 2011 American Academy of Forensic Sciences.

A New Technique for Conchal Cartilage Harvest.

PubMed

Kim, Joon Young; Yang, Ho Jik; Jeong, Ji Won

2017-03-01

The goal of auricular cartilage harvest is to obtain a sufficient amount for reconstruction and to minimize the change in ear shape. The cartilage can be harvested by a posterior or anterior approach, and each method has advantages and disadvantages. The posterior approach presents the advantage of scar concealment, but there are limits to the amount of cymba cartilage that may be harvested. In contrast, the anterior approach may cause a noticeable scar. However, as cartilage is collected, the anterior approach provides a view that facilitates the preservation ear structure. In addition, it is possible to obtain a greater amount of cartilage. From January 2014 to December 2015, we harvested auricular cartilage graft material in 17 patients. To prevent the development of trapdoor scars or linear scar contracture, short incisions were made on the superior border of the cymba and cavum. Two small and narrow incisions were made, resulting in suboptimal exposure of the surgical site, which heightens the potential for damaging the cartilage when using existing tools. To minimize this, the authors used a newly invented ball-type elevator. All patients recovered without complications after surgery and reported satisfaction with the shape of the ear.

A New Technique for Conchal Cartilage Harvest

PubMed Central

Kim, Joon Young; Jeong, Ji Won

2017-01-01

The goal of auricular cartilage harvest is to obtain a sufficient amount for reconstruction and to minimize the change in ear shape. The cartilage can be harvested by a posterior or anterior approach, and each method has advantages and disadvantages. The posterior approach presents the advantage of scar concealment, but there are limits to the amount of cymba cartilage that may be harvested. In contrast, the anterior approach may cause a noticeable scar. However, as cartilage is collected, the anterior approach provides a view that facilitates the preservation ear structure. In addition, it is possible to obtain a greater amount of cartilage. From January 2014 to December 2015, we harvested auricular cartilage graft material in 17 patients. To prevent the development of trapdoor scars or linear scar contracture, short incisions were made on the superior border of the cymba and cavum. Two small and narrow incisions were made, resulting in suboptimal exposure of the surgical site, which heightens the potential for damaging the cartilage when using existing tools. To minimize this, the authors used a newly invented ball-type elevator. All patients recovered without complications after surgery and reported satisfaction with the shape of the ear. PMID:28352607

Biological, biochemical and biomechanical characterisation of articular cartilage from the porcine, bovine and ovine hip and knee.

PubMed

Fermor, H L; McLure, S W D; Taylor, S D; Russell, S L; Williams, S; Fisher, J; Ingham, E

2015-01-01

This study aimed to determine the optimal starting material for the development of an acellular osteochondral graft. Osteochondral tissues from three different species were characterised; pig (6 months), cow (18 months) and two ages of sheep (8-12 months and >4 year old). Tissues from the acetabulum and femoral head of the hip, and the groove, medial and lateral condyles and tibial plateau of the knee were assessed. Histological analysis of each tissue allowed for qualification of cartilage histoarchitecture, glycosaminoglycan (GAG) distribution, assessment of cellularity and cartilage thickness. Collagen and GAG content were quantified and cartilage water content was defined. Following biomechanical testing, the percentage deformation, permeability and equilibrium elastic modulus was determined. Results showed that porcine cartilage had the highest concentration of sulphated proteoglycans and that the condyles and groove of the knee showed higher GAG content than other joint areas. Cartilage from younger tissues (porcine and young ovine) had higher cell content and was thicker, reflecting the effects of age on cartilage structure. Cartilage from older sheep had a much higher elastic modulus and was less permeable than other species.

Critical temperature transitions in laser-mediated cartilage reshaping

NASA Astrophysics Data System (ADS)

Wong, Brian J.; Milner, Thomas E.; Kim, Hong H.; Telenkov, Sergey A.; Chew, Clifford; Kuo, Timothy C.; Smithies, Derek J.; Sobol, Emil N.; Nelson, J. Stuart

1998-07-01

In this study, we attempted to determine the critical temperature [Tc] at which accelerated stress relaxation occurred during laser mediated cartilage reshaping. During laser irradiation, mechanically deformed cartilage tissue undergoes a temperature dependent phase transformation which results in accelerated stress relaxation. When a critical temperature is attained, cartilage becomes malleable and may be molded into complex new shapes that harden as the tissue cools. Clinically, reshaped cartilage tissue can be used to recreate the underlying cartilaginous framework of structures such as the ear, larynx, trachea, and nose. The principal advantages of using laser radiation for the generation of thermal energy in tissue are precise control of both the space-time temperature distribution and time- dependent thermal denaturation kinetics. Optimization of the reshaping process requires identification of the temperature dependence of this phase transformation and its relationship to observed changes in cartilage optical, mechanical, and thermodynamic properties. Light scattering, infrared radiometry, and modulated differential scanning calorimetry (MDSC) were used to measure temperature dependent changes in the biophysical properties of cartilage tissue during fast (laser mediated) and slow (conventional calorimetric) heating. Our studies using MDSC and laser probe techniques have identified changes in cartilage thermodynamic and optical properties suggestive of a phase transformation occurring near 60 degrees Celsius.

Cartilage microindentation using cylindrical and spherical optical fiber indenters with integrated Bragg gratings as force sensors

NASA Astrophysics Data System (ADS)

Marchi, G.; Canti, O.; Baier, V.; Micallef, W.; Hartmann, B.; Alberton, P.; Aszodi, A.; Clausen-Schaumann, H.; Roths, J.

2018-02-01

Fiber optic microindentation sensors that have the potential to be integrated into arthroscopic instruments and to allow localizing degraded articular cartilage are presented in this paper. The indenters consist of optical fibers with integrated Bragg gratings as force sensors. In a basic configuration, the tip of the fiber optic indenter consists of a cleaved fiber end, forming a cylindrical flat punch indenter geometry. When using this indenter geometry, high stresses at the edges of the cylinder are present, which can disrupt the tissue structure. This is avoided with an improved version of the indenter. A spherical indenter tip that is formed by melting the end of the glass fiber. The spherical fiber tip shows the additional advantage of strongly reducing reflections from the fiber end. This allows a reduction of the length of the fiber optic sensor element from 65 mm of the flat punch type to 27 mm of the spherical punch. In order to compare the performance of both indenter types, in vitro stress-relaxation indentation experiments were performed on bovine articular cartilage with both indenter types, to assess biomechanical properties of bovine articular cartilage. For indentation depths between 60 μm and 300 μm, the measurements with both indenter types agreed very well with each other. This shows that both indenter geometries are suitable for microindentation measuremnts . The spherical indenter however has the additional advantage that it minimizes the risk to damage the surface of the tissue and has less than half dimensions than the flat indenter.

Chitosan/γ-poly(glutamic acid) scaffolds with surface-modified albumin, elastin and poly-l-lysine for cartilage tissue engineering.

PubMed

Kuo, Yung-Chih; Ku, Hao-Fu; Rajesh, Rajendiran

2017-09-01

Cartilage has limited ability to self-repair due to the absence of blood vessels and nerves. The application of biomaterial scaffolds using biomimetic extracellular matrix (ECM)-related polymers has become an effective approach to production of engineered cartilage. Chitosan/γ-poly(glutamic acid) (γ-PGA) scaffolds with different mass ratios were prepared using genipin as a cross-linker and a freeze-drying method, and their surfaces were modified with elastin, human serum albumin (HSA) and poly-l-lysine (PLL). The scaffolds were formed through a complex between NH 3 + of chitosan and COO - of γ-PGA, confirmed by Fourier transform infrared spectroscopy, and exhibited an interconnected porous morphology in field emission scanning electron microscopy analysis. The prepared chitosan/γ-PGA scaffolds, at a 3:1 ratio, obtained the required porosity (90%), pore size (≥100μm), mechanical strength (compressive strength>4MPa, Young's modulus>4MPa) and biodegradation (30-60%) for articular cartilage tissue engineering applications. Surface modification of the scaffolds showed positive indications with improved activity toward cell proliferation (deoxyribonucleic acid), cell adhesion and ECM (glycoaminoglycans and type II collagen) secretion of bovine knee chondrocytes compared with unmodified scaffolds. In caspase-3 detection, elastin had a higher inhibitory effect on chondrocyte apoptosis in vitro, followed by HSA, and then PLL. We concluded that utilizing chitosan/γ-PGA scaffolds with surface active biomolecules, including elastin, HSA and PLL, can effectively promote the growth of chondrocytes, secrete ECM and improve the regenerative ability of cartilaginous tissues. Copyright © 2017 Elsevier B.V. All rights reserved.

Autologous Cartilage Chip Transplantation Improves Repair Tissue Composition Compared With Marrow Stimulation.

PubMed

Christensen, Bjørn Borsøe; Olesen, Morten Lykke; Lind, Martin; Foldager, Casper Bindzus

2017-06-01

Repair of chondral injuries by use of cartilage chips has recently demonstrated clinical feasibility. To investigate in vivo cartilage repair outcome of autologous cartilage chips compared with marrow stimulation in full-thickness cartilage defects in a minipig model. Controlled laboratory study. Six Göttingen minipigs received two 6-mm chondral defects in the medial and lateral trochlea of each knee. The two treatment groups were (1) autologous cartilage chips embedded in fibrin glue (ACC) (n = 12) and (2) marrow stimulation (MST) (n = 12). The animals were euthanized after 6 months, and the composition of repair tissue was quantitatively determined using histomorphometry. Semiquantitative evaluation was performed by means of the International Cartilage Repair Society (ICRS) II score. Collagen type II staining was used to further evaluate the repair tissue composition. Significantly more hyaline cartilage was found in the ACC (17.1%) compared with MST (2.9%) group ( P < .01). Furthermore, the ACC group had significantly less fibrous tissue (23.8%) compared with the MST group (41.1%) ( P < .01). No significant difference in fibrocartilage content was found (54.7% for ACC vs 50.8% for MST). The ACC group had significantly higher ICRS II scores for tissue morphological characteristics, matrix staining, cell morphological characteristics, surface assessment, mid/deep assessment, and overall assessment ( P < .05). The ACC-treated defects had significantly more collagen type II staining (54.5%) compared with the MST-treated defects (28.1%) ( P < .05). ACC transplant resulted in improved quality of cartilage repair tissue compared with MST at 6 months postoperatively. Further studies are needed to investigate ACC as a possible alternative first-line treatment for focal cartilage injuries in the knee.

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.

Failure of in vitro-differentiated mesenchymal stem cells from the synovial membrane to form ectopic stable cartilage in vivo.

PubMed

De Bari, Cosimo; Dell'Accio, Francesco; Luyten, Frank P

2004-01-01

We previously reported the identification in a nude mouse assay of molecular markers predictive of the capacity of articular cartilage-derived cells (ACDCs) to form ectopic stable cartilage that is resistant to vascular invasion and endochondral ossification. In the present study, we investigated whether in vitro-differentiated mesenchymal stem cells (MSCs) from the synovial membrane (SM) express the stable-chondrocyte markers and form ectopic stable cartilage in vivo. Chondrogenesis was induced in micromass culture with the addition of transforming growth factor beta1 (TGFbeta1). After acquisition of the cartilage phenotype, micromasses were implanted subcutaneously into nude mice. Alternatively, cells were released enzymatically and either replated in monolayer or injected intramuscularly into nude mice. Marker analysis was performed by quantitative reverse transcription-polymerase chain reaction. Cell death was detected with TUNEL assay. Cartilage-like micromasses and released cells expressed the stable-chondrocyte markers at levels comparable with those expressed by stable ACDCs. The released cells lost chondrocyte marker expression by 24 hours in monolayer and failed to form cartilage when injected intramuscularly into nude mice. Instead, myogenic differentiation was detected. When intact TGFbeta1-treated micromasses were implanted subcutaneously, they partially lost their cartilage phenotype and underwent cell death and neoangiogenesis within 1 week. At later time points (15-40 days), we retrieved neither cartilage nor bone, and human cells were not detectable. The chondrocyte-like phenotype of human SM MSCs, induced in vitro under specific conditions, appears to be unstable and is not sufficient to obtain ectopic formation of stable cartilage in vivo. Studies in animal models of joint surface defect repair are necessary to evaluate the stability of the SM MSC chondrocyte-like phenotype within the joint environment.

Evaluation of articular cartilage repair using biodegradable nanofibrous scaffolds in a swine model: a pilot study.

PubMed

Li, Wan-Ju; Chiang, Hongsen; Kuo, Tzong-Fu; Lee, Hsuan-Shu; Jiang, Ching-Chuan; Tuan, Rocky S

2009-01-01

The aim of this study was to evaluate a cell-seeded nanofibrous scaffold for cartilage repair in vivo. We used a biodegradable poly(epsilon-caprolactone) (PCL) nanofibrous scaffold seeded with allogeneic chondrocytes or xenogeneic human mesenchymal stem cells (MSCs), or acellular PCL scaffolds, with no implant as a control to repair iatrogenic, 7 mm full-thickness cartilage defects in a swine model. Six months after implantation, MSC-seeded constructs showed the most complete repair in the defects compared to other groups. Macroscopically, the MSC-seeded constructs regenerated hyaline cartilage-like tissue and restored a smooth cartilage surface, while the chondrocyte-seeded constructs produced mostly fibrocartilage-like tissue with a discontinuous superficial cartilage contour. Incomplete repair containing fibrocartilage or fibrous tissue was found in the acellular constructs and the no-implant control group. Quantitative histological evaluation showed overall higher scores for the chondrocyte- and MSC-seeded constructs than the acellular construct and the no-implant groups. Mechanical testing showed the highest equilibrium compressive stress of 1.5 MPa in the regenerated cartilage produced by the MSC-seeded constructs, compared to 1.2 MPa in the chondrocyte-seeded constructs, 1.0 MPa in the acellular constructs and 0.2 MPa in the no-implant group. No evidence of immune reaction to the allogeneically- and xenogeneically-derived regenerated cartilage was observed, possibly related to the immunosuppressive activities of MSCs, suggesting the feasibility of allogeneic or xenogeneic transplantation of MSCs for cell-based therapy. Taken together, our results showed that biodegradable nanofibrous scaffolds seeded with MSCs effectively repair cartilage defects in vivo, and that the current approach is promising for cartilage repair. 2008 John Wiley & Sons, Ltd

Evaluation of articular cartilage repair using biodegradable nanofibrous scaffolds in a swine model: a pilot study

PubMed Central

Li, Wan-Ju; Chiang, Hongsen; Kuo, Tzong-Fu; Lee, Hsuan-Shu; Jiang, Ching-Chuan; Tuan, Rocky S.

2013-01-01

The aim of this study was to evaluate a cell-seeded nanofibrous scaffold for cartilage repair in vivo. We used a biodegradable poly(ε-caprolactone) (PCL) nanofibrous scaffold seeded with allogeneic chondrocytes or xenogeneic human mesenchymal stem cells (MSCs), or acellular PCL scaffolds, with no implant as a control to repair iatrogenic, 7 mm full-thickness cartilage defects in a swine model. Six months after implantation, MSC-seeded constructs showed the most complete repair in the defects compared to other groups. Macroscopically, the MSC-seeded constructs regenerated hyaline cartilage-like tissue and restored a smooth cartilage surface, while the chondrocyte-seeded constructs produced mostly fibrocartilage-like tissue with a discontinuous superficial cartilage contour. Incomplete repair containing fibrocartilage or fibrous tissue was found in the acellular constructs and the no-implant control group. Quantitative histological evaluation showed overall higher scores for the chondrocyte- and MSC-seeded constructs than the acellular construct and the no-implant groups. Mechanical testing showed the highest equilibrium compressive stress of 1.5 MPa in the regenerated cartilage produced by the MSC-seeded constructs, compared to 1.2 MPa in the chondrocyte-seeded constructs, 1.0 MPa in the acellular constructs and 0.2 MPa in the no-implant group. No evidence of immune reaction to the allogeneically- and xenogeneically-derived regenerated cartilage was observed, possibly related to the immunosuppressive activities of MSCs, suggesting the feasibility of allogeneic or xenogeneic transplantation of MSCs for cell-based therapy. Taken together, our results showed that biodegradable nanofibrous scaffolds seeded with MSCs effectively repair cartilage defects in vivo, and that the current approach is promising for cartilage repair. PMID:19004029

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.

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 the field of joint surgery.

Scavenger receptor class A type I/II determines matrix metalloproteinase-mediated cartilage destruction and chondrocyte death in antigen-induced arthritis.

PubMed

van Lent, P L E M; Hofkens, W; Blom, A B; Grevers, L; Sloetjes, A; Takahashi, N; van Tits, L J; Vogl, T; Roth, J; de Winther, M P; van den Berg, W B

2009-10-01

Scavenger receptor class A type I (SR-AI) and SR-AII are expressed by macrophages in particular and bind and internalize a broad range of molecules (including endotoxins, apoptotic bodies, and oxidized low-density lipoprotein). This study was undertaken to investigate the role of SR-AI/II in mediating severe cartilage destruction in antigen-induced arthritis (AIA). AIA was induced in the knee joints of SR-AI/II(-/-) mice and wild-type (WT) controls. Joint inflammation and cartilage destruction (chondrocyte death) were measured by examining the histology of total knee joints. Matrix metalloproteinase (MMP)-mediated neoepitopes were measured by immunolocalization using anti-VDIPEN antibodies and chondrocyte activation with anti-S100A8 antibodies. Messenger RNA (mRNA) levels were determined in inflamed synovium using microarray analysis and quantitative reverse transcriptase-polymerase chain reaction. In synovial washouts, cytokines (interleukin-1beta [IL-1beta], IL-10, and tumor necrosis factor alpha) and S100A8/S100A9 were measured using Luminex and enzyme-linked immunosorbent assay. Levels of SR-AI/II mRNA were strongly elevated in inflamed synovium in AIA. On days 2, 8, and 14 after AIA induction, joint inflammation (exudates/infiltrate) was similar between the 2 groups. In WT mice, severe cartilage destruction was found in multiple cartilage surfaces of the inflamed knee joint on day 14 after AIA induction. MMP-mediated matrix destruction ranged between 40% and 60%, and chondrocyte death was prominent in 40-75% of the cartilage surfaces. In striking contrast, in SR-AI/II(-/-) mice, despite comparable joint inflammation, pronounced cartilage destruction was almost completely absent. Levels of IL-1beta and S100A8/S100A9 were significantly lower on days 7 and 14 after AIA induction, but levels of mRNA for various MMPs (MMP-2, MMP-3, MMP-9, and MMP-13) were comparable. Our findings indicate that SR-AI and SR-AII are crucial receptors involved in mediating severe cartilage destruction in AIA.

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.

Hierarchy revealed in the specification of three skeletal fates by Sox9 and Runx2.

PubMed

Eames, B Frank; Sharpe, Paul T; Helms, Jill A

2004-10-01

Across vertebrates, there are three principal skeletal tissues: bone, persistent cartilage, and replacement cartilage. Although each tissue has a different evolutionary history and functional morphology, they also share many features. For example, they function as structural supports, they are comprised of cells embedded in collagen-rich extracellular matrix, and they derive from a common embryonic stem cell, the osteochondroprogenitor. Occasionally, homologous skeletal elements can change tissue type through phylogeny. Together, these observations raise the possibility that skeletal tissue identity is determined by a shared set of genes. Here, we show that misexpression of either Sox9 or Runx2 can substitute bone with replacement cartilage or can convert persistent cartilage into replacement cartilage and vice versa. Our data also suggest that these transcription factors function in a molecular hierarchy in which chondrogenic factors dominate. We propose a binary molecular code that determines whether skeletal tissues form as bone, persistent cartilage, or replacement cartilage. Finally, these data provide insights into the roles that master regulatory genes play during evolutionary change of the vertebrate skeleton.

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.

Capitellar Erosion after Radial Head Arthroplasty: A Comparative Biomechanical Study of Operated Radial Head Fractures on Cadaveric Specimens.

PubMed

Chytas, I D; Antonopoulos, C; Cheva, A; Givissis, P

2018-03-23

We asked whether either open reduction and internal fixation (ORIF) or radial head arthroplasty (RHA), common techniques used for the confrontation of displaced or comminuted radial head fractures, are correlated with cartilage wear of the capitulum. We hypothesized that neither ORIF nor RHA are correlated with capitellar cartilage wear. On 5 cadaveric elbow specimens, osteotomies were employed to simulate radial head comminuted fractures followed with ORIF by Herbert screws. Radial heads were also excised from other 5 cadaveric elbow specimens and were replaced by metallic monopolar implants. Finally 2 elbows were not operated and used as a control group. Custom-made rotary machines, working unstoppably, generated 700.000 pronation and supination forearm movements at an 110° arc of motion. The elbow joints were examined with pre- and postoperative Magnetic Resonance Imaging (MRI) scans and the articular surfaces of the capitula were resected and sent for histopathology study. In the 2 cadaveric elbows of the control group and the 4 elbows treated with ORIF no cartilage damage was found. The fifth one displayed cartilage fissures which were classified according to International Cartilage Repair Society (ICRS) grading system as grade I cartilage damage. On the contrary, all 5 elbows treated with RHA sustained complete cartilage loss, exposure of the subchondral bone and were classified as ICRS grade IV cartilage damage. Our study suggests that metallic monopolar RHA after a displaced or comminuted radial head fracture carries a high risk of rapidly evolving cartilage loss of the capitulum. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Human umbilical cord-derived mesenchymal stem cells reduce monosodium iodoacetate-induced apoptosis in cartilage

PubMed Central

Chang, Yu-Hsun; Wu, Kun-Chi; Liu, Hwan-Wun; Chu, Tang-Yuan; Ding, Dah-Ching

2018-01-01

Objective: The present study investigated the therapeutic potential and underlying mechanisms of human umbilical cord mesenchymal stem cells (HUCMSCs) on joint cartilage destruction induced by monosodium iodoacetate (MIA) in mice. Materials and Methods: HUCMSCs were tested for mesenchymal stem cell (MSC) characteristics including surface markers by flow cytometry and mesoderm differentiation (adipogenesis, osteogenesis, and chondrogenesis). Terminal deoxynucleotidyl transferase dUTP nick end labeling assay and Western blot assay were used to evaluate MIA-induced chondrocyte apoptosis. In the in vivo study, 18 mice were divided into three groups (n = 6 each); normal saline (control), MIA-treated, and MIA-treated/HUCMSC-transplantation. Rota-Rods tests were used to evaluate MIA-induced cartilage destruction behaviors in mice. Histological changes in the mice cartilage were examined by immunohistochemistry. Results: HUCMSCs had an immunophenotype similar to bone marrow-derived MSCs and were able to differentiate into adipocytes, osteocytes, and chondrocytes. Conditioned medium of the HUCMSCs exhibited an anti-apoptotic effect and inhibited expression of caspase 3 in MIA-treated chondrocytes. HUCMSC transplantation assisted in recovery from movement impairment (from 30% on day 7 to 115% on day 14) and in regeneration and repair of cartilage damaged by MIA. (International Cartilage Repair Society score: 3.8 in the MIA group vs. 10.2 in the HUCMSC-treated group); HUCMSC transplantation ameliorated cartilage apoptosis through the caspase 3 pathway in MIA-induced cartilage destruction in mice. Conclusion: Taken together, these observations suggest that HUCMSC transplantation appears to be effective in protecting cartilage from MIA damage. PMID:29875586

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

The Wnt5a Receptor, Receptor Tyrosine Kinase-Like Orphan Receptor 2, Is a Predictive Cell Surface Marker of Human Mesenchymal Stem Cells with an Enhanced Capacity for Chondrogenic Differentiation.

PubMed

Dickinson, Sally C; Sutton, Catherine A; Brady, Kyla; Salerno, Anna; Katopodi, Theoni; Williams, Rhys L; West, Christopher C; Evseenko, Denis; Wu, Ling; Pang, Suzanna; Ferro de Godoy, Roberta; Goodship, Allen E; Péault, Bruno; Blom, Ashley W; Kafienah, Wael; Hollander, Anthony P

2017-11-01

Multipotent mesenchymal stem cells (MSCs) have enormous potential in tissue engineering and regenerative medicine. However, until now, their development for clinical use has been severely limited as they are a mixed population of cells with varying capacities for lineage differentiation and tissue formation. Here, we identify receptor tyrosine kinase-like orphan receptor 2 (ROR2) as a cell surface marker expressed by those MSCs with an enhanced capacity for cartilage formation. We generated clonal human MSC populations with varying capacities for chondrogenesis. ROR2 was identified through screening for upregulated genes in the most chondrogenic clones. When isolated from uncloned populations, ROR2+ve MSCs were significantly more chondrogenic than either ROR2-ve or unfractionated MSCs. In a sheep cartilage-repair model, they produced significantly more defect filling with no loss of cartilage quality compared with controls. ROR2+ve MSCs/perivascular cells were present in developing human cartilage, adult bone marrow, and adipose tissue. Their frequency in bone marrow was significantly lower in patients with osteoarthritis (OA) than in controls. However, after isolation of these cells and their initial expansion in vitro, there was greater ROR2 expression in the population derived from OA patients compared with controls. Furthermore, osteoarthritis-derived MSCs were better able to form cartilage than MSCs from control patients in a tissue engineering assay. We conclude that MSCs expressing high levels of ROR2 provide a defined population capable of predictably enhanced cartilage production. Stem Cells 2017;35:2280-2291. © 2017 AlphaMed Press.

Dietary 2-oxoglutarate mitigates gastrectomy-evoked structural changes in cartilage of female rats.

PubMed

Dobrowolski, Piotr; Tomaszewska, Ewa; Kurlak, Paulina; Pierzynowski, Stefan G

2016-01-01

Gastrectomy (Gx) leads to osteopenia/osteoporosis in humans and animals. However, little is known about the influence of Gx on the cartilage in this regard. Recent studies have demonstrated a protective effect of 2-oxoglutaric acid (2-Ox) on bone and cartilage. Hence, the purpose of this study was to investigate whether 2-Ox can mitigate eventual Gx-induced cartilage impairment. Twenty female Sprague-Dawley rats were subjected to Gx and randomly divided into two groups: Gx + 2-Ox and Gx. Another 20 rats were sham-operated (ShO) and randomly divided into two groups: ShO + 2-Ox and ShO. The daily dose of 2-Ox administered to the rats in the drinking water was 0.43 g per 100 g rat. After eight weeks, rats were euthanized and femora and tibiae were collected. Histology and histomorphometry analyses of the articular cartilage and the growth plate were done. Gx resulted in a 32% (±44.5 femur, ±35.8 tibia) decrease in overall thickness of articular cartilage in both bones (femur: ShO 279.1 ± 48.5 vs. Gx 190.2 ± 38.4 µm, tibia: ShO 222.9 ± 50.3 µm vs. Gx 151.3 ± 52.6 µm) (in some zones up to 58 ± 28.0%), and in the growth plate up to 20% (±22.4) (femur: ShO 243.0 ± 34.0 vs. Gx 207.0 ± 33.7 µm, tibia: ShO 220.0 ± 24.6 µm vs. Gx 171.1 ± 16.1 µm). Gx altered the spatial distribution of thick and thin collagen fibers, and chondrocyte shape and size. 2-Ox administration prevented the reduction in both cartilages thickness (Gx + 2-Ox: articular cartilage 265.2 ± 53.8 µm, 235.6 ± 42.7 µm, growth plate 236.7 ± 39.2 µm, 191.3 ± 16.5 µm in femur and tibia, respectively), and abolished the spatial changes in collagen distribution and structure induced by Gx. Gx affects cartilage structure and thickness, however, 2-Ox administration mitigates these effects and showed protective and stimulatory properties. Our observations suggest that dietary 2-Ox can be used to offset some of the changes in hyaline cartilage, in particular articular cartilage, following bariatric surgeries. © 2016 by the Society for Experimental Biology and Medicine.

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

Calcium-containing (CaC) crystals, including basic calcium phosphate (BCP) and calcium pyrophosphate dihydrate (CPP), are associated with destructive forms of osteoarthritis (OA). We assessed their distribution and biochemical and morphologic features in human knee OA cartilage. We prospectively included 20 patients who underwent total knee replacement (TKR) for primary OA. CaC crystal characterization and identification involved Fourier-transform infra-red spectrometry and scanning electron microscopy of 8 to 10 cartilage zones of each knee, including medial and lateral femoral condyles and tibial plateaux and the intercondyle zone. Differential expression of genes involved in the mineralization process between cartilage with and without calcification was assessed in samples from 8 different patients by RT-PCR. Immunohistochemistry and histology studies were performed in 6 different patients. Mean (SEM) age and body mass index of patients at the time of TKR was 74.6 (1.7) years and 28.1 (1.6) kg/m², respectively. Preoperative X-rays showed joint calcifications (chondrocalcinosis) in 4 cases only. The medial femoro-tibial compartment was the most severely affected in all cases, and mean (SEM) Kellgren-Lawrence score was 3.8 (0.1). All 20 OA cartilages showed CaC crystals. The mineral content represented 7.7% (8.1%) of the cartilage weight. All patients showed BCP crystals, which were associated with CPP crystals for 8 joints. CaC crystals were present in all knee joint compartments and in a mean of 4.6 (1.7) of the 8 studied areas. Crystal content was similar between superficial and deep layers and between medial and femoral compartments. BCP samples showed spherical structures, typical of biological apatite, and CPP samples showed rod-shaped or cubic structures. The expression of several genes involved in mineralization, including human homolog of progressive ankylosis, plasma-cell-membrane glycoprotein 1 and tissue-nonspecific alkaline phosphatase, was 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.

Protective effects of total fraction of avocado/soybean unsaponifiables on the structural changes in experimental dog osteoarthritis: inhibition of nitric oxide synthase and matrix metalloproteinase-13.

PubMed

Boileau, Christelle; Martel-Pelletier, Johanne; Caron, Judith; Msika, Philippe; Guillou, Georges B; Baudouin, Caroline; Pelletier, Jean-Pierre

2009-01-01

The aims of this study were, first, to investigate the in vivo effects of treatment with avocado/soybean unsaponifiables on the development of osteoarthritic structural changes in the anterior cruciate ligament dog model and, second, to explore their mode of action. Osteoarthritis was induced by anterior cruciate ligament transection of the right knee in crossbred dogs. There were two treatment groups (n = 8 dogs/group), in which the animals received either placebo or avocado/soybean unsaponifiables (10 mg/kg per day), which were given orally for the entire duration of the study (8 weeks). We conducted macroscopic and histomorphological analyses of cartilage and subchondral bone of the femoral condyles and/or tibial plateaus. We also conducted immunohistochemical analyses in cartilage for the following antigens: inducible nitric oxide synthase, matrix metalloproteinase (MMP)-1, MMP-13, a disintegrin and metalloproteinase domain with thrombospondin motifs (ADAMTS)4 and ADAMTS5. The size of macroscopic lesions on the tibial plateaus was decreased (P = 0.04) in dogs treated with the avocado/soybean unsaponifiables. Histologically, in these animals the severity of cartilage lesions on both tibial plateaus and femoral condyles, and the cellular infiltration in synovium were significantly decreased (P = 0.0002 and P = 0.04, respectively). Treatment with avocado/soybean unsaponifiables also reduced loss of subchondral bone volume (P < 0.05) and calcified cartilage thickness (P = 0.01) compared with placebo. Immunohistochemical analysis of cartilage revealed that avocado/soybean unsaponifiables significantly reduced the level of inducible nitric oxide synthase (P < 0.05) and MMP-13 (P = 0.01) in cartilage. This study demonstrates that treatment with avocado/soybean unsaponifiables can reduce the development of early osteoarthritic cartilage and subchondral bone lesions in the anterior cruciate ligament dog model of osteoarthritis. This effect appears to be mediated through the inhibition of inducible nitric oxide synthase and MMP-13, which are key mediators of the structural changes that take place in osteoarthritis.

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.

Challenges in engineering osteochondral tissue grafts with hierarchical structures.

PubMed

Gadjanski, Ivana; Vunjak-Novakovic, Gordana

2015-01-01

A major hurdle in treating osteochondral (OC) defects is the different healing abilities of two types of tissues involved - articular cartilage and subchondral bone. Biomimetic approaches to OC-construct engineering, based on recapitulation of biological principles of tissue development and regeneration, have potential for providing new treatments and advancing fundamental studies of OC tissue repair. This review on state of the art in hierarchical OC tissue graft engineering is focused on tissue engineering approaches designed to recapitulate the native milieu of cartilage and bone development. These biomimetic systems are discussed with relevance to bioreactor cultivation of clinically sized, anatomically shaped human cartilage/bone constructs with physiologic stratification and mechanical properties. The utility of engineered OC tissue constructs is evaluated for their use as grafts in regenerative medicine, and as high-fidelity models in biological research. A major challenge in engineering OC tissues is to generate a functionally integrated stratified cartilage-bone structure starting from one single population of mesenchymal cells, while incorporating perfusable vasculature into the bone, and in bone-cartilage interface. To this end, new generations of advanced scaffolds and bioreactors, implementation of mechanical loading regimens and harnessing of inflammatory responses of the host will likely drive the further progress.

Medial meniscal posterior root/horn radial tears correlate with cartilage degeneration detected by T1ρ relaxation mapping.

PubMed

Takahashi, Kenji; Hashimoto, Sanshiro; Nakamura, Hiroshi; Mori, Atsushi; Sato, Akiko; Majima, Tokifumi; Takai, Shinro

2015-06-01

This study aimed to identify factors on routine pulse sequence MRI associated with cartilage degeneration observed on T1ρ relaxation mapping. This study included 137 subjects with knee pain. T1ρ values were measured in the regions of interest on the surface layer of the cartilage on mid-coronal images of the femorotibial joint. Assessment of cartilage, subchondral bone, meniscus and ligaments was performed using routine pulse sequence MRI. Radiographic evaluation for osteoarthritis was also performed. Multiple regression analysis revealed posterior root/horn tears to be independent factors increasing the T1ρ values of the cartilage in the medial compartment of the femorotibial joint. Even when adjusted for radiographically defined early-stage osteoarthritis, medial posterior meniscal radial tears significantly increased the T1ρ values. This study showed that posterior root/horn radial tears in the medial meniscus are particularly important MRI findings associated with cartilage degeneration observed on T1ρ relaxation mapping. Morphological factors of the medial meniscus on MRI provide findings useful for screening early-stage osteoarthritis. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

[Infrared radiation and magnetic field therapy ameliorates cartilage damage in rabbits with knee osteoarthritis].

PubMed

Sun, Jia-li; Fan, Jian-zhong; Song, Gui-zhi; Tan, Xiao-ming; Peng, Nan

2007-12-01

To evaluate the effect of infrared radiation and magnetic field therapy on cartilage damage in rabbits with knee osteoarthritis. Knee osteoarthritis was induced in 24 adult New Zealand rabbits by prolonged fixation of the knee joint in extension for 6 weeks. The rabbits were subsequently randomized into control group (without treatment), infrared therapy group, magnetic field therapy group and the combined infrared and magnetic field therapy group. At the end of the first, second and third weeks of the therapy, respectively, 2 rabbits from each group were sacrificed to observe the general changes and histopathology of the condylar cartilage of the femur, and the findings were assessed using Mankin scores. Compared with other groups, the rabbits in the combined therapy group showed significantly milder cartilage damage (including injury of the cartilage surface and chondrocyte's proliferation and disarrangement) with significantly lower Mankin scores (P<0.05). No significant differences were found in the findings between the two groups with exclusive infrared or magnetic field therapy (P>0.1). Combined infrared and magnetic field therapy can effectively alleviate cartilage destruction, shortens the disease course and enhance the therapeutic effects in rabbits with knee osteoarthritis.

Large, stratified, and mechanically functional human cartilage grown in vitro by mesenchymal condensation

PubMed Central

Bhumiratana, Sarindr; Eton, Ryan E.; Oungoulian, Sevan R.; Wan, Leo Q.; Ateshian, Gerard A.; Vunjak-Novakovic, Gordana

2014-01-01

The efforts to grow mechanically functional cartilage from human mesenchymal stem cells have not been successful. We report that clinically sized pieces of human cartilage with physiologic stratification and biomechanics can be grown in vitro by recapitulating some aspects of the developmental process of mesenchymal condensation. By exposure to transforming growth factor-β, mesenchymal stem cells were induced to condense into cellular bodies, undergo chondrogenic differentiation, and form cartilagenous tissue, in a process designed to mimic mesenchymal condensation leading into chondrogenesis. We discovered that the condensed mesenchymal cell bodies (CMBs) formed in vitro set an outer boundary after 5 d of culture, as indicated by the expression of mesenchymal condensation genes and deposition of tenascin. Before setting of boundaries, the CMBs could be fused into homogenous cellular aggregates giving rise to well-differentiated and mechanically functional cartilage. We used the mesenchymal condensation and fusion of CMBs to grow centimeter-sized, anatomically shaped pieces of human articular cartilage over 5 wk of culture. For the first time to our knowledge biomechanical properties of cartilage derived from human mesenchymal cells were comparable to native cartilage, with the Young’s modulus of >800 kPa and equilibrium friction coeffcient of <0.3. We also demonstrate that CMBs have capability to form mechanically strong cartilage–cartilage interface in an in vitro cartilage defect model. The CMBs, which acted as “lego-like” blocks of neocartilage, were capable of assembling into human cartilage with physiologic-like structure and mechanical properties. PMID:24778247

Feasibility of autologous bone marrow mesenchymal stem cell-derived extracellular matrix scaffold for cartilage tissue engineering.

PubMed

Tang, Cheng; Xu, Yan; Jin, Chengzhe; Min, Byoung-Hyun; Li, Zhiyong; Pei, Xuan; Wang, Liming

2013-12-01

Extracellular matrix (ECM) materials are widely used in cartilage tissue engineering. However, the current ECM materials are unsatisfactory for clinical practice as most of them are derived from allogenous or xenogenous tissue. This study was designed to develop a novel autologous ECM scaffold for cartilage tissue engineering. The autologous bone marrow mesenchymal stem cell-derived ECM (aBMSC-dECM) membrane was collected and fabricated into a three-dimensional porous scaffold via cross-linking and freeze-drying techniques. Articular chondrocytes were seeded into the aBMSC-dECM scaffold and atelocollagen scaffold, respectively. An in vitro culture and an in vivo implantation in nude mice model were performed to evaluate the influence on engineered cartilage. The current results showed that the aBMSC-dECM scaffold had a good microstructure and biocompatibility. After 4 weeks in vitro culture, the engineered cartilage in the aBMSC-dECM scaffold group formed thicker cartilage tissue with more homogeneous structure and higher expressions of cartilaginous gene and protein compared with the atelocollagen scaffold group. Furthermore, the engineered cartilage based on the aBMSC-dECM scaffold showed better cartilage formation in terms of volume and homogeneity, cartilage matrix content, and compressive modulus after 3 weeks in vivo implantation. These results indicated that the aBMSC-dECM scaffold could be a successful novel candidate scaffold for cartilage tissue engineering. © 2013 Wiley Periodicals, Inc. and International Center for Artificial Organs and Transplantation.

Advances in Application of Mechanical Stimuli in Bioreactors for Cartilage Tissue Engineering.

PubMed

Li, Ke; Zhang, Chunqiu; Qiu, Lulu; Gao, Lilan; Zhang, Xizheng

2017-08-01

Articular cartilage (AC) is the weight-bearing tissue in diarthroses. It lacks the capacity for self-healing once there are injuries or diseases due to its avascularity. With the development of tissue engineering, repairing cartilage defects through transplantation of engineered cartilage that closely matches properties of native cartilage has become a new option for curing cartilage diseases. The main hurdle for clinical application of engineered cartilage is how to develop functional cartilage constructs for mass production in a credible way. Recently, impressive hyaline cartilage that may have the potential to provide capabilities for treating large cartilage lesions in the future has been produced in laboratories. The key to functional cartilage construction in vitro is to identify appropriate mechanical stimuli. First, they should ensure the function of metabolism because mechanical stimuli play the role of blood vessels in the metabolism of AC, for example, acquiring nutrition and removing wastes. Second, they should mimic the movement of synovial joints and produce phenotypically correct tissues to achieve the adaptive development between the micro- and macrostructure and function. In this article, we divide mechanical stimuli into three types according to forces transmitted by different media in bioreactors, namely forces transmitted through the liquid medium, solid medium, or other media, then we review and summarize the research status of bioreactors for cartilage tissue engineering (CTE), mainly focusing on the effects of diverse mechanical stimuli on engineered cartilage. Based on current researches, there are several motion patterns in knee joints; but compression, tension, shear, fluid shear, or hydrostatic pressure each only partially reflects the mechanical condition in vivo. In this study, we propose that rolling-sliding-compression load consists of various stimuli that will represent better mechanical environment in CTE. In addition, engineers often ignore the importance of biochemical factors to the growth and development of engineered cartilage. In our point of view, only by fully considering synergistic effects of mechanical and biochemical factors can we find appropriate culture conditions for functional cartilage constructs. Once again, rolling-sliding-compression load under appropriate biochemical conditions may be conductive to realize the adaptive development between the structure and function of engineered cartilage in vitro.

Associations between measures of adiposity over 10 years and patella cartilage in population-based asymptomatic women.

PubMed

Gunardi, A J; Brennan, S L; Wang, Y; Cicuttini, F M; Pasco, J A; Kotowicz, M A; Nicholson, G C; Wluka, A E

2013-12-01

Osteoarthritis (OA) most commonly affects the patellofemoral compartment of the knee, and is a major cause of pain and disability. Structural changes that evolve prior to the onset of symptoms can be visualised using magnetic resonance imaging (MRI). There is little known information about the role of adiposity on the early structural changes in the patella cartilage in younger, asymptomatic adult females. One hundred and sixty asymptomatic women (20-49 years) participating in the Geelong Osteoporosis Study underwent knee MRI (2006-8). Weight and body mass index (BMI) were measured 10 years prior (1994-7, baseline) and at the time of MRI (current), with change over the period calculated (current-baseline). Relationships between measures of adiposity and patella cartilage volume and defects were examined. After adjustment for age and patella bone volume, there was a reduction of 13 ml (95% confidence interval (95% CI), -25.7, -0.55) in patella cartilage volume for every 1 unit increase in current BMI, and a reduction of 27 ml (95% CI -52.6, -1.5) per BMI unit increase over 10 years (P=0.04 for both). No significant association was observed between baseline BMI and patella cartilage volume (P=0.16). Increased baseline and current weight and BMI were associated with increased prevalence of patella cartilage defects (all P<0.001). Adiposity and weight gain during midlife are associated with detrimental structural change at the patella in young to middle-aged healthy non-osteoarthritic women. Maintaining a healthy weight and avoiding weight gain in younger asymptomatic women may be important in the prevention of patellofemoral OA.

Growth Factor Stimulation Improves the Structure and Properties of Scaffold-Free Engineered Auricular Cartilage Constructs

PubMed Central

Rosa, Renata G.; Joazeiro, Paulo P.; Bianco, Juares; Kunz, Manuela; Weber, Joanna F.; Waldman, Stephen D.

2014-01-01

The reconstruction of the external ear to correct congenital deformities or repair following trauma remains a significant challenge in reconstructive surgery. Previously, we have developed a novel approach to create scaffold-free, tissue engineering elastic cartilage constructs directly from a small population of donor cells. Although the developed constructs appeared to adopt the structural appearance of native auricular cartilage, the constructs displayed limited expression and poor localization of elastin. In the present study, the effect of growth factor supplementation (insulin, IGF-1, or TGF-β1) was investigated to stimulate elastogenesis as well as to improve overall tissue formation. Using rabbit auricular chondrocytes, bioreactor-cultivated constructs supplemented with either insulin or IGF-1 displayed increased deposition of cartilaginous ECM, improved mechanical properties, and thicknesses comparable to native auricular cartilage after 4 weeks of growth. Similarly, growth factor supplementation resulted in increased expression and improved localization of elastin, primarily restricted within the cartilaginous region of the tissue construct. Additional studies were conducted to determine whether scaffold-free engineered auricular cartilage constructs could be developed in the 3D shape of the external ear. Isolated auricular chondrocytes were grown in rapid-prototyped tissue culture molds with additional insulin or IGF-1 supplementation during bioreactor cultivation. Using this approach, the developed tissue constructs were flexible and had a 3D shape in very good agreement to the culture mold (average error <400 µm). While scaffold-free, engineered auricular cartilage constructs can be created with both the appropriate tissue structure and 3D shape of the external ear, future studies will be aimed assessing potential changes in construct shape and properties after subcutaneous implantation. PMID:25126941

Cricoid cartilage masquerading as a tumour on thyroid ultrasound.

PubMed

Strauss, S

1999-07-01

On ultrasound scanning of the thyroid gland in a sagittal plane, the cricoid cartilage can falsely create the impression of a mass in the gland if the transducer is angled slightly medially. The illusion of a mass is fortified on transverse view if the cricothyroid and inferior pharyngeal constrictor muscles, which lie between the upper pole of the thyroid gland and the cricoid cartilage, are misinterpreted as a solid lesion. The purpose of this study was to describe the ultrasound features of the cricoid cartilage and to determine the frequency in which a pseudolesion is created. In 15 of 26 volunteers the cartilage was seen as a hypoechoic structure surrounded by an anechoic halo and containing foci of calcification, closely resembling a thyroid nodule. In 11 of the subjects, with a mean age of 55 years, the cartilage was heavily calcified, poorly visualized and did not simulate a thyroid lesion. Awareness of the cause and appearance of this pseudolesion should help radiologists avoid a potential pitfall and prevent unnecessary invasive procedures.

Automatic knee cartilage delineation using inheritable segmentation

NASA Astrophysics Data System (ADS)

Dries, Sebastian P. M.; Pekar, Vladimir; Bystrov, Daniel; Heese, Harald S.; Blaffert, Thomas; Bos, Clemens; van Muiswinkel, Arianne M. C.

2008-03-01

We present a fully automatic method for segmentation of knee joint cartilage from fat suppressed MRI. The method first applies 3-D model-based segmentation technology, which allows to reliably segment the femur, patella, and tibia by iterative adaptation of the model according to image gradients. Thin plate spline interpolation is used in the next step to position deformable cartilage models for each of the three bones with reference to the segmented bone models. After initialization, the cartilage models are fine adjusted by automatic iterative adaptation to image data based on gray value gradients. The method has been validated on a collection of 8 (3 left, 5 right) fat suppressed datasets and demonstrated the sensitivity of 83+/-6% compared to manual segmentation on a per voxel basis as primary endpoint. Gross cartilage volume measurement yielded an average error of 9+/-7% as secondary endpoint. For cartilage being a thin structure, already small deviations in distance result in large errors on a per voxel basis, rendering the primary endpoint a hard criterion.

An update on risk factors for cartilage loss in knee osteoarthritis assessed using MRI-based semiquantitative grading methods.

PubMed

Alizai, Hamza; Roemer, Frank W; Hayashi, Daichi; Crema, Michel D; Felson, David T; Guermazi, Ali

2015-03-01

Arthroscopy-based semiquantitative scoring systems such as Outerbridge and Noyes' scores were the first to be developed for the purpose of grading cartilage defects. As magnetic resonance imaging (MRI) became available for evaluation of the osteoarthritic knee joint, these systems were adapted for use with MRI. Later on, grading methods such as the Whole Organ Magnetic Resonance Score, the Boston-Leeds Osteoarthritis Knee Score and the MRI Osteoarthritis Knee Score were designed specifically for performing whole-organ assessment of the knee joint structures, including cartilage. Cartilage grades on MRI obtained with these scoring systems represent optimal outcome measures for longitudinal studies, and are designed to enhance understanding of the knee osteoarthritis disease process. The purpose of this narrative review is to describe cartilage assessment in knee osteoarthritis using currently available MRI-based semiquantitative whole-organ scoring systems, and to provide an update on the risk factors for cartilage loss in knee osteoarthritis as assessed with these scoring systems.

Cartilage tissue engineering approaches applicable in orthopaedic surgery: the past, the present, and the future.

PubMed

Khan, Wasim S; Hardingham, Timothy E

2012-01-01

Tissue is frequently damaged or lost in injury and disease. There has been an increasing interest in stem cell applications and tissue engineering approaches in surgical practice to deal with damaged or lost tissue. Although there have been developments in almost all surgical disciplines, the greatest advances are being made in orthopaedics, especially in cartilage repair. This is due to many factors including the familiarity with bone marrow derived mesenchymal stem cells and cartilage being a relatively simpler tissue to engineer. Unfortunately significant hurdles remain to be overcome in many areas before tissue engineering becomes more routinely used in clinical practice. In this paper we discuss the structure, function and embryology of cartilage and osteoarthritis. This is followed by a review of current treatment strategies for the repair of cartilage and the use of tissue engineering.

Cell Therapy and Tissue Engineering Approaches for Cartilage Repair and/or Regeneration

PubMed Central

Mardones, Rodrigo; Jofré, Claudio M.; Minguell, José J.

2015-01-01

Articular cartilage injuries caused by traumatic, mechanical and/or by progressive degeneration result in pain, swelling, subsequent loss of joint function and finally osteoarthritis. Due to the peculiar structure of the tissue (no blood supply), chondrocytes, the unique cellular phenotype in cartilage, receive their nutrition through diffusion from the synovial fluid and this limits their intrinsic capacity for healing. The first cellular avenue explored for cartilage repair involved the in situ transplantation of isolated chondrocytes. Latterly, an improved alternative for the above reparative strategy involved the infusion of mesenchymal stem cells (MSC), which in addition to a self-renewal capacity exhibit a differentiation potential to chondrocytes, as well as a capability to produce a vast array of growth factors, cytokines and extracellular matrix compounds involved in cartilage development. In addition to the above and foremost reparative options up till now in use, other therapeutic options have been developed, comprising the design of biomaterial substrates (scaffolds) capable of sustaining MSC attachment, proliferation and differentiation. The implantation of these engineered platforms, closely to the site of cartilage damage, may well facilitate the initiation of an ‘in situ’ cartilage reparation process. In this mini-review, we examined the timely and conceptual development of several cell-based methods, designed to repair/regenerate a damaged cartilage. In addition to the above described cartilage reparative options, other therapeutic alternatives still in progress are portrayed. PMID:26019754

Cell Therapy and Tissue Engineering Approaches for Cartilage Repair and/or Regeneration.

PubMed

Mardones, Rodrigo; Jofré, Claudio M; Minguell, José J

2015-05-01

Articular cartilage injuries caused by traumatic, mechanical and/or by progressive degeneration result in pain, swelling, subsequent loss of joint function and finally osteoarthritis. Due to the peculiar structure of the tissue (no blood supply), chondrocytes, the unique cellular phenotype in cartilage, receive their nutrition through diffusion from the synovial fluid and this limits their intrinsic capacity for healing. The first cellular avenue explored for cartilage repair involved the in situ transplantation of isolated chondrocytes. Latterly, an improved alternative for the above reparative strategy involved the infusion of mesenchymal stem cells (MSC), which in addition to a self-renewal capacity exhibit a differentiation potential to chondrocytes, as well as a capability to produce a vast array of growth factors, cytokines and extracellular matrix compounds involved in cartilage development. In addition to the above and foremost reparative options up till now in use, other therapeutic options have been developed, comprising the design of biomaterial substrates (scaffolds) capable of sustaining MSC attachment, proliferation and differentiation. The implantation of these engineered platforms, closely to the site of cartilage damage, may well facilitate the initiation of an 'in situ' cartilage reparation process. In this mini-review, we examined the timely and conceptual development of several cell-based methods, designed to repair/regenerate a damaged cartilage. In addition to the above described cartilage reparative options, other therapeutic alternatives still in progress are portrayed.

Use of a Bioactive Scaffold to Stimulate ACL Healing Also Minimizes Post-traumatic Osteoarthritis after Surgery

PubMed Central

Murray, Martha M.; Fleming, Braden C.

2013-01-01

Background While ACL reconstruction is the treatment gold standard for ACL injury, it does not reduce the risk of post-traumatic osteoarthritis. Therefore, new treatments that minimize this postoperative complication are of interest. Bio-enhanced ACL repair, in which a bioactive scaffold is used to stimulate healing of an ACL transection, has shown considerable promise in short term studies. The long-term results of this technique and the effects of the bio-enhancement on the articular cartilage have not been previously evaluated in a large animal model. Hypothesis 1) The structural (tensile) properties of the porcine ACL at 6 and 12 months after injury are similar when treated with bio-enhanced ACL repair, bio-enhanced ACL reconstruction, or conventional ACL reconstruction, and all treatments yield results superior to untreated ACL transection. 2) After one year, macroscopic cartilage damage following bio-enhanced ACL repair is similar to bio-enhanced ACL reconstruction and less than conventional ACL reconstruction and untreated ACL transection. Study Design Controlled laboratory study (porcine model) Methods Sixty-two Yucatan mini-pigs underwent ACL transection and randomization to four experimental groups: 1) no treatment, 2) conventional ACL reconstruction, 3) “bio-enhanced” ACL reconstruction using a bioactive scaffold, and 4) “bio-enhanced” ACL repair using a bioactive scaffold. The biomechanical properties of the ligament or graft and macroscopic assessments of the cartilage surfaces were performed after 6 and 12 months of healing. Results The structural properties (i.e., linear stiffness, yield and maximum loads) of the ligament following bio-enhanced ACL repair were not significantly different from bio-enhanced ACL reconstruction or conventional ACL reconstruction, but were significantly greater than untreated ACL transection after 12 months of healing. Macroscopic cartilage damage after bio-enhanced ACL repair was significantly less than untreated ACL transection and bio-enhanced ACL reconstruction, and there was a strong trend (p=.068) that it was less than conventional ACL reconstruction in the porcine model at 12 months. Conclusions Bio-enhanced ACL repair produces a ligament that is biomechanically similar to an ACL graft and provides chondroprotection to the joint following ACL surgery. Clinical Relevance Bio-enhanced ACL repair may provide a new less invasive treatment option that reduces cartilage damage following joint injury. PMID:23857883

[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.

Management of prominent ears: personal approach.

PubMed

Pérez-Macias, José Manuel

2008-03-01

Various methods for correcting prominent ears have been reported. Although anterior cartilage antihelix abrasion combined with posterior retention sutures is a conventional procedure, it does not include anterior conchal cartilage abrasion and thus allows easier reduction of the condromastoid angle. A simple and effective technique is described that involves using a rasp to score the whole anterior surface of the auricular cartilage, including the concha, in combination with Mustarde-type conchal-antihelical and conchal-mastoid retention sutures. This method was applied to 342 patients (675 ears) over 23 years, who were followed up for periods varying from 18 to 24 months. Good results were obtained for all patients with minimal complications.

MRI EVALUATION OF KNEE CARTILAGE

PubMed Central

Rodrigues, Marcelo Bordalo; Camanho, Gilberto Luís

2015-01-01

Through the ability of magnetic resonance imaging (MRI) to characterize soft tissue noninvasively, it has become an excellent method for evaluating cartilage. The development of new and faster methods allowed increased resolution and contrast in evaluating chondral structure, with greater diagnostic accuracy. In addition, physiological techniques for cartilage assessment that can detect early changes before the appearance of cracks and erosion have been developed. In this updating article, the various techniques for chondral assessment using knee MRI will be discussed and demonstrated. PMID:27022562

[Imaging assessment of bone and cartilage destruction in rheumatoid arthritis].

PubMed

Hirata, Shintaro; Tanaka, Yoshiya

2015-12-01

Rheumatoid arthritis (RA) is characterized by synovitis and subsequent joint destruction involving bone and cartilage. Recent therapeutic development have improved outcomes including disease activity and structural progression in RA, and standardized procedures of imaging assessment including modified total Sharp score (mTSS) have contributed largely for the development of therapeutic strategy. In addition, ultrasonography and MRI of joints have been recently emerging as novel imaging methods for RA. Here, we review current imaging assessments of bone and cartilage destruction in RA.

Smart Polymeric Hydrogels for Cartilage Tissue Engineering: A Review on the Chemistry and Biological Functions.

PubMed

Eslahi, Niloofar; Abdorahim, Marjan; Simchi, Abdolreza

2016-11-14

Stimuli responsive hydrogels (SRHs) are attractive bioscaffolds for tissue engineering. The structural similarity of SRHs to the extracellular matrix (ECM) of many tissues offers great advantages for a minimally invasive tissue repair. Among various potential applications of SRHs, cartilage regeneration has attracted significant attention. The repair of cartilage damage is challenging in orthopedics owing to its low repair capacity. Recent advances include development of injectable hydrogels to minimize invasive surgery with nanostructured features and rapid stimuli-responsive characteristics. Nanostructured SRHs with more structural similarity to natural ECM up-regulate cell-material interactions for faster tissue repair and more controlled stimuli-response to environmental changes. This review highlights most recent advances in the development of nanostructured or smart hydrogels for cartilage tissue engineering. Different types of stimuli-responsive hydrogels are introduced and their fabrication processes through physicochemical procedures are reported. The applications and characteristics of natural and synthetic polymers used in SRHs are also reviewed with an outline on clinical considerations and challenges.

A biomimetic three-dimensional woven composite scaffold for functional tissue engineering of cartilage

NASA Astrophysics Data System (ADS)

Moutos, Franklin T.; Freed, Lisa E.; Guilak, Farshid

2007-02-01

Tissue engineering seeks to repair or regenerate tissues through combinations of implanted cells, biomaterial scaffolds and biologically active molecules. The rapid restoration of tissue biomechanical function remains an important challenge, emphasizing the need to replicate structural and mechanical properties using novel scaffold designs. Here we present a microscale 3D weaving technique to generate anisotropic 3D woven structures as the basis for novel composite scaffolds that are consolidated with a chondrocyte-hydrogel mixture into cartilage tissue constructs. Composite scaffolds show mechanical properties of the same order of magnitude as values for native articular cartilage, as measured by compressive, tensile and shear testing. Moreover, our findings showed that porous composite scaffolds could be engineered with initial properties that reproduce the anisotropy, viscoelasticity and tension-compression nonlinearity of native articular cartilage. Such scaffolds uniquely combine the potential for load-bearing immediately after implantation in vivo with biological support for cell-based tissue regeneration without requiring cultivation in vitro.

Multimodal nonlinear optical imaging of cartilage development in mouse model

NASA Astrophysics Data System (ADS)

He, Sicong; Xue, Wenqian; Sun, Qiqi; Li, Xuesong; Huang, Jiandong; Qu, Jianan Y.

2017-02-01

Kinesin-1 is a kind of motor protein responsible for intracellular transportation and has been studied in a variety of tissues. However, its roles in cartilage development are not clear. In this study, a kinesin-1 heavy chain (Kif5b) knockout mouse model is used to study the functions of kinesin-1 in the cartilage development. We developed a multimodal nonlinear optical (NLO) microscope system integrating stimulated Raman scattering (SRS), second harmonic generation (SHG) and two-photon excited fluorescence (TPEF) to investigate the morphological and biomedical characteristics of fresh tibial cartilage from normal and mutant mice at different developmental stages. The combined forward and backward SHG imaging resolved the fine structure of collagen fibrils in the extracellular matrix of cartilage. Meanwhile, the chondrocyte morphology in different zones of cartilage was visualized by label-free SRS and TPEF images. The results show that the fibrillar collagen in the superficial zone of cartilage in postnatal day 10 and 15 (P10 and P15) knockout mice was significantly less than that of control mice. Moreover, we observed distorted morphology and disorganization of columnar arrangement of chondrocytes in the growth plate cartilage of mutant mice. This study reveals the significant roles of kinesin-1 in collagen formation and chondrocyte morphogenesis.

Isolated effects of external bath osmolality, solute concentration, and electrical charge on solute transport across articular cartilage.

PubMed

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

2016-12-01

The metabolic function of cartilage primarily depends on transport of solutes through diffusion mechanism. In the current study, we use contrast enhanced micro-computed tomography to determine equilibrium concentration of solutes through different cartilage zones and solute flux in the cartilage, using osteochondral plugs from equine femoral condyles. Diffusion experiments were performed with two solutes of different charge and approximately equal molecular weight, namely iodixanol (neutral) and ioxaglate (charge=-1) in order to isolate the effects of solute's charge on diffusion. Furthermore, solute concentrations as well as bath osmolality were changed to isolate the effects of steric hindrance on diffusion. Bath concentration and bath osmolality only had minor effects on the diffusion of the neutral solute through cartilage at the surface, middle and deep zones, indicating that the diffusion of the neutral solute was mainly Fickian. The negatively charged solute diffused considerably slower through cartilage than the neutral solute, indicating a large non-Fickian contribution in the diffusion of charged molecules. The numerical models determined maximum solute flux in the superficial zone up to a factor of 2.5 lower for the negatively charged solutes (charge=-1) as compared to the neutral solutes confirming the importance of charge-matrix interaction in diffusion of molecules across cartilage. Copyright © 2016 IPEM. Published by Elsevier Ltd. All rights reserved.

Tribological properties of PVA/PVP blend hydrogels against articular cartilage.

PubMed

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

2018-02-01

This research investigated in-vitro tribological performance of the articulation of cartilage-on- polyvinyl alcohol (PVA) and polyvinyl pyrrolidone (PVP) blend hydrogels using a custom-designed multi-directional wear rig. The hydrogels were prepared by repeated freezing-thawing cycles at different concentrations and PVA to PVP fractions at a given concentration. PVA/PVP blend hydrogels showed low coefficient of friction (COF) values (between 0.12 ± 0.01 and 0.14 ± 0.02) which were closer to the cartilage-on-cartilage articulation (0.03 ± 0.01) compared to the cartilage-on-stainless steel articulation (0.46 ± 0.06). The COF increased with increasing hydrogel concentration (p = 0.03) and decreasing PVP content at a given concentration (p < 0.05). The cartilage-on-hydrogel tests showed only the surface layers of the cartilage being removed (average volume loss of the condyles was 12.5 ± 4.2mm 3 ). However, the hydrogels were found to be worn/deformed. The hydrogels prepared at a higher concentration showed lower apparent volume loss. A strong correlation (R 2 = 0.94) was found between the COF and compressive moduli of the hydrogel groups, resulting from decreasing contact congruency. It was concluded that the hydrogels were promising as hemiarthroplasty materials, but that improved mechanical behaviour was required for clinical use. Copyright © 2017 Elsevier Ltd. All rights reserved.

Additive manufacturing and mechanical characterization of graded porosity scaffolds designed based on triply periodic minimal surface architectures.

PubMed

Afshar, M; Anaraki, A Pourkamali; Montazerian, H; Kadkhodapour, J

2016-09-01

Since the advent of additive manufacturing techniques, triply periodic minimal surfaces have emerged as a novel tool for designing porous scaffolds. Whereas scaffolds are expected to provide multifunctional performance, spatially changing pore patterns have been a promising approach to integrate mechanical characteristics of different architectures into a unique scaffold. Smooth morphological variations are also frequently seen in nature particularly in bone and cartilage structures and can be inspiring for designing of artificial tissues. In this study, we carried out experimental and numerical procedures to uncover the mechanical properties and deformation mechanisms of linearly graded porosity scaffolds for two different mathematically defined pore structures. Among TPMS-based scaffolds, P and D surfaces were subjected to gradient modeling to explore the mechanical responses for stretching and bending dominated deformations, respectively. Moreover, the results were compared to their corresponding uniform porosity structures. Mechanical properties were found to be by far greater for the stretching dominated structure (P-Surface). For bending dominated architecture (D-Surface), although there was no global fracture for uniform structures, graded structure showed a brittle fracture at 0.08 strain. A layer by layer deformation mechanism for stretching dominated structure was observed. For bending dominated scaffolds, deformation was accompanied by development of 45° shearing bands. Finite element simulations were also performed and the results showed a good agreement with the experimental observations. Copyright © 2016 Elsevier Ltd. All rights reserved.

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 to contribute to tissue renewal and homeostasis, the derivation, biological function, and application potential of stem/progenitor cells found in adult human articular cartilage are incompletely understood. This study reports the derivation of a population of cartilage stem/progenitor cells from fully differentiated chondrocytes under specific culture conditions, which have the potential to reassume their chondrocytic phenotype for efficient cartilage regeneration. These findings support the possibility of using in vitro amplified chondrocyte-derived progenitor cells for joint cartilage repair. PMID:27130221

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 contribute to tissue renewal and homeostasis, the derivation, biological function, and application potential of stem/progenitor cells found in adult human articular cartilage are incompletely understood. This study reports the derivation of a population of cartilage stem/progenitor cells from fully differentiated chondrocytes under specific culture conditions, which have the potential to reassume their chondrocytic phenotype for efficient cartilage regeneration. These findings support the possibility of using in vitro amplified chondrocyte-derived progenitor cells for joint cartilage repair. ©AlphaMed Press.

Toward understanding the role of cartilage particulates in synovial inflammation.

PubMed

Silverstein, A M; Stefani, R M; Sobczak, E; Tong, E L; Attur, M G; Shah, R P; Bulinski, J C; Ateshian, G A; Hung, C T

2017-08-01

Arthroscopy with lavage and synovectomy can remove tissue debris from the joint space and the synovial lining to provide pain relief to patients with osteoarthritis (OA). Here, we developed an in vitro model to study the interaction of cartilage wear particles with fibroblast-like synoviocytes (FLS) to better understand the interplay of cartilage particulates with cytokines on cells of the synovium. In this study sub-10 μm cartilage particles or 1 μm latex particles were co-cultured with FLS ±10 ng/mL interleukin-1α (IL-1α) or tumor necrosis factor-α (TNF-α). Samples were analyzed for DNA, glycosaminoglycan (GAG), and collagen, and media samples were analyzed for media GAG, nitric oxide (NO) and prostaglandin-E2 (PGE2). The nature of the physical interaction between the particles and FLS was determined by microscopy. Both latex and cartilage particles could be phagocytosed by FLS. Cartilage particles were internalized and attached to the surface of both dense monolayers and individual cells. Co-culture of FLS with cartilage particulates resulted in a significant increase in cell sheet DNA and collagen content as well as NO and PGE2 synthesis compared to control and latex treated groups. The proliferative response of FLS to cartilage wear particles resulted in an overall increase in extracellular matrix (ECM) content, analogous to the thickening of the synovial lining observed in OA patients. Understanding how cartilage particles interface with the synovium may provide insight into how this interaction contributes to OA progression and may guide the role of lavage and synovectomy for degenerative disease. Copyright © 2017 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

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.

PTH [1-34]-induced alterations of the subchondral bone provoke early osteoarthritis.

PubMed

Orth, P; Cucchiarini, M; Wagenpfeil, S; Menger, M D; Madry, H

2014-06-01

To test the hypothesis that changes in the subchondral bone induced by parathyroid hormone (PTH [1-34]) reciprocally affect the integrity of the articular cartilage within a naïve osteochondral unit in vivo. Daily subcutaneous injections of 10 μg PTH [1-34]/kg were given to adult rabbits for 6 weeks, controls received saline. Blood samples were continuously collected to monitor renal function. The subchondral bone plate and subarticular spongiosa of the femoral heads were separately assessed by micro-computed tomography. Articular cartilage was evaluated by macroscopic and histological osteoarthritis scoring, polarized light microscopy, and immunohistochemical determination of type-I, type-II, type-X collagen contents, PTH [1-34] receptor and caspase-3 expression. Absolute and relative extents of hyaline and calcified articular cartilage layers were measured histomorphometrically. The correlation between PTH-induced changes in subchondral bone and articular cartilage was determined. PTH [1-34] enhanced volume, mineral density, and trabecular thickness within the subarticular spongiosa, and increased thickness of the calcified cartilage layer (all P < 0.05). Moreover, PTH [1-34] led to cartilage surface irregularities and reduced matrix staining (both P < 0.03). These early osteoarthritic changes correlated with and were ascribed to the increased thickness of the calcified cartilage layer (P = 0.026) and enhanced mineral density of the subarticular spongiosa (P = 0.001). Modifications of the subarticular spongiosa by PTH [1-34] cause broadening of the calcified cartilage layer, resulting in osteoarthritic cartilage degeneration. These findings identify a mechanism by which PTH-induced alterations of the normal subchondral bone microarchitecture may provoke early osteoarthritis. Copyright © 2014 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Distribution of Basement Membrane Molecules, Laminin and Collagen Type IV, in Normal and Degenerated Cartilage Tissues.

PubMed

Foldager, Casper Bindzus; Toh, Wei Seong; Gomoll, Andreas H; Olsen, Bjørn Reino; Spector, Myron

2014-04-01

The objective of the present study was to investigate the presence and distribution of 2 basement membrane (BM) molecules, laminin and collagen type IV, in healthy and degenerative cartilage tissues. Normal and degenerated tissues were obtained from goats and humans, including articular knee cartilage, the intervertebral disc, and meniscus. Normal tissue was also obtained from patella-tibial enthesis in goats. Immunohistochemical analysis was performed using anti-laminin and anti-collagen type IV antibodies. Human and goat skin were used as positive controls. The percentage of cells displaying the pericellular presence of the protein was graded semiquantitatively. When present, laminin and collagen type IV were exclusively found in the pericellular matrix, and in a discrete layer on the articulating surface of normal articular cartilage. In normal articular (hyaline) cartilage in the human and goat, the proteins were found co-localized pericellularly. In contrast, in human osteoarthritic articular cartilage, collagen type IV but not laminin was found in the pericellular region. Nonpathological fibrocartilaginous tissues from the goat, including the menisci and the enthesis, were also positive for both laminin and collagen type IV pericellularly. In degenerated fibrocartilage, including intervertebral disc, as in degenerated hyaline cartilage only collagen type IV was found pericellularly around chondrocytes but with less intense staining than in non-degenerated tissue. In calcified cartilage, some cells were positive for laminin but not type IV collagen. We report differences in expression of the BM molecules, laminin and collagen type IV, in normal and degenerative cartilaginous tissues from adult humans and goats. In degenerative tissues laminin is depleted from the pericellular matrix before collagen type IV. The findings may inform future studies of the processes underlying cartilage degeneration and the functional roles of these 2 extracellular matrix proteins, normally associated with BM.

Middle Ear Mechanics of Cartilage Tympanoplasty Evaluated by Laser Holography and Vibrometry

PubMed Central

Aarnisalo, Antti A.; Cheng, Jeffrey T.; Ravicz, Michael E.; Hulli, Nesim; Harrington, Ellery J.; Hernandez-Montes, Maria S.; Furlong, Cosme; Merchant, Saumil N.; Rosowski, John J.

2010-01-01

Goals To assess the effects of thickness and position of cartilage used to reconstruct the tympanic membrane (TM) using a novel technique, time-averaged laser holography. Background Cartilage is commonly used in TM reconstruction to prevent formation of retraction pockets. The thickness, position, and shape of the cartilage graft may adversely affect TM motion and hearing. We sought to systematically investigate these parameters in an experimental setting. Methods Computer-assisted optoelectronic laser holography was used in 4 human cadaveric temporal bones to study sound-induced TM motion for 500 Hz to 8 kHz. Stapes velocity was measured with a laser Doppler vibrometer. Baseline (control) measurements were made with the TM intact. Measurements were repeated after a 0.5- or 1.0-mm-thick oval piece of conchal cartilage was placed on the medial TM surface in the posterior-superior quadrant. The cartilage was rotated so that it was either in contact with the bony tympanic rim and manubrium or not. Results At frequencies less than 4 kHz, the cartilage graft had only minor effects on the overall TM fringe patterns. The different conditions had no effects on stapes velocity. Greater than 4 kHz, TM motion was reduced over the grafted TM, both with 0.5- and 1.0-mm-thick grafts. No significant differences in stapes velocity were seen with the 2 different thicknesses of cartilage compared with control. Conclusion Computer-assisted optoelectronic laser holography is a promising technique to investigate middle ear mechanics after tympanoplasty. Such positioning may prevent postoperative TM retraction. These findings and conclusions apply to cartilage placed in the posterior-superior TM quadrant. PMID:19779389

Delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) of cadaveric shoulders: comparison of contrast dynamics in hyaline and fibrous cartilage after intraarticular gadolinium injection.

PubMed

Wiener, E; Hodler, J; Pfirrmann, C W A

2009-01-01

Delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC) is a novel method to investigate cartilaginous and fibrocartilaginous structures. To investigate the contrast dynamics in hyaline and fibrous cartilage of the glenohumeral joint after intraarticular injection of gadopentetate dimeglumine. Transverse T(1) maps were acquired on a 1.5T scanner before and after intraarticular injection of 2.0 mmol/l gadopentetate dimeglumine in five cadaveric shoulders using a dual flip angle three-dimensional gradient echo (3D-GRE) sequence. The acquisition time for the T(1) maps was 5 min 5 s for the whole shoulder. Measurements were repeated every 15 min over 2.5 hours. Regions of interest (ROIs) covering the glenoid cartilage and the labrum were drawn to assess the temporal evolution of the relaxation parameters. T(1) of unenhanced hyaline cartilage of the glenoid was 568+/-34 ms. T(1) of unenhanced fibrous cartilage of the labrum was 552+/-38 ms. Significant differences (P=0.002 and 0.03) in the relaxation parameters were already measurable after 15 min. After 2 to 2.5 hours, hyaline and fibrous cartilage still demonstrated decreasing relaxation parameters, with a larger range of the T(1)(Gd) values in fibrous cartilage. T(1) and triangle Delta R(1) values of hyaline and fibrous cartilage after 2.5 hours were 351+/-16 ms and 1.1+/-0.09 s(-1), and 332+/-31 ms and 1.2+/-0.1 s(-1), respectively. A significant decrease in T(1)(Gd) was found 15 min after intraarticular contrast injection. Contrast accumulation was faster in hyaline than in fibrous cartilage. After 2.5 hours, contrast accumulation showed a higher rate of decrease in hyaline cartilage, but neither hyaline nor fibrous cartilage had reached equilibrium.

ESTABLISHING A LIVE CARTILAGE-ON-CARTILAGE INTERFACE FOR TRIBOLOGICAL TESTING.

PubMed

Trevino, Robert L; Stoia, Jonathan; Laurent, Michel P; Pacione, Carol A; Chubinskaya, Susan; Wimmer, Markus A

2017-03-01

Mechano-biochemical wear encompasses the tribological interplay between biological and mechanical mechanisms responsible for cartilage wear and degradation. The aim of this study was to develop and start validating a novel tribological testing system, which better resembles the natural joint environment through incorporating a live cartilage-on-cartilage articulating interface, joint specific kinematics, and the application of controlled mechanical stimuli for the measurement of biological responses in order to study the mechano-biochemical wear of cartilage. The study entailed two parts. In Part 1, the novel testing rig was used to compare two bearing systems: (a) cartilage articulating against cartilage (CoC) and (b) metal articulating against cartilage (MoC). The clinically relevant MoC, which is also a common tribological interface for evaluating cartilage wear, should produce more wear to agree with clinical observations. In Part II, the novel testing system was used to determine how wear is affected by tissue viability in live and dead CoC articulations. For both parts, bovine cartilage explants were harvested and tribologically tested for three consecutive days. Wear was defined as release of glycosaminoglycans into the media and as evaluation of the tissue structure. For Part I, we found that the live CoC articulation did not cause damage to the cartilage, to the extent of being comparable to the free swelling controls, whereas the MoC articulation caused decreased cell viability, extracellular matrix disruption, and increased wear when compared to CoC, and consistent with clinical data. These results provided confidence that this novel testing system will be adequate to screen new biomaterials for articulation against cartilage, such as in hemiarthroplasty. For Part II, the live and dead cartilage articulation yielded similar wear as determined by the release of proteoglycans and aggrecan fragments, suggesting that keeping the cartilage alive may not be essential for short term wear tests. However, the biosynthesis of glycosaminoglycans was significantly higher due to live CoC articulation than due to the corresponding live free swelling controls, indicating that articulation stimulated cell activity. Moving forward, the cell response to mechanical stimuli and the underlying mechano-biochemical wear mechanisms need to be further studied for a complete picture of tissue degradation.

Refixation of Osteochondral Fractures by an Ultrasound-Activated Pin System - An Ovine In Vivo Examination Using CT and Scanning Electron Microscope.

PubMed

H, Neumann; A P, Schulz; S, Breer; A, Unger; B, Kienast

2015-01-01

Osteochondral injuries, if not treated appropriately, often lead to severe osteoarthritis of the affected joint. Without refixation of the osteochondral fragment, human cartilage only repairs these defects imperfectly. All existing refixation systems for chondral defects have disadvantages, for instance bad MRI quality in the postoperative follow-up or low anchoring forces. To address the problem of reduced stability in resorbable implants, ultrasound-activated pins were developed. By ultrasound-activated melting of the tip of these implants a higher anchoring is assumed. Aim of the study was to investigate, if ultrasound-activated pins can provide a secure refixation of osteochondral fractures comparing to conventional screw and conventional, resorbable pin osteosynthesis. CT scans and scanning electron microscopy should proovegood refixation results with no further tissue damage by the melting of the ultrasound-activated pins in comparison to conventional osteosynthesis. Femoral osteochondral fragments in sheep were refixated with ultrasound-activated pins (SonicPin™), Ethipins(®) and screws (Asnis™). The quality of the refixated fragments was examined after three month of full weight bearing by CT scans and scanning electron microscopy of the cartilage surface. The CT examination found almost no statistically significant difference in the quality of refixation between the three different implants used. Concerning the CT morphology, ultrasound-activated pins demonstrated at least the same quality in refixation of osteochondral fragments as conventional resorbable pins or screws. The scanning electron microscopy showed no major surface damage by the three implants, especially any postulated cartilage damage induced by the heat of the ultrasound-activated pin. The screws protruded above the cartilage surface, which may affect the opposingtibial surface. Using CT scans and scanning electron microscopy, the SonicPin™, the Ethipin(®) and screws were at least equivalent in refixation quality of osteochondral fragments.

Prediction of the mid-tracheal level using surface anatomical landmarks in adults

PubMed Central

Jang, Young-Eun; Kim, Eun-Hee; Song, In-Kyung; Lee, Ji-Hyun; Ryu, Ho-Geoul; Kim, Hee-Soo; Kim, Jin-Tae

2017-01-01

Abstract Endotracheal tube (ETT) should be placed at the optimal level to avoid single lung ventilation or accidental extubation. This study was performed to estimate the mid-tracheal level by using surface anatomical landmarks in adult patients. Neck computed tomography images of 329 adult patients between the ages of 16 and 79 years were reviewed. In the midline sagittal plane, the levels corresponding to the vocal cords, cricoid cartilage, suprasternal notch, manubriosternal junction, and carina were identified. The surface distances from the cricoid cartilage to the suprasternal notch (extCC-SSN) and that from the suprasternal notch to the manubriosternal junction (extSSN-MSJ) were measured. The relationship between mid-tracheal level and the surface distances was analyzed using Bland–Altman plot. The difference between the extCC-SSN and the mid-tracheal level was −6.6 (12.5) mm, and the difference between the extSSN-MSJ and the mid-tracheal level was −19.2 (6.1) mm. The difference between the extCC-SSN and the mid-tracheal level was smaller in females compared with males [−1.7 (11.7) mm vs −12.8 (10.7) mm; P < 0.001]. The mid-tracheal level, which is helpful in planning the insertion depth of an ETT, can be predicted by the surface distance between the cricoid cartilage and suprasternal notch in adults, especially in females. PMID:28328810

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 chondrocytes from the middle, deep and calcified zones of normal articular cartilage, and superficial and deep zones of osteoarthritic cartilage. PMID:20525390

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.

Relationship of compartment-specific structural knee status at baseline with change in cartilage morphology: a prospective observational study using data from the osteoarthritis initiative

PubMed Central

Eckstein, Felix; Wirth, Wolfgang; Hudelmaier, Martin I; Maschek, Susanne; Hitzl, Wolfgang; Wyman, Bradley T; Nevitt, Michael; Hellio Le Graverand, Marie-Pierre; Hunter, David

2009-01-01

Introduction The aim was to investigate the relationship of cartilage loss (change in medial femorotibial cartilage thickness measured with magnetic resonance imaging (MRI)) with compartment-specific baseline radiographic findings and MRI cartilage morphometry features, and to identify which baseline features can be used for stratification of fast progressors. Methods An age and gender stratified subsample of the osteoarthritis (OA) initiative progression subcohort (79 women; 77 men; age 60.9 ± 9.9 years; body mass index (BMI) 30.3 ± 4.7) with symptomatic, radiographic OA in at least one knee was studied. Baseline fixed flexion radiographs were read centrally and adjudicated, and cartilage morphometry was performed at baseline and at one year follow-up from coronal FLASH 3 Tesla MR images of the right knee. Results Osteophyte status at baseline was not associated with medial cartilage loss. Knees with medial joint space narrowing tended to show higher rates of change than those without, but the relationship was not statistically significant. Knees with medial femoral subchondral bone sclerosis (radiography), medial denuded subchondral bone areas (MRI), and low cartilage thickness (MRI) at baseline displayed significantly higher cartilage loss than those without, both with and without adjusting for age, sex, and BMI. Participants with denuded subchondral bone showed a standardized response mean of up to -0.64 versus -0.33 for the entire subcohort. Conclusions The results indicate that radiographic and MRI cartilage morphometry features suggestive of advanced disease appear to be associated with greater cartilage loss. These features may be suited for selecting patients with a higher likelihood of fast progression in studies that attempt to demonstrate the cartilage-preserving effect of disease-modifying osteoarthritis drugs. PMID:19534783

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.

Mesenchymal Stem Cells for Cartilage Regeneration of TMJ Osteoarthritis

PubMed Central

Li, Hongyu; Xu, Xin; Ye, Ling; Zhou, Xuedong

2017-01-01

Temporomandibular joint osteoarthritis (TMJ OA) is a degenerative disease, characterized by progressive cartilage degradation, subchondral bone remodeling, synovitis, and chronic pain. Due to the limited self-healing capacity in condylar cartilage, traditional clinical treatments have limited symptom-modifying and structure-modifying effects to restore impaired cartilage as well as other TMJ tissues. In recent years, stem cell-based therapy has raised much attention as an alternative approach towards tissue repair and regeneration. Mesenchymal stem cells (MSCs), derived from the bone marrow, synovium, and even umbilical cord, play a role as seed cells for the cartilage regeneration of TMJ OA. MSCs possess multilineage differentiation potential, including chondrogenic differentiation as well as osteogenic differentiation. In addition, the trophic modulations of MSCs exert anti-inflammatory and immunomodulatory effects under aberrant conditions. Furthermore, MSCs combined with appropriate scaffolds can form cartilaginous or even osseous compartments to repair damaged tissue and impaired function of TMJ. In this review, we will briefly discuss the pathogenesis of cartilage degeneration in TMJ OA and emphasize the potential sources of MSCs and novel approaches for the cartilage regeneration of TMJ OA, particularly focusing on the MSC-based therapy and tissue engineering. PMID:29123550

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.

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.

Septal Cartilage/Ethmoid Bone Composite Graft: A New and Improved Method for the Correction Underdeveloped Nasal Septum in Patients with Short Noses.

PubMed

Lee, Soo Hyang; Koo, Mun Geun; Kang, Eun Taek

2017-04-01

Septal extension grafts are an effective means of extending nasal length in patients with a short nose. However, such grafts can be challenging in patients who only have small quantities of weak septal cartilage, such as some East Asian patients. We developed a rhinoplasty technique using ethmoid bone to create a cartilage-bone complex to overcome this issue, allowing adequate nasal lengthening. Sixty-four women with short noses and inadequate septal cartilage determined by preoperative computed tomography underwent septal extension grafting with a cartilage-bone complex between January 2009 and December 2014. Septal cartilage and ethmoid bone were harvested during open rhinoplasty and secured to the septal cartilage. Most patients were in their twenties or thirties. All patients underwent septal extension grafting using a cartilage-bone complex and dorsal augmentation with silicone implants. Short nasal length, decreased nasolabial angle and increased nostril show, were rectified. There was no recurrence during a mean follow-up period of 12.3 months, although one patient (1.5%) requested revision surgery. Septal extension grafting with a cartilage-bone complex can be used to correct a short nose, especially in Asians who have relatively small amounts of septal cartilage. The ethmoid bone augments the inadequate septum and provides structural support. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

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.

Cartilage ablation studies using mid-IR free electron laser

NASA Astrophysics Data System (ADS)

Youn, Jong-In; Peavy, George M.; Venugopalan, Vasan

2005-04-01

The ablation rate of articular cartilage and fibrocartilage (meniscus), were quantified to examine wavelength and tissue-composition dependence of ablation efficiency for selected mid-infrared wavelengths. The wavelengths tested were 2.9 um (water dominant absorption), 6.1 (protein and water absorption) and 6.45 um (protein dominant absorption) generated by the Free Electron Laser (FEL) at Vanderbilt University. The measurement of tissue mass removal using a microbalance during laser ablation was conducted to determine the ablation rates of cartilage. The technique can be accurate over methods such as profilometer and histology sectioning where tissue surface and the crater morphology may be affected by tissue processing. The ablation efficiency was found to be dependent upon the wavelength. Both articular cartilage and meniscus (fibrocartilage) ablations at 6.1 um were more efficient than those at the other wavelengths evaluated. We observed the lowest ablation efficiency of both types of cartilage with the 6.45 um wavelength, possibly due to the reduction in water absorption at this wavelength in comparison to the other wavelengths that were evaluated.

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.

[Research of repairing rabbit knee joint cartilage defect by compound material of fibrin glue and decalcified bone matrix (DBM) and chondrocytes].

PubMed

He, Jie; Yang, Xiang; Yue, Peng-ju; Wang, Guan-yu; Guo, Ting; Zhao, Jian-ning

2009-07-01

To investigate the feasibility and effectivity of using compound material of fibrin glue and DBM as scaffolds for cartilage tissue engineering. Chondrocytes isolated from articular cartilage were seeded into prepared scaffolds, after incubation for 4 weeks in vitro. Chondrocytes and fibrin glue and DBM constructs were implanted in the joint cave of rabbit. The specimens were excised at the 4th, 8th, 12th week, examined grossly analyzed by haematoxylin cosine, toluidine blues staining and type II collagen immunohistochemistry reaction. Wakitani score was counted to evaluate the repairing effect. Grossly analysis showed some ivory tissue filled the caves after 4 weeks and the caves were full filled with smooth surface after 12 weeks. The microscope showed a good deal of chondrocytes appeared after 8 weeks and more type II collagen than 4 weeks. Twelve weeks later, cartilage lacuna could be observed. The cells arrangement and the amount of type II collagen both showed the same as the natural one. Complicated material of fibrin glue and DBM as scaffolds can be used as scaffolds for cartilage tissue engineering.

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 established if sliding motion follows until a fresh SF is entrained into the contact. This theoretical prediction is open for experimental verifications.

Repair of rabbit cartilage defect based on the fusion of rabbit bone marrow stromal cells and Nano-HA/PLLA composite material.

PubMed

Zhu, Weimin; Guo, Daiqi; Peng, Liangquan; Chen, Yun Fang; Cui, Jiaming; Xiong, Jianyi; Lu, Wei; Duan, Li; Chen, Kang; Zeng, Yanjun; Wang, Daping

2017-02-01

Objective To assess the effect of the fusion of rabbit bone marrow stromal cells (rBMSCs) and Nano-hydroxyapatite/poly (l-lactic acid) (Nano-HA/PLLA) in repairing the rabbit knee joint with full-thickness cartilage defect. Method The rBMSCs were isolated and cultured in vitro, and the third generation of rBMSCs was co-cultured with the Nano-HA/PLLA to construct the tissue-engineered cartilage (TEC). Eighteen New Zealand white rabbits were selected and randomly divided into three groups, namely, TEC group, Nano-HA/PLLA group, and control group. A cartilage defect model with the diameter of 4.5 mm and depth of 5 mm was constructed on the articular surface of medial malleolus of rabbit femur. General observation, histological observation, and Wakitani's histological scoring were conducted in the 12th and 24th week postoperatively. Results The results of TEC group indicated that new cartilage tissue was formed on the defect site and subchondral bone achieved physiological integration basically. Histological and immunohistochemical analyses indicated the generation of massive extracellular matrix. In contrast, limited regeneration and reconstruction of cartilage was achieved in the Nano-HA/PLLA group and control group, with a significant difference from the TEC group (p < 0.05). Moreover, the effect of cartilage repair was positively correlated with time. Conclusion The porous Nano-HA/PLLA combined with BMSCs promoted the repair of weight-bearing bone of adult rabbit's knee joint with cartilage defect.

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.

Subregional effects of meniscal tears on cartilage loss over 2 years in knee osteoarthritis.

PubMed

Chang, Alison; Moisio, Kirsten; Chmiel, Joan S; Eckstein, Felix; Guermazi, Ali; Almagor, Orit; Cahue, September; Wirth, Wolfgang; Prasad, Pottumarthi; Sharma, Leena

2011-01-01

Meniscal tears have been linked to knee osteoarthritis progression, presumably by impaired load attenuation. How meniscal tears affect osteoarthritis is unclear; subregional examination may help to elucidate whether the impact is local. This study examined the association between a tear within a specific meniscal segment and subsequent 2-year cartilage loss in subregions that the torn segment overlies. Participants with knee osteoarthritis underwent bilateral knee MRI at baseline and 2 years. Mean cartilage thickness within each subregion was quantified. Logistic regression with generalised estimating equations were used to analyse the relationship between baseline meniscal tear in each segment and baseline to 2-year cartilage loss in each subregion, adjusting for age, gender, body mass index, tear in the other two segments and extrusion. 261 knees were studied in 159 individuals. Medial meniscal body tear was associated with cartilage loss in external subregions and in central and anterior tibial subregions, and posterior horn tear specifically with posterior tibial subregion loss; these relationships were independent of tears in the other segments and persisted in tibial subregions after adjustment for extrusion. Lateral meniscal body and posterior horn tear were also associated with cartilage loss in underlying subregions but not after adjustment for extrusion. Cartilage loss in the internal subregions, not covered by the menisci, was not associated with meniscal tear in any segment. These results suggest that the detrimental effect of meniscal tears is not spatially uniform across the tibial and femoral cartilage surfaces and that some of the effect is experienced locally.

From intricate to integrated: Biofabrication of articulating joints.

PubMed

Groen, Wilhelmina Margaretha; Diloksumpan, Paweena; van Weeren, Paul René; Levato, Riccardo; Malda, Jos

2017-10-01

Articulating joints owe their function to the specialized architecture and the complex interplay between multiple tissues including cartilage, bone and synovium. Especially the cartilage component has limited self-healing capacity and damage often leads to the onset of osteoarthritis, eventually resulting in failure of the joint as an organ. Although in its infancy, biofabrication has emerged as a promising technology to reproduce the intricate organization of the joint, thus enabling the introduction of novel surgical treatments, regenerative therapies, and new sets of tools to enhance our understanding of joint physiology and pathology. Herein, we address the current challenges to recapitulate the complexity of articulating joints and how biofabrication could overcome them. The combination of multiple materials, biological cues and cells in a layer-by-layer fashion, can assist in reproducing both the zonal organization of cartilage and the gradual transition from resilient cartilage toward the subchondral bone in biofabricated osteochondral grafts. In this way, optimal integration of engineered constructs with the natural surrounding tissues can be obtained. Mechanical characteristics, including the smoothness and low friction that are hallmarks of the articular surface, can be tuned with multi-head or hybrid printers by controlling the spatial patterning of printed structures. Moreover, biofabrication can use digital medical images as blueprints for printing patient-specific implants. Finally, the current rapid advances in biofabrication hold significant potential for developing joint-on-a-chip models for personalized medicine and drug testing or even for the creation of implants that may be used to treat larger parts of the articulating joint. © 2017 The Authors. Journal of Orthopaedic Research Published by Wiley Periodicals, Inc. on behalf of the Orthopaedic Research Society. J Orthop Res 35:2089-2097, 2017. © 2017 The Authors. Journal of Orthopaedic Research Published by Wiley Periodicals, Inc.

Evaluation of Single-Impact-Induced Cartilage Degeneration by Optical Coherence Tomography

PubMed Central

de Bont, Florence; Brill, Nicolai; Schmitt, Robert; Tingart, Markus; Pufe, Thomas; Jahr, Holger; Nebelung, Sven

2015-01-01

Posttraumatic osteoarthritis constitutes a major cause of disability in our increasingly elderly population. Unfortunately, current imaging modalities are too insensitive to detect early degenerative changes of this disease. Optical coherence tomography (OCT) is a promising nondestructive imaging technique that allows surface and subsurface imaging of cartilage, at near-histological resolution, and is principally applicable in vivo during arthroscopy. Thirty-four macroscopically normal human cartilage-bone samples obtained from total joint replacements were subjected to standardized single impacts in vitro (range: 0.25 J to 0.98 J). 3D OCT measurements of impact area and adjacent tissue were performed prior to impaction, directly after impaction, and 1, 4, and 8 days later. OCT images were assessed qualitatively (DJD classification) and quantitatively using established parameters (OII, Optical Irregularity Index; OHI, Optical Homogeneity Index; OAI, Optical Attenuation Index) and compared to corresponding histological sections. While OAI and OHI scores were not significantly changed in response to low- or moderate-impact energies, high-impact energies significantly increased mean DJD grades (histology and OCT) and OII scores. In conclusion, OCT-based parameterization and quantification are able to reliably detect loss of cartilage surface integrity after high-energy traumatic insults and hold potential to be used for clinical screening of early osteoarthritis. PMID:26229959

Ultrasound arthroscopy of human knee cartilage and subchondral bone in vivo.

PubMed

Liukkonen, Jukka; Lehenkari, Petri; Hirvasniemi, Jukka; Joukainen, Antti; Virén, Tuomas; Saarakkala, Simo; Nieminen, Miika T; Jurvelin, Jukka S; Töyräs, Juha

2014-09-01

Arthroscopic ultrasound imaging enables quantitative evaluation of articular cartilage. However, the potential of this technique for evaluation of subchondral bone has not been investigated in vivo. In this study, we address this issue in clinical arthroscopy of the human knee (n = 11) by determining quantitative ultrasound (9 MHz) reflection and backscattering parameters for cartilage and subchondral bone. Furthermore, in each knee, seven anatomical sites were graded using the International Cartilage Repair Society (ICRS) system based on (i) conventional arthroscopy and (ii) ultrasound images acquired in arthroscopy with a miniature transducer. Ultrasound enabled visualization of articular cartilage and subchondral bone. ICRS grades based on ultrasound images were higher (p < 0.05) than those based on conventional arthroscopy. The higher ultrasound-based ICRS grades were expected as ultrasound reveals additional information on, for example, the relative depth of the lesion. In line with previous literature, ultrasound reflection and scattering in cartilage varied significantly (p < 0.05) along the ICRS scale. However, no significant correlation between ultrasound parameters and structure or density of subchondral bone could be demonstrated. To conclude, arthroscopic ultrasound imaging had a significant effect on clinical grading of cartilage, and it was found to provide quantitative information on cartilage. The lack of correlation between the ultrasound parameters and bone properties may be related to lesser bone change or excessive attenuation in overlying cartilage and insufficient power of the applied miniature transducer. Copyright © 2014 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

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.

Challenges in engineering osteochondral tissue grafts with hierarchical structures Ivana Gadjanski, Gordana Vunjak Novakovic

PubMed Central

Gadjanski, Ivana; Vunjak-Novakovic, Gordana

2015-01-01

Introduction A major hurdle in treating osteochondral (OC) defects are the different healing abilities of two types of tissues involved - articular cartilage and subchondral bone. Biomimetic approaches to OC-construct-engineering, based on recapitulation of biological principles of tissue development and regeneration, have potential for providing new treatments and advancing fundamental studies of OC tissue repair. Areas covered This review on state of the art in hierarchical OC tissue graft engineering is focused on tissue engineering approaches designed to recapitulate the native milieu of cartilage and bone development. These biomimetic systems are discussed with relevance to bioreactor cultivation of clinically sized, anatomically shaped human cartilage/bone constructs with physiologic stratification and mechanical properties. The utility of engineered OC tissue constructs is evaluated for their use as grafts in regenerative medicine, and as high-fidelity models in biological research. Expert opinion A major challenge in engineering OC tissues is to generate a functionally integrated stratified cartilage-bone structure starting from one single population of mesenchymal cells, while incorporating perfusable vasculature into the bone, and in bone-cartilage interface. To this end, new generations of advanced scaffolds and bioreactors, implementation of mechanical loading regimens, and harnessing of inflammatory responses of the host will likely drive the further progress. PMID:26195329

Use of a 3-Telsa magnet to perform delayed gadolinium-enhanced magnetic resonance imaging of the distal interphalangeal joint of horses with and without naturally occurring osteoarthritis.

PubMed

Bischofberger, Andrea S; Fürst, Anton E; Torgerson, Paul R; Carstens, Ann; Hilbe, Monika; Kircher, Patrick

2018-03-01

OBJECTIVE To characterize delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) features of healthy hyaline cartilage of the distal interphalangeal joint (DIPJ) of horses, to determine whether dGEMRIC can be used to differentiate various stages of naturally occurring osteoarthritis of the DIPJ, and to correlate relaxation times determined by dGEMRIC with the glycosaminoglycan concentration, water content, and macroscopic and histologic findings of hyaline cartilage of DIPJs with and without osteoarthritis. SAMPLE 1 cadaveric forelimb DIPJ from each of 12 adult warmblood horses. PROCEDURES T1-weighted cartilage relaxation times were obtained for predetermined sites of the DIPJ before (T1 preGd ) and after (T1 postGd ) intra-articular gadolinium administration. Corresponding cartilage sites underwent macroscopic, histologic, and immunohistochemical evaluation, and cartilage glycosaminoglycan concentration and water content were determined. Median T1 preGd and T1 postGd were correlated with macroscopic, histologic, and biochemical data. Mixed generalized linear models were created to evaluate the effects of cartilage site, articular surface, and macroscopic and histologic scores on relaxation times. RESULTS 122 cartilage specimens were analyzed. Median T1 postGd was lower than the median T1 preGd for normal and diseased cartilage. Both T1 preGd and T1 postGd were correlated with macroscopic and histologic scores, whereby T1 preGd increased and T1 postGd decreased as osteoarthritis progressed. There was topographic variation of T1 preGd and T1 postGd within the DIPJ. Cartilage glycosaminoglycan concentration and water content were significantly correlated with T1 preGd and macroscopic and histologic scores but were not correlated with T1 postGd . CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that dGEMRIC relaxation times varied for DIPJs with various degrees of osteoarthritis. These findings may help facilitate early detection of osteoarthritis.

Osteoarthritic bone marrow lesions almost exclusively colocate with denuded cartilage: a 3D study using data from the Osteoarthritis Initiative.

PubMed

Bowes, Michael A; McLure, Stewart Wd; Wolstenholme, Christopher Bh; Vincent, Graham R; Williams, Sophie; Grainger, Andrew; Conaghan, Philip G

2016-10-01

The aetiology of bone marrow lesions (BMLs) in knee osteoarthritis (OA) is poorly understood. We employed three-dimensional (3D) active appearance modelling (AAM) to study the spatial distribution of BMLs in an OA cohort and compare this with the distribution of denuded cartilage. Participants were selected from the Osteoarthritis Initiative progressor cohort with Kellgren-Lawrence scores ≥2, medial joint space narrowing and osteophytes. OA and ligamentous BMLs and articular cartilage were manually segmented. Bone surfaces were automatically segmented by AAM. Cartilage thickness of <0.5 mm was defined as denuded and ≥0.5-1.5 mm as severely damaged. Non-quantitative assessment and 3D population maps were used for analysing the comparative position of BMLs and damaged cartilage. 88 participants were included, 45 men, mean age (SD) was 61.3 (9.9) years and mean body mass index was 31.1 (4.6) kg/m(2). 227 OA and 107 ligamentous BMLs were identified in 86.4% and 73.8% of participants; OA BMLs were larger. Denuded cartilage was predominantly confined to a central region on the medial femur and tibia, and the lateral facet of the trochlear femur. 67% of BMLs were colocated with denuded cartilage and a further 21% with severe cartilage damage. In the remaining 12%, 25/28 were associated with cartilage defects. 74% of all BMLs were directly opposing (kissing) another BML across the joint. There was an almost exclusive relationship between the location of OA BML and cartilage denudation, which itself had a clear spatial pattern. We propose that OA, ligamentous and traumatic BMLs represent a bone response to abnormal loading. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

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 resorption inhibitors as potential disease-modifying pharmaco-therapies.

Evaluation of magnesium-yttrium alloy as an extraluminal tracheal stent.

PubMed

Luffy, Sarah A; Chou, Da-Tren; Waterman, Jenora; Wearden, Peter D; Kumta, Prashant N; Gilbert, Thomas W

2014-03-01

Tracheomalacia is a relatively rare problem, but can be challenging to treat, particularly in pediatric patients. Due to the presence of mechanically deficient cartilage, the trachea is unable to resist collapse under physiologic pressures of respiration, which can lead to acute death if left untreated. However, if treated, the outcome for patients with congenital tracheomalacia is quite good because the cartilage tends to spontaneously mature over a period of 12 to 18 months. The present study investigated the potential for the use of degradable magnesium-3% yttrium alloy (W3) to serve as an extraluminal tracheal stent in a canine model. The host response to the scaffold included the formation of a thin, vascularized capsule consisting of collagenous tissue and primarily mononuclear cells. The adjacent cartilage structure was not adversely affected as observed by bronchoscopic, gross, histologic, and mechanical analysis. The W3 stents showed reproducible spatial and temporal fracture patterns, but otherwise tended to corrode quite slowly, with a mix of Ca and P rich corrosion product formed on the surface and observed focal regions of pitting. The study showed that the approach to use degradable magnesium alloys as an extraluminal tracheal stent is promising, although further development of the alloys is required to improve the resistance to stress corrosion cracking and improve the ductility. Copyright © 2013 Wiley Periodicals, Inc.

Microscale frictional strains determine chondrocyte fate in loaded cartilage.

PubMed

Bonnevie, Edward D; Delco, Michelle L; Bartell, Lena R; Jasty, Naveen; Cohen, Itai; Fortier, Lisa A; Bonassar, Lawrence J

2018-06-06

Mounting evidence suggests that altered lubricant levels within synovial fluid have acute biological consequences on chondrocyte homeostasis. While these responses have been connected to increased friction, the mechanisms behind this response remain unknown. Here, we combine a frictional bioreactor with confocal elastography and image-based cellular assays to establish the link between cartilage friction, microscale shear strain, and acute, adverse cellular responses. Our incorporation of cell-scale strain measurements reveals that elevated friction generates high shear strains localized near the tissue surface, and that these elevated strains are closely associated with mitochondrial dysfunction, apoptosis, and cell death. Collectively, our data establish two pathways by which chondrocytes negatively respond to friction: an immediate necrotic response and a longer term pathway involving mitochondrial dysfunction and apoptosis. Specifically, in the surface region, where shear strains can exceed 0.07, cells are predisposed to acute death; however, below this surface region, cells exhibit a pathway consistent with apoptosis in a manner predicted by local shear strains. These data reveal a mechanism through which cellular damage in cartilage arises from compromised lubrication and show that in addition to boundary lubricants, there are opportunities upstream of apoptosis to preserve chondrocyte health in arthritis therapy. Copyright © 2018 Elsevier Ltd. All rights reserved.

On Detailed Contrast of Biomedical Object in X-ray Dark-Field Imaging

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

Shimao, Daisuke; Mori, Koichi; Sugiyama, Hiroshi

2007-01-19

Over the past 10 years, refraction-based X-ray imaging has been studied together with a perspective view to clinical application. X-ray Dark-Field Imaging that utilizes a Laue geometry analyzer has recently been proposed and has the proven ability to depict articular cartilage in an intact human finger. In the current study, we researched detailed image contrast using X-ray Dark-Field Imaging by observing the edge contrast of an acrylic rod as a simple case, and found differences in image contrast between the right and left edges of the rod. This effect could cause undesirable contrast in the thin articular cartilage on themore » head of the phalanx. To avoid overlapping with this contrast at the articular cartilage, which would lead to a wrong diagnosis, we suggest that a joint surface on which articular cartilage is located should be aligned in the same sense as the scattering vector of the Laue case analyzer crystal. Defects of articular cartilage were successfully detected under this condition. When utilized under appropriate imaging conditions, X-ray Dark-Field Imaging will be a powerful tool for the diagnosis of arthropathy, as minute changes in articular cartilage may be early-stage features of this disease.« less

Chemical changes demonstrated in cartilage by synchrotron infrared microspectroscopy in an antibody-induced murine model of rheumatoid arthritis

NASA Astrophysics Data System (ADS)

Croxford, Allyson M.; Selva Nandakumar, Kutty; Holmdahl, Rikard; Tobin, Mark J.; McNaughton, Don; Rowley, Merrill J.

2011-06-01

Collagen antibody-induced arthritis develops in mice following passive transfer of monoclonal antibodies (mAbs) to type II collagen (CII) and is attributed to effects of proinflammatory immune complexes, but transferred mAbs may react directly and damagingly with CII. To determine whether such mAbs cause cartilage damage in vivo in the absence of inflammation, mice lacking complement factor 5 that do not develop joint inflammation were injected intravenously with two arthritogenic mAbs to CII, M2139 and CIIC1. Paws were collected at day 3, decalcified, paraffin embedded, and 5-μm sections were examined using standard histology and synchrotron Fourier-transform infrared microspectroscopy (FTIRM). None of the mice injected with mAb showed visual or histological evidence of inflammation but there were histological changes in the articular cartilage including loss of proteoglycan and altered chondrocyte morphology. Findings using FTIRM at high lateral resolution revealed loss of collagen and the appearance of a new peak at 1635 cm-1 at the surface of the cartilage interpreted as cellular activation. Thus, we demonstrate the utility of synchrotron FTIRM for examining chemical changes in diseased cartilage at the microscopic level and establish that arthritogenic mAbs to CII do cause cartilage damage in vivo in the absence of inflammation.

Ultrasound Elastography for Estimation of Regional Strain of Multilayered Hydrogels and Tissue-Engineered Cartilage

PubMed Central

Chung, Chen-Yuan; Heebner, Joseph; Baskaran, Harihara; Welter, Jean F.; Mansour, Joseph M.

2015-01-01

Tissue-engineered (TE) cartilage constructs tend to develop inhomogeneously, thus, to predict the mechanical performance of the tissue, conventional biomechanical testing, which yields average material properties, is of limited value. Rather, techniques for evaluating regional and depth-dependent properties of TE cartilage, preferably non-destructively, are required. The purpose of this study was to build upon our previous results and to investigate the feasibility of using ultrasound elastography to non-destructively assess the depth-dependent biomechanical characteristics of TE cartilage while in a sterile bioreactor. As a proof-of-concept, and to standardize an assessment protocol, a well-characterized three-layered hydrogel construct was used as a surrogate for TE cartilage, and was studied under controlled incremental compressions. The strain field of the construct predicted by elastography was then validated by comparison with a poroelastic finite-element analysis (FEA). On average, the differences between the strains predicted by elastography and the FEA were within 10%. Subsequently engineered cartilage tissue was evaluated in the same test fixture. Results from these examinations showed internal regions where the local strain was 1–2 orders of magnitude greater than that near the surface. These studies document the feasibility of using ultrasound to evaluate the mechanical behaviors of maturing TE constructs in a sterile environment. PMID:26077987

Anatomic analysis of the conchal bowl cartilage.

PubMed

Brockhoff, Hans C; Morris, Christopher D; Throckmorton, Gaylord S; Finn, Rick

2014-11-01

The conchal bowl is a portion of auricular cartilage commonly used as an autologous graft for various maxillofacial procedures. Few studies have attempted to describe the anatomy of this region in detail, particularly in relation to the curvature of the conchal bowl. The present study has provided detailed information about the anatomy of the auricular cartilage in the conchal bowl region that could assist in the surgical design of graft harvesting. A total of 35 pairs of cadaver ears without gross deformity (15 male, 20 female; aged 39 to 99 years) were dissected to completely expose the cartilage skeleton. Each cartilage was stabilized, and the conchal bowl was mapped. The starting reference point was defined as the intersection of the lateral border of the antihelix and the superiormost aspect of the inferior crux. A prefabricated grid was then used to imprint a 4 × 5 matrix of pinpoint ink spots on the surface of each cartilage, with 6-mm increments between each spot. The grid's y and x axes were then aligned with the landmarks above. Next, a MicroScribe 3-dimensional digitizer (ghost3d.com) was used to capture the 3-dimensional coordinates for each point on the ear's surface and the coordinates were transferred into an Excel spreadsheet. After digitization, a Boley gauge was used to measure the thickness of the cartilage at each premarked spot. The gathered data points and measurements were examined to describe our parameters of interest (ie, depth, thickness, and curvature). The average maximum conchal bowl depth was 10.5 ± 3.0 mm in the female ears and 10.7 ± 2.5 mm in the male ears. In general, the conchal bowl depth at each point did not differ significantly between the males and females. The mean cartilage thickness ranged from 0.77 to 1.79 mm (mean 1.15 ± 0.26) in the females and 0.95 to 1.45 mm (mean 1.25 ± 0.23) in the males. Both genders showed an increase in the conchal bowl depth from inferiorly to superiorly and from posteriorly to anteriorly. The cartilage thickness also increased from posteriorly to anteriorly; however, the exact shape is complex. A detailed understanding of the facial anatomy is important in the practice of facial surgery. The results we have presented will provide surgeons with information on the overall dimensions, thickness, and curvature of the conchal bowl that could allow more advantageous donor site selection. Copyright © 2014 American Association of Oral and Maxillofacial Surgeons. All rights reserved.

Evaluation of patellar chondromalacia with MR: comparison between T2-weighted FSE SPIR and GE MTC.

PubMed

Macarini, Luca; Perrone, Alessandra; Murrone, Mario; Marini, Stefania; Stefanelli, Michele

2004-09-01

To compare two different MR sequences to tissue signal suppression in the study of patellar cartilage abnormalities. We examined 26 patients with magnetic resonance (MR) imaging: sequences included spectral presaturation with inversion recovery (SPIR), with fat suppression and T2-weighted images, magnetization transfer contrast (MTC) sequences, T1-weighted and T2-weighted spin-echo sequences. All patients underwent conventional knee arthroscopy and in all patients a hyaline cartilage lesion was assessed in three articular zones: the patellar medial facet, the lateral facet and the patellar crista. Was assessed 78 articular facets. The lesions were classified using a standard arthroscopic grading system adapted to MR imaging: normal cartilage that corresponds to the grade 0 according to the Noyes grading system, low grade lesions that correspond to the grade I e IIa and high grade lesions that correspond to grades IIb and III. The arthroscopic results were compared with MR images. We assessed the MR diagnostic accuracy, sensitivity, specificity and MR positive predictive value and negative predictive value of the two sequences taking into consideration total lesions, and high-grade and low grade lesions separately. Twenty-four low grade lesions (16 grade I e 8 grade IIa) and 18 high grade lesions (10 grade IIb e 8 grade III) were diagnosed by arthroscopy. Regarding low grade and high-grade lesions together, the accuracy was 77% for MTC sequences and 90% for SPIR sequences. In identifying low-grade lesions, the sensitivity was 88% for SPIR sequence and 42% for MTC sequences. Specificity for the detection of all lesions was 89% for the SPIR sequences and 94% for the MTC sequences. The SPIR sequence visualised water content abnormalities in degenerating cartilage, which are representative of low-grade lesions. The sensitivity of the sequence enabled us to obtain improved contrast for detecting cartilage surface irregularities. The MTC sequences allowed us to grade high-grade lesions susceptible to surgery and small cartilage defects in the presence of joint fluid. The MTC sequences were insufficient in the diagnosis of early stages of chondromalacia because the suppression of the signal of bonded water reduced the contrast among areas of articular cartilage with different water content. For this reason cartilage oedema and early superficial fibrillation were not identified. In our experience the SPIR sequence proved superior to the MTC sequence in the identification of low grade lesions of the patellar cartilage. The overall value of such sequences in the study of articular pathology also needs to be assessed in the others sites where the articular cartilage is thinner and surfaces more curvilinear.

Cartilaginous Epiphyses in Extant Archosaurs and Their Implications for Reconstructing Limb Function in Dinosaurs

PubMed Central

Holliday, Casey M.; Ridgely, Ryan C.; Sedlmayr, Jayc C.; Witmer, Lawrence M.

2010-01-01

Extinct archosaurs, including many non-avian dinosaurs, exhibit relatively simply shaped condylar regions in their appendicular bones, suggesting potentially large amounts of unpreserved epiphyseal (articular) cartilage. This “lost anatomy” is often underappreciated such that the ends of bones are typically considered to be the joint surfaces, potentially having a major impact on functional interpretation. Extant alligators and birds were used to establish an objective basis for inferences about cartilaginous articular structures in such extinct archosaur clades as non-avian dinosaurs. Limb elements of alligators, ostriches, and other birds were dissected, disarticulated, and defleshed. Lengths and condylar shapes of elements with intact epiphyses were measured. Limbs were subsequently completely skeletonized and the measurements repeated. Removal of cartilaginous condylar regions resulted in statistically significant changes in element length and condylar breadth. Moreover, there was marked loss of those cartilaginous structures responsible for joint architecture and congruence. Compared to alligators, birds showed less dramatic, but still significant changes. Condylar morphologies of dinosaur limb bones suggest that most non-coelurosaurian clades possessed large cartilaginous epiphyses that relied on the maintenance of vascular channels that are otherwise eliminated early in ontogeny in smaller-bodied tetrapods. A sensitivity analysis using cartilage correction factors (CCFs) obtained from extant taxa indicates that whereas the presence of cartilaginous epiphyses only moderately increases estimates of dinosaur height and speed, it has important implications for our ability to infer joint morphology, posture, and the complicated functional movements in the limbs of many extinct archosaurs. Evidence suggests that the sizes of sauropod epiphyseal cartilages surpassed those of alligators, which account for at least 10% of hindlimb length. These data suggest that large cartilaginous epiphyses were widely distributed among non-avian archosaurs and must be considered when making inferences about locomotor functional morphology in fossil taxa. PMID:20927347

Cartilaginous epiphyses in extant archosaurs and their implications for reconstructing limb function in dinosaurs.

PubMed

Holliday, Casey M; Ridgely, Ryan C; Sedlmayr, Jayc C; Witmer, Lawrence M

2010-09-30

Extinct archosaurs, including many non-avian dinosaurs, exhibit relatively simply shaped condylar regions in their appendicular bones, suggesting potentially large amounts of unpreserved epiphyseal (articular) cartilage. This "lost anatomy" is often underappreciated such that the ends of bones are typically considered to be the joint surfaces, potentially having a major impact on functional interpretation. Extant alligators and birds were used to establish an objective basis for inferences about cartilaginous articular structures in such extinct archosaur clades as non-avian dinosaurs. Limb elements of alligators, ostriches, and other birds were dissected, disarticulated, and defleshed. Lengths and condylar shapes of elements with intact epiphyses were measured. Limbs were subsequently completely skeletonized and the measurements repeated. Removal of cartilaginous condylar regions resulted in statistically significant changes in element length and condylar breadth. Moreover, there was marked loss of those cartilaginous structures responsible for joint architecture and congruence. Compared to alligators, birds showed less dramatic, but still significant changes. Condylar morphologies of dinosaur limb bones suggest that most non-coelurosaurian clades possessed large cartilaginous epiphyses that relied on the maintenance of vascular channels that are otherwise eliminated early in ontogeny in smaller-bodied tetrapods. A sensitivity analysis using cartilage correction factors (CCFs) obtained from extant taxa indicates that whereas the presence of cartilaginous epiphyses only moderately increases estimates of dinosaur height and speed, it has important implications for our ability to infer joint morphology, posture, and the complicated functional movements in the limbs of many extinct archosaurs. Evidence suggests that the sizes of sauropod epiphyseal cartilages surpassed those of alligators, which account for at least 10% of hindlimb length. These data suggest that large cartilaginous epiphyses were widely distributed among non-avian archosaurs and must be considered when making inferences about locomotor functional morphology in fossil taxa.

Self-Assembled Infrapatellar Fat-Pad Progenitor Cells on a Poly-ε-Caprolactone Film For Cartilage Regeneration.

PubMed

Prabhakar, Alisha; Lynch, Amy P; Ahearne, Mark

2016-04-01

Cartilage defects resulting from osteoarthritis (OA) or physical injury can severely reduce the quality of life for sufferers. Current treatment options are costly and not always effective in producing stable hyaline cartilage. Here we investigated a new treatment option that could potentially repair and regenerate damaged cartilage tissue. This novel approach involves the application of infrapatellar fat-pad derived chondroprogenitor cells onto a mechanically stable biodegradable polymer film that can be easily implanted into a defect site. Poly-ε-caprolactone (PCL) films were fabricated via solvent casting in either acetone or chloroform. The hydrophobicity, mechanical properties, and surface morphology of the films were examined. Progenitor cells from infrapatellar fat-pad were isolated, expanded, and then seeded onto the films. The cells were allowed to self-assemble on films, and these were then cultured in a chemically defined chondrogenic media for 28 days. The self-assembled tissue was characterized via histological staining, gene expression analysis, immunohistochemistry, and biochemical analysis. Chondrogenic differentiation was induced to generate a cartilaginous matrix upon the films. Despite differences between in the appearance, surface morphology, and mechanical properties of the films cast in chloroform or acetone, both methods produced tissues rich in sulfated glycosaminoglycan and collagen, although the extracellular matrix produced on chloroform-cast films appeared to contain more collagen type II and less collagen type I than acetone-cast films. These self-assembled constructs have the potential to be implanted into defect sites as a potential treatment for cartilage defect regeneration. Copyright © 2015 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

Histopomorphic Evaluation of Radiofrequency Mediated Débridement Chondroplasty

PubMed Central

Ganguly, Kumkum; McRury, Ian D; Goodwin, Peter M; Morgan, Roy E; Augé II, Wayne K

2010-01-01

The use of radiofrequency devices has become widespread for surgical ablation procedures. When ablation devices have been deployed in treatment settings requiring tissue preservation like débridement chondroplasty, adoption has been limited due to the collateral damage caused by these devices in healthy tissue surrounding the treatment site. Ex vivo radiofrequency mediated débridement chondroplasty was performed on osteochondral specimens demonstrating surface fibrillation obtained from patients undergoing knee total joint replacement. Three radiofrequency systems designed to perform débridement chondroplasty were tested each demonstrating different energy delivery methods: monopolar ablation, bipolar ablation, and non-ablation energy. Treatment outcomes were compared with control specimens as to clinical endpoint and histopomorphic characteristics. Fibrillated cartilage was removed in all specimens; however, the residual tissue remaining at the treatment site displayed significantly different characteristics attributable to radiofrequency energy delivery method. Systems that delivered ablation-based energies caused tissue necrosis and collateral damage at the treatment site including corruption of cartilage Superficial and Transitional Zones; whereas, the non-ablation system created a smooth articular surface with Superficial Zone maintenance and without chondrocyte death or tissue necrosis. The mechanism of radiofrequency energy deposition upon tissues is particularly important in treatment settings requiring tissue preservation. Ablation-based device systems can cause a worsened state of articular cartilage from that of pre-treatment. Non-ablation energy can be successful in modifying/preconditioning tissue during débridement chondroplasty without causing collateral damage. Utilizing a non-ablation radiofrequency system provides the ability to perform successful débridement chondroplasty without causing additional articular cartilage tissue damage and may allow for other cartilage intervention success. PMID:20721322

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

Artificial Auricular Cartilage Using Silk Fibroin and Polyvinyl Alcohol Hydrogel

PubMed Central

Lee, Jung Min; Sultan, Md. Tipu; Kim, Soon Hee; Kumar, Vijay; Yeon, Yeung Kyu; Lee, Ok Joo; Park, Chan Hum

2017-01-01

Several methods for auricular cartilage engineering use tissue engineering techniques. However, an ideal method for engineering auricular cartilage has not been reported. To address this issue, we developed a strategy to engineer auricular cartilage using silk fibroin (SF) and polyvinyl alcohol (PVA) hydrogel. We constructed different hydrogels with various ratios of SF and PVA by using salt leaching, silicone mold casting, and freeze-thawing methods. We characterized each of the hydrogels in terms of the swelling ratio, tensile strength, pore size, thermal properties, morphologies, and chemical properties. Based on the cell viability results, we found a blended hydrogel composed of 50% PVA and 50% SF (P50/S50) to be the best hydrogel among the fabricated hydrogels. An intact 3D ear-shaped auricular cartilage formed six weeks after the subcutaneous implantation of a chondrocyte-seeded 3D ear-shaped P50/S50 hydrogel in rats. We observed mature cartilage with a typical lacunar structure both in vitro and in vivo via histological analysis. This study may have potential applications in auricular tissue engineering with a human ear-shaped hydrogel. PMID:28777314

Experimental Study on 3D Chi - Hap Scaffolds for Thyroid Cartilage Repairing

NASA Astrophysics Data System (ADS)

Sun, Nannan; Shi, Tingchun; Fan, Yuan; Hu, Binbin

2018-01-01

Due to the limitation of self-repairing capability for cartilage injury, the construction of tissue engineering in vitro has been an ideal treatment to repair tissue injury. In this paper, hydroxyapatite (Hap) and chitosan (Chi) were selected to fabricate the scaffold through low temperature deposition manufacturing (LDM) technique. The scaffold was characterized with interconnected structure and high porosity, as well as lower toxicity to cells (TDC-5-EGPE). Animal experiment was performed, Twelve white New Zealand rabbits were randomly divided into two groups, the side of the thyroid cartilage was removed, Chi-HAP composite scaffold was implanted into the cartilage defect as the experimental group A. Group B was treated for thyroid cartilage defects without any treatment. After 10 weeks, hematoxylin-eosin (HE) staining and S-O staining were carried out on the injured tissues. The result showed that newborn chondrocytes were found in repaired areas for group A, and there are no new cells found for group B. Therefore, Chi-HAP composite scaffolds formed by LDM possess biological activity for repairing injury cartilage.

Systems Based Study of the Therapeutic Potential of Small Charged Molecules for the Inhibition of IL-1 Mediated Cartilage Degradation

PubMed Central

Kar, Saptarshi; Smith, David W.; Gardiner, Bruce S.; Grodzinsky, Alan J.

2016-01-01

Inflammatory cytokines are key drivers of cartilage degradation in post-traumatic osteoarthritis. Cartilage degradation mediated by these inflammatory cytokines has been extensively investigated using in vitro experimental systems. Based on one such study, we have developed a computational model to quantitatively assess the impact of charged small molecules intended to inhibit IL-1 mediated cartilage degradation. We primarily focus on the simplest possible computational model of small molecular interaction with the IL-1 system—direct binding of the small molecule to the active site on the IL-1 molecule itself. We first use the model to explore the uptake and release kinetics of the small molecule inhibitor by cartilage tissue. Our results show that negatively charged small molecules are excluded from the negatively charged cartilage tissue and have uptake kinetics in the order of hours. In contrast, the positively charged small molecules are drawn into the cartilage with uptake and release timescales ranging from hours to days. Using our calibrated computational model, we subsequently explore the effect of small molecule charge and binding constant on the rate of cartilage degradation. The results from this analysis indicate that the small molecules are most effective in inhibiting cartilage degradation if they are either positively charged and/or bind strongly to IL-1α, or both. Furthermore, our results showed that the cartilage structural homeostasis can be restored by the small molecule if administered within six days following initial tissue exposure to IL-1α. We finally extended the scope of the computational model by simulating the competitive inhibition of cartilage degradation by the small molecule. Results from this model show that small molecules are more efficient in inhibiting cartilage degradation by binding directly to IL-1α rather than binding to IL-1α receptors. The results from this study can be used as a template for the design and development of more pharmacologically effective osteoarthritis drugs, and to investigate possible therapeutic options. PMID:27977731

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 volume estimation of 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. Furthermore, the performance of the segmentation method used for the extraction of the femoral, tibial, and patellar cartilages is assessed with a Dice similarity coefficient, sensitivity, and specificity measure providing high agreement to manual segmentation. Conclusions: The CI-RBF method provides a fast, accurate, and robust 3D model reconstruction that matches Carr’s RBF method, 3D DOCTOR, and a manual benchmark method in accuracy and significantly improves upon Carr’s RBF method in data requirement and computational speed. In addition, the visualization tool has been designed to quickly segment MR images requiring only four mouse clicks per MR image slice.« less

Anatomical significance of a posterior horn of medial meniscus: the relationship between its radial tear and cartilage degradation of joint surface.

PubMed

Kan, Akinori; Oshida, Midori; Oshida, Shigemi; Imada, Masato; Nakagawa, Takumi; Okinaga, Shuji

2010-01-12

Traumatic injury and surgical meniscectomy of a medial meniscus are known to cause subsequent knee osteoarthritis. However, the difference in the prevalence of osteoarthritis caused by the individual type of the medial meniscal tear has not been elucidated. The aim of this study was to investigate what type of tear is predominantly responsible for the degradation of articular cartilage in the medial compartment of knee joints. Five hundred and forty eight cadaveric knees (290 male and 258 female) were registered in this study. The average age of cadavers at death was 78.8 years old (range: 52-103 years). The knees were macroscopically examined and their medial menisci were classified into four groups according to types of tears: "no tear", "radial tear of posterior horn", "other types of tear" and "worn-out meniscus" groups. The severity of cartilage degradation in their medial compartment of knee joints was evaluated using the international cartilage repair society (ICRS) grading system. We statistically compared the ICRS grades among the groups using Mann-Whitney U test. The knees were assigned into the four groups: 416 "no tear" knees, 51 "radial tear of posterior horn" knees, 71 "other types of tear" knees, and 10 "worn-out meniscus" knees. The knees with substantial meniscal tears showed the severer ICRS grades of cartilage degradation than those without meniscal tears. In addition, the ICRS grades were significantly severer in the "radial tear of posterior horn" group than in the "other types of tear" group, suggesting that the radial tear of posterior horn in the medial meniscus is one of the risk factors for cartilage degradation of joint surface. We have clarified the relationship between the radial tear of posterior horn in the medial meniscus and the severer grade of cartilage degradation. This study indicates that the efforts should be made to restore the anatomical role of the posterior horn in keeping the hoop strain, when patients' physical activity levels are high and the tear pattern is simple enough to be securely sutured.

The clinical utility and diagnostic performance of magnetic resonance imaging for identification of early and advanced knee osteoarthritis: a systematic review.

PubMed

Quatman, Carmen E; Hettrich, Carolyn M; Schmitt, Laura C; Spindler, Kurt P

2011-07-01

Current diagnostic strategies for detection of structural articular cartilage abnormalities, the earliest structural signs of osteoarthritis, often do not capture the condition until it is too far advanced for the most potential benefit of noninvasive interventions. To systematically review the literature relative to the following questions: (1) Is magnetic resonance imaging (MRI) a valid, sensitive, specific, accurate, and reliable instrument to identify knee articular cartilage abnormalities compared with arthroscopy? (2) Is MRI a sensitive tool that can be utilized to identify early cartilage degeneration? Systematic review. A systematic search was performed in November 2010 using PubMed MEDLINE (from 1966), CINAHL (from 1982), SPORTDiscus (from 1985), SCOPUS (from 1996), and EMBASE (from 1974) databases. Fourteen level I and 13 level II studies were identified that met inclusion criteria and provided information related to diagnostic performance of MRI compared with arthroscopic evaluation. The diagnostic performance of MRI demonstrated a large range of sensitivities, specificities, and accuracies. The sensitivity for identifying articular cartilage abnormalities in the knee joint was reported between 26% and 96%. Specificity and accuracy were reported between 50% and 100% and between 49% and 94%, respectively. The sensitivity, specificity, and accuracy for identifying early osteoarthritis were reported between 0% and 86%, 48% and 95%, and 5% and 94%, respectively. As a result of inconsistencies between imaging techniques and methodological shortcomings of many of the studies, a meta-analysis was not performed, and it was difficult to fully synthesize the information to state firm conclusions about the diagnostic performance of MRI. There is evidence in some MRI protocols that MRI is a relatively valid, sensitive, specific, accurate, and reliable clinical tool for identifying articular cartilage degeneration. Because of heterogeneity of MRI sequences, it is not possible to make definitive conclusions regarding its global clinical utility for guiding diagnosis and treatment strategies. Traumatic sports injuries to the knee may be significant precursor events to early onset of posttraumatic osteoarthritis. Magnetic resonance imaging may aid in early identification of structural injuries to articular cartilage as evidenced by articular cartilage degeneration grading.

The Clinical Utility and Diagnostic Performance of MRI for Identification of Early and Advanced Knee Osteoarthritis: A Systematic Review

PubMed Central

Quatman, Carmen E.; Hettrich, Carolyn M.; Schmitt, Laura C.; Spindler, Kurt P.

2013-01-01

Background Current diagnostic strategies for detection of structural articular cartilage abnormalities, the earliest structural signs of osteoarthritis, often do not capture the condition until it is too far advanced for the most potential benefit of non-invasive interventions. Purpose Systematically review the literature relative to the following questions: (1) Is MRI a valid, sensitive, specific, accurate and reliable instrument to identify knee articular cartilage abnormalities compared to arthroscopy? (2) Is MRI a sensitive tool that can be utilized to identify early cartilage degeneration? Study Design Systematic Review Methods A systematic search was performed in November 2010 using PubMed MEDLINE (from 1966), CINAHL (from 1982), SPORTDiscus (from 1985), and SCOPUS (from 1996) databases. Results Fourteen level I and 13 level II studies were identified that met inclusion criteria and provided information related to diagnostic performance of MRI compared to arthroscopic evaluation. The diagnostic performance of MRI demonstrated a large range of sensitivities, specificities, and accuracies. The sensitivity for identifying articular cartilage abnormalities in the knee joint was reported between 26–96%. Specificity and accuracy was reported between 50–100% and 49–94%, respectively. The sensitivity, specificity, and accuracy for identifying early osteoarthritis were reported between 0–86%, 48–95%, and 5–94%, respectively. As a result of inconsistencies between imaging techniques and methodological shortcomings of many of the studies, a meta-analysis was not performed and it was difficult to fully synthesize the information to state firm conclusions about the diagnostic performance of MRI. Conclusions There is evidence in some MRI protocols that MRI is a relatively valid, sensitive, specific, accurate, and reliable clinical tool for identifying articular cartilage degeneration. Due to heterogeneity of MRI sequences it is not possible to make definitive conclusions regarding its global clinical utility for guiding diagnosis and treatment strategies. Clinical Relevance Traumatic sports injuries to the knee may be significant precursor events to early onset of posttraumatic osteoarthritis. MRI may aid in early identification of structural injuries to articular cartilage as evidenced by articular cartilage degeneration grading. PMID:21730207

A Preclinical Assessment of Early Continuous Passive Motion and Treadmill Therapeutic Exercises for Generating Chondroprotective Effects After Anterior Cruciate Ligament Rupture.

PubMed

Chang, Nai-Jen; Lee, Kuan-Wei; Chu, Chih-Jou; Shie, Ming-You; Chou, Pei-Hsi; Lin, Chih-Chan; Liang, Peir-In

2017-08-01

Anterior cruciate ligament (ACL) injury is a well-known risk factor for the development of posttraumatic osteoarthritis (PTOA). However, whether using continuous passive motion (CPM) with or without additional treadmill exercise (TRE) in early ACL injury might provide chondroprotective effects and further decrease the risk of PTOA has yet to be determined. CPM may offer an enhanced chondroprotective effect, but TRE may attenuate that effect due to the mechanical stress on the joint and inflammatory cytokines in the joint. Controlled laboratory study. Thirty adult New Zealand White male rabbits were randomly allocated to sedentary (SED), CPM, TRE, or CPM+TRE groups. Each rabbit underwent an ACL transection (ACLT) on the right knee, with the contralateral knee used as an internal control (sham). The 4 joint surfaces (ie, medial and lateral femoral condyles and tibial plateaus) were evaluated 4 weeks after surgery for gross appearance, histological characteristics, and quantitative osteoarthritis (OA) scores. Overall, at the end of testing, the CPM group experienced the best protective therapeutic effects in all compartments. In gross appearance, CPM resulted in normal articular surfaces, while the TRE and SED groups exhibited surface abrasion. Histological analysis showed significant differences in articular cartilage status. The CPM group had significantly better histological OA scores ( P < .01), corresponding to the smoothest cartilage surface and sound chondrocyte and collagen arrangement. This group also showed abundant glycosaminoglycan (GAG) content and a sound growth microenvironment, with significantly lower expression levels of the inflammatory cytokine tumor necrosis factor α and the apoptotic marker caspase 3. In contrast, the TRE and SED groups showed several features of damage: distinct graded cartilage abrasion; damaged collagen fibers, corresponding to noticeable collagen type X (osteoarthritic cartilage); reduced cartilage thickness; fewer cartilaginous cells; and the appearance of chondrocyte clusters. These groups also showed loss of GAG, corresponding to higher levels of inflammatory cytokines and apoptosis of articular chondrocytes. Furthermore, the CPM+TRE group displayed visible pathological changes in the superficial cartilage, indicating that early loading exercise may contribute to osteoarthritis. The sham treatment showed no difference in the changes in all compartments between groups. Immediate CPM therapy produces a superior in situ microenvironment for reducing the occurrence of PTOA after ACL injury without reconstruction in rabbits. These data suggest that immediate application of CPM therapy may be necessary to create a sound microenvironment in joints and possibly to decrease the risk of PTOA without or while awaiting ACL reconstruction. In contrast, both early active loading exercise and inactivity lead to the development of PTOA.

Development of an Equine Groove Model to Induce Metacarpophalangeal Osteoarthritis: A Pilot Study on 6 Horses

PubMed Central

Maninchedda, Ugo; Lepage, Olivier M.; Gangl, Monika; Hilairet, Sandrine; Remandet, Bernard; Meot, Francoise; Penarier, Geraldine; Segard, Emilie; Cortez, Pierre; Jorgensen, Christian; Steinberg, Régis

2015-01-01

The aim of this work was to develop an equine metacarpophalangeal joint model that induces osteoarthritis that is not primarily mediated by instability or inflammation. The study involved six Standardbred horses. Standardized cartilage surface damage or “grooves” were created arthroscopically on the distal dorsal aspect of the lateral and medial metacarpal condyles of a randomly chosen limb. The contralateral limb was sham operated. After 2 weeks of stall rest, horses were trotted 30 minutes every other day for 8 weeks, then evaluated for lameness and radiographed. Synovial fluid was analyzed for cytology and biomarkers. At 10 weeks post-surgery, horses were euthanized for macroscopic and histologic joint evaluation. Arthroscopic grooving allowed precise and identical damage to the cartilage of all animals. Under the controlled exercise regime, this osteoarthritis groove model displayed significant radiographic, macroscopic, and microscopic degenerative and reactive changes. Histology demonstrated consistent surgically induced grooves limited to non-calcified cartilage and accompanied by secondary adjacent cartilage lesions, chondrocyte necrosis, chondrocyte clusters, cartilage matrix softening, fissuring, mild subchondral bone inflammation, edema, and osteoblastic margination. Synovial fluid biochemistry and cytology demonstrated significantly elevated total protein without an increase in prostaglandin E2, neutrophils, or chondrocytes. This equine metacarpophalangeal groove model demonstrated that standardized non-calcified cartilage damage accompanied by exercise triggered altered osteochondral morphology and cartilage degeneration with minimal or inefficient repair and little inflammatory response. This model, if validated, would allow for assessment of disease processes and the effects of therapy. PMID:25680102

Development of an equine groove model to induce metacarpophalangeal osteoarthritis: a pilot study on 6 horses.

PubMed

Maninchedda, Ugo; Lepage, Olivier M; Gangl, Monika; Hilairet, Sandrine; Remandet, Bernard; Meot, Francoise; Penarier, Geraldine; Segard, Emilie; Cortez, Pierre; Jorgensen, Christian; Steinberg, Régis

2015-01-01

The aim of this work was to develop an equine metacarpophalangeal joint model that induces osteoarthritis that is not primarily mediated by instability or inflammation. The study involved six Standardbred horses. Standardized cartilage surface damage or "grooves" were created arthroscopically on the distal dorsal aspect of the lateral and medial metacarpal condyles of a randomly chosen limb. The contralateral limb was sham operated. After 2 weeks of stall rest, horses were trotted 30 minutes every other day for 8 weeks, then evaluated for lameness and radiographed. Synovial fluid was analyzed for cytology and biomarkers. At 10 weeks post-surgery, horses were euthanized for macroscopic and histologic joint evaluation. Arthroscopic grooving allowed precise and identical damage to the cartilage of all animals. Under the controlled exercise regime, this osteoarthritis groove model displayed significant radiographic, macroscopic, and microscopic degenerative and reactive changes. Histology demonstrated consistent surgically induced grooves limited to non-calcified cartilage and accompanied by secondary adjacent cartilage lesions, chondrocyte necrosis, chondrocyte clusters, cartilage matrix softening, fissuring, mild subchondral bone inflammation, edema, and osteoblastic margination. Synovial fluid biochemistry and cytology demonstrated significantly elevated total protein without an increase in prostaglandin E2, neutrophils, or chondrocytes. This equine metacarpophalangeal groove model demonstrated that standardized non-calcified cartilage damage accompanied by exercise triggered altered osteochondral morphology and cartilage degeneration with minimal or inefficient repair and little inflammatory response. This model, if validated, would allow for assessment of disease processes and the effects of therapy.

Composite poly(l-lactic-acid)/silk fibroin scaffold prepared by electrospinning promotes chondrogenesis for cartilage tissue engineering.

PubMed

Li, Zhengqiang; Liu, Peng; Yang, Ting; Sun, Ying; You, Qi; Li, Jiale; Wang, Zilin; Han, Bing

2016-05-01

Nanofibrous materials produced by electrospinning have attracted considerable attention from researchers in regenerative medicine. A combination of nanofibrous scaffold and chondrocytes is considered promising for repair of cartilage defect or damage. In the present study, we fabricated a poly(l-lactic-acid) (PLLA)/silk fibroin (SF) nanofibrous scaffold by electrospinning and evaluated its chondrogenic potential. The PLLA/SF nanofibers were characterized for diameter, surface wettability, swelling ratio, and tensile strength. Throughin vitroexperiments, PLLA/SF scaffold-chondrocyte interactions were investigated relative to the unmodified PLLA scaffold with regard to cellular adhesion, spreading, and proliferation by scanning electron microscopy and confocal laser scanning microscopy, and through analyses of DNA, sulfated glycosaminoglycan, and collagen. In addition, hematoxylin-eosin and Alcian blue-nuclear fast red staining were used to observe growth of chondrocytes, and secretion and distribution of cartilage-specific extracellular matrices in the scaffolds. Expressions of cartilage-related genes (collagen II, aggrecan, sox9, collagen I, and collagen X) were detected by real-time quantitative PCR. The PLLA/SF scaffold had better hydrophilicity, and could support chondrocytes adhesion and spreading more effectively than the unmodified PLLA scaffold. Chondrocytes secreted more cartilage-specific extracellular matrices and maintained their phenotype on the PLLA/SF scaffold. So it is concluded that the PLLA/SF scaffold is more conducive toin vitroformation of cartilage-like new tissues than the unmodified PLLA scaffold, and may be a promising material in cartilage tissue engineering. © The Author(s) 2016.

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