A Moderate-Intensity Static Magnetic Field Enhances Repair of Cartilage Damage in Rabbits (original) (raw)
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Magnetization transfer in cartilage and its constituent macromolecules
Magnetic Resonance in Medicine, 1995
The goal of this work was to investigate magnetization transfer (MT) in cartilage by measuring water proton signals MJM,, as an indicator of MT, in (i) single-component systems of the tissue's constituent macromolecules and (ii) intact cartilage under control conditions and after two pathomimetic interventions. MJM, was quantified with a 12-pT saturation pulse applied 6 kHz off resonance. Both glycosaminoglycans (GAG) and collagen exhibited concentration dependent effects on MJ M,, being approximately linear for GAG solutions (MJM, =-0.0137[% GAG] + 1.02) and exponential for collagen suspensions (MJMo = 0.80 x exp[-(Y0collagen)/6.60l+ 0.20); the direct saturation of water could not account for the measured MJM,,. Although the effect of collagen on MJMo is much stronger than for a corresponding concentration of GAG, MJM, is not very sensitive to changes in collagen concentration in the physiological range. Tissue degradation with 25 mg/ml trypsin led to an increase inMJM, from the baseline value of 0.2 (finamnitial values = 1.15 2 0.13, n = 11, P < 0.001). In contrast, a 10-day treatment of cartilage with 100 ng/ml of intetieukin-lp (IL-1p) caused a 19% decrease in MJM, (finaVinitial values = 0.81-c 0.08, n = 3, P = 0.085). The changes in hydration and macromolecular content for the two treatments were comparable, suggesting that MJM, is sensitive to macromolecular structure as well as concentration. In conclusion, whereas the baseline MJM, value in cartilage may be primarily due to the tissue collagen concentration, changes in MJM, may be due to physiological or pathophysiological changes in GAG concentration and tissue structure, and the measured MJM, may difterentiate between various pathomimetic degradative procedures.
Magnetization transfer analysis of cartilage repair tissue: a preliminary study
Skeletal Radiology, 2006
To evaluate the magnetization transfer ratio (MTR) after two different cartilage repair procedures, and to compare these data with the MTR of normal cartilage. Twenty-seven patients with a proven cartilage defect were recruited: 13 were treated with autologous chondrocyte implantation (ACI) and 14 were treated with the microfracture technique (MFR). All patients underwent MRI examinations with MT-sequences before the surgical treatment, after 12 months (26 patients) and after 24 months (11 patients). Eleven patients received a complete follow-up study at all three time points (five of the ACI group and six of the MFR group). All images were transferred to a workstation to calculate MTR images. For every MT image set, different ROIs were delineated by two radiologists. Means were calculated per ROI type in the different time frames and in both groups of cartilage repair. The data were analyzed with unpaired t- and ANOVA tests, and by calculating Pearson's correlation coefficient. No significant differences were found in the MTR of fatty bone marrow, muscle and normal cartilage in the different time frames. There was a significant but small difference between the MTR of normal cartilage and the cartilage repair area after 12 months for both procedures. After 24 months, the MTR of ACI repaired cartilage (0.31+/-0.07) was not significantly different from normal cartilage MTR (0.34+/-0.05). The MTR of MFR repaired cartilage (0.28+/-0.02), still showed a significant difference from normal cartilage. The differences between damaged and repaired cartilage MTR are too small to enable MT-imaging to be a useful tool for postoperative follow-up of cartilage repair procedures. There is, however, an evolution towards normal MTR-values in the cartilage repair tissue (especially after ACI repair).
Magnetic Resonance Imaging, 2001
We investigated the role of collagen in the magnetization transfer (MT) effect in contrast to other macromolecules. By means of phantoms made of collagen, chondroitin sulfate (CS) and albumin, MR parameters have been optimized in order to reduce the acquisition time and improve the sensitivity, as well as to minimize the contributions from CS and albumin to the MT induced signal attenuation. The same method was used to study cartilage ex vivo (bovine articular and nasal cartilage plugs) and in vivo (goat knee femoral chondyle). In phantom samples, the MT signal attenuation depended on the collagen concentration while contributions from the other macromolecules were found to be minimal. In average, analysis of MT images revealed a ϳ25%, ϳ35% and ϳ30% signal attenuation in 10% w/v type I collagen gels, cartilage plugs, and cartilage from the weight-bearing areas of the goat knee, respectively. Biochemical data revealed that treatment of cartilage plugs with bacterial collagenase led to collagen depletion and correspondingly to a decrease of the MT response. In contrast, trypsin-induced proteoglycan loss in cartilage plugs did not alter the MT effect. A significant correlation was observed between the collagen content in these plugs and their respective MT ratios and the rate constant k for the exchange process bound versus free water. Finally, data obtained from in vivo MT measurement of the goat knee demonstrated that intra-articular injection of papain might not only cause degradation of proteoglycans but also a change in collagen integrity in a dose-dependent manner. We conclude that in vivo measurement of MT ratios gives quantitative and qualitative information on the collagen status and may be applied for the routine evaluation of normal and abnormal articular cartilage.
New trends in MRI of cartilage: Advances and limitations in small animal studies
Bio-medical materials and engineering, 2010
Due to the actual interest for bioengineering in the osteoarthritis (OA) healing context, researchers need accurate qualitative and quantitative methodologies to evaluate in vivo the integration and functionality of their cartilage-like biomaterials. As in clinical diagnostic strategies, advances in Magnetic Resonance Imaging (MRI) seem promising for non-vulnerant assessments of articular cartilage bio-architecture and morphology in small animal models. These experimental models are commonly used to monitor the physiopathology of OA and to evaluate therapeutic responses mediated by chondroprotective drugs or tissue engineering. Nowadays, the application of MR protocols to in vivo small animal cartilage imaging is achievable with the development of high magnetic fields and the adaptation of methodologies to reach the required spatial resolution and contrast. The purpose of this article is to summarize these current MRI strategies used for in vivo small animal articular cartilage asse...
Immunochemical and Mechanical Characterization of Cartilage Subtypes in Rabbit
Journal of Histochemistry & Cytochemistry, 2002
Cartilage is categorized into three general subgroups, hyaline, elastic, and fibrocartilage, based primarily on morphologic criteria and secondarily on collagen (Types I and II) and elastin content. To more precisely define the different cartilage subtypes, rabbit cartilage isolated from joint, nose, auricle, epiglottis, and meniscus was characterized by immunohistochemical (IHC) localization of elastin and of collagen Types I, II, V, VI, and X, by biochemical analysis of total glycosaminoglycan (GAG) content, and by biomechanical indentation assay. Toluidine blue staining and safranin-O staining were used for morphological assessment of the cartilage subtypes. IHC staining of the cartilage samples showed a characteristic pattern of staining for the collagen antibodies that varied in both location and intensity. Auricular cartilage is discriminated from other subtypes by interterritorial elastin staining and no staining for Type VI collagen. Epiglottal cartilage is characterized by positive elastin staining and intense staining for Type VI collagen. The unique pattern for nasal cartilage is intense staining for Type V collagen and collagen X, whereas articular cartilage is negative for elastin (interterritorially) and only weakly positive for collagen Types V and VI. Meniscal cartilage shows the greatest intensity of staining for Type I collagen, weak staining for collagens V and VI, and no staining with antibody to collagen Type X. Matching cartilage samples were categorized by total GAG content, which showed increasing total GAG content from elastic cartilage (auricle, epiglottis) to fibrocartilage (meniscus) to hyaline cartilage (nose, knee joint). Analysis of aggregate modulus showed nasal and auricular cartilage to have the greatest stiffness, epiglottal and meniscal tissue the lowest, and articular cartilage intermediate. This study illustrates the differences and identifies unique characteristics of the different cartilage subtypes in rabbits. The results provide a baseline of data for generating and evaluating engineered repair cartilage tissue synthesized in vitro or for post-implantation analysis.
Journal of Biomedical Materials Research Part A, 2005
We evaluated the efficacy of a magnetic liposomal delivery system of transforming growth factor (TGF)- 1 in the treatment of articular cartilage defects in a rabbit model. Articular cartilage defects were created in the patellar groove of rabbits, and a permanent magnet or a nonmagnetic alloy was implanted in the defect site. Magnetic liposomal drugs, prepared by the conventional film method and sonication, were injected into the defect site 1 week after surgery. First, the efficacy of the magnetic liposomal delivery system was evaluated by using a model compound fluorescence-labeled dextran 40,000 (FD-40). Then, the therapeutic efficiency of magnetic liposomal TGF- 1 was evaluated by cartilage histological scoring at 4, 8, and 12 weeks after surgery. The injected magnetic liposomal FD-40 accu-mulated at the target site where a permanent magnet had been implanted. The histological score showed that the injection of magnetic liposomal TGF- 1 under magnetic force was significantly effective in the repair of the defect site over 12 weeks after surgery. Injection of TGF- 1 into the cartilage defect was effective as a magnetic liposomal preparation under magnetic force, resulting in acceleration of the cartilage repair, probably because of the desirable accumulation of TGF- 1 at the target site.
Articular cartilage repair using an intra-articular magnet and synovium-derived cells
Journal of Orthopaedic Research, 2011
The purpose of this study was to investigate whether it is possible to regenerate degenerated human cartilage in vitro by use of magnetically labeled mesenchymal stem cells (MSCs) and an external magnetic device. Methods: MSCs from human bone marrow were cultured and magnetically labeled. Degenerated human cartilage was obtained during total knee arthroplasty. The osteochondral fragments were attached to the sidewall of tissue culture flasks, and magnetically labeled MSCs were injected into the flasks. By use of an external magnetic device, a magnetic force was applied for 6 hours to the direction of the cartilage, and then the degenerated cartilage was cultured in chondrogenic differentiation medium for 3 weeks. In the control group a magnetic force was not applied. The specimens were evaluated histologically. Results: A cell layer was formed on the degenerated cartilage as shown by H&E staining. The cell layer was also stained in toluidine blue and safranin O and with anti-collagen type II immunostaining, indicating that the cell layer contained an extracellular matrix. In the control group a cell layer was not observed on the cartilage. Conclusions: We were able to show that our system could deliver MSCs onto degenerated human cartilage and then form an extracellular matrix on the degenerated cartilage in vitro. Clinical Relevance: Our novel cell delivery system using magnetic force may lead toward a new treatment option for osteoarthritis.
Journal of Orthopaedic Research, 2008
The effect of pulsed electromagnetic fields (PEMFs) on the integration of osteochondral autografts was evaluated in sheep. After osteochondral grafts were performed, the animals were treated with PEMFs for 6 h/day or sham-treated. Six animals were sacrificed at 1 month. Fourteen animals were treated for 2 months and sacrificed at 6 months. At 1 month, the osteogenic activity at the transplant-host subchondral bone interface was increased in PEMF-treated animals compared to controls. Articular cartilage was healthy in controls and stimulated animals. At 6 months, complete resorption was observed in four control grafts only. Cyst-like resorption areas were more frequent within the graft of sham-treated animals versus PEMF-treated. The average volume of the cysts was not significantly different between the two groups; nevertheless, analysis of the variance of the volumes demonstrated a significant difference. The histological score showed no significant differences between controls and stimulated animals, but the percentage of surface covered by fibrous tissue was higher in the control group than in the stimulated one. Interleukin-1 and tumor necrosis factor-a concentration in the synovial fluid was significantly lower, and transforming growth factor-b1 was significantly higher, in PEMF-treated animals compared to controls. One month after osteochondral graft implantation, we observed larger bone formation in PEMFtreated grafts which favors early graft stabilization. In the long term, PEMF exposure limited the bone resorption in subchondral bone; furthermore, the cytokine profile in the synovial fluid was indicative of a more favorable articular environment for the graft. ß
Tissue Engineering, 2006
Objective: To generate a cartilage biomaterial using a suspension culture with biophysical properties similar to native articular cartilage. Design: A novel cartilage tissue equivalent (CTE) using a no-scaffold, high-density suspension culture of neonatal porcine chondrocytes was formed on poly 2-hydroxyethyl methacrylate-treated plates for up to 16 weeks. Equilibrium aggregate modulus and hydraulic permeability were measured at 8 and 16 weeks using confined compression stress relaxation experiments. The CTE proteoglycan composition was characterized using sodium and T 1q magnetic resonance imaging methods after 8 weeks. Results: The resultant CTE produces a biomaterial consistent with a hyaline cartilage phenotype in appearance and expression of type II collagen and aggrecan. The equilibrium aggregate modulus and permeability for the 8-week specimens were 41.6 (standard deviation (SD) 4.3) kPa and 2.85 À13 (SD 2.45 À13) m 4 /Ns, respectively, and, for the 16-week specimens, 35.2 (SD 7.6) kPa and 2.67 À13 (SD 1.06 À13) m 4 /Ns, respectively. Average sodium concentration of the 8-week CTE ranged from 260 to 278 mM and average T 1q relaxation times from 105 to 107 ms, indicating proteoglycan content similar to that of native articular cartilage. Conclusion: The high-density culture method produced a CTE with characteristics that approach those of native articular cartilage. The CTE mechanical properties are similar to those of the native cartilage. The CTE developed in this study represents a promising methodological advancement in cartilage tissue engineering and cartilage repair.
A New Animal Model for Assessing Cartilage Repair and Regeneration at a Nonarticular Site
Tissue Engineering Part A, 2010
The aim of this study was to establish a critical-sized nonjoint chondral defect animal model and to evaluate its feasibility for testing cartilage regeneration strategies. Dermal biopsy punches 1-4 mm in diameter were used to create cylindrical full-thickness defects in the center of athymic rat xiphoids. The 3 and 4 mm defects remained unhealed 35 days postsurgery, with a large area in the center that had low proteoglycan content based on contrast-enhanced microCT (EPIC-microCT), radiographic, and histological analyses. In a second step, tissueengineered cartilage was synthesized by culturing primary bovine articular chondrocytes on poly-L-lactic acid (PLA) scaffolds in a perfusion-shear bioreactor for 28 days. These chondrocyte/PLA constructs or primary bovine chondrocytes were implanted into 3-mm-diameter defects. Empty defects and defects implanted with empty PLA scaffolds were used as controls. Xiphoids were harvested 28 days after surgery and examined with faxitron, microCT, and histology using hematoxylin and eosin and safranin-O staining. Both chondrocyte/PLA constructs and chondrocytes alone formed neocartilage. The results indicate that a 3 mm cylindrical defect in a rat xiphoid is an economic, feasible, and reproductive model to evaluate the potential of various constructs for nonjoint cartilage repair.