A multilayer biomaterial for osteochondral regeneration shows superiority vs microfractures for the treatment of osteochondral lesions in a multicentre randomized trial at 2 years.

PURPOSE: The increasing awareness on the role of subchondral bone in the etiopathology of articular surface lesions led to the development of osteochondral scaffolds. While safety and promising results have been suggested, there are no trials proving the real potential of the osteochondral regenerative approach. Aim was to assess the benefit provided by a nanostructured collagen-hydroxyapatite (coll-HA) multilayer scaffold for the treatment of chondral and osteochondral knee lesions. METHODS: In this multicentre randomized controlled clinical trial, 100 patients affected by symptomatic chondral and osteochondral lesions were treated and evaluated for up to 2 years (51 study group and 49 control group). A biomimetic coll-HA scaffold was studied, and bone marrow stimulation (BMS) was used as reference intervention. Primary efficacy measurement was IKDC subjective score at 2 years. Secondary efficacy measurements were: KOOS, IKDC Knee Examination Form, Tegner and VAS Pain scores evaluated at 6, 12 and 24 months. Tissue regeneration was evaluated with MRI MOCART scoring system at 6, 12 and 24 months. An external independent agency was involved to ensure data correctness and objectiveness. RESULTS: A statistically significant improvement of all clinical scores was obtained from basal evaluation to 2-year follow-up in both groups, although no overall statistically significant differences were detected between the two treatments. Conversely, the subgroup of patients affected by deep osteochondral lesions (i.e. Outerbridge grade IV and OCD) showed a statistically significant better IKDC subjective outcome (+12.4 points, p = 0.036) in the coll-HA group. Statistically significant better results were also found for another challenging group: sport active patients (+16.0, p = 0.027). Severe adverse events related to treatment were documented only in three patients in the coll-HA group and in one in the BMS group. The MOCART score showed no statistical difference between the two groups. CONCLUSIONS: This study highlighted the safety and potential of a biomimetic implant. While no statistically significant differences were found compared to BMS for chondral lesions, this procedure can be considered a suitable option for the treatment of osteochondral lesions. LEVEL OF EVIDENCE: I.

Influence of cryopreservation, cultivation time and patient's age on gene expression in Hyalograft® C cartilage transplants.

PURPOSE: Our aim was to evaluate the impact of cryopreservation, cultivation time and patient's age on the expression of specific chondrogenic markers in Hyalograft® C transplants. METHODS: Gene expression of chondrocyte markers [collagen type I (COL1A1), COL2A1, aggrecan, versican, melanoma inhibitory activity (MIA) and interleukin (IL)-1ß] was analysed in cartilage biopsies (n = 17) and Hyalograft® C transplant samples (non-cryopreserved = 78, cryopreserved = 13) by quantitative real-time polymerase chain reaction (PCR). Correlation analyses were performed to evaluate the influence of the above-named parameters on the level of gene expression. RESULTS: Cryopreservation of cells was found to decrease COL2A1 and MIA significantly (4.6-fold, p < 0.01 and 2-fold, p < 0.045, respectively). The duration of cryopreservation had no further influence on the expression of these factors. No correlation was detected between cultivation time (75 ± 31 days) and the expression level of any gene. Cartilage transplants from older patients (>35 years) exhibited a significantly higher IL-1ß expression (3.7-fold, p < 0.039) than transplants from younger patients (≤ 35 years). CONCLUSIONS: Our data demonstrate that cryopreservation has a profound impact on chondrocyte metabolic activity by decreasing the expression of COL2A1 and MIA in Hyalograft® C transplants, independent of the duration of cryopreservation.

Empfehlungen der AG Klinische Geweberegeneration zur Behandlung von Knorpelschäden am Kniegelenk. / Empfehlungen der AG Klinische Geweberegeneration zur Behandlung von Knorpelschäden am Kniegelenk.

The Working Group of the German Orthopedic and Trauma Society (DGOU) on Tissue Regeneration has published recommendations on the indication of different surgical approaches for treatment of full-thickness cartilage defects in the knee joint in 2004, 2013 and 2016. Based upon new scientific knowledge and new developments, this recommendation is an update based upon the best clinical evidence available. In addition to prospective randomised controlled clinical trials, this also includes studies with a lower level of evidence. In the absence of evidence, the decision is based on a consensus process within the members of the working group.The principle of making decision dependent on defect size has not been changed in the new recommendation either. The indication for arthroscopic microfracturing has been reduced up to a defect size of 2 cm2 maximum, while autologous chondrocyte implantation is the method of choice for larger cartilage defects. Additionally, matrix-augmented bone marrow stimulation (mBMS) has been included in the recommendation for defects ranging from 1 to 4.5 cm2. For the treatment of smaller osteochondral defects, in addition to osteochondral transplantation (OCT), mBMS is also recommended. For larger defects, matrix-augmented autologous chondrocyte implantation (mACI/mACT) in combination with augmentation of the subchondral bone is recommended.

Obesity-related juvenile form of cartilage lesions: a new affliction in the knees of morbidly obese children and adolescents.

OBJECTIVES: Overweight and obesity are afflictions that lead to an increased risk of health problems including joint problems. The aim of the study was to assess the condition of articular cartilage in obese adolescent patients suffering from knee pain. METHODS: MRI of 24 knees of 20 morbidly obese patients, mean age 14.2 years, was performed in an open 1.0 Tesla MR system, where the cartilage, the quality and structure of the menisci, and the presence or absence of surrounding changes was examined. RESULTS: In all patients a cartilage lesion in at least one region of the knee could be detected. Retropatellar cartilage lesions have been found in 19 knees. Ten cartilage lesions grade I, and four lesions grade II have been described in the lateral compartment of the knee, whereas the medial compartment showed in eight cases a grade I, in 13 cases a grade II and in two cases a grade III cartilage lesion. Meniscal changes were assessed in most patients. CONCLUSION: Morbidly obese children and adolescents show major abnormalities in the articular cartilage of the knee. Whether obesity alone is the causal factor for the development of the pattern of these changes, remains to be seen. KEY POINTS: • Morbidly obese children and adolescents often suffer from knee pain • Prospective study showed cartilage and meniscal lesions in morbidly obese adolescents • MRI is an adequate tool for assessing cartilage lesions even in morbidly obese patients • It is unclear whether cartilage abnormalities are mainly due to mechanical overload.

Advanced morphological 3D magnetic resonance observation of cartilage repair tissue (MOCART) scoring using a new isotropic 3D proton-density, turbo spin echo sequence with variable flip angle distribution (PD-SPACE) compared to an isotropic 3D steady-state free precession sequence (True-FISP) and standard 2D sequences.

PURPOSE: To evaluate a new isotropic 3D proton-density, turbo-spin-echo sequence with variable flip-angle distribution (PD-SPACE) sequence compared to an isotropic 3D true-fast-imaging with steady-state-precession (True-FISP) sequence and 2D standard MR sequences with regard to the new 3D magnetic resonance observation of cartilage repair tissue (MOCART) score. MATERIALS AND METHODS: Sixty consecutive MR scans on 37 patients (age: 32.8 ± 7.9 years) after matrix-associated autologous chondrocyte transplantation (MACT) of the knee were prospectively included. The 3D MOCART score was assessed using the standard 2D sequences and the multiplanar-reconstruction (MPR) of both isotropic sequences. Statistical, Bonferroni-corrected correlation as well as subjective quality analysis were performed. RESULTS: The correlation of the different sequences was significant for the variables defect fill, cartilage interface, bone interface, surface, subchondral lamina, chondral osteophytes, and effusion (Pearson coefficients 0.514-0.865). Especially between the standard sequences and the 3D True-FISP sequence, the variables structure, signal intensity, subchondral bone, and bone marrow edema revealed lower, not significant, correlation values (0.242-0.383). Subjective quality was good for all sequences (P ≥ 0.05). Artifacts were most often visible on the 3D True-FISP sequence (P < 0.05). CONCLUSION: Different isotropic sequences can be used for the 3D evaluation of cartilage repair with the benefits of isotropic 3D MRI, MPR, and a significantly reduced scan time, where the 3D PD-SPACE sequence reveals the best results.

Morphological and biochemical T2 evaluation of cartilage repair tissue based on a hybrid double echo at steady state (DESS-T2d) approach.

PURPOSE: To use a new approach which provides, based on the widely used three-dimensional double-echo steady-state (DESS) sequence, in addition to the morphological information, the generation of biochemical T2 maps in one hybrid sequence. MATERIALS AND METHODS: In 50 consecutive MRIs at 3.0 Tesla (T) after matrix-associated autologous chondrocyte transplantation (MACT) of the knee, by the use this new DESS-T2d approach, the morphological Magnetic resonance Observation of CArtilage Repair Tissue (MOCART) score, as well as biochemical T2d values were assessed. Furthermore, these results were correlated to standard morphological sequences as well as to standard multi-echo spin-echo T2 mapping. RESULTS: The MOCART score correlated (Pearson:0.945; P < 0.001) significantly as assessed with standard morphological sequences (68.8 ± 13.2) and the morphological images of the DESS T2d sequence (68.7 ± 12.6). T2 and T2d relaxation times (ms) were comparable in between the control cartilage (T2: 52.5 ± 11.4; T2d: 46.6 ± 10.3) and the repair tissue (T2: 54.4 ± 11.4; T2d: 47.5 ± 13.0) (T2: P = 0.157; T2d: P = 0.589). As expected, T2d values were lower than the standard-T2 values, however, both functional relaxation times correlated significantly (Pearson:0.429; P < 0.001). CONCLUSION: The presented hybrid approach provides the possibility to combine morphological and biochemical MRI in one fast 3D sequence, and thus, may attract for the clinical use of biochemical MRI.

Fracture dislocation of the lateral condyle and medial epicondyle of the humerus associated with complete radial nerve transection.

The combination of lateral condyle and medial epicondyle fractures of the humerus and a radial nerve transection is extremely rare. We could not find a similar case in the literature. Hereby we report such a case. An eight-year old female fell down while playing. She had wrist, thumb and fingers drop associated with hypoaesthesia over the first web space indicating radial nerve palsy. Plain X-ray of the left elbow showed fracture of the lateral condyle and avulsed fracture of the medial epicondyle. The Lateral condyle fracture was fixed with 2 screws and the medial epicondyle fracture was fixed with 2 K wires. The radial nerve was completely transected which was repaired primarily through a lateral approach. Six months later, the patient had full recovery of the wrist and elbow functions without any deformity.

The MOCART (Magnetic Resonance Observation of Cartilage Repair Tissue) 2.0 Knee Score and Atlas.

OBJECTIVE: Since the first introduction of the MOCART (Magnetic Resonance Observation of Cartilage Repair Tissue) score, significant progress has been made with regard to surgical treatment options for cartilage defects, as well as magnetic resonance imaging (MRI) of such defects. Thus, the aim of this study was to introduce the MOCART 2.0 knee score - an incremental update on the original MOCART score - that incorporates this progression. MATERIALS AND METHODS: The volume of cartilage defect filling is now assessed in 25% increments, with hypertrophic filling of up to 150% receiving the same scoring as complete repair. Integration now assesses only the integration to neighboring native cartilage, and the severity of surface irregularities is assessed in reference to cartilage repair length rather than depth. The signal intensity of the repair tissue differentiates normal signal, minor abnormal, or severely abnormal signal alterations. The assessment of the variables "subchondral lamina," "adhesions," and "synovitis" was removed and the points were reallocated to the new variable "bony defect or bony overgrowth." The variable "subchondral bone" was renamed to "subchondral changes" and assesses minor and severe edema-like marrow signal, as well as subchondral cysts or osteonecrosis-like signal. Overall, a MOCART 2.0 knee score ranging from 0 to 100 points may be reached. Four independent readers (two expert readers and two radiology residents with limited experience) assessed the 3 T MRI examinations of 24 patients, who had undergone cartilage repair of a femoral cartilage defect using the new MOCART 2.0 knee score. One of the expert readers and both inexperienced readers performed two readings, separated by a four-week interval. For the inexperienced readers, the first reading was based on the evaluation sheet only. For the second reading, a newly introduced atlas was used as an additional reference. Intrarater and interrater reliability was assessed using intraclass correlation coefficients (ICCs) and weighted kappa statistics. ICCs were interpreted according to Koo and Li; weighted kappa statistics were interpreted according to the criteria of Landis and Koch. RESULTS: The overall intrarater (ICC = 0.88, P < 0.001) as well as the interrater (ICC = 0.84, P < 0.001) reliability of the expert readers was almost perfect. Based on the evaluation sheet of the MOCART 2.0 knee score, the overall interrater reliability of the inexperienced readers was poor (ICC = 0.34, P < 0.019) and improved to moderate (ICC = 0.59, P = 0.001) with the use of the atlas. CONCLUSIONS: The MOCART 2.0 knee score was updated to account for changes in the past decade and demonstrates almost perfect interrater and intrarater reliability in expert readers. In inexperienced readers, use of the atlas may improve interrater reliability and, thus, increase the comparability of results across studies.

Quantitative T2 mapping of knee cartilage: differentiation of healthy control cartilage and cartilage repair tissue in the knee with unloading--initial results.

PURPOSE: To prospectively determine on T2 cartilage maps the effect of unloading during a clinical magnetic resonance (MR) examination in the postoperative follow-up of patients after matrix-associated autologous chondrocyte transplantation (MACT) of the knee joint. MATERIALS AND METHODS: Ethical approval for this study was provided by the local ethics commission, and written informed consent was obtained. Thirty patients (mean age, 35.4 years +/- 10.5) with a mean postoperative follow-up period of 29.1 months +/- 24.4 were enrolled. A multiecho spin-echo T2-weighted sequence was performed at the beginning (early unloading) and end (late unloading) of the MR examination, with an interval of 45 minutes. Mean and zonal region of interest T2 measurements were obtained in control cartilage and cartilage repair tissue. Statistical analysis of variance was performed. RESULTS: The change in T2 values of control cartilage (early unloading, 50.2 msec +/- 8.4; late unloading, 51.3 msec +/- 8.5) was less pronounced than the change in T2 values of cartilage repair tissue (early unloading, 51.8 msec +/- 11.7; late unloading, 56.1 msec +/- 14.4) (P = .024). The difference between control cartilage and cartilage repair tissue was not significant for early unloading (P = .314) but was significant for late unloading (P = .036). Zonal T2 measurements revealed a higher dependency on unloading for the superficial cartilage layer. CONCLUSION: Our results suggest that T2 relaxation can be used to assess early and late unloading values of articular cartilage in a clinical setting and that the time point of the quantitative T2 measurement affects the differentiation between native and abnormal articular cartilage. (c) RSNA, 2010.

T2 and T2* mapping in patients after matrix-associated autologous chondrocyte transplantation: initial results on clinical use with 3.0-Tesla MRI.

OBJECTIVES: To use T2 and T2* mapping in patients after matrix-associated autologous chondrocyte transplantation (MACT) of the knee, and to compare and correlate both methodologies. METHODS: 3.0-Tesla MRI was performed on 30 patients (34.6 +/- 9.9 years) with a follow-up period of 28.1 +/- 18.8 months after MACT. Multi-echo, spin-echo-based T2 mapping using six echoes and gradient-echo-based T2* mapping using six echoes were prepared. T2 and T2* maps were obtained using a pixel-wise, mono-exponential, non-negative least-squares fit analysis. Region-of-interest analysis was performed for mean (full-thickness) as well as deep and superficial aspects of the cartilage repair tissue and control cartilage sites. RESULTS: Mean T2 values (ms) were comparable for the control cartilage (53.4 +/- 11.7) and the repair tissue (55.5 +/- 11.6) (p > 0.05). Mean T2* values (ms) for control cartilage (30.9 +/- 6.6) were significantly higher than those of the repair tissue (24.5 +/- 8.1) (p < 0.001). Zonal stratification was more pronounced for T2* than for T2. The correlation between T2 and T2* was highly significant (p < 0.001), with a Pearson coefficient between 0.276 and 0.433. CONCLUSION: T2 and T2* relaxation time measurements in the evaluation of cartilage repair tissue and its zonal variation show promising results, although the properties visualised by T2 and T2* may differ.

Dedifferentiation of human articular chondrocytes is associated with alterations in expression patterns of GDF-5 and its receptors.

Human articular chondrocytes are expanded in monolayer culture in order to obtain sufficient cells for matrix-associated cartilage transplantation. During this proliferation process, the cells change their shape as well as their expression profile. These changes resemble those that occur during embryogenesis, when the limb anlagen form the interzone that later develops the joint cleft. We analysed the expression profile of genes that are reportedly important for these changes during embryogenesis within the dedifferentiation process of adult articular chondrocytes. We found GDF-5, BMPR-Ib and connexin 43 up-regulated, as well as a down-regulation of BMPR-Ia and noggin. Connexin 32 could not be detected in either native cartilage or in dedifferentiated cells. The newly synthesized proteins were detected by immunofluorescence. There is evidence from our results that dedifferentiated chondrocytes resemble the cells from the interzone in developing synovial joints.

Evaluation and comparison of cartilage repair tissue of the patella and medial femoral condyle by using morphological MRI and biochemical zonal T2 mapping.

The objective of this study was to use advanced MR techniques to evaluate and compare cartilage repair tissue after matrix-associated autologous chondrocyte transplantation (MACT) in the patella and medial femoral condyle (MFC). Thirty-four patients treated with MACT underwent 3-T MRI of the knee. Patients were treated on either patella (n = 17) or MFC (n = 17) cartilage and were matched by age and postoperative interval. For morphological evaluation, the MR observation of cartilage repair tissue (MOCART) score was used, with a 3D-True-FISP sequence. For biochemical assessment, T2 mapping was prepared by using a multiecho spin-echo approach with particular attention to the cartilage zonal structure. Statistical evaluation was done by analyses of variance. The MOCART score showed no significant differences between the patella and MFC (p > or = 0.05). With regard to biochemical T2 relaxation, higher T2 values were found throughout the MFC (p < 0.05). The zonal increase in T2 values from deep to superficial was significant for control cartilage (p < 0.001) and cartilage repair tissue (p < 0.05), with an earlier onset in the repair tissue of the patella. The assessment of cartilage repair tissue of the patella and MFC afforded comparable morphological results, whereas biochemical T2 values showed differences, possibly due to dissimilar biomechanical loading conditions.

Impact of 3D-culture on the expression of differentiation markers and hormone receptors in growth plate chondrocytes as compared to articular chondrocytes.

In this study we compared the expression of hormone receptors and markers of differentiation in growth plate chondrocytes (GPC) and articular chondrocytes (AC) under different culture conditions by real-time PCR and immunofluorescence. After one week of monolayer culture, porcine GPC and AC of 6-8-week-old piglets were either seeded in alginate beads or further grown in monolayer culture up to 5 weeks. During monolayer culture the expression of Col2, Col1, Col10, aggrecan, ERalpha and ERbeta decreased dramatically, whereas culture in alginate beads restored an expression pattern similar to native tissue. The receptors IGF-1R, IGF-2R and GHR were, however, increased in monolayer culture compared to alginate culture or native tissue. The relative proportion of ERalpha and ERbeta expression was different in GPC when compared to AC. All of our results on mRNA expression during culture in alginate beads were also verified to be translated to the protein level. Thus, the expression of hormone rereptors and differentiation markers were found to be highly influenced by culture conditions. Moreover, the porcine model is promising as defined by tissue availability, expression of relevant hormonal receptors and comparability to human conditions, in particular in the area of basic growth research.

Alterations in CD44 isoforms and HAS expression in human articular chondrocytes during the de- and re-differentiation processes.

The purpose of this study was to investigate the expression of different CD44 and hyaluronan synthase isoforms in cartilage, their alterations during the chondrocyte dedifferentiation process in monolayer culture and during the redifferentiation process on 3D scaffolds. Chondrocytes isolated from human articular cartilage were cultured as a monolayer for up to 36 days and were seeded on two different 3D scaffolds (HYAFF 11 and Bio-Gide). Expression levels of CD44s, CD44-lt, CD44-st, HAS1, HAS2, HAS3 and UDPGD were determined by real-time RT-PCR at different time points. At the protein level CD44 and CD90 were analyzed by flow cytometry. HAS2 was found to be the predominantly expressed hyaluronan synthase in chondrocytes and was not subjected to any regulation during the dedifferentiation process. CD44s, CD44-lt, CD44-st and UDPGD, however, were upregulated immediately after cell isolation. In addition, a high cell density was found to significantly increase CD44-st and CD44-lt expression. Redifferentiation on 3D scaffolds reversed the increase of the CD44 expression. Our data point out that CD44 expression does not correlate with matrix assembly in chondrocytes and that CD44 has a regulatory function in chondrocytes, not necessarily on differentiation, but probably on proliferation.

Initial results of in vivo high-resolution morphological and biochemical cartilage imaging of patients after matrix-associated autologous chondrocyte transplantation (MACT) of the ankle.

OBJECTIVE: The aim of this study was to use morphological as well as biochemical (T2 and T2* relaxation times and diffusion-weighted imaging (DWI)) magnetic resonance imaging (MRI) for the evaluation of healthy cartilage and cartilage repair tissue after matrix-associated autologous chondrocyte transplantation (MACT) of the ankle joint. MATERIALS AND METHODS: Ten healthy volunteers (mean age, 32.4 years) and 12 patients who underwent MACT of the ankle joint (mean age, 32.8 years) were included. In order to evaluate possible maturation effects, patients were separated into short-term (6-13 months) and long-term (20-54 months) follow-up cohorts. MRI was performed on a 3.0-T magnetic resonance (MR) scanner using a new dedicated eight-channel foot-and-ankle coil. Using high-resolution morphological MRI, the magnetic resonance observation of cartilage repair tissue (MOCART) score was assessed. For biochemical MRI, T2 mapping, T2* mapping, and DWI were obtained. Region-of-interest analysis was performed within native cartilage of the volunteers and control cartilage as well as cartilage repair tissue in the patients subsequent to MACT. RESULTS: The overall MOCART score in patients after MACT was 73.8. T2 relaxation times (approximately 50 ms), T2* relaxation times (approximately 16 ms), and the diffusion constant for DWI (approximately 1.3) were comparable for the healthy volunteers and the control cartilage in the patients after MACT. The cartilage repair tissue showed no significant difference in T2 and T2* relaxation times (p > or = 0.05) compared to the control cartilage; however, a significantly higher diffusivity (approximately 1.5; p < 0.05) was noted in the cartilage repair tissue. CONCLUSION: The obtained results suggest that besides morphological MRI and biochemical MR techniques, such as T2 and T2* mapping, DWI may also deliver additional information about the ultrastructure of cartilage and cartilage repair tissue in the ankle joint using high-field MRI, a dedicated multichannel coil, and sophisticated sequences.

Cartilage T2 assessment at 3-T MR imaging: in vivo differentiation of normal hyaline cartilage from reparative tissue after two cartilage repair procedures--initial experience.

PURPOSE: To prospectively compare cartilage T2 values after microfracture therapy (MFX) and matrix-associated autologous chondrocyte transplantation (MACT) repair procedures. MATERIALS AND METHODS: The study had institutional review board approval by the ethics committee of the Medical University of Vienna; informed consent was obtained. Twenty patients who underwent MFX or MACT (10 in each group) were enrolled. For comparability, patients of each group were matched by mean age (MFX, 40.0 years +/- 15.4 [standard deviation]; MACT, 41.0 years +/- 8.9) and postoperative interval (MFX, 28.6 months +/- 5.2; MACT, 27.4 months +/- 13.1). Magnetic resonance (MR) imaging was performed with a 3-T MR imager, and T2 maps were calculated from a multiecho spin-echo measurement. Global, as well as zonal, quantitative T2 values were calculated within the cartilage repair area and within cartilage sites determined to be morphologically normal articular cartilage. Additionally, with consideration of the zonal organization, global regions of interest were subdivided into deep and superficial areas. Differences between cartilage sites and groups were calculated by using a three-way analysis of variance. RESULTS: Quantitative T2 assessment of normal native hyaline cartilage showed similar results for all patients and a significant trend of increasing T2 values from deep to superficial zones (P < .05). In cartilage repair areas after MFX, global mean T2 was significantly reduced (P < .05), whereas after MACT, mean T2 was not reduced (P > or = .05). For zonal variation, repair tissue after MFX showed no significant trend between different depths (P > or = .05), in contrast to repair tissue after MACT, in which a significant increase from deep to superficial zones (P < .05) could be observed. CONCLUSION: Quantitative T2 mapping seems to reflect differences in repair tissues formed after two surgical cartilage repair procedures. (c) RSNA, 2008.

Longitudinal evaluation of cartilage composition of matrix-associated autologous chondrocyte transplants with 3-T delayed gadolinium-enhanced MRI of cartilage.

OBJECTIVE: The purposes of this study were to use delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) to evaluate the zonal distribution of glycosaminoglycans (GAGs) in normal cartilage and repair tissue and to use 3-T MRI to monitor the GAG content in matrix-associated autologous chondrocyte transplants. SUBJECTS AND METHODS: Fifteen patients who underwent matrix-associated autologous chondrocyte transplantation in the knee joint underwent MRI at baseline and 3-T follow-up MRI 1 year later. Total and zonal changes in longitudinal relaxivity (deltaR1) and relative deltaR1 were calculated for repair tissue and normal hyaline cartilage and compared by use of analysis of variance. RESULTS: There was a significant difference between the mean deltaR1 of repair tissue and that of reference cartilage at baseline and follow-up (p < 0.001). There was a significant increase in deltaR1 value and a decrease in GAG content from the deep layer to the superficial layer in the reference cartilage and almost no variation and significantly higher values for the repair tissue at both examinations. At 1-year follow-up imaging, there was a 22.7% decrease in deltaR1 value in the deep zone of the transplant. CONCLUSION: T1 mapping with dGEMRIC at 3 T shows the zonal structure of normal hyaline cartilage, highly reduced zonal variations in repair tissue, and a tendency toward an increase in global and zonal GAG content 1 year after transplantation.

Scaffold-dependent differentiation of human articular chondrocytes.

Matrix-associated autologous chondrocyte transplantation (MACT) is a tissue-engineered approach for the treatment of cartilage defects and combines autologous chondrocytes seeded on biomaterials. The objective of the study is the analysis of growth and differentiation behaviour of human articular chondrocytes grown on three different matrices used for MACT. Human articular chondrocytes were kept in monolayer culture for 42 days and then seeded on matrices consisting of either collagen type I/III, hyaluronan, or gelatine. During the culture time of 4 weeks the constructs were analyzed weekly. Morphological criteria were studied by scanning and transmission electron microscopy. The expression of the main type collagens was analyzed by real-time PCR. The collagen type I/III matrix supported a differentiation that closely resembled the tissue organisation of native cartilage, but cell number and type II collagen synthesis were low and differentiation occurred rather late in the cultivation period. The hyaluronan matrix and the gelatine-based matrix supported a rather rapid differentiation, with a high number of cells and a relatively high amount of type II collagen, but there was no spatial assembly that mimicked native cartilage. These facts indicate that the nature of the matrix is of great influence in the differentiation behaviour of dedifferentiated chondrocytes.

High-resolution magnetic resonance imaging and conventional magnetic resonance imaging on a standard field-strength magnetic resonance system compared to arthroscopy in patients with suspected meniscal tears.

RATIONALE AND OBJECTIVES: We sought to evaluate the diagnostic performance of high-resolution magnetic resonance imaging (MRI) and conventional MRI of the knee on a standard-field-strength MRI system compared to arthroscopic findings in patients with suspected meniscal tears. MATERIALS AND METHODS: Forty-two patients (20 women, 22 men), referred from the department of trauma surgery, with suspected medial meniscal tears and planned arthroscopy of the knee joint were included in the study. MRI was performed on a 1.0-T MRI scanner with two different protocols: (1) conventional MRI using a circular, polarized knee coil (coil diameter: 17 cm) with a sagittal dual fast spin-echo sequence (repetition time [TR]: 2500 ms; echo time [TE]: first, shortest, second, 120 ms; turbo spin echo [TSE] factor: 12; field of view: 180 mm; matrix: 256 x 512; scan percentage: 100; slice thickness: 3 mm) or (2) high-resolution MRI with a surface dual-loop coil of the medial knee compartment (temporomandibular joint, coil diameter: 8 cm) with a sagittal dual fast spin-echo sequence (TR: 2400 ms; TE: first, shortest; second, 120 ms; TSE factor: 12; field of view: 120 mm; matrix: 512 x 512; slice thickness: 2 mm). The menisci were evaluated on the basis of an adapted score (0 = normal meniscus, 1 = intrameniscal, T2-weighted hyperintense signal, 2 = discontinuity of the surface, 3 = fragmentation). Lesions that received a score of 2 or 3 were graded as meniscal tears. The MRI results were compared to the arthroscopic reports, which represented the gold standard, and the sensitivity of both protocols in detecting a meniscal tear was determined. RESULTS: Of the 42 patients included in the study, 25 (11 women and 14 men) underwent arthroscopy and all demonstrated a meniscal tear. A meniscal tear was correctly diagnosed in 76% of cases with conventional MRI and in 88% of cases with high-resolution MRI (P = .0087). CONCLUSION: High-resolution MRI, using a surface dual-loop coil and specific sequences, which can be performed on every standard-field-strength MRI scanner, is able to significantly improve diagnostic performance for the detection of a meniscal tear of the knee joint.

Steady-state diffusion imaging for MR in-vivo evaluation of reparative cartilage after matrix-associated autologous chondrocyte transplantation at 3 tesla--preliminary results.

OBJECTIVES: To demonstrate the feasibility of time-reversed fast imaging with steady-state precession (FISP) called PSIF for diffusion-weighted imaging of cartilage and cartilage transplants in a clinical study. MATERIAL AND METHODS: In a cross-sectional study 15 patients underwent MRI using a 3D partially balanced steady-state gradient echo pulse sequence with and without diffusion weighting at two different time points after matrix-associated autologous cartilage transplantation (MACT). Mean diffusion quotients (signal intensity without diffusion-weighting divided by signal intensity with diffusion weighting) within the cartilage transplants were compared to diffusion quotients found in normal cartilage. RESULTS: The global diffusion quotient found in repair cartilage was significantly higher than diffusion values in normal cartilage (p<0.05). There was a decrease between the earlier and the later time point after surgery. CONCLUSIONS: In-vivo diffusion-weighted imaging based on the PSIF technique is possible. Our preliminary results show follow-up of cartilage transplant maturation in patients may provide additional information to morphological assessment.