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.

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.

[Significance of Matrix-augmented Bone Marrow Stimulation for Treatment of Cartilage Defects of the Knee: A Consensus Statement of the DGOU Working Group on Tissue Regeneration]. / Stellenwert der matrixaugmentierten Knochenmarkstimulation in der Behandlung von Knorpelschäden des Kniegelenks: Konsensusempfehlungen der AG Klinische Geweberegeneration der DGOU.

Surgical principles for treatment of full-thickness cartilage defects of the knee include bone marrow stimulation techniques (i.e. arthroscopic microfracturing) and transplantation techniques (i.e. autologous chondrocyte implantation and osteochondral transplantation). On the basis of increasing scientific evidence, indications for these established therapeutical concepts have been specified and clear recommendations for practical use have been given. Within recent years, matrix-augmented bone marrow stimulation has been established as a new treatment concept for chondral lesions. To date, scientific evidence is limited and specific indications are still unclear. The present paper gives an overview of available products as well as preclinical and clinical scientific evidence. On the basis of the present evidence and an expert consensus from the "Working Group on Tissue Regeneration" of the German Orthopaedic and Trauma Society (DGOU), indications are specified and recommendations for the use of matrix-augmented bone marrow stimulation are given. In principle, it can be stated that the various products offered in this field differ considerably in terms of the number and quality of related studies (evidence level). Against the background of the current data situation, their application is currently seen in the border area between cell transplantation and bone marrow stimulation techniques, but also as an improvement on traditional bone marrow stimulation within the indication range of microfracturing. The recommendations of the Working Group have preliminary character and require re-evaluation after improvement of the study situation.

Matrix-associated chondrocyte transplantation for reconstruction of articulating surfaces in the temporomandibular joint: a pilot study covering medium- and long-term outcomes of 6 patients.

OBJECTIVE: Matrix-associated chondrocyte transplantation is routinely used in joints of the extremities but not in the temporomandibular joint (TMJ). STUDY DESIGN: We report the first case series in 7 patients of a tissue engineering approach to regenerate severely degraded articulating surfaces in the TMJ by simultaneously completely resurfacing both the mandibular condyle and the articular eminence/glenoid fossa with a commercially available collagen sponge seeded with autologous cells stabilized within a fibrin matrix. To facilitate healing, we temporarily employed a silicone membrane to protect the engineered tissues. The indications for surgery were posttraumatic fibro-osseous ankylosis, ankylosing osteoarthritis, or late-stage osteoarthritis. RESULTS: Six of the patients were recalled for follow-up after 3 years 6 months to 12 years 1 month. The maximum incisal opening was 18.2 ± 9.2 mm (range, 9-33 mm) before and 31.2 ± 13.6 mm (range, 12-47 mm) at the latest follow-up. Histologic specimens taken at 4 months showed beginning differentiation of fibrocytes into chondrocytes, whereas at 3 and 11 years, mature hyaline cartilage-not typical for the TMJ-was present. CONCLUSIONS: We conclude that the reconstruction of TMJ surfaces by matrix-associated chondrocyte transplantation may become a routine method for cartilage regeneration in the TMJ in the future.

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.

Redifferentiation of aged human articular chondrocytes by combining bone morphogenetic protein-2 and melanoma inhibitory activity protein in 3D-culture.

Melanoma inhibitory activity (MIA) affects the differentiation to hyaline cartilage and can inhibit the osteogenic potential of bone morphogenetic protein (BMP)-2 in mesenchymal stem cells (MSC). The aim of this study was to investigate if MIA also inhibits the osteogenic potential of BMP-2 in human articular chondrocytes during redifferentiation, which may lead to a higher grade of differentiation without calcification. HAC of four female patients (mean age: 73.75 ±6.98) were seeded into 3D culture for 28 days; after adding the recombinant proteins, four groups were formed (Control, BMP-2, MIA, BMP-2+MIA). Samples were analysed for gene expression, glycosaminoglycan (GAG) content and histology on day 0, 14 and 28. Collagen type 2 (COL2A1) was significantly increased in the BMP-2 containing groups on day 28; BMP-2 (100-fold, p = 0.001), BMP-2+MIA (65-fold, p = 0.009) and similar to the level of native cartilage. Higher aggrecan (Agg) levels were present in the BMP-2 (3-fold, p = 0.007) and BMP-2+MIA (4-fold, p = 0.002) group after 14 days and in the BMP-2 (9-fold, p = 0.001) group after 28 days. Collagen type 10 (COL10A1) was increased in the BMP-2 containing groups (6-fold, p = 0.006) but these levels were significantly below native cartilage. Alkaline phosphatase (ALP), collagen type 1 (COL1A1) and the glycosaminoglycan (GAG) content did not reveal any relevant differences between groups. BMP-2 is a potent inducer for differentiation of HAC. A significant enhancement of this effect in combination with MIA could not be observed. Furthermore no significant reduction of osteogenic markers during re-differentiation of chondrocytes was present combining BMP-2 and MIA.

Matrix Production Affects MRI Outcomes After Matrix-Associated Autologous Chondrocyte Transplantation in the Knee.

BACKGROUND: Matrix-associated autologous chondrocyte transplantation (MACT) has been an effective therapy for large, full-thickness cartilage lesions for years. However, little is known about how graft maturation is affected by characteristics of transplanted chondrocytes. PURPOSE: To investigate the influence of gene expression of chondrocytes at the time of transplantation on MRI outcomes up to 2 years after MACT. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: This study included 25 patients with 27 symptomatic traumatic defects of articular cartilage, who had undergone MACT in the knee. Postoperative MRI examinations were conducted at 3, 6, 12, and 24 months after surgery. Biochemical graft maturation was assessed by measuring T2 relaxation time values of the transplant and healthy native cartilage areas. The MOCART (magnetic resonance observation of cartilage repair tissue) score was used to evaluate the morphological quality of regeneration tissue. Gene expression (collagen type I, collagen type II, aggrecan, versican, and interleukin-1ß) was determined by real-time polymerase chain reaction (PCR) in transplant residuals at the time point of transplantation and was correlated with MRI outcomes using Spearman's rank correlation coefficient. A Friedman test with post hoc analysis (Wilcoxon signed rank test) conducted with a Bonferroni correction was applied to compare scores at different time points. RESULTS: T2 relaxation time of regeneration tissue improved from a mean ± SD of 74.6 ± 20.1 milliseconds at 3 months to 47.9 ±13.3 milliseconds at 24 months ( P < .003). These values were similar to the T2 relaxation times of the native surrounding cartilage (50.9 ± 15 ms). The calculated T2 index (ratio of regeneration tissue to native cartilage) improved from 1.63 ± 0.76 at 3 months to 1.0 ± 0.4 at 24 months ( P < .011). The MOCART score increased from 51.6 ± 15 points to 72.4 ± 12.2 points ( P < .001). Improvement of the T2 index over time significantly correlated with aggrecan, COL1A1, COL2A1, and versican expression ( rs = 0.9, P < .001; rs = 0.674, P < .012; rs = 0.553, P < .05; and rs = 0.575, P < .04, respectively). No correlation was found for IL-1ß. CONCLUSION: These data demonstrate that matrix production in transplanted chondrocytes affects maturation of MACT grafts in MRI 2 years after surgery.

Clinical and radiological long-term outcomes after matrix-induced autologous chondrocyte transplantation: a prospective follow-up at a minimum of 10 years.

BACKGROUND: It is unclear whether matrix-associated autologous chondrocyte transplantation (MACT) results in objective and subjective clinical improvements at 10 years after surgery. HYPOTHESIS: Matrix-associated autologous chondrocyte transplantation will result in clinical and radiological improvements in patients with symptomatic, traumatic chondral defects of the knee joint. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: A total of 16 patients with chondral defects of the knee were treated with MACT between November 2000 and April 2002 and evaluated for up to 10 years after the intervention. The International Knee Documentation Committee (IKDC) form, Knee Injury and Osteoarthritis Outcome Score (KOOS), Tegner activity score, Brittberg score, Noyes sports activity rating scale, and visual analog scale (VAS) for pain as well as 3-T magnetic resonance imaging (MRI) using the magnetic resonance observation of cartilage repair tissue (MOCART) score and functional evaluation by the limb symmetry index (LSI) formed the basis of this study. The Friedman test and the Wilcoxon signed-rank test were performed for a comparison between all time points and 2 separate time points, respectively. If significant differences were revealed, a Bonferroni adjustment to the α level was applied so that P values <.007 (<.05/7) were regarded as significant in the paired comparisons. RESULTS: Significant improvements (P < .05) from baseline to 120 months postoperatively were observed for the IKDC score (mean, 44.1 ± 26.9 to 59.0 ± 27.4), Noyes sports activity rating score (mean, 37.7 ± 30.1 to 62.1 ± 31.3), and KOOS Quality of Life and Pain subscores, whereas no statistically significant improvement was detected for the Brittberg score, Tegner activity score, or VAS score. After 5 years, a slight downward tendency of all clinical scores was evident. After 10 years, the mean MOCART score was 70.4 ± 16.1. Complete filling of the defect was observed in 73.9% of cases, and osteophytes were present in 78.3%. In 65.2% of the cases, a subchondral bone edema <1 cm was visible, whereas in 21.7% of the cases, a subchondral bone edema >1 cm was seen. The mean LSI for the single-legged hop test was 95.6% ± 16.2% and for the triple hop test for distance was 91.3% ± 12.2%. The mean VAS score for self-perceived stability was 60.2 ± 3.5 (range, 0-9.5) for the injured and 60.7 ± 3.8 (range, 0-10) for the uninjured leg. No adhesions or effusions were seen regarding the clinical and radiological outcomes. CONCLUSION: The significantly improved results on 3 outcome measures after 10 years suggest that MACT represents a suitable option in the treatment of local cartilage defects in the knee.

[Prevention of venous thromboembolism in musculoskeletal surgery]. / Thromboseprophylaxe in der muskuloskelettalen Chirurgie.

Musculoskeletal surgery is associated with a high risk of venous thrombosis and pulmonary embolism. The introduction of direct oral anticoagulants (DOAK) has broadened the possibilities for prevention of venous thromboembolism in the course of orthopedic and trauma surgery. Addressing this recent development, the Austrian Societies of Orthopedics and Orthopedic Surgery (ÖGO), Trauma Surgery (ÖGU), Hematology and Oncology (OeGHO) and of Anaesthesiology, Reanimation und Intensive Care Medicine (ÖGARI) have taken the initiative to create Austrian guidelines for the prevention of thromboembolism after total hip and knee replacement, hip fracture surgery, interventions at the spine and cases of minor orthopedic and traumatic surgery. Furthermore, the pharmacology of the DOAK and the pivotal trial data for each of the three currently available substances - apixaban, dabigatran, and rivaroxaban - are briefly presented. Separate chapters are dedicated to "anticoagulation and neuroaxial anesthesia" and "bridging".

Influence of cell differentiation and IL-1ß expression on clinical outcomes after matrix-associated chondrocyte transplantation.

BACKGROUND: Several patient- and defect-specific factors influencing clinical outcomes after matrix-associated chondrocyte transplantation (MACT) have been identified, including the patient's age, location of the defect, or duration of symptoms before surgery. Little is known, however, about the influence of cell-specific characteristics on clinical results after transplantation. PURPOSE: The aim of the present study was to investigate the influence of cell differentiation and interleukin-1 ß (IL-1ß) expression on clinical outcomes up to 5 years after MACT. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Twenty-seven patients who underwent MACT of the tibiofemoral joint area of the knee were included in this study. Clinical assessments were performed preoperatively as well as 6, 12, 24, and 60 months after transplantation by using the following scores: the Knee injury and Osteoarthritis Outcome Score (KOOS), the International Knee Documentation Committee (IKDC) Subjective Knee Form, the Noyes sports activity rating scale, the Brittberg clinical score, and a visual analog scale (VAS) for pain. The quality of repair tissue was assessed by magnetic resonance imaging using the magnetic resonance observation of cartilage repair tissue (MOCART) score at 1 and 5 years. Cell differentiation (defined as collagen type II:type I expression ratio), aggrecan, and IL-1ß expression were determined by real-time polymerase chain reaction in transplant residuals and were correlated with clinical outcomes. RESULTS: The largest improvements in clinical scores were found during the first year. Two years postoperatively, a stable improvement was reached until 5 years after transplantation, with a mean IKDC score of 34.4 ± 8.6 preoperatively to 77.9 ± 16 after 24 months (P < .001). Cell differentiation showed a significant positive correlation with nearly all clinical scores at different time points, especially after 12 months (P < .05). IL-1ß expression negatively influenced clinical outcomes at 24 months (Brittberg score) and 60 months (Brittberg and VAS scores) after surgery (P < .05). No correlation was found between the MOCART score and clinical outcomes or gene expression. CONCLUSION: Our data demonstrate that cell differentiation and IL-1ß expression influence clinical outcomes up to 5 years after MACT.

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.

Ability to return to sports 5 years after matrix-associated autologous chondrocyte transplantation in an average population of active patients.

BACKGROUND: Cartilage injuries often occur during sports activities, and return to sports after cartilage surgery is an important outcome parameter for different treatment methods in the competitive as well as the recreationally active population. HYPOTHESIS: At the time of midterm follow-up after matrix-associated autologous chondrocyte transplantation (MACT), return to recreational sports at the preinjury level will be possible. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Seventy patients (51 men, 19 women; age [mean ± standard deviation], 34.9 ± 8.6 y; range, 18-55 y) were clinically evaluated 5 years after MACT through subjective clinical scores such as the Knee Injury and Osteoarthritis Outcome Score (KOOS) sport and recreation subscales, the Tegner activity scale, and the Noyes sports activity rating scale. The level of sports participation was included in the investigation. RESULTS: The results 5 years after MACT showed mean values of 60.1 for the KOOS-sport, 67.4 for the Noyes, and 3.8 for the Tegner scores, meaning that regular sports activity such as cycling or running on flat ground, as well as medium-level manual labor, is possible. We noted that 74.3% of our patients returned to at least their preinjury sports level. CONCLUSION: Midterm postoperative results after MACT show that in a moderately active population, participation in regular sports is possible for most patients, at least at their preinjury recreational level and intensity, and there is a good rate of return to sports.

Clinical and radiological outcomes 5 years after matrix-induced autologous chondrocyte implantation in patients with symptomatic, traumatic chondral defects.

BACKGROUND: To date, few studies have been published reporting the 5-year follow-up of clinical and radiological outcomes for chondral defects treated with matrix-induced autologous chondrocyte implantation (MACI). HYPOTHESIS: A significant improvement in clinical and radiological outcomes after treatment of symptomatic, traumatic chondral defects of the knee with the MACI implant will be maintained up to 5 years after surgery. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: A prospective evaluation of the MACI procedure was performed in 21 patients with chondral defects of the knee. After the MACI procedure, patients were clinically assessed with the Knee injury and Osteoarthritis Outcome Score (KOOS), the Tegner-Lysholm score, the International Knee Documentation Committee (IKDC) Subjective Knee Form, and the modified Cincinnati score at years 1, 2, and 5. The quality of repair tissue was assessed by magnetic resonance imaging using the magnetic resonance observation of cartilage repair tissue (MOCART) score at months 3 and 6 and years 1, 2, and 5. RESULTS: Significant improvements (P < .05) were observed for all 5 KOOS subcategories at year 1 and were maintained through year 5 in 90.5% of patients (19/21). Treatment failure occurred in only 9.5% of patients (2/21). Significant improvements (P < .05) from baseline to year 5 were also observed for the IKDC score (30.1 to 74.3), the modified Cincinnati score (38.1 to 79.6), and the Tegner-Lysholm activity score (1.8 to 4.3). Similarly, the MOCART score significantly improved (P < .001) from baseline to year 5 (52.9 to 75.8). After 5 years, complete filling (83%) and integration (82%) of the graft were seen in the majority of patients. Signs of subchondral bone edema were still present in 47% of patients at 5 years. No product-specific adverse events were reported over the 5-year follow-up period. CONCLUSION: Patients treated with a MACI implant demonstrated significant clinical improvement and good quality repair tissue 5 years after surgery. The MACI procedure was shown to be a safe and effective treatment for symptomatic, traumatic chondral knee defects in this study.

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.

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.

Evaluation of cartilage repair tissue after matrix-associated autologous chondrocyte transplantation using a hyaluronic-based or a collagen-based scaffold with morphological MOCART scoring and biochemical T2 mapping: preliminary results.

BACKGROUND: In cartilage repair, bioregenerative approaches using tissue engineering techniques have tried to achieve a close resemblance to hyaline cartilage, which might be visualized using advanced magnetic resonance imaging. PURPOSE: To compare cartilage repair tissue at the femoral condyle noninvasively after matrix-associated autologous chondrocyte transplantation using Hyalograft C, a hyaluronic-based scaffold, to cartilage repair tissue after transplantation using CaReS, a collagen-based scaffold, with magnetic resonance imaging using morphologic scoring and T2 mapping. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: Twenty patients after matrix-associated autologous chondrocyte transplantation (Hyalograft C, n = 10; CaReS, n = 10) underwent 3-T magnetic resonance imaging 24 months after surgery. Groups were matched by age and defect size/localization. For clinical outcome, the Brittberg score was assessed. Morphologic analysis was applied using the magnetic resonance observation of cartilage repair tissue score, and global and zonal biochemical T2 mapping was performed to reflect biomechanical properties with regard to collagen matrix/content and hydration. RESULTS: The clinical outcome was comparable in each group. The magnetic resonance observation of cartilage repair tissue score showed slightly but not significantly (P= .210) better results in the CaReS group (76.5) compared to the Hyalograft C group (70.0), with significantly better (P= .004) constitution of the surface of the repair tissue in the CaReS group. Global T2 relaxation times (milliseconds) for healthy surrounding cartilage were comparable in both groups (Hyalograft C, 49.9; CaReS, 51.9; P= .398), whereas cartilage repair tissue showed significantly higher results in the CaReS group (Hyalograft C, 48.2; CaReS, 55.5; P= .011). Zonal evaluation showed no significant differences (P > or = .05). CONCLUSION: Most morphologic parameters provided comparable results for both repair tissues. However, differences in the surface and higher T2 values for the cartilage repair tissue that was based on a collagen scaffold (CaReS), compared to the hyaluronic-based scaffold, indicated differences in the composition of the repair tissue even 2 years postimplantation. CLINICAL RELEVANCE: In the follow-up of cartilage repair procedures using matrix-associated autologous chondrocyte transplantation, differences due to scaffolds have to be taken into account.

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.

Diffusion-weighted imaging for the follow-up of patients after matrix-associated autologous chondrocyte transplantation.

OBJECTIVE: To evaluate the use of diffusion-weighted imaging (DWI) for the assessment of cartilage maturation in patients after matrix-associated autologous chondrocyte transplantation (MACT). MATERIALS AND METHODS: Fifteen patients after MACT were examined by 3.0-T magnetic-resonance-tomography; the examination was up to 13 month after surgery in group 1, and later than 13 month after surgery in group 2. Both groups had a follow-up one-year later. DWI was acquired using a steady-state gradient-echo sequence. Mean values of the diffusion quotients of regions of interest within cartilage repair tissue and of reference regions were assessed. Each region-of-interest was subdivided into a deep, and a superficial area. RESULTS: Mean diffusion quotients of cartilage repair tissues were 1.44 (baseline), and 1.44 (follow-up). Mean diffusion quotients of reference tissues were 1.29 (baseline) and 1.28 (follow-up). At the follow-up diffusion quotients of cartilage repair tissue were significantly higher than those of reference cartilage. In group 1 the diffusion quotients were significantly lower at the follow-up (1.45 versus 1.65); in group 2 no statistically significant differences between follow-up (1.39) and baseline (1.41) were found. Reference cartilages and cartilage repair tissues of group 2 showed a decrease of diffusion quotients from the deep to the superficial area being stable at the follow-up. In group 1 initially a significant increase (1.49 versus 1.78) of the diffusion quotients from deep to superficial area of the cartilage repair tissue was found changing into a decrease (1.65 versus 1.52) at the follow-up. CONCLUSIONS: DWI detected changes of diffusion within cartilage repair tissue that may reflect cartilage maturation. Changes in diffusity occurred up to two years after surgery and were stable later. Zonal variations within cartilage could be measured.

Effect of accelerated weightbearing after matrix-associated autologous chondrocyte implantation on the femoral condyle on radiographic and clinical outcome after 2 years: a prospective, randomized controlled pilot study.

BACKGROUND: There is no consensus about the optimal time for weightbearing activities after matrix-associated autologous chondrocyte implantation (MACI) of the femoral condyle. HYPOTHESIS: A comprehensive protocol after MACI on the femoral condyle with accelerated weightbearing leads to a better functional and radiographic outcome compared with the same comprehensive protocol with delayed weightbearing. STUDY DESIGN: Randomized controlled trial; Level of evidence, 1. METHODS: Thirty-one patients (22 male, 9 female) after MACI on the femoral condyle were randomly assigned to the accelerated weightbearing group (group A) or the delayed weightbearing group (group B). Aside from increase and time of full weightbearing, both groups adhered to the same rehabilitation protocol and exercises. Patients were assessed preoperatively and at 4, 12, 24, 52, and 104 weeks after surgery. Clinical evaluation was performed by determining the subjective form of the International Knee Documentation Committee (IKDC), the Tegner activity scale, and the Knee Injury and Osteoarthritis Outcome Score (KOOS). Radiological outcome was evaluated by the MOCART score and the size and amount of bone marrow edema and effusion. RESULTS: In both groups, there were no differences with regard to the clinical outcome. For the radiological outcome, group A showed a higher prevalence of bone marrow edema after 6 months without correlation to the clinical outcome (P = .06-.1). However, after 104 weeks, there were no differences in the radiological outcome between group A and group B. CONCLUSION: A rehabilitation protocol with accelerated weightbearing leads to good clinical and functional outcome after 2 years without jeopardizing the healing graft.