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.

Pre-Osteoarthritis: Definition and Diagnosis of an Elusive Clinical Entity.

OBJECTIVE: An attempt to define pre-osteoarthritis (OA) versus early OA and definitive osteoarthritis. METHODS: A group of specialists in the field of cartilage science and treatment was formed to consider the nature of OA onset and its possible diagnosis. RESULTS: Late-stage OA, necessitating total joint replacement, is the end stage of a biological process, with many previous earlier stages. Early-stage OA has been defined and involves structural changes identified by arthroscopy or radiography. The group argued that before the "early-stage OA" there must exist a stage where cellular processes, due to the presence of risk factors, have kicked into action but have not yet resulted in structural changes. The group suggested that this stage could be called "pre-osteoarthritis" (pre-OA). CONCLUSIONS: The group suggests that defining points of initiation for OA in the knee could be defined, for example, by traumatic episodes or surgical meniscectomy. Such events may set in motion metabolic processes that could be diagnosed by modern MRI protocols or arthroscopy including probing techniques before structural changes of early OA have developed. Preventive measures should preferably be applied at this pre-OA stage in order to stop the projected OA "epidemic."

Effect of accelerated weightbearing after matrix-associated autologous chondrocyte implantation on the femoral condyle: a prospective, randomized controlled study presenting MRI-based and clinical outcomes after 5 years.

BACKGROUND: Long-term effects of different weightbearing (WB) modalities after matrix-associated autologous chondrocyte implantation (MACI) on changes in knee articular cartilage and clinical outcomes are needed to establish more evidence-based recommendations for postoperative rehabilitation. HYPOTHESIS: There will be no differences between accelerated WB compared with delayed WB regarding knee articular cartilage or patient self-reported knee function or activity level 5 years after MACI. Furthermore, significant correlations between magnetic resonance imaging (MRI)-based outcomes and patient-reported outcome measures 5 years postoperatively will exist. STUDY DESIGN: Randomized controlled trial; Level of evidence, 1. METHODS: After MACI, 31 patients (23 male, 8 female) were randomly assigned to the accelerated WB group (AWB group) or to the delayed WB group (DWB group). With the exception of time and increase to full WB, both groups underwent the same rehabilitation program. The AWB group was allowed full WB after 6 weeks and the DWB group after 10 weeks. Assessments were performed 3 months, 2 years, and 5 years postoperatively, but this long-term follow-up study only included changes from 2 to 5 years postoperatively. The magnetic resonance observation of cartilage repair tissue (MOCART) score (primary outcome), the MRI-based variables of bone edema and effusion, the Knee Injury and Osteoarthritis Outcome Score (KOOS), and the Tegner scale were included. In addition, the association between MRI-based outcomes and the KOOS at 5 years postoperatively was investigated. RESULTS: There was a significant decrease in the MOCART score and a significant increase in bone edema 2 and 5 years postoperatively but no significant group differences. The only significant correlation between the MRI-based variables and the KOOS was found for bone edema and the KOOS subscale of pain (r=-0.435, P<.05) at 5-year follow-up. CONCLUSION: There were no significant differences in the MRI-based or clinical outcomes between the AWB group and DWB group 5 years after MACI. While the clinical outcomes remained stable, a decline of the MRI-based findings was observed between 2 and 5 years postoperatively. Furthermore, a significant association between bone edema and pain was found. No occurrence of unintended effects was observed.

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.

3D-isotropic high-resolution morphological imaging and quantitative T2 mapping as biomarkers for gender related differences after matrix-associated autologous chondrocyte transplantation (MACT).

The aim of this study was to determine in vivo high-resolution morphological and biochemical gender related differences in cartilage repair tissue (MACT). Forty patients were examined clinically and by MR scans at 3T-MRI (coronal 3D True-FISP sequence for morphologic assessment and multi-echo spin-echo T2-mapping for biochemical assessment of healthy cartilage and MACT cartilage). Mean T2 values in repair tissue in the deep zone showed significantly shorter T2 times in females (p = 0.009, female 43.5 ± 9.8 vs. male 48.2 ± 7.7 ms). The superficial zone showed higher T2 values than the deep zone in both the groups (female 48.5 ± 9.8, males 52.6 ± 11.0 ms) without significant difference between female and male patients. Native control cartilage showed no statistically significant differences for T2 between females and males. The subdivisions "structure of the repair tissue" and "subchondral bone" of the MOCART score showed statistically significant differences between females and males (p = 0.026 and p = 0.007) as well as the Lysholm score (p = 0.03). Our investigations revealed differences between female and male patients after MACT of the knee in clinical outcome and advanced morphological and biochemical MRI. The presented imaging biomarkers can depict subtle changes after cartilage regeneration procedures and might help to understand gender related differences after cartilage repair procedures.

Results 2 Years After Matrix-Associated Autologous Chondrocyte Transplantation Using the Novocart 3D Scaffold: An Analysis of Clinical and Radiological Data.

BACKGROUND: A range of scaffolds is available from various manufacturers for cartilage repair through matrix-associated autologous chondrocyte transplantation (MACT), with good medium- to long-term results. PURPOSE: To evaluate clinical and magnetic resonance imaging (MRI) outcomes 2 years after MACT on the knee joint using the Novocart 3D scaffold based on a bilayered collagen type I sponge. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Of 28 initial patients, 23 were clinically and radiologically evaluated 24 months after transplantation. Indications for MACT were chondral or osteochondral lesions on the knee joint with a defect size >2 cm2, no instability, and no malalignment (axis deviation <5°). Then, MRI was performed on a 3-T scanner to assess the magnetic resonance observation of cartilage repair tissue (MOCART) and 3-dimensional (3D) MOCART scores. A variety of subjective scores (International Knee Documentation Committee [IKDC], Knee injury and Osteoarthritis Outcome Score [KOOS], Noyes sports activity rating scale, Tegner activity scale, and visual analog scale [VAS] for pain) were used for clinical evaluation. RESULTS: Two years after MACT, the MRI evaluation showed a mean MOCART score of 73.2 ± 12.4 and a 3D MOCART score of 73.4 ± 9.7. Clinical results showed mean values of 69.8 ± 15.2 for the IKDC; 51.6 ± 21.2, 86.5 ± 13.9, 54.5 ± 23.6, 65.0 ± 8.0, and 91.5 ± 10.6 for the KOOS subscales (Quality of Life, Pain, Sports and Recreation, Symptoms, and Activities of Daily Living, respectively); 77.5 ± 12.7 for the Noyes scale; 4.4 ± 1.6 for the Tegner activity scale; and 1.8 ± 1.7 for the VAS, with statistically significant improvement in all scores other than KOOS-Symptoms. CONCLUSION: Undergoing MACT using the Novocart 3D scaffold is an applicable method to treat large focal chondral and osteochondral defects, with good short-term clinical and radiological results.

[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.

Is magnetic resonance imaging reliable in predicting clinical outcome after articular cartilage repair of the knee? A systematic review and meta-analysis.

BACKGROUND: While MRI can provide a detailed morphological evaluation after articular cartilage repair, its additional value in determining clinical outcome has yet to be determined. PURPOSE: To evaluate the correlation between MRI and clinical outcome after cartilage repair and to identify parameters that are most important in determining clinical outcome. STUDY DESIGN: Systematic review and meta-analysis. METHODS: A systematic search was performed in Embase, MEDLINE, and the Cochrane Collaboration. Articles were screened for relevance and appraised for quality. Guidelines in the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) Statement were used. Chi-square tests were performed to find variables that could determine correlation between clinical and radiological parameters. RESULTS: A total of 32 articles (total number of patients, 1019) were included. A majority (81%) were case series or cohort studies that used similar standardized MRI techniques. The mean Coleman score was 63 (range, 42-96). For the majority of MRI parameters, limited or no correlation was found. Nine studies (28%) found a correlation between clinical outcome and the composite magnetic resonance observation of cartilage repair tissue (MOCART) or Henderson score and 7 (22%) with defect fill. In 5 studies, a weak to moderate correlation was found between clinical outcome and the T2 index (mean Pearson coefficient r = .53). CONCLUSION: Strong evidence to determine whether morphological MRI is reliable in predicting clinical outcome after cartilage repair is lacking. Future research aiming specifically at clinical sensitivity of advanced morphological and biochemical MRI techniques after articular cartilage repair could be of great importance to the field.

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.