Matrix-associated Autologous Chondrocyte Transplantation Research Articles

Two-Year Results of Injectable Matrix-Associated Autologous Chondrocyte Transplantation in the Hip Joint: Significant Improvement in Clinical and Radiological Assessment.

Articular cartilage defects are a prevalent consequence of femoroacetabular impingement (FAI) in young active patients. In accordance with current guidelines, large chondral lesions of the hip joint over 2 cm2 are recommended to be treated with matrix-associated, autologous chondrocyte transplantation (MACT); however, the conditions in the hip joint are challenging for membrane-based MACT options. Injectable MACT products can solve this problem. The purpose of the trial was to assess clinical and radiological outcomes 24 months after injectable MACT of focal chondral lesions caused by FAI. We present data of 21 patients with focal cartilage defects of the hip [3.0 ± 1.4 cm2 (mean ± SD)], ICRS Grade III and IV caused by CAM-type impingement, who underwent arthroscopic MACT (NOVOCART® Inject) and FAI correction. The outcome was evaluated with the patient-reported outcome instruments iHOT33 and EQ-5D-5L (index value and VAS), whilst graft morphology was assessed based on the MOCART score over a follow-up period of 24 months. The iHOT33 score increased significantly from 52.9 ± 21.1 (mean ± SD) preoperatively to 85.8 ± 14.8 (mean ± SD; p < 0.0001) 24 months postoperatively. The EQ-5D-5L index value (p = 0.0004) and EQ-5D VAS (p = 0.0006) showed a statistically significant improvement as well. MRI evaluation after 24 months showed successful integration of the implant in all patients with a complete defect filling in 11 of 14 patients. Injectable MACT for the treatment of full-thickness chondral lesions of the hip joint due to FAI in combination with FAI correction improved symptoms, function, and quality of life in the treated cohort. Alongside the treatment of the underlying pathology by the FAI correction, the developed cartilage defect can be successfully repaired by MACT, which is of considerable clinical relevance.

Sandwich Technique for Large Osteochondral Lesions of the Knee.

ObjectiveTo evaluate whether a sandwich technique procedure for large osteochondral lesions (OCL) of the medial femur condyle reduces clinical symptoms and improves activity level as well as to assess repair tissue integration on MRI over 2 years.DesignTwenty-one patients (median age: 29 years, 18-44 years) who received matrix-associated autologous chondrocyte transplantation (MACT) combined with cancellous bone grafting at the medial femur condyle in a 1-step procedure were prospectively included. Patients were evaluated before surgery (baseline) as well as 3, 6, 12, and 24 months postoperatively, including clinical evaluation, Lysholm score, Tegner Activity Rating Scale, and MRI with Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) score and a modified Whole-Organ Magnetic Resonance Imaging Score (WORMS).ResultsSeventeen patients were available for the 24-month (final) follow-up (4 dropouts). Lysholm significantly improved from 48 preoperatively stepwise to 95 at final follow-up (P < 0.05). Tegner improvement from 2.5 at baseline to 4.0 at final follow-up was not significant (P = 1.0). MOCART score improved significantly and stepwise from 65 at 3 months to 90 at 24 months (P < 0.05). Total WORMS improved from 14.5 at surgery to 7.0 after 24 months (P < 0.05). Body mass index and defect size at surgery correlated with total WORMS at final follow-up (P < 0.05) but did not correlate with clinical scores or defect filling.ConclusionMACT combined with cancellous bone grafting at the medial femoral condyle reduces symptoms continuously over 2 years. A 1-step procedure may reduce perioperative morbidity. However, despite improvements, patients’ activity levels remain low, even 2 years after surgery.

Freeze-Dried Curdlan/Whey Protein Isolate-Based Biomaterial as Promising Scaffold for Matrix-Associated Autologous Chondrocyte Transplantation-A Pilot In-Vitro Study.

The purpose of this pilot study was to establish whether a novel freeze-dried curdlan/whey protein isolate-based biomaterial may be taken into consideration as a potential scaffold for matrix-associated autologous chondrocyte transplantation. For this reason, this biomaterial was initially characterized by the visualization of its micro- and macrostructures as well as evaluation of its mechanical stability, and its ability to undergo enzymatic degradation in vitro. Subsequently, the cytocompatibility of the biomaterial towards human chondrocytes (isolated from an orthopaedic patient) was assessed. It was demonstrated that the novel freeze-dried curdlan/whey protein isolate-based biomaterial possessed a porous structure and a Young’s modulus close to those of the superficial and middle zones of cartilage. It also exhibited controllable degradability in collagenase II solution over nine weeks. Most importantly, this biomaterial supported the viability and proliferation of human chondrocytes, which maintained their characteristic phenotype. Moreover, quantitative reverse transcription PCR analysis and confocal microscope observations revealed that the biomaterial may protect chondrocytes from dedifferentiation towards fibroblast-like cells during 12-day culture. Thus, in conclusion, this pilot study demonstrated that novel freeze-dried curdlan/whey protein isolate-based biomaterial may be considered as a potential scaffold for matrix-associated autologous chondrocyte transplantation.

Clinical evaluation after matrix-associated autologous chondrocyte transplantation : a comparison of four different graft types.

AimsThe aim of this retrospective study was to determine if there are differences in short-term clinical outcomes among four different types of matrix-associated autologous chondrocyte transplantation (MACT).MethodsA total of 88 patients (mean age 34 years (SD 10.03), mean BMI 25 kg/m2 (SD 3.51)) with full-thickness chondral lesions of the tibiofemoral joint who underwent MACT were included in this study. Clinical examinations were performed preoperatively and 24 months after transplantation. Clinical outcomes were evaluated using the International Knee Documentation Committee (IKDC) Subjective Knee Form, the Brittberg score, the Tegner Activity Scale, and the visual analogue scale (VAS) for pain. The Kruskal-Wallis test by ranks was used to compare the clinical scores of the different transplant types.ResultsThe mean defect size of the tibiofemoral joint compartment was 4.28 cm2 (SD 1.70). In total, 11 patients (12.6%) underwent transplantation with Chondro-Gide (matrix-associated autologous chondrocyte implantation (MACI)), 40 patients (46.0%) with Hyalograft C (HYAFF), 21 patients (24.1%) with Cartilage Regeneration System (CaReS), and 15 patients (17.2%) with NOVOCART 3D. The mean IKDC Subjective Knee Form score improved from 35.71 (SD 6.44) preoperatively to 75.26 (SD 18.36) after 24 months postoperatively in the Hyalograft group, from 35.94 (SD 10.29) to 71.57 (SD 16.31) in the Chondro-Gide (MACI) group, from 37.06 (SD 5.42) to 71.49 (SD 6.76) in the NOVOCART 3D group, and from 45.05 (SD 15.83) to 70.33 (SD 19.65) in the CaReS group. Similar improvements were observed in the VAS and Brittberg scores.ConclusionTwo years postoperatively, there were no significant differences in terms of outcomes. Our data demonstrated that MACT, regardless of the implants used, resulted in good clinical improvement two years after transplantation for localized tibiofemoral defects.Cite this article: Bone Joint Res 2021;10(7):370–379.

Three-dimensional, Scaffold-Free, Autologous Chondrocyte Transplantation: A Systematic Review

Background:A 3-dimensional, scaffold-free, and completely autologous form of chondrocyte transplantation (ACT3D) has been developed and applied in clinical practice in the past decade to overcome disadvantages of previous-generation procedures.Purpose:To document and analyze the available literature on the results of ACT3D in the treatment of articular chondral lesions in the knee and hip joints.Study Design:Systematic review; Level of evidence, 4.Methods:All studies published in English addressing ACT3D were identified and included those that fulfilled the following criteria: (1) level 1 through 4 evidence, (2) measures of radiological or functional/clinical outcome, and (3) outcome related to cartilage lesions of the knee and hip joints.Results:A total of 10 studies were selected: 2 randomized controlled trials, 1 cohort study, and 7 case series. The studies revealed significant increases in patients’ subjective quality of life, satisfaction, pain reduction, and improvement in joint function at short- to medium-term follow-up. Magnetic resonance imaging-assisted examination and second-look arthroscopy showed a hyaline-like repair tissue with a high degree of defect filling and integration.Conclusion:ACT3D shows promising results in the therapy of articular cartilage defects in the knee as well as in the hip, but well-designed, long-term studies are lacking. ACT3D might have relevant advantages over common matrix-associated autologous chondrocyte transplantation products, but systematic evaluation and randomized controlled studies are crucial to verify the potential of this tissue-engineered approach.

Arthroscopic matrix-associated, injectable autologous chondrocyte transplantation of the hip: significant improvement in patient-related outcome and good transplant quality in MRI assessment.

Acetabular chondral lesions are common in patients with FAI. For large full-thickness cartilage defects, arthroscopic matrix-associated autologous chondrocyte transplantation (MACT) using an injectable in situ crosslinking product is an option. Aim of the study was to evaluate clinical and MRI results 12 months after MACT of acetabular cartilage defects in FAI patients. We report data on 21 patients with a focal cartilage defect of the hip [2.97 ± 1.44 cm2 (mean ± SD)] caused by FAI treated with an arthroscopically conducted MACT combined with FAI surgery. The results were assessed with patient-reported outcome measures (iHOT33, EQ-5D) pre- as well as post-operatively and by MRI using MOCART scoring system 6 and 12 months post-operatively. The iHOT33 score improved from 52.9 ± 21.14 (mean ± SD) pre-operative to 81.08 ± 22.04 (mean ± SD; p = 0.0012) 12 months post-operatively. The lower the pre-operative iHOT33 score and the larger the defect size, the greater the observed improvement compared to pre-operative scores at 12 months. Patients showed a significant improvement in EQ-5D-5L index value (p = 0.0015) and EQ-5D VAS (p = 0.0006). MRI analysis after 12 months revealed a complete integration of the transplant in 16 of 20 patients. Injectable MACT is a promising minimally invasive treatment option for full-thickness cartilage defects of the hip caused by FAI. A significant improvement in symptoms and function associated with an increase in quality of life was detected in patients treated with injectable MACT combined with FAI surgery. This is of considerable clinical relevance, since, in addition to the elimination of the mechanical cause, MACT allows the successful therapy of consequential cartilage damage. Level 4, case series.

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-1β) 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-1β. Conclusion: These data demonstrate that matrix production in transplanted chondrocytes affects maturation of MACT grafts in MRI 2 years after surgery.

Evaluating the cartilage adjacent to the site of repair surgery with glycosaminoglycan-specific magnetic resonance imaging

The glycosaminoglycan (GAG) chemical exchange saturation transfer (CEST) imaging method (gagCEST) makes it possible to assess and quantify the GAG concentration in human cartilage. This biochemical imaging technique facilitates detection of the loss of GAG in the course of osteoarthritis. The gagCEST technique was used to analyse the perilesional zone (PLZ) adjacent to repair tissue after cartilage repair surgery, to determine whether there are biochemical changes present in the sense of degeneration. Asymmetries in the PLZ of cartilage defects in 11 patients, who had been treated by microfracturing or matrix-associated autologous chondrocyte transplantation (MACT), were measured by gagCEST on a 7-T whole-body system. These results were correlated with gagCEST asymmetries of healthy reference cartilage (RC), measured anterior and posterior to the PLZ and to the repair tissue (RT). The mean gagCEST asymmetry for the anterior PLZ was 4.8% (±4.4), for the posterior PLZ 5.4% (±2.3), for the anterior RC 6.6% (±3.5) and 7.2% (±3.3) for the posterior RC and 4.5% (±2.3) for the RT. The difference between the anterior PLZ and the anterior RC (p = 0.019), the posterior PLZ and the posterior RC (p = 0.005), and the mean RC and the RT (p = 0.021) were all statistically significant. The measurements between RT and mean PLZ did not reveal significant results (p = 0.398). The gagCEST method provides a potentially useful biomarker for the loss of GAGs, indicating cartilage degeneration in the PLZ. Pre-operative and post-operative monitoring of the biomechanical state of the cartilage might influence intra-operative decision-making concerning the extent of cartilage resection or might give information of the success of the treatment post-operatively.

Chondrogenic Gene Expression Differences between Chondrocytes from Osteoarthritic and Non-OA Trauma Joints in a 3D Collagen Type I Hydrogel

Objective The purpose of the current study was to compare the donor age variation of chondrocytes from non-OA (osteoarthritic) trauma joints in patients of young to middle age (20.5 ± 3.7, 31.8 ± 1.9, 41.9 ± 4.1 years) embedded in matrix-associated autologous chondrocyte transplantation (MACT) grafts (CaReS). The chondrocyte-specific gene expression of CaReS grafts were then compared to chondrocytes from OA joints (in patients aged 63.8 ± 10 years) embedded in a collagen type I hydrogel. Design OA chondrocytes and articular chondrocyte-laden grafts were cultured over 14 days in chondrogenic growth medium. We performed reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) to evaluate the mRNA expression levels of chondrocyte-specific and hypertrophic markers. Results Gene expression analysis with RT-qPCR revealed no significant difference in chondrocyte-specific genes ( COL2A1, ACAN, SOX9, SOX5, SOX6) among 3 different age group of patients with CaReS grafts. In a comparative analysis of OA chondrocytes to articular chondrocytes, chondrogenic markers ( COL2A1, SOX6) exhibited higher expression in OA chondrocytes ( P < 0.05). Hypertrophic or OA cartilage pathogenesis marker ( MMP3, MMP13) expression was higher and COL1A1 had significantly lower expression ( P < 0.05) in OA chondrocytes than articular chondrocytes when cultivated in collagen type I hydrogels. Conclusion In summary, we identify that donor age variation does not influence the chondrogenic gene expression of the CaReS system. We also identified that freshly isolated OA chondrocytes embedded in collagen type I hydrogels can exhibit chondrogenic gene expression as observed in articular chondrocytes on the CaReS grafts. Transforming OA chondrocytes to articular chondrocytes can be regarded as an alternative option in the MACT technique.

Cartilage evaluation with biochemical MR imaging using in vivo Knee compression at 3 T-comparison of patients after cartilage repair with healthy volunteers

Magnetic resonance (MR) transverse relaxation time (T2) mapping has been frequently used to evaluate collagen content and its organization.In this study, MR T2 mapping, using the multi-slice, multi-echo Carr–Purcell–Meiboom–Gill technique, was performed in volunteers and patients after matrix-associated autologous chondrocyte transplantation (MACT) under unloading and loading conditions with an MR-compatible compression device.In the volunteer study, a statistically significant decrease in the cartilage MR T2 values was observed during the loading phase when compared to the initial load-free measurement. During the recovery period, a statistically significant increase in the T2 values was found in the central superficial layer (p=0.001), the central deep layer (p=0.005), the posterior deep layer (p=0.001), and in the tibia superficial layer (p=0.01) when compared to measurements under loading. In patients after MACT, during unloading or loading conditions, statistically significant changes in T2 values were observed in the transplant deep zone (p=0.005), in the posterior deep zone (p=0.004), and in the tibia superficial zone (p=0.012).The results of this study show that MR T2 mapping under loading conditions may provide additional information about cartilage repair tissue composition and organization during the postoperative follow-up, and may help to evaluate the efficacy of cartilage-repair surgery techniques.

Sodium magnetic resonance imaging of ankle joint in cadaver specimens, volunteers, and patients after different cartilage repair techniques at 7 T: initial results.

The goal of cartilage repair techniques such as microfracture (MFX) or matrix-associated autologous chondrocyte transplantation (MACT) is to produce repair tissue (RT) with sufficient glycosaminoglycan (GAG) content. Sodium magnetic resonance imaging (MRI) offers a direct and noninvasive evaluation of the GAG content in native cartilage and RT. In the femoral cartilage, this method was able to distinguish between RTs produced by MFX and MACT having different GAG contents. However, it needs to be clarified whether sodium MRI can be useful for evaluating RT in thin ankle cartilage. Thus, the aims of this 7-T study were (1) to validate our sodium MRI protocol in cadaver ankle samples, (2) to evaluate the sodium corrected signal intensities (cSI) in cartilage of volunteers, (3) and to compare sodium values in RT between patients after MFX and MACT treatment. Five human cadaver ankle samples as well as ankles of 9 asymptomatic volunteers, 6 MFX patients and 6 MACT patients were measured in this 7-T study. Sodium values from the ankle samples were compared with histochemically evaluated GAG content. In the volunteers, sodium cSI values were calculated in the cartilages of ankle and subtalar joint. In the patients, sodium cSI in RT and reference cartilage were measured, morphological appearance of RT was evaluated using the magnetic resonance observation of cartilage repair tissue (MOCART) scoring system, and clinical outcome before and after surgery was assessed using the American Orthopaedic Foot and Ankle Society score and Modified Cincinnati Knee Scale. All regions of interest were defined on morphological images and subsequently transferred to the corresponding sodium images. Analysis of variance, t tests, and Pearson correlation coefficients were evaluated. In the patients, significantly lower sodium cSI values were found in RT than in reference cartilage for the MFX (P = 0.007) and MACT patients (P = 0.008). Sodium cSI and MOCART scores in RT did not differ between the MFX and MACT patients (P = 0.185). No significant difference in sodium cSI was found between reference cartilage of the volunteers and the patients (P = 0.355). The patients showed significantly higher American Orthopaedic Foot and Ankle Society and Modified Cincinnati scores after treatment than they did before treatment. In the volunteers, sodium cSI was significantly higher in the tibial cartilage than in the talar cartilage of ankle joint (P = 0.002) and in the talar cartilage than in the calcaneal cartilage of subtalar joint (P < 0.001). Data from the cadaver ankle samples showed a strong linear relationship between the sodium values and the histochemically determined GAG content (r = 0.800; P < 0.001; R = 0.639). This study demonstrates the feasibility of in vivo quantification of sodium cSI, which can be used for GAG content evaluation in thin cartilages of ankle and subtalar joints at 7 T. A strong correlation observed between the histochemically evaluated GAG content and the sodium values proved the sufficient sensitivity of sodium MRI to changes in the GAG content of cartilages in the ankle. Both MFX and MACT produced RT with lower sodium cSI and, thus, of lower quality compared with reference cartilage in the patients or in the volunteers. Our results suggest that MFX and MACT produce RT with similar GAG content and similar morphological appearance in patients with similar surgery outcome. Sodium MRI at 7 T allows a quantitative evaluation of RT quality in the ankle and may thus be useful in the noninvasive assessment of new cartilage repair procedures.

Clinical and Radiological Long-term Outcomes After Matrix-Induced Autologous Chondrocyte Transplantation

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

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.

Whole joint MRI assessment of surgical cartilage repair of the knee: Cartilage Repair OsteoArthritis Knee Score (CROAKS)

To develop amagnetic resonance imaging (MRI) scoring system for follow-up of knee cartilage repair procedures integrating assessment of the repair site and the whole joint called Cartilage Repair OsteoArthritis Knee Score (CROAKS), and to assess its reliability. MRI examinations of 20 patients that had undergone matrix-associated autologous chondrocyte transplantation (MACT) of the knee 12 months before were semi-quantitatively assessed for the repair site using features of the magnetic resonance observation of cartilage repair tissue (MOCART) system and for the whole joint based on experiences with the MRI Osteoarthritis Knee Score (MOAKS) instrument. Intra- and inter-observer reliability was calculated using weighted (w) kappa statistics for plates (medial/lateral tibia, medial/lateral femur, trochlea, patella), compartments (medial tibio-femoral, lateral tibio-femoral, patello-femoral) and the whole joint. For certain features with low prevalence the overall percent agreement was calculated in addition. For cartilage, reliability on a plate level ranged between 0.48 (lateral femur) and 1.00 (medial femur). BML assessment showed comparable results ranging on a plate level between 0.46 and 1.00 with overall percent agreement between 83.3% and 100%. Meniscal morphology assessment ranged between 0.62 and 0.94. For repair site assessment reliability ranged from 0.41 (signal intensity inter-observer) to 1.00 (several features). Overall percent agreement was above 80% for 17 of 22 features assessed (intra- and inter-observer results combined). Combined scoring of the repair site and whole joint assessment for common osteoarthritis features using CROAKS, which is based on experience with two established semi-quantitative scoring tools, is feasible and may be performed with good to excellent reliability.

Treatment of Full-Thickness Chondral Defects With Hyalograft C in the Knee

Background: Matrix-associated autologous chondrocyte transplantation (MACT) has become an established articular cartilage repair technique. It provides good short-term and midterm results; however, long-term results are lacking. Purpose: To prospectively assess the clinical outcome after MACT in the knee to report long-term results. Study Design: Case series; Level of evidence, 4. Methods: Fifty-three subjects (females/males, 22/31; mean age, 32 ± 12 years) were treated between 2000 and 2006 with a hyaluronan-based MACT product and were followed prospectively. The mean body mass index (BMI) was 24.5 ± 3.8 kg/m2 and the mean defect size was 4.4 ± 1.9 cm2. Fifty patients had single defects and 3 had multiple defects (41 medial femoral condyle, 6 lateral femoral condyle, 2 patella, 1 tibia). Two patients had 2 defects (medial femoral condyle [MFC]/lateral femoral condyle and tibial/MFC), and in 1 case, multiple defects on the MFC were treated. The patients were stratified into 23 “simple,” 22 “complex,” and 8 “salvage” cases. Instability or malalignment was treated before or at the time of graft implantation. For 6 patients with small defects (<2 cm2), microfracturing was used as first-line treatment before MACT. Clinical assessment was performed once a year with the subjective and objective International Knee Documentation Committee (IKDC) scores, Lysholm score, and a modified Cincinnati Knee Rating System. Results: The mean follow-up time was 9.07 ± 2.9 years (range, 5-12 years). Treatment failure occurred in 12 of 53 cases (22.6%) an average of 2.99 ± 1.40 years after surgery. There was 1 failure (4.3%) among the simple cases, 4 failures (18.2%) in complex cases, and 7 failures (87.5%) in salvage cases. Statistically significant increases were observed in all scores at all time points compared with presurgery levels (P < .05). The subjective IKDC score improved from median 40.4 preoperatively to 74.7 at 10-year follow-up (n = 13 patients; P < .05). Conclusion: MACT is an excellent surgical therapy for full-thickness cartilage defects of the knee, with good long-term results for simple defects. However, it should not be used in salvage cases.

In vivo evaluation of biomechanical properties in the patellofemoral joint after matrix-associated autologous chondrocyte transplantation by means of quantitative T2 MRI

To determine in vivo biomechanical properties of articular cartilage and cartilage repair tissue of the patella, using biochemical MRI by means of quantitative T2 mapping. Twenty MR scans were achieved at 3T MRI, using a new 8-channel multi-function coil allowing controlled bending of the knee. Multi-echo spin-echo T2 mapping was prepared in healthy volunteers and in age- and sex-matched patients after matrix-associated autologous chondrocyte transplantation (MACT) of the patella. MRI was performed at 0° and 45° of flexion of the knee after 0 min and after 1 h. A semi-automatic region-of-interest analysis was performed for the whole patella cartilage. To allow stratification with regard to the anatomical (collagen) structure, further subregional analysis was carried out (deep-middle-superficial cartilage layer). Statistical analysis of variance was performed. During 0° flexion (decompression), full-thickness T2 values showed no significant difference between volunteers (43 ms) and patients (41 ms). Stratification was more pronounced for healthy cartilage compared to cartilage repair tissue. During 45° flexion (compression), full-thickness T2 values within volunteers were significantly increased (54 ms) compared to patients (44 ms) (p < 0.001). Again, stratification was more pronounced in volunteers compared to patients. The volunteer group showed no significant increase in T2 values measured in straight position and in bended position. There was no significant difference between the 0- and the 60-min MRI examination. T2 values in the patient group increased between the 0- and the 60-min examination. However, the increase was only significant in the superior cartilage layer of the straight position (p = 0.021). During compression (at 45° flexion), healthy patellar cartilage showed a significant increase in T2-values, indicating adaptations of water content and collagen fibril orientation to mechanical load. This could not be observed within the patella cartilage after cartilage repair (MACT) of the patella, most obvious due to a lack of biomechanical adjustment. III.

The effect of exercise levels on biomarker in a knee osteoarthritis model of rats

The effect of exercise levels on biomarker in a knee osteoarthritis model of rats

Cartilage repair of the knee with Hyalograft C:® Magnetic Resonance Imaging assessment of the glycosaminoglycan content at midterm

The aim of this study was to assess the stability of the glycosaminoglycan (GAG) content in the long term after matrix-associated autologous chondrocyte transplantation (MACT) with Hyalograft C in the knee over a follow-up period of one year. In this cross-sectional evaluation, 11 patients after MACT of the knee consented to delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC) measurements. The mean post-operative interval before the first MR examination was 40.6 ± 22.0 months, and the second MR examination was carried out after another 12 months. The Lysholm score was assessed for clinical evaluation. Quantitative T1 measurements after intravenous negatively charged MR contrast agent administration were performed. Global post-contrast T1 of the reference cartilage and the repair tissue and a relative post-contrast T1 value were calculated. The Lysholm score improved significantly from 59.8 ± 12.9 at baseline to 86.1 ± 15.7 at the second visit (p < 0.01). The mean global T1 of the repair tissue (1st visit 581.3 ± 126.4 ms; 2nd visit 684.1 ± 169.9 ms; p = 0.104) and the mean relative T1 value showed stable results over one year (1st visit 0.81 ± 0.28; 2nd visit 0.76 ± 0.32; p = 0.4). The study demonstrated stable glycosaminoglycan content of the repair tissue after MACT at midterm.

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.