Matrix-based Autologous Chondrocyte Implantation Research Articles

The Effect of Smoking on the Outcome of Matrix-Based Autologous Chondrocyte Implantation: Data from the German Cartilage Registry.

Smoking is known to have various deleterious effects on health. However, it is not clear whether smoking negatively affects the postoperative outcome following matrix-based autologous cartilage implantation (MACI) in the knee. The purpose of this study was to evaluate the effect of smoking on the outcome of MACI in the knee. A total of 281 patients receiving MACI in the knee between 2015 and 2018 were registered in the German Cartilage Database. The cohort was divided into ex-smokers, smokers, and nonsmokers. Data regarding the Knee Injury and Osteoarthritis Outcome Score (KOOS), the numeric rating scale (NRS) for pain, and satisfaction with the outcome were analyzed and compared. Follow-ups were performed at 6, 12, and 24 months after surgery. Of the 281 patients, 225 (80.1%) were nonsmokers, 43 (15.3%) were smokers, and 13 (4.6%) were ex-smokers. The three groups were comparable with respect to age, sex, body mass index (BMI), height, defect size, the need for additional reconstruction of the subchondral bone defect, number of previous knee surgeries, and defect location. However, nonsmokers had a significantly lower weight as compared with smokers. Besides a significantly lower preoperative NRS of nonsmokers as compared with smokers, there were no significant differences between the three groups with respect to KOOS, NRS, and satisfaction at 6, 12, and 24 months of follow-ups. The present study of data retrieved from the German Cartilage Registry suggests that the smoking status does not influence the outcome of MACI in the knee.

Third-generation autologous chondrocyte implantation after failed bone marrow stimulation leads to inferior clinical results.

Third-generation autologous chondrocyte implantation (ACI) is an established and frequently used method and successful method for the treatment of full-thickness cartilage defects in the knee. There are also an increasing number of patients with autologous chondrocyte implantation as a second-line therapy that is used after failed bone marrow stimulation in the patient's history. The purpose of this study is to investigate the effect of previous bone marrow stimulation on subsequent autologous chondrocyte implantation therapy. In this study, the clinical results after the matrix-based autologous chondrocyte implantation in the knee in a follow-up over 3years postoperatively were analysed. Forty patients were included in this study. A total of 20 patients with cartilage defects of the knee were treated with third-generation autologous chondrocyte implantation (Novocart® 3D) as first-line therapy. The mean defect size was 5.4 cm2 (SD 2.6). IKDC subjective score and VAS were used for clinical evaluation after 6, 12, 24 and 36months postoperatively. The results of these patients were compared with 20 matched patients with autologous chondrocyte implantation as second-line therapy. Matched pair analysis was performed by numbers of treated defects, defect location, defect size, gender, age and BMI. Both the first-line (Group I) and second-line group (Group II) showed significantly better clinical results in IKDC score and VAS score in the follow-up over 3years compared with the preoperative findings. In addition, Group I showed significantly better results in the IKDC and VAS during the whole postoperative follow-up after 6, 12, 24 and 36months compared to Group II with second-line autologous chondrocyte implantation (IKDC 6months p = 0.015, 1year p = 0.001, 2years p = 0.001, 3years p = 0.011). Additionally, we found a lower failure rate in Group I. No revision surgery was performed in Group I. The failure rate in the second-line Group II was 30%. This study showed that third-generation autologous chondrocyte implantation is a suitable method for the treatment of full-thickness cartilage defects. Both, Group I and Group II showed significant improvement in our follow-up. However, in comparing the results of the two groups, autologous chondrocyte implantation after failed bone marrow stimulation leads to worse clinical results. III.

Graft Hypertrophy After Third-Generation Autologous Chondrocyte Implantation Has No Correlation With Reduced Cartilage Quality: Matched-Pair Analysis Using T2-Weighted Mapping

Background: Graft hypertrophy is common after matrix-based autologous chondrocyte implantation (ACI) in the knee joint. However, it is not clear whether graft hypertrophy is a complication or an adjustment reaction in the cartilage regeneration after ACI. Purpose: To analyze the cartilage quality of the ACI regeneration with graft hypertrophy using T2-weighted mapping. Study Design: Cohort study; Level of evidence, 2. Methods: A total of 91 patients with isolated cartilage defects (International Cartilage Repair Society [ICRS] grade III-IV) of the knee were treated with Novocart 3D, a third-generation, matrix-based, ACI procedure in the knee joint. All patients were evaluated with a standardized magnetic resonance imaging protocol after 3, 6, 12, 24, 36, and 48 months postoperatively. For morphological and biochemical assessment, the T2-weighted relaxation times of the ACI grafts as well as the healthy surrounding cartilage were determined. The results of the 20 patients with graft hypertrophy (hypertrophic group) were compared with the results of 21 matched patients without graft hypertrophy (nonhypertrophic group) after ACI. Match-paired analysis was performed by comparison of age, defect size, and body mass index. Results: The T2-weighted relaxation times of the ACI graft showed significant improvement, with values decreasing from 52.1 milliseconds to 33.3 milliseconds after 48 months. After 12 months, the T2-weighted relaxation times were constant and comparable with the healthy surrounding cartilage. Graft hypertrophy was seen in 22% (n = 20) of the patients who underwent ACI. A significant difference in T2-weighted relaxation times between the hypertrophic and nonhypertrophic ACI grafts could not be found except after 36 months (hypertrophic T2-weighted relaxation time/nonhypertrophic T2-weighted relaxation time: 3 months, 48.0/56.4 ms, P = .666; 6 months, 45.6/42.5 ms, P = .280; 12 months, 39.3/34.7 ms, P = .850; 24 months, 34.8/32.2 ms, P = .742; 36 months, 34.6/38.2 ms, P = .030; 48 months, 34.2/32.3 ms, P = .693). Conclusion: The T2-weighted relaxation time of the ACI graft cartilage showed significant improvements over the observation period of 4 years postoperatively. After 2 years, graft maturation was completed. Graft hypertrophy after ACI was seen in 22% of the patients. Reduced cartilage quality could not be found in patients with graft hypertrophy after ACI.

High impact sport after autologous chondrocyte implantation in the knee

Aims and Objectives:Matrix-based autologous chondrocyte implantation is a well-established treatment for full cartilage defects. When to resume to high impact sports after matrix-based autologous chondrocyte implantation is controversial.Materials and Methods:Forty-four patients with cartilage defects of the knee were treated with autologous chondrocyte implantation (Novocart®3D). All patients were assessed preoperatively and after a period of 24 months with the University of California Los Angeles (UCLA) Activity score. The return to high impact sports (soccer, basketball, running, etc.) after matrix-based autologous chondrocyte implantation was documented. Patients were evaluated using the International Knee Documentation Committee Knee Examination Form and visual analogue scale for pain after 6, 12 and 24 months.Results:The average return to physical activities or sports after matrix-based autologous chondrocyte implantation procedure was 10.2 months. Patients with a later return of high impact sports after 12 months showed significantly better clinical results after two years. Fifty-five percent showed an unchanged level of physical activity in the UCLA Activity score in the postoperative course. About 35% showed a lower level and 10% a higher level of physical activity.Conclusion:Resuming to high impact sport in the first 12 months after ACI procedure leads to inferior outcomes up to 24 months after matrix-based autologous chondrocyte implantation.

Analysis of graft maturation after autologous chondrocyte implantation with T2 mapping

Aims and Objectives:It has been shown in numerous clinical studies that matrix-based autologous chondrocyte implantation (mb-ACI) leads to good clinical results in the medium-term course. But chondrogenic development of ACI grafts and the time of graft maturation are still unclear. The aim of this study was to investigate the graft maturation after mb-ACI with T2 mapping in the postoperative course of four years.Materials and Methods:In a total of 90 patients could be included after matrix-based autologous chondrocyte transplantation of the knee. All cartilage defects were treated with NOVOCART® 3D. The evaluation of the ACI grafts was conducted after 3, 6, 12, 24, 36 and 48 months by MRI. The T2 relaxation time values of the ACI graft and healthy native cartilage areas were determined to assess graft maturation using T2 mapping. MOCART score were used for morphological evaluation of ACI grafts.Results:The T2 relaxation time of ACI grafts showed a significant improvement during the postoperative course at all time points. The T2 relaxation improved from 48.0 ms after 3 months to 34.6 ms after four years. We found a significant influence of the patient’s age and the defect localization on the T2 relaxation time measuring. It could be detected an increasing integration of the ACI grafts into the healthy surrounding cartilage. No significant differences between the T2 relaxation time of ACI grafts and the surrounding healthy cartilage were found after 12 months postoperatively.Conclusion:Graft maturation after ACI in the knee joint needs at least 1 year, with ongoing adjustment of the T2 relaxation time values compared with native surrounding cartilage. Regarding the age and defect localization, significantly worse T2 relaxation times of the ACI grafts could be found with higher age and in cases with treated patellar defects.

Analysis of the autologous chondrocyte quality of matrix-based autologous chondrocyte implantation in the knee joint.

Matrix based autologous chondrocyte implantation is an established method for treatment of full cartilage defects in the knee joint, but little is known about the influence of the implanted autologous chondrocyte quality and its clinical value. The aim of this study is to evaluate the influence of the gene expression of the implanted autologous chondrocytes on the clinical outcomes in the follow-up period of three years. Biological parameters of the implanted chondrocytes were analysed histologically and immunohistologically. An analysis of the gene expression of the relevant chondrogenic dedifferentiation markers was performed as well. In order to detect the rate of apoptosis, we analysed specific apoptosis markers. To evaluate the clinical outcome, the International Knee Documentation Committee (IKDC) subjective score and the visual analogue scale (VAS) were used pre-operatively and after 0.5, one, two and three years. Significantly improved clinical scores were observed. The subjective IKDC score increased from 50.6 ± 20.7 points to 69.3 ± 26.1 points at three years (p = 0.001). The implanted chondrocytes showed a typical expression of the chondrogenic markers with a high rate of collagen type II expression without dedifferentiation. The analysed differentiation, dedifferentiation and apoptosis markers showed no influence on the clinical outcome. The implanted autologous chondrocytes have a high chondrogenic quality with a high rate of collagen type II expression without dedifferentiation. An influence of differentiation, de-differentiation and apoptosis marker gene expression on the clinical outcomes could not be found in a follow-up period of three years. Case series; Level of evidence, 3.

Bone Marrow Edema in the Knee and Its Influence on Clinical Outcome After Matrix-Based Autologous Chondrocyte Implantation

Background: Third-generation autologous chondrocyte implantation (ACI) is an established method for treatment of full-thickness cartilage defects in the knee joint. Subchondral bone marrow edema (BME) is frequently observed after ACI, with unknown pathogenesis and clinical relevance. Purpose: To investigate the occurrence and clinical relevance of BME after third-generation ACI in the knee joint during the postoperative course of 36 months. Study Design: Cohort study; Level of evidence, 3. Methods: A total of 38 circumscribed full-thickness cartilage defects in 30 patients were included in this study. All defects were treated with third-generation ACI (Novocart 3D). A standardized MRI examination was carried out after 1.5, 3, 6, 12, 24, and 36 months. Bone marrow edema was observed in 78.9% of defects over the postoperative course, with initial occurrence in the first 12 months. The size of the BMEs were determined according to their maximum diameter and were classified as small (<1 cm), medium (<2 cm), large (<4 cm), and very large (diffuse; >4 cm). Clinical outcomes in patients were analyzed by use of the International Knee Documentation Committee (IKDC) scoring system and a visual analog scale for pain. Results: There were 5.3% (n = 2) small, 28.9% (n = 11) medium, 34.2% (n = 13) large, and 10.5% (n = 4) very large BMEs. In a subgroup analysis, cartilage defects of the medial femoral condyle showed significantly higher frequency of BME than did patellar defects. Clinical scores showed significant improvements throughout the entire study course (P < .05). Clinical patient outcome did not correlate with presence of BME at any time period (P > .05). Conclusion: Midterm clinical results of the matrix-based third-generation ACI showed a substantial amount of BME over a 36-month follow-up, but this did not correlate with worse clinical outcome. Patients with femoral cartilage defects were more often affected than were those with patellar cartilage defects.

Early resumption of physical activities leads to inferior clinical outcomes after matrix-based autologous chondrocyte implantation in the knee

Matrix-based autologous chondrocyte implantation is a well-established operation procedure for full cartilage defects. When to resume physical activity after matrix-based autologous chondrocyte implantation is controversial. Our hypothesis was that early resumption of physical activity leads to a worse clinical outcome after matrix-based autologous chondrocyte implantation in the knee two years post-operatively. Physical activity is defined as any kind of impact sport. Forty-four patients with cartilage defects of the knee were treated with matrix-based autologous chondrocyte implantation (Novocart3D). All patients were assessed preoperatively and after a period of 24 months with the University of California Los Angeles (UCLA) Activity score. The return to physical activities or sports after matrix-based autologous chondrocyte implantation was documented. Patients were evaluated using the International Knee Documentation Committee Knee Examination Form and visual analogue scale for pain after 6, 12 and 24 months. Fifty-five percent showed an unchanged level of physical activity in the UCLA Activity score post-operatively. About 35% showed a lower level and 10% a higher level of physical activity. The average return to physical activities or sports after matrix-based autologous chondrocyte implantation procedure was 10.2 months. Patients with a later return of sports after 12 months showed significantly better clinical results after two years. In particular, patients who started practicing impact sport after 12 months post-operatively showed significantly better results. Resuming physical activity including impact sports without waiting at least 12 months after the operation leads to inferior outcomes up to 24 months after matrix-based autologous chondrocyte implantation. Level IV.

Graft hypertrophy of matrix-based autologous chondrocyte implantation: a two-year follow-up study of NOVOCART 3D implantation in the knee

Graft hypertrophy is a major complication in the treatment for localized cartilage defects with autologous chondrocyte implantation (ACI) using periosteal flap and its further development, Novocart (a matrix-based ACI procedure). The aim of the present study is to investigate individual criteria for the development of graft hypertrophy by NOVOCART 3D implantation of the knee in the post-operative course of 2 years. Forty-one consecutive patients with 44 isolated cartilage defects of the knee were treated with NOVOCART 3D implants. Individual criteria and defect-associated criteria were collected. Follow-up MRIs were performed at 3, 6, 12 and 24 months. The NOVOCART 3D implants were measured and classified. The modified MOCART Score was used to evaluate quality and integration of the NOVOCART 3D implants in MRI. Graft hypertrophy was observed in a total of 11 patients at all post-operative time points. We were able to show that NOVOCART 3D implantation of cartilage defects after acute trauma and osteochondritis dissecans (OCD) led to a significantly increased proportion of graft hypertrophy. No other individual criteria (age, gender, BMI) or defect-associated criteria (concomitant surgery, second-line treatment, defect size, fixation technique) showed any influence on the development of graft hypertrophy. The modified MOCART Score results revealed a significant post-operative improvement within 2 years. The aetiology of cartilage defects appears to have a relevant influence for the development of graft hypertrophy. Patients, who were treated with NOVOCART 3D implants after an acute event (acute trauma or OCD), are especially at risk for developing a graft hypertrophy in the post-operative course of two years. Case series, Level IV.

Stem cell- and growth factor-based regenerative therapies for avascular necrosis of the femoral head

Avascular necrosis (AVN) of the femoral head is a debilitating disease of multifactorial genesis, predominately affects young patients, and often leads to the development of secondary osteoarthritis. The evolving field of regenerative medicine offers promising treatment strategies using cells, biomaterial scaffolds, and bioactive factors, which might improve clinical outcome. Early stages of AVN with preserved structural integrity of the subchondral plate are accessible to retrograde surgical procedures, such as core decompression to reduce the intraosseous pressure and to induce bone remodeling. The additive application of concentrated bone marrow aspirates, ex vivo expanded mesenchymal stem cells, and osteogenic or angiogenic growth factors (or both) holds great potential to improve bone regeneration. In contrast, advanced stages of AVN with collapsed subchondral bone require an osteochondral reconstruction to preserve the physiological joint function. Analogously to strategies for osteochondral reconstruction in the knee, anterograde surgical techniques, such as osteochondral transplantation (mosaicplasty), matrix-based autologous chondrocyte implantation, or the use of acellular scaffolds alone, might preserve joint function and reduce the need for hip replacement. This review summarizes recent experimental accomplishments and initial clinical findings in the field of regenerative medicine which apply cells, growth factors, and matrices to address the clinical problem of AVN.

The Incidence and Clinical Relevance of Graft Hypertrophy After Matrix-Based Autologous Chondrocyte Implantation

Background: Graft hypertrophy is the most common complication of periosteal autologous chondrocyte implantation (p-ACI). Purpose: The aim of this prospective study was to analyze the development, the incidence rate, and the persistence of graft hypertrophy after matrix-based autologous chondrocyte implantation (mb-ACI) in the knee joint within a 2-year postoperative course. Study Design: Case series; Level of evidence, 4. Methods: Between 2004 and 2007, a total of 41 patients with 44 isolated cartilage defects of the knee were treated with the mb-ACI technique. The mean age of the patients was 35.8 years (standard deviation [SD], 11.3 years), and the mean body mass index was 25.9 (SD, 4.2; range, 19-35.3). The cartilage defects were arthroscopically classified as Outerbridge grades III and IV. The mean area of the cartilage defect measured 6.14 cm2 (SD, 2.3 cm2). Postoperative clinical and magnetic resonance imaging (MRI) examinations were conducted at 3, 6, 12, and 24 months to analyze the incidence and course of the graft. Results: Graft hypertrophy developed in 25% of the patients treated with mb-ACI within a postoperative course of 1 year; 16% of the patients developed hypertrophy grade 2, and 9% developed hypertrophy grade 1. Graft hypertrophy occurred primarily in the first 12 months and regressed in most cases within 2 years. The International Knee Documentation Committee (IKDC) and visual analog scale (VAS) scores improved during the postoperative follow-up time of 2 years. There was no difference between the clinical results regarding the IKDC and VAS pain scores and the presence of graft hypertrophy. Conclusion: The mb-ACI technique does not lead to graft hypertrophy requiring treatment as opposed to classic p-ACI. The frequency of occurrence of graft hypertrophy after p-ACI and mb-ACI is comparable. Graft hypertrophy can be considered as a temporary excessive growth of regenerative cartilage tissue rather than a true graft hypertrophy. It is therefore usually not a persistent or systematic complication in the treatment of circumscribed cartilage defects with mb-ACI.

Osteochondrale Molekülmarker als quantitative Verlaufsparameter nach matrixgekoppelter autologer Chondrozytentransplantation CaRes®

In this study we attempt to evaluate whether or not osteochondral markers of the synovial fluid can be helpful in defining objectively the repair process following matrix-based autologous chondrocyte implantation (ACI) CaReS (Cartilage Regeneration System). As a part of a clinical prospective pilot study, synovial fluid of 19 patients was examined before, as well as 6, 12, 26, and 52 weeks after matrix-based ACI. A synovial fluid analysis was performed and markers of bone and cartilage metabolism were evaluated. Molecular markers routinely examined included MMP-1, MMP-3, MMP-13, TIMP, hCOMP, PICP und MIA. The levels were referenced to the total protein concentration of the synovial fluid and compared with clinical parameters (IKDC) and magnetic resonance imaging (MRI). With the exception of MMP3 all markers showed a drop of the concentration below preoperative levels at 6 weeks. All marker levels returned to below the preoperative concentration at 26 as well as 52 weeks after surgery. The MIA, MMP-3, PICP, hCOMP and TIMP levels showed significant changes over the period of 52 weeks (p<0.01). Statistically significant correlations between the marker levels and the clinical scores could only be observed at several times of assessment. Under consideration of missing correlations to clinical parameters (IKDC/MRI) non-specific osteochondral marker proteins of the synovial fluid cannot be used without further scrutiny to document changes in cartilage and osseous metabolism following matrix-supported ACI over the time of 52 weeks objectively. The drop of the concentrations below preoperative levels at 6 weeks can possibly be explained by the reduced traumatization of the joint with the CaRes procedure compared to the classic ACI. Specific markers for cartilage metabolism should be defined to permit a direct and objective comparison of the various conservative and operative methods presently available for the treatment of chondral lesions of the knee joint.

Matrix-based autologous chondrocyte implantation for cartilage repair with Hyalograft ®C: Two-year follow-up by magnetic resonance imaging

Objective Monitoring of articular cartilage repair after matrix-associated autologous chondrocyte implantation with Hyalograft ®C by a new grading system based on non-invasive high-resolution magnetic resonance imaging. Patients and methods In 23 patients, postoperative magnetic resonance imaging (MRI) was performed between 76 and 120 weeks. In nine of these patients, five MRI examinations were performed at 4, 12, 24, 52 and 104 weeks after Hyalograft ®C implant. The repair tissue was described with separate variables: degree of defect repair in width and length, signal intensity of the repair tissue and status of the subchondral bone. For these variables a grading system with point scale evaluation was applied. Results A complete filling of the defect by repair tissue was found in 15 patients. A moderate hypertrophy of the repair tissue was found in two patients. An underfilling of the defect by repair tissue was observed in four patients. In one patient, a partial detachment of the implant with associated subchondral cyst and edema was seen, and in one patient, a complete detachment of the graft was observed. The filling of the defect parallel to cartilage surface (integration) was complete in 18 cases. A split-like incomplete integration was present in one patient. Incomplete integration was found in four patients. The signal intensity of the implant on FSE and on 3D-GRE + FS was isointense compared to native normal cartilage in all cases after 12 months. The subchondral bone was normal in 14 patients. An edema-like signal alteration was found in three cases. In six patients, a non-edema abnormality of the subchondral bone (granulation tissue, cysts or sclerosis) was present. On follow-up exams performed in nine patients at the same postoperative intervals dynamic processes such as filling of partial defects, vanishing of hypertrophies and change of signal intensity of implant to isointensity with native articular cartilage were observed. A comparison between filling of the defect on MRI and clinical outcome showed a good correlation in 21 patients and a poor correlation in only two patients. Conclusion High-resolution MRI provides a non-invasive tool for monitoring the development of cartilage repair tissue following Hyalograft ®C technology, shows a good correlation with clinical outcome and may help to differentiate abnormal repair tissue from a normal maturation process.

Matrix-based autologous chondrocyte implantation for cartilage repair: noninvasive monitoring by high-resolution magnetic resonance imaging

Monitoring of articular cartilage repair after matrix-associated autologous chondrocyte implantation (MACI) by a new grading and point-scale system based on noninvasive cartilage-specific magnetic resonance imaging (MRI) protocol. In 20 patients, postoperative high-resolution MRI follow-up examinations at 4, 12, 24 and 52 weeks after matrix-based ACI for cartilage repair were initiated. The repair tissue was described with separate variables: degree of defect repair in width and length, surface, structure and signal intensity of the repair tissue, and status of the subchondral lamina and bone. For these variables, a grading system with point-scale evaluation was applied, and the mean average values were calculated for every follow-up MR exam of each patient. In 10 patients, an incomplete filling of the defect improved to complete filling (6 patients) or less incomplete (4 patients) filling of the defect. Three cases of implant hypertrophy returned to normal within 1 year. Complete filling of the defect by repair tissue was found in 2 patients from the beginning. Integration was complete in 10 cases. Improvement of incomplete to complete integration was found in 3 patients. The signal intensity of the implant developed to native cartilage signal in 13 patients. The mean average values increased from the 4th to the 52 nd week in 17 of 20 patients and decreased in 3 of 20 patients. High-resolution MRI provides a noninvasive tool for monitoring the development of cartilage repair tissue in MACI over time and helps to differentiate abnormal repair tissue from a normal maturation process.