A Prospective, Randomized, Open-Label, Multicenter, Phase III Noninferiority Trial to Compare the Clinical Efficacy of Matrix-Associated Autologous Chondrocyte Implantation With Spheroid Technology Versus Arthroscopic Microfracture for Cartilage Defects of the Knee

Background:Autologous chondrocyte implantation (ACI) and microfracture are established treatments for large, full-thickness cartilage defects, but there is still a need to expand the clinical and health economic knowledge of these procedures.Purpose:To confirm the noninferiority of ACI compared with microfracture.Study Design:Randomized controlled trial; Level of evidence, 2.Methods:Patients were randomized to be treated with matrix-associated ACI using spheroid technology (n = 52) or microfracture (n = 50). Both procedures followed standard methods. Patients were assessed by the Knee injury and Osteoarthritis Outcome Score (KOOS), MOCART (magnetic resonance observation of cartilage repair tissue) scoring system, Bern score, modified Lysholm score, International Cartilage Repair Society (ICRS) rating (histological and immunochemical scoring after rebiopsy 24 months after implantation), and International Knee Documentation Committee (IKDC) examination form. The main assessments were conducted 24 months after study treatment.Results:In the primary intention-to-treat analysis, the overall KOOS score for both ACI and microfracture yielded a statistically significant improvement relative to baseline. According to the between-group analysis, ACI passed the test of noninferiority compared with microfracture; thus, the primary goal of the study was achieved. The KOOS subscores yielded the same qualitative results as the overall KOOS score (ie, for each of these, noninferiority was demonstrated), and in 1 case (Activities of Daily Living subscore), the threshold for superiority was passed. The subgroup analyses did not yield any clear evidence of an association between treatment effect and any of the categories investigated (age, diagnosis, defect localization, sex). A histological analysis of biopsies from 16 patients (ACI: n = 9; microfracture: n = 7) suggested a better quality of repair in the patients treated with ACI.Conclusion:The efficacy of both ACI and microfracture was demonstrated with respect to both functional outcomes and morphological repair. The primary analysis confirmed the statistical hypothesis of the noninferiority of ACI, even for relatively small cartilage defects (1-4 cm2) treated in this study, the indication for which microfracture is generally accepted as the standard of care. ACI showed significant superiority in the KOOS subscores of Activities of Daily Living at 24 months and Knee-related Quality of Life at 12 months.Registration:NCT01222559 ( ClinicalTrials.gov identifier).

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Matrix-Associated Autologous Chondrocyte Implantation with Spheroid Technology Is Superior to Arthroscopic Microfracture at 36 Months Regarding Activities of Daily Living and Sporting Activities after Treatment

Cartilage ◽

10.1177/1947603519897290 ◽

2020 ◽

pp. 194760351989729 ◽

Cited By ~ 1

Author(s):

Arnd Hoburg ◽

Philipp Niemeyer ◽

Volker Laute ◽

Wolfgang Zinser ◽

Christoph Becher ◽

...

Keyword(s):

Treatment Failure ◽

Activities Of Daily Living ◽

Clinical Outcomes ◽

Daily Living ◽

Autologous Chondrocyte Implantation ◽

Phase Iii ◽

Cartilage Defects ◽

Chondrocyte Implantation ◽

Sport And Recreation ◽

Autologous Chondrocyte

Objective Matrix-associated autologous chondrocyte implantation (ACI) and microfracture (MF) are well-established treatments for cartilage defects of the knee. However, high-level evidence comparing microfracture and spheroid technology ACI is limited. Design Prospective, phase III clinical trial with patients randomized to ACI ( N = 52) or MF ( N = 50). Level of evidence: 1, randomized controlled trial. Both procedures followed standard protocols. For ACI 10 to 70 spheroids/cm2 were administered. Primary outcome measure was the Knee Injury and Osteoarthritis Outcome Score (KOOS). This report presents results for 36 months after treatment. Results Both ACI and MF showed significant improvement over the entire 3-year observation period. For the overall KOOS, noninferiority of ACI (the intended primary goal of the study) was formally confirmed; additionally, for the subscores “Activities of Daily Living” and “Sport and Recreation,” superiority of ACI over MF was shown at descriptive level. Occurrence of adverse events were not different between both treatments (ACI 77%; MF 74%). Four patients in the MF group required reoperation which was defined as treatment failure. No treatment failure was reported for the ACI group. Conclusions Patients treated with matrix-associated ACI with spheroid technology showed substantial improvement in various clinical outcomes after 36 months. The advantages of ACI compared with microfracture was underlined by demonstrating noninferiority, in overall KOOS and superiority in the KOOS subscores “Activities of Daily Living” and “Sport and Recreation.” In the present study, subgroups comparing different age groups and defect sizes showed comparable clinical outcomes.

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Evolution of Autologous Chondrocyte Repair and Comparison to Other Cartilage Repair Techniques

BioMed Research International ◽

10.1155/2014/272481 ◽

2014 ◽

Vol 2014 ◽

pp. 1-11 ◽

Cited By ~ 65

Author(s):

Ashvin K. Dewan ◽

Matthew A. Gibson ◽

Jennifer H. Elisseeff ◽

Michael E. Trice

Keyword(s):

Cartilage Repair ◽

Autologous Chondrocyte Implantation ◽

Young Patients ◽

Cartilage Defects ◽

Chondral Defects ◽

Chondrocyte Implantation ◽

Osteochondral Grafting ◽

And Cartilage ◽

Autologous Chondrocyte ◽

Repair Techniques

Articular cartilage defects have been addressed using microfracture, abrasion chondroplasty, or osteochondral grafting, but these strategies do not generate tissue that adequately recapitulates native cartilage. During the past 25 years, promising new strategies using assorted scaffolds and cell sources to induce chondrocyte expansion have emerged. We reviewed the evolution of autologous chondrocyte implantation and compared it to other cartilage repair techniques.Methods. We searched PubMed from 1949 to 2014 for the keywords “autologous chondrocyte implantation” (ACI) and “cartilage repair” in clinical trials, meta-analyses, and review articles. We analyzed these articles, their bibliographies, our experience, and cartilage regeneration textbooks.Results. Microfracture, abrasion chondroplasty, osteochondral grafting, ACI, and autologous matrix-induced chondrogenesis are distinguishable by cell source (including chondrocytes and stem cells) and associated scaffolds (natural or synthetic, hydrogels or membranes). ACI seems to be as good as, if not better than, microfracture for repairing large chondral defects in a young patient’s knee as evaluated by multiple clinical indices and the quality of regenerated tissue.Conclusion. Although there is not enough evidence to determine the best repair technique, ACI is the most established cell-based treatment for full-thickness chondral defects in young patients.

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Increased Failure Rate of Autologous Chondrocyte Implantation after Previous Treatment with Marrow Stimulation Techniques

The American Journal of Sports Medicine ◽

10.1177/0363546508330137 ◽

2009 ◽

Vol 37 (5) ◽

pp. 902-908 ◽

Cited By ~ 280

Author(s):

Tom Minas ◽

Andreas H. Gomoll ◽

Ralf Rosenberger ◽

Ronald O. Royce ◽

Tim Bryant

Keyword(s):

Failure Rate ◽

Cartilage Repair ◽

Subchondral Bone ◽

Autologous Chondrocyte Implantation ◽

Prior Treatment ◽

Cartilage Defects ◽

Persistent Symptoms ◽

Marrow Stimulation ◽

Chondrocyte Implantation ◽

Autologous Chondrocyte

Background Marrow stimulation techniques such as drilling or microfracture are first-line treatment options for symptomatic cartilage defects. Common knowledge holds that these treatments do not compromise subsequent cartilage repair procedures with autologous chondrocyte implantation. Hypothesis Cartilage defects pretreated with marrow stimulation techniques will have an increased failure rate. Study Design Cohort study; Level of evidence, 2. Methods The first 321 consecutive patients treated at one institution with autologous chondrocyte implantation for full-thickness cartilage defects that reached more than 2 years of follow-up were evaluated by prospectively collected data. Patients were grouped based on whether they had undergone prior treatment with a marrow stimulation technique. Outcomes were classified as complete failure if more than 25% of a grafted defect area had to be removed in later procedures because of persistent symptoms. Results There were 522 defects in 321 patients (325 joints) treated with autologous chondrocyte implantation. On average, there were 1.7 lesions per patient. Of these joints, 111 had previously undergone surgery that penetrated the subchondral bone; 214 joints had no prior treatment that affected the subchondral bone and served as controls. Within the marrow stimulation group, there were 29 (26%) failures, compared with 17 (8%) failures in the control group. Conclusion Defects that had prior treatment affecting the subchondral bone failed at a rate 3 times that of nontreated defects. The failure rates for drilling (28%), abrasion arthroplasty (27%), and microfracture (20%) were not significantly different, possibly because of the lower number of microfracture patients in this cohort (25 of 110 marrow-stimulation procedures). The data demonstrate that marrow stimulation techniques have a strong negative effect on subsequent cartilage repair with autologous chondrocyte implantation and therefore should be used judiciously in larger cartilage defects that could require future treatment with autologous chondrocyte implantation.

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A Comparison of 2-Year Outcomes in Patients Undergoing Tibiofemoral or Patellofemoral Matrix-Induced Autologous Chondrocyte Implantation

The American Journal of Sports Medicine ◽

10.1177/0363546517724761 ◽

2017 ◽

Vol 45 (14) ◽

pp. 3243-3253 ◽

Cited By ~ 22

Author(s):

Jay R. Ebert ◽

Adrian Schneider ◽

Michael Fallon ◽

David J. Wood ◽

Gregory C. Janes

Keyword(s):

Quality Of Life ◽

Daily Living ◽

Autologous Chondrocyte Implantation ◽

Composite Score ◽

Significant Group ◽

Chondrocyte Implantation ◽

Femoral Condyles ◽

Over Time ◽

Autologous Chondrocyte

Background: Matrix-induced autologous chondrocyte implantation (MACI) has demonstrated encouraging clinical results in the treatment of knee chondral defects. However, earlier studies suggested that chondrocyte implantation in the patellofemoral (PF) joint was less effective than in the tibiofemoral (TF) joint. Purpose: To compare the radiological and clinical outcomes of those undergoing MACI to either the femoral condyles or PF joint. Study Design: Cohort study; Level of evidence, 3. Methods: A total of 194 patients were included in this analysis, including 127 undergoing MACI to the medial (n = 94) and lateral (n = 33) femoral condyle, as well as 67 to the patella (n = 35) or trochlea (n = 32). All patients were evaluated clinically (Knee injury and Osteoarthritis Outcome Score [KOOS], visual analog scale, Short Form–36) before surgery and at 3, 12, and 24 months after surgery, while magnetic resonance imaging (MRI) was undertaken at 3, 12, and 24 months, with the MOCART (magnetic resonance observation of cartilage repair tissue) scoring system employed to evaluate the quality and quantity of repair tissue, as well as an MRI composite score. Patient satisfaction was evaluated. Results: No significant group differences ( P > .05) were seen in demographics, defect size, prior injury, or surgical history, while the majority of clinical scores were similar preoperatively. All clinical scores significantly improved over time ( P < .05), with a significant group effect observed for KOOS activities of daily living ( P = .008), quality of life ( P = .008), and sport ( P = .017), reflecting better postoperative scores in the TF group. While the PF group had significantly lower values at baseline for the KOOS activities of daily living and quality of life subscales, it actually displayed a similar net improvement over time compared with the TF group. At 24 months, 93.7% (n = 119) and 91.0% (n = 61) of patients were satisfied with the ability of MACI to relieve their knee pain, 74.0% (n = 94) and 65.7% (n = 44) with their ability to participate in sport, and 90.5% (n = 115) and 83.6% (n = 56) satisfied overall, in the TF and PF groups, respectively. MRI evaluation via the MOCART score revealed a significant time effect ( P < .05) for the MRI composite score and graft infill over the 24-month period. While subchondral lamina scored significantly better ( P = .002) in the TF group, subchondral bone scored significantly worse ( P < .001). At 24 months, the overall MRI composite score was classified as good/excellent in 98 TF patients (77%) and 54 PF patients (81%). Conclusion: MACI in the PF joint with concurrent correction of PF maltracking if required leads to similar clinical and radiological outcomes compared with MACI on the femoral condyles.

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