Treatment of Large Cartilage Defects in the Knee by Hydrogel-Based Autologous Chondrocyte Implantation: Two-Year Results of a Prospective, Multicenter, Single-Arm Phase III Trial

Abstract

Objective To evaluate the clinical outcome of a hydrogel-based autologous chondrocyte implantation (ACI) for large articular cartilage defects in the knee joint. Design Prospective, multicenter, single-arm, phase III clinical trial. ACI was performed in 100 patients with focal full-thickness cartilage defects ranging from 4 to 12 cm2 in size. The primary outcome measure was the responder rate at 2 years using the Knee Injury and Osteoarthritis Outcome Score (KOOS). Results Two years after ACI treatment, 93% of patients were KOOS responders having improved by ≥10 points compared with their pre-operative level. The primary endpoint of the study was met and demonstrated that the KOOS response rate is markedly greater than 40% with a lower 95% CI (confidence interval) of 86.1, more than twice the pre-specified no-effect level. KOOS improvement (least squares mean) was 42.0 ± 1.8 points (95% CI between 38.4 and 45.7). Mean changes from baseline were significant in the overall KOOS and in all 5 KOOS subscores from Month 3 (first measurement) to Month 24 (inclusive) ( P < 0.0001). The mean MOCART (Magnetic Resonance Observation of Cartilage Repair Tissue) score after 24 months reached 80.0 points (95% CI: 70.0-90.0 points) and 92.1 points in lesions ≤ 5 cm2. Conclusions Overall, hydrogel-based ACI proved to be a valuable treatment option for patients with large cartilage defects in the knee as demonstrated by early, statistically significant, and clinically meaningful improvement up to 2 years follow-up. Parallel to the clinical improvements, MRI analyses suggested increasing maturation, re-organization, and integration of the repair tissue. Trial Registration NCT03319797; EudraCT No.: 2016-002817-22.

Adjacent cartilage tissue structure after successful transplantation: a quantitative MRI study using T2 mapping and texture analysis

“…In our study, the analysis showed a significant decrease in mean T 2 between 12 and 24 months only in repair cartilage (Δ = 5.82 ± 6.48, p < 0.001). Decreased T 2 values in combination with a high morphological score (MOCART) indicated a favorable clinical outcome, which is in correspondence with the clinical results of this study published by Niemeyer et al [27]. A decrease in the mean T 2 value of a selected ROI is very general and represents only one mean quantitative value for the whole area without providing information about changes in cartilage texture; therefore, texture analysis might be a useful add-on.…”

“…Five patients from the MRI cohort were excluded, due to a small defect size, resulting in 20 evaluable patients (with overall 23 lesions). Detailed information about postoperative recovery and rehabilitation of all patients can be found in Niemeyer et al [27].…”

In Vitro Comparison of 2 Clinically Applied Biomaterials for Autologous Chondrocyte Implantation: Injectable Hydrogel Versus Collagen Scaffold

“…42 A recent prospective clinical trial reported high MOCART (Magnetic Resonance Observation of Cartilage Repair Tissue) score up to 80 points for hyaluronic acid-based ACI as used in this study in comparison with previously reported ACI products indicating superior regenerative tissue. 43 Therefore, the reported clinical results may reflect a superior chrondrogenic graft maturation as seen in our laboratory study.…”

“…48 Clinically, no delamination has been reported for the HA. 43 In addition, strong graft incorpotation may allow early weightbearing, which is crucial to allow for mechano-induced chondrocyte differentiation. 23 Mechanotransduction is an important mechanism of graft maturation.…”

Research progress of self-assembling peptide hydrogels in repairing cartilage defects

“…Consequently, the current strategy is to use tissue-engineered scaffolds to maintain the differentiated state of chondrocytes and impel cells to chondrogenesis (Liu et al, 2019). In a prospective multicenter phase III clinical study, hydrogels with autologous chondrocytes were implanted to treat knee articular cartilage defects, and over a 2-year followup, repair tissues matured, recombined, and integrated with surrounding tissues, demonstrating that hydrogel-based ACI was a valuable measure for the treatment of knee cartilage defects in patients (Niemeyer et al, 2022). Other exogenous MSCs could also play a similar role in the treatment of cartilage defects as autologous chondrocytes.…”