Time Matters: Knee Cartilage Defect Expansion and High-Grade Lesion Formation while Awaiting Autologous Chondrocyte Implantation

Objective The objective of this study was to assess potential risk factors, including time delay until implantation, for knee cartilage defect expansion or new high-grade defect formation between biopsy and Autologous Chondrocyte Implantation (ACI) or Matrix Autologous Chondrocyte Implantation (MACI). Study design Consecutive knee ACI and MACI cases by a single surgeon ( n = 111) were reviewed. The relationship between time between biopsy and staged implantation and (1) progression in primary cartilage defect size and (2) development of a new high-grade (Outerbridge grade ≥3) cartilage defect were determined with adjustment for demographics, body mass index, smoking status, coronal alignment, initial cartilage status, and prior surgery. Results Average size of the primary defect at time of biopsy was 4.50 cm2. Mean time to chondrocyte implantation was 155 days. Defect expansion increased 0.11 cm2 (standard error = 0.03) per month delay to implantation ( P = 0.001). Independent predictors of defect expansion were male sex, smaller initial defect size, and delay to implantation (adjusted mean = 0.15 cm2 expansion per month). A total of 16.2% of patients ( n = 18/111) developed a new high-grade defect. Independent predictors of a new secondary defect were Outerbridge grade 2 changes (vs. 0-1) on the surface opposing the index defect and delayed implantation (per month increase, adjusted odds ratio = 1.21, 95% confidence interval: 1.01-1.44; P = 0.036). Conclusions Patients undergoing 2-stage cell-based cartilage restoration with either ACI or MACI demonstrated long delays between stages of surgery, placing them at risk for expanding defects and development of new high-grade cartilage defects. Patients who were male, had smaller initial defect size, and longer time between surgeries were at greater risk for defect expansion. Level of Evidence III, retrospective comparative study.

Scaffolds for knee chondral lesions – indications and technical tips

Chondral lesions following an injury to the knee joint have poor healing potential and may lead to osteoarthritis. Nowadays, more and more research is focused on tissue regeneration and the prevention of osteoarthritis development. Efforts to restore the articular cartilage using advanced procedures like autologous chondrocyte implantation led to the development of scaffolds. Although the use of a scaffold-based technique is a reliable and effective method of cartilage repair, only the appropriate qualification can lead to good clinical outcomes.

Short-term radiological results after spheroid-based autologous chondrocyte implantation in the knee are independent of defect localisation

BACKGROUND: Lesions of articular cartilage represent a crucial risk factor for the early development of osteoarthritis. Autologous chondrocyte implantation (ACI) is a well-established procedure in therapy of those lesions in the knee. The aim of the presented study is to detect differences in short-term radiological outcome depending on defect localization (femoral condyle vs. retropatellar) after spheroid-based ACI. OBJECTIVE: This study aimed to demonstrate that radiological outcome after spheroid-based ACI in the knee is independent of defect localization. METHODS: MRI-scans after retropatellar ACI and ACI of the medial/lateral femoral condyle, with a preoperative Outerbridge grade of III or IV were evaluated regarding MOCART 2.0. RESULTS: The mean defect-size was 5.0 ± 1.8 cm2, with a minimum size of 2 cm2 and a maximum size of 9 cm2. Scans were performed 7.7 months (± 3.1 months) postoperatively. The mean MOCART 2.0 score was 78.5 ± 15.6. No statistically significant influence neither of the localization (p= 0.159), the gender (p= 0.124) nor defect size (< 5 cm2 vs. ⩾ 5 cm2; p= 0.201) could be observed. CONCLUSIONS: The presented data demonstrate good to excellent radiological short-term results after spheroid-based ACI. Data indicates, that at least radiological results are independent of gender, defect-size and defect-localization.

Etiology of Cartilage Lesions Does Not Affect Clinical Outcomes of Patellofemoral Autologous Chondrocyte Implantation

Objective To determine the relationship between cartilage lesion etiology and clinical outcomes after second-generation autologous chondrocyte implantation (ACI) in the patellofemoral joint (PFJ) with a minimum of 2 years’ follow-up. Methods A retrospective review of all patients that underwent ACI in the PFJ by a single surgeon was performed. Seventy-two patients with a mean follow-up of 4.2 ± 2.0 years were enrolled in this study and were stratified into 3 groups based on the etiology of PFJ cartilage lesions: patellar dislocation (group 1; n = 23); nontraumatic lesions, including chondromalacia, osteochondritis dissecans, and degenerative defects (group 2; n = 28); and other posttraumatic lesions besides patellar dislocations (group 3; n = 21). Patient’s mean age was 29.6 ± 8.7 years. Patients in group 1 were significantly younger (25.4 ± 7.9 years) than group 2 (31.7 ± 9.6 years; P = 0.025) and group 3 (31.5 ± 6.6 years; P = 0.05). Body mass index averaged 26.2 ± 4.3 kg/m2, with a significant difference between group 1 (24.4 ± 3.2 kg/m2) and group 3 (28.7 ± 4.5 kg/m2; P = 0.005). A clinical comparison was established between groups based on patient-reported outcome measures (PROMs) and failure rates. Results Neither pre- nor postoperative PROMs differed between groups ( P > 0.05). No difference was seen in survivorship between groups (95.7% vs. 82.2% vs. 90.5%, P > 0.05). Conclusion Cartilage lesion etiology did not influence clinical outcome in this retrospective study after second generation ACI in the PFJ. Level of Evidence Level III, retrospective comparative study.

Role of Matrix-Associated Autologous Chondrocyte Implantation with Spheroids in the Treatment of Large Chondral Defects in the Knee: A Systematic Review

Autologous chondrocyte implantation (ACI) is a cell therapy for the treatment of focal cartilage defects. The ACI product that is currently approved for use in the European Union (EU) consists of spheroids of autologous matrix-associated chondrocytes. These spheroids are spherical aggregates of ex vivo expanded human autologous chondrocytes and their self-synthesized extracellular matrix. The aim is to provide an overview of the preclinical and nonclinical studies that have been performed to ensure reproducible quality, safety, and efficacy of the cell therapy, and to evaluate the clinical data on ACI with spheroids. A systematic review was performed to include all English publications on self-aggregated spheroids of chondrocytes cultured in autologous serum without other supplements. A total of 20 publications were included, 7 pre- and nonclinical and 13 clinical research publications. The pre- and nonclinical research publications describe the development from concept to in vivo efficacy and quality- and safety-related aspects such as biodistribution, tumorigenicity, genetic stability, and potency. The evaluation of clinical research shows short- to mid-term safety and efficacy for the ACI with spheroid-based treatment of cartilage defects in both randomized clinical trials with selected patients, as well as in routine treatment providing real-world data in more complex patients.

LOOSE BODY VERSUS TROCHLEAR BIOPSY MATRIX-INDUCED AUTOLOGOUS CHONDROCYTE IMPLANTATION (MACI) MOCART SCORES AND IKDC REPORTED OUTCOMES IN PEDIATRIC PATIENTS

Background: Third generation autologous chondrocyte implantation (ACI) has traditionally used biopsies from non-weightbearing sites within the knee for culture and growth. Given the potential risk of functional deficits from this procedure, other donor sites are being investigated. A recent study showed no difference in the viability of the MACI implant using biopsies from the standard intercondylar region compared to biopsies from the osteochondral loose body. However, clinical outcomes using these two different donor sites remains unknown. The purpose of this study was to asses differences in clinical outcomes as measured by Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART 2.0) and International Knee Documentation Committee (IKDC) scores at a minimum of 2 years post-implantation in patients who underwent a MACI procedure in the knee using cartilage grown from either the intercondylar notch or the osteochondral loose bodies. Methods: A retrospective study was performed on all ACI procedures from 2014 to 2017 at a single institution. Patients were split into two groups: one group having their cartilage derived from a standard intercondylar biopsy while the other group had their cartilage derived from osteochondral loose bodies. At a minimum 1-year post-implantation, MRIs of the implantation site were performed and three individual orthopaedic surgeons used the MOCART 2.0 knee score to assess the cartilage. Interclass correlation coefficients (ICC) were calculated between the 2 groups. IKDC scores were determined at a minimum 2 years after implantation. Differences between outcomes were compared using a Wilcoxon rank-sum test. Results: The intraclass coefficient between examiners for the MOCART scoring was excellent at 0.94. With regards to the MOCART score, the loose body group had a statistically insignificant 15-point lower median score at 65 (IQR 61-83) compared to the intercondylar group at 80 (IQR 60-89) (p=0.46). With regards to the IKDC, the loose body group had a statistically insignificant 1-point higher median score at 85 (IQR 69-96) compared to the intercondylar group at 84 (IQR 53-99) (p=0.79). Conclusions: This study demonstrates no difference in MOCART and patient reported outcomes in patients who had MACI from cartilage derived from either a standard intercondylar biopsy or an osteochondral loose body. Surgeons should be aware that using cartilage derived from osteochondral loose bodies is a viable option for MACI as it eliminates donor site morbidity and has comparable MOCART and functional outcomes at 2 years post-implantation compared to the standard intercondylar biopsy. Level of evidence: Level III

Arthroscopy versus mini-arthrotomy approach for matrix-induced autologous chondrocyte implantation in the knee: a systematic review

Background Matrix-induced autologous chondrocyte implantation (mACI) can be performed in a full arthroscopic or mini-open fashion. A systematic review was conducted to investigate whether arthroscopy provides better surgical outcomes compared with the mini-open approach for mACI in the knee at midterm follow-up. Methods This systematic review was conducted following the PRISMA guidelines. The literature search was performed in May 2021. All the prospective studies reporting outcomes after mACI chondral defects of the knee were accessed. Only studies that clearly stated the surgical approach (arthroscopic or mini-open) were included. Only studies reporting a follow-up longer than 12 months were eligible. Studies reporting data from combined surgeries were not eligible, nor were those combining mACI with less committed cells (e.g., mesenchymal stem cells). Results Sixteen studies were included, and 770 patients were retrieved: 421 in the arthroscopy group, 349 in the mini-open. The mean follow-up was 44.3 (12–60) months. No difference between the two groups was found in terms of mean duration of symptoms, age, body mass index (BMI), gender, defect size (P > 0.1). No difference was found in terms of Tegner Score (P = 0.3), Lysholm Score (P = 0.2), and International Knee Documentation Committee (IKDC) Score (P = 0.1). No difference was found in the rate of failures (P = 0.2) and revisions (P = 0.06). Conclusion Arthroscopy and mini-arthrotomy approaches for mACI in knee achieve similar outcomes at midterm follow-up. Level of evidence II, systematic review of prospective studies.