Repair of Damaged Articular Cartilage: Current Approaches and Future Directions.

Articular hyaline cartilage is extensively hydrated, but it is neither innervated nor vascularized, and its low cell density allows only extremely limited self-renewal. Most clinical and research efforts currently focus on the restoration of cartilage damaged in connection with osteoarthritis or trauma. Here, we discuss current clinical approaches for repairing cartilage, as well as research approaches which are currently developing, and those under translation into clinical practice. We also describe potential future directions in this area, including tissue engineering based on scaffolding and/or stem cells as well as a combination of gene and cell therapy. Particular focus is placed on cell-based approaches and the potential of recently characterized chondro-progenitors; progress with induced pluripotent stem cells is also discussed. In this context, we also consider the ability of different types of stem cell to restore hyaline cartilage and the importance of mimicking the environment in vivo during cell expansion and differentiation into mature chondrocytes.

Acid ceramidase treatment enhances the outcome of autologous chondrocyte implantation in a rat osteochondral defect model.

OBJECTIVE: The overall aim of this study was to evaluate how supplementation of chondrocyte media with recombinant acid ceramidase (rhAC) influenced cartilage repair in a rat osteochondral defect model. METHODS: Primary chondrocytes were grown as monolayers in polystyrene culture dishes with and without rhAC (added once at the time of cell plating) for 7 days, and then seeded onto Bio-Gide® collagen scaffolds and grown for an additional 3 days. The scaffolds were then introduced into osteochondral defects created in Sprague-Dawley rat trochlea by a microdrilling procedure. Analysis was performed 6 weeks post-surgery macroscopically, by micro-CT, histologically, and by immunohistochemistry. RESULTS: Treatment with rhAC led to increased cell numbers and glycosaminoglycan (GAG) production (∼2 and 3-fold, respectively) following 7 days of expansion in vitro. Gene expression of collagen 2, aggrecan and Sox-9 also was significantly elevated. After seeding onto Bio-Gide®, more rhAC treated cells were evident within 4 h. At 6 weeks post-surgery, defects containing rhAC-treated cells exhibited more soft tissue formation at the articular surface, as evidenced by microCT, as well as histological evidence of enhanced cartilage repair. Notably, collagen 2 immunostaining revealed greater surface expression in animals receiving rhAC treated cells as well. Collagen 10 staining was not enhanced. CONCLUSION: The results further demonstrate the positive effects of rhAC treatment on chondrocyte growth and phenotype in vitro, and reveal for the first time the in vivo effects of the treated cells on cartilage repair.

Delayed gadolinium-enhanced MRI of cartilage and T2 mapping for evaluation of reparative cartilage-like tissue after autologous chondrocyte implantation associated with Atelocollagen-based scaffold in the knee.

OBJECTIVE: To elucidate the quality of tissue-engineered cartilage after an autologous chondrocyte implantation (ACI) technique with Atelocollagen gel as a scaffold in the knee in the short- to midterm postoperatively, we assessed delayed gadolinium-enhanced magnetic resonance imaging (MRI) of cartilage (dGEMRIC) and T2 mapping and clarified the relationship between T1 and T2 values and clinical results. MATERIALS AND METHODS: In this cross-sectional study, T1 and T2 mapping were performed on 11 knees of 8 patients (mean age at ACI, 37.2 years) with a 3.0-T MRI scanner. T1implant and T2implant values were compared with those of the control cartilage region (T1control and T2control). Lysholm scores were also assessed for clinical evaluation. The relationships between the T1 and T2 values and the clinical Lysholm score were also assessed. RESULTS: There were no significant differences in the T1 values between the T1implant (386.64 ± 101.78 ms) and T1control (375.82 ± 62.89 ms) at the final follow-up. The implants showed significantly longer T2 values compared to the control cartilage (53.83 ± 13.89 vs. 38.21 ± 4.43 ms). The postoperative Lysholm scores were significantly higher than the preoperative scores. A significant correlation was observed between T1implant and clinical outcomes, but not between T2implant and clinical outcomes. CONCLUSION: Third-generation ACI implants might have obtained an almost equivalent glycosaminoglycan concentration compared to the normal cartilage, but they had lower collagen density at least 3 years after transplantation. The T1implant value, but not the T2 value, might be a predictor of clinical outcome after ACI.

Second-look assessment after all-arthroscopic autologous chondrocyte implantation with spheroides at the knee joint.

PURPOSE: To report arthroscopic second look as well as clinical results after arthroscopic autologous chondrocyte implantation (ACI) for articular cartilage repair at the knee joint. METHODS: A second-look assessment after arthroscopic ACI using spheroides was performed in 41 patients with 57 full-size articular cartilage defects of the knee. The median time from ACI to second-look arthroscopy was 10 (6-72) months. The ACI was assessed macroscopically and by probing according to the International Cartilage Repair Score (ICRS)-Cartilage Repair Assessment (CRA) to get information on the amount and quality of regeneration. Clinical follow-up with subjective outcome scores was performed an average of 34.5 ± 19.2 months after ACI. Twenty-seven (65.8 %) of ACI's were combined with additional procedures. RESULTS: The ICRS-CRA was rated "normal" or "nearly normal" in 52 of 57 (91.3 %) and "abnormal" in 5 (8.8 %) of all cartilage defects. At follow-up, evaluation of KOOS was an average of 81.0 ± 12.9 for pain, 76.8 ± 16.6 for symptoms, 85.1 ± 14.9 for activities of daily living, 55.3 ± 27.7 for sport and recreation and 50.6 ± 23.8 for quality of live. IKDC was 63.0 ± 18.8, Lysholm score was 79.0 ± 18.0, and Tegner score was 4 (1-6). Subjective assessment according to the VAS scale was an average of 7.4 ± 2.1 for overall satisfaction and 6.7 ± 2.5 satisfaction for the operated knee. Seven patients (22.6 %) showed low subjective outcome scores at last follow-up-of these, 2 patients showed a CRA 3 and 5 a CRA 1 or 2. CONCLUSION: At second-look arthroscopy, 52 (91.3 %) of all cartilage defects showed a normal or nearly normal macroscopic articular cartilage regeneration after arthroscopic ACI using spheroides. Twenty-four patients (77.4 %) showed good subjective clinical results. The high number of concomitant surgery reflexes the complex aetiology of cartilage lesions and complexity of treatment. Thus, a strict indication and surgical planing is necessary to avoid clinical failures. LEVEL OF EVIDENCE: IV.

Rate of Conversion to Matrix-Induced Autologous Chondrocyte Implantation After a Biopsy: A Multisurgeon Study.

Background: Autologous chondrocyte implantation (ACI) and matrix-induced autologous chondrocyte implantation (MACI) are performed to treat focal chondral defects (FCDs); both are 2-step procedures involving a biopsy, followed by transplantation. There is little published research evaluating ACI/MACI in patients who undergo a biopsy alone. Purpose: To determine (1) the value of ACI/MACI cartilage biopsies and concomitant procedures in patients with FCDs of the knee and (2) the conversion rate to cartilage transplantation as well as the rate of reoperation. Study Design: Case series; Level of evidence, 4. Methods: A retrospective review was performed of 46 patients (63% female) who underwent a MACI (or ACI) biopsy between January 2013 and January 2018. Preoperative data, intraoperative data, and postoperative outcomes were assessed at a minimum of 2 years after the biopsy. The conversion rate from a biopsy to transplantation and the reoperation rate were calculated and analyzed. Results: Among the 46 patients included, 17 (37.0%) underwent subsequent surgery, with only 12 undergoing cartilage restoration surgery, for an overall transplantation rate of 26.1%. Of these 12 patients, 9 underwent MACI/ACI, 2 underwent osteochondral allograft transplantation (OCA), and 1 underwent particulated juvenile articular cartilage implantation at 7.2 ± 7.5 months after the biopsy. The reoperation rate was 16.7% (1 patient after MACI/ACI and 1 patient after OCA) at 13.5 ± 2.3 months after transplantation. Conclusion: Arthroscopic surgery with debridement, chondroplasty, loose body removal, meniscectomy/meniscal repair, and other treatment approaches of knee compartment abnormalities at the time of a biopsy appeared to be sufficient in improving function and reducing pain in patients with knee FCDs.

The Role of Hypertension in Cartilage Restoration: Increased Failure Rate After Autologous Chondrocyte Implantation but Not After Osteochondral Allograft Transplantation.

Objectives. The purpose of this study was to examine whether patients with diagnosed hypertension have an increased risk of graft failure following cartilage repair with either autologous chondrocyte implantation (ACI) or osteochondral allograft transplantation (OCA). We hypothesized that hypertension is related to higher ACI and OCA graft failure. Design. Patients who underwent ACI or OCA transplantation between February 2009 and December 2016 were included in this study. Inclusion criteria were (1) at least 2 years' follow-up, (2) available information related to the living habits (smoking and medication status), and (3) available information related to the presence of hypertension, diabetes mellitus, or hyperlipidemia. To identify potential independent risk factors of graft failure, univariate screening was performed and factors with significance at a level of P < 0.1 were entered in multivariate logistic regression models. Results. A total of 368 patients (209 ACI and 159 OCA) were included into our study. In the ACI group, 61 patients' (29.1%) graft failed. Univariate screening identified older age, female gender, defect size, higher prevalence of hypertension, and smoking as a predictor of graft failure. Following, multivariate logistic regression revealed female gender (odds ratio [OR] 1.02, P = 0.048), defect size (OR 1.07, P = 0.035), and hypertension (OR 3.73, P = 0.023) as significant independent risk factors predicting graft failure after ACI. In the OCA group, 29 patients' (18.2%) graft failed and none of the included factors demonstrated to be a potential risk factor for graft failure. Conclusion. Hypertension, defect size, and female gender seem to predict ACI graft failure but not OCA failure.

Scientific Developments and Clinical Applications Utilizing Chondrons and Chondrocytes with Matrix for Cartilage Repair.

Injuries to articular cartilage of the knee are increasingly common. The operative management of these focal chondral lesions continues to be problematic for the treating orthopedic surgeon secondary to the limited regenerative capacity of articular cartilage. The pericellular matrix (PCM) is a specialized, thin layer of the extracellular matrix that immediately surrounds chondrocytes forming a unit together called the chondron. The advancements in our knowledge base with regard to the PCM/chondrons as well as interterritorial matrix has permeated and led to advancements in product development in conjunction with minced cartilage, marrow stimulation, osteochondral allograft, and autologous chondrocyte implantation (ACI). This review intends to summarize recent progress in chondrocytes with matrix research, with an emphasis on the role the PCM/extracellular matrix (ECM) plays for favorable chondrogenic gene expression, as a barrier/filtration unit, and in osteoarthritis. The bulk of the review describes cutting-edge and evolving clinical developments and discuss these developments in light of underlying basic science applications. Clinical applications of chondrocytes with matrix science include Reveille Cartilage Processor, Cartiform, and ACI with Spherox (which was recently recommended for the treatment of grade III or IV articular cartilage defects over 2 cm2 by the National Institute of Health and Care Excellence [NICE] in the United Kingdom). The current article presents a comprehensive overview of both the basic science and clinical results of these next-generation cartilage repair techniques by focusing specifically on the scientific evolution in each category as it pertains with underlying chondrocytes with matrix theory.

Return to Work After Autologous Chondrocyte Implantation of the Knee in Patients with Workers Compensation Insurance.

OBJECTIVE: This retrospective analysis aimed to evaluate patient and defect characteristics on return to work after autologous chondrocyte implantation (ACI) for all patients with workers compensation insurance in our clinic. METHODS: Retrospective analysis of medical records of patients with workers compensation treated with ACI in our clinic over 10 years (August 2004 to November 2014). Data were collected on demographics, lesion size and location, number of defects, duration of symptoms, and outcomes. RESULTS: A total of 28 patients with 30 ACI procedures were included in this analysis. Patients had a mean age of 40.0 years, were mostly male, and tended to be overweight (mean body mass index = 31.5 kg/m2). Most patients were employed in occupations with high physical demand (85.7%) compared with lower physical demand jobs (14.3%). The mean number of lesions per knee = 1.73. Overall, the mean total surface area of the defect was large (12.6 cm2), with large mean individual lesion size of 7.39 cm2. All 28 patients returned to work in some capacity, with a total of 22 (79%) returning to full work, and 6 (21%) returning to modified work. There were no significant differences in the comparison of patients who returned to full versus modified work, in mean age, body mass index, high versus low physical demand occupation, or lesion characteristics (size, chronicity, or location). CONCLUSIONS: Our results demonstrate that in a challenging workers compensation cohort, in patients with multiple large defects, treatment with ACI allows a high percentage of patients to return to their normal vigorous work activities within 9 months to 1 year following cartilage restoration. This study is a level IV retrospective case series.

Is implantation of autologous chondrocytes superior to microfracture for articular-cartilage defects of the knee? A systematic review of 5-year follow-up data.

BACKGROUND: Autologous chondrocyte implantation (ACI) and microfracture are two of the main surgical treatment options for articular cartilage lesions of the knee. Consensus regarding the best clinical options to repair knee cartilage lesions is lacking. We undertook a systematic review to clarify the clinical efficacy of ACI and microfracture at minimum mean 5-year follow-up. METHODS: A literature search was conducted using the MEDLINE, Embase and Cochrane Library databases up to August 2018. Only comparative clinical studies of ACI and microfracture for the treatment of articular cartilage lesions of the knee with level I/Ⅱ evidence were included. Clinical outcomes and the prevalence of treatment failure from each study were extracted and compared. The methodological quality of the included studies was analyzed by means of the PEDro scale. RESULTS: Five comparative studies (three randomized controlled trials and two prospective cohort studies) met our eligibility criteria. ACI and microfracture elicited significant improvement in clinical outcomes after 5 years. However, better clinical results with significant differences were found with modified versions of ACI (ACI with a modified collagen membrane [ACI-C] or matrix-applied chondrocyte implantation [MACI]) than with microfracture as determined by the Knee Injury and Osteoarthritis Outcome Score, activities of daily living assessment, Tegner Activity Scale score, and the International Knee Documentation Committee objective and subjective scores. No significant difference was observed in the treatment failure rate between these two methods within a particular study. CONCLUSIONS: Currently, the best-available evidence suggests that some clinical outcomes of articular cartilage lesions of the knee treated with modified versions of ACI (ACI-C or MACI) can significantly improve patient outcomes at the mid-term follow-up of 5 years compared with those obtained using microfracture.

Regenerative Medicine: A Review of the Evolution of Autologous Chondrocyte Implantation (ACI) Therapy.

Articular cartilage is composed of chondrons within a territorial matrix surrounded by a highly organized extracellular matrix comprising collagen II fibrils, proteoglycans, glycosaminoglycans, and non-collagenous proteins. Damaged articular cartilage has a limited potential for healing and untreated defects often progress to osteoarthritis. High hopes have been pinned on regenerative medicine strategies to meet the challenge of preventing progress to late osteoarthritis. One such strategy, autologous chondrocyte implantation (ACI), was first reported in 1994 as a treatment for deep focal articular cartilage defects. ACI has since evolved to become a worldwide well-established surgical technique. For ACI, chondrocytes are harvested from the lesser weight bearing edge of the joint by arthroscopy, their numbers expanded in monolayer culture for at least four weeks, and then re-implanted in the damaged region under a natural or synthetic membrane via an open joint procedure. We consider the evolution of ACI to become an established cell therapy, its current limitations, and on-going strategies to improve its efficacy. The most promising developments involving cells and natural or synthetic biomaterials will be highlighted.

Two independent proteomic approaches provide a comprehensive analysis of the synovial fluid proteome response to Autologous Chondrocyte Implantation.

BACKGROUND: Autologous chondrocyte implantation (ACI) has a failure rate of approximately 20%, but it is yet to be fully understood why. Biomarkers are needed that can pre-operatively predict in which patients it is likely to fail, so that alternative or individualised therapies can be offered. We previously used label-free quantitation (LF) with a dynamic range compression proteomic approach to assess the synovial fluid (SF) of ACI responders and non-responders. However, we were able to identify only a few differentially abundant proteins at baseline. In the present study, we built upon these previous findings by assessing higher-abundance proteins within this SF, providing a more global proteomic analysis on the basis of which more of the biology underlying ACI success or failure can be understood. METHODS: Isobaric tagging for relative and absolute quantitation (iTRAQ) proteomic analysis was used to assess SF from ACI responders (mean Lysholm improvement of 33; n = 14) and non-responders (mean Lysholm decrease of 14; n = 13) at the two stages of surgery (cartilage harvest and chondrocyte implantation). Differentially abundant proteins in iTRAQ and combined iTRAQ and LF datasets were investigated using pathway and network analyses. RESULTS: iTRAQ proteomic analysis confirmed our previous finding that there is a marked proteomic shift in response to cartilage harvest (70 and 54 proteins demonstrating ≥ 2.0-fold change and p < 0.05 between stages I and II in responders and non-responders, respectively). Further, it highlighted 28 proteins that were differentially abundant between responders and non-responders to ACI, which were not found in the LF study, 16 of which were altered at baseline. The differential expression of two proteins (complement C1s subcomponent and matrix metalloproteinase 3) was confirmed biochemically. Combination of the iTRAQ and LF proteomic datasets generated in-depth SF proteome information that was used to generate interactome networks representing ACI success or failure. Functional pathways that are dysregulated in ACI non-responders were identified, including acute-phase response signalling. CONCLUSIONS: Several candidate biomarkers for baseline prediction of ACI outcome were identified. A holistic overview of the SF proteome in responders and non-responders to ACI  has been profiled, providing a better understanding of the biological pathways underlying clinical outcome, particularly the differential response to cartilage harvest in non-responders.

Long-term follow-up evaluation of autologous chondrocyte implantation for symptomatic cartilage lesions of the knee: A single-centre prospective study.

INTRODUCTION: Autologous Chondrocyte Implantation (ACI) has been the first technique in reconstruction of a valid articular surface. The aim of this study was to evaluate clinical results of this technique at an average follow up of 162±27months (range 88-208) in a group of patients who underwent ACI. MATERIALS AND METHODS: 32 patients were operated between 1997 and 2007 for chondral lesions or osteochondritis dissecans of the knee. Mean size of the defect was 5.48cm2±1.53 (range 2-9). Nine patients were treated with I generation technique and 23 with II generation. All patients were evaluated with Subjective IKDC and Tegner Activity Scales for clinical outcomes and with EQ-VAS for a quantitative measure of health after intervention, starting from pre-operative period and at regular follow up (minimum 88 months-maximum 208 months). RESULTS: A significant increment of all scores was noticed comparing preoperative and postoperative results. In particular medium IKDC score increased from 40.3±9.6 in preoperative evaluation to 74.2±11.6 at one year (p<0.00001) and to 83.9±10.4 at 5 years follow up (p<0.001). Mean IKDC values at the last follow-up were 80.3±14.2, showing no statistical differences with those obtained at five-year follow-up. Tegner Activity Scale values increased from 2.8±1.1 preoperatively to 4.1±1.1 (p<0.0001) after one year and to 6±1.1 at five years (p<0.0001). Mean Tegner Activity Scale values decreased to 4.8±1.4 at the last follow-up. EQ-VAS evaluation showed superposable results comparing the 5 years evaluation with the ones at a medium follow up of 162±27months. DISCUSSION: The most important finding is the reliability at long-term of ACI technique, which in our series gave excellent clinical results. No statistical differences were observed between first- and second-generation. Clinical outcomes were significantly better for defects in the femoral condyles, influenced by age (worse results over 30 years old). CONCLUSIONS: ACI represents a valid technique for chondral and osteochondral lesions of the knee in a population heterogeneous for age, sex and activity level with good results even at a long term follow up.

Transplantation of autologous chondrocytes ex-vivo expanded using Thermoreversible Gelation Polymer in a rabbit model of articular cartilage defect.

Graft failure due to de-differentiation of the chondrocytes during in vitro culture and after transplantation is a major hurdle in Autologous Chondrocyte Implantation (ACI). We, herein, report the transplantation of autologous chondrocytes ex vivo expanded using a Thermo-reversible Gelation Polymer (TGP) in a rabbit model. A full thickness chondral defect was created in one of the knee joints in each of the six rabbits of the study and autologous chondrocytes in vitro expanded using TGP scaffold were transplanted after 10 weeks. H & E staining of the biopsy after 6 months revealed maintenance of articular cartilage phenotype.

Orthopedic Surgical Options for Joint Cartilage Repair and Restoration.

The limited natural capacity for articular cartilage to regenerate has led to a continuously broadening array of surgical interventions. Used once patients' symptoms are not relieved by nonoperative management, these share the goals of joint preservation and restoration. Techniques include bone marrow stimulation, whole-tissue transplantation, and cell-based strategies, each with its own variations. Many of these interventions are performed arthroscopically or with extended-portal techniques. Indications, operative techniques, unique benefits, and limitations are presented.

Chondrocyte and mesenchymal stem cell-based therapies for cartilage repair in osteoarthritis and related orthopaedic conditions.

Osteoarthritis (OA) represents a final and common pathway for all major traumatic insults to synovial joints. OA is the most common form of degenerative joint disease and a major cause of pain and disability. Despite the global increase in the incidence of OA, there are no effective pharmacotherapies capable of restoring the original structure and function of damaged articular cartilage. Consequently cell-based and biological therapies for osteoarthritis (OA) and related orthopaedic disorders have become thriving areas of research and development. Autologous chondrocyte implantation (ACI) has been used for treatment of osteoarticular lesions for over two decades. Although chondrocyte-based therapy has the capacity to slow down the progression of OA and delay partial or total joint replacement surgery, currently used procedures are associated with the risk of serious adverse events. Complications of ACI include hypertrophy, disturbed fusion, delamination, and graft failure. Therefore there is significant interest in improving the success rate of ACI by improving surgical techniques and preserving the phenotype of the primary chondrocytes used in the procedure. Future tissue-engineering approaches for cartilage repair will also benefit from advances in chondrocyte-based repair strategies. This review article focuses on the structure and function of articular cartilage and the pathogenesis of OA in the context of the rising global burden of musculoskeletal disease. We explore the challenges associated with cartilage repair and regeneration using cell-based therapies that use chondrocytes and mesenchymal stem cells (MSCs). This paper also explores common misconceptions associated with cell-based therapy and highlights a few areas for future investigation.

Autologous chondrocyte implantation and anteromedialization for isolated patellar articular cartilage lesions: 5- to 11-year follow-up.

BACKGROUND: Isolated chondral lesions of the patella are particularly challenging to treat, and long-term studies of treated isolated patellar lesions are limited. Previous short-term studies have reported favorable outcomes of autologous chondrocyte implantation (ACI) of the patella and/or trochlea, with a trend toward improvement when anteromedialization (AMZ) of the tibial tubercle was performed with the procedure. HYPOTHESIS: Autologous chondrocyte implantation with concomitant AMZ for symptomatic isolated patellar lesions provides functional and symptomatic improvement in patients at a minimum 5-year follow-up. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Patients with failed primary treatment of isolated patellar full-thickness articular cartilage defects and patellofemoral malalignment who were treated with ACI and AMZ of the tibial tubercle at least 5 years prior were contacted for final postoperative outcome scores. Outcome scales including the International Knee Documentation Committee (IKDC), Lysholm, modified Cincinnati Knee Rating System, and 12-item Short Form Health Survey (SF-12) scores were assessed at baseline and final follow-up. RESULTS: Of 27 eligible patients, 23 (25 knees) were available for assessment at a mean follow-up of 7.6 years (range, 5.1-11.4 years). Significant improvements from baseline to final follow-up were observed in the IKDC score (from 42.5 to 75.7; P < .0001), modified Cincinnati Knee Rating System score (from 3.0 to 7.0; P < .0001), Lysholm score (from 40.2 to 79.3; P < .0001), and SF-12 score (physical component score: from 41.2 to 47.6; P = .002; mental component score: from 48.1 to 60.7; P = .0001). Most patients (83%; 19/23) rated their surgery as good or excellent. The overall reoperation rate was 40% (10/25) largely because of periosteal hypertrophy (33%). One patient failed at 5.9 years postoperatively and underwent patellofemoral arthroplasty. CONCLUSION: Combined ACI and AMZ resulted in significant improvements in symptoms and function with a low incidence of adverse events in patients with isolated symptomatic patellar chondral defects after a mean follow-up of more than 7 years.

Correlation between magnetic resonance imaging and clinical outcomes after cartilage repair surgery in the knee: a systematic review and meta-analysis.

BACKGROUND: Magnetic resonance imaging (MRI) is often used to assess cartilage after surgical repair. The correlation between MRI and clinical outcomes is not well understood. HYPOTHESIS: Postoperative MRI findings correlate with clinical outcome measures in patients after articular cartilage surgery of the knee. STUDY DESIGN: Meta-analysis. METHODS: A systematic review of the literature was performed to identify studies in which MRI and clinical outcomes were correlated after autologous chondrocyte implantation (ACI), osteochondral autograft transfer system (OATS), or microfracture. Studies that reported correlation coefficients (r) for different MRI parameters were then included in a meta-analysis. RESULTS: A total of 26 studies were identified for inclusion in this systematic review, 15 of which were included in the meta-analysis. Most of the studies (n = 19) involved ACI, although studies were available for OATS (n = 5) and microfracture (n = 4). The strongest MRI correlates with clinical outcomes after ACI were graft hypertrophy (r = 0.72) and repair tissue signal (r = 0.71). After microfracture, the strongest MRI correlates were the Henderson score (r = 0.97), subchondral edema (r = 0.77), and repair tissue signal (r = 0.76). Correlations after OATS were not as strong, with defect fill (r = 0.53) and repair tissue structure (r = 0.51) being the strongest. CONCLUSION: The MRI findings do correlate with clinical outcomes after cartilage repair surgery in the knee, although the specific parameters that correlate best vary by the type of procedure performed. No current MRI classification system has been shown to correlate with clinical outcomes after all types of cartilage repair surgery.