Matrix-assisted Autologous Chondrocyte Transplantation Research Articles

Sex does not influence the long-term outcome of matrix-assisted autologous chondrocyte transplantation.

Regenerative techniques for articular cartilage lesions demonstrated heterogeneous clinical results. Several factors may influence the outcome, with sex being one of the most debated. This study aimed at quantifying the long-term influence of sex on the clinical outcome obtained with a regenerative procedure for knee chondral lesions. Matrix-assisted autologous chondrocyte transplantation (MACT) was used to treat 235 knees which were prospectively evaluated with the International Knee Documentation Committee (IKDC), EuroQol visual analogue scale,and Tegner scores at 14-year mean follow-up. A multilevel analysis was performed with the IKDC subjective scores standardised according to the age/sex category of each patientand/or the selection of a match-paired subgroup to compare homogeneous men and women patients. At 14 years, men and women showed a failure rate of 10.7% and 28.8%, respectively (p < 0.0005). An overall improvement was observed in both sexes. Women had more patellar lesions and men more condylar lesions (p = 0.001), and the latter also presented a higher preinjury activity level (p < 0.0005). Men had significantly higher IKDC subjective scores at all follow-ups (at 14 years: 77.2 ± 18.9 vs.62.8 ± 23.1; p < 0.0005). However, the analysis of homogeneous match-paired populations of men and women, with standardised IKDC subjective scores, showed no differences between men and women (at 14 years: -1.6 ± 1.7 vs. -1.9 ± 1.6). Men and women treated with MACT for knee chondral lesions presented a significant improvement and stable long-term results. When both sexes are compared with homogeneous match-paired groups, they have similar results over time. However, women present more often unfavourable lesion patterns, which proved more challenging in terms of long-term outcome after MACT. Level II.

Paper 43: Long-term Outcomes of an All-Arthroscopic Matrix-Assisted Autologous Chondrocyte Transplantation Technique

Objectives:To evaluate the long-term clinical and magnetic resonance imaging outcomes of patients treated with an all-arthroscopic matrix-assisted autologous chondrocyte transplantation (MACT) technique for articular cartilage lesions of the knee.Methods:A total of 63 patients (21 women, 42 men) with a mean age of 35 ± 9.2 years, were treated with an all-arthroscopic MACT technique for articular cartilage lesions of the knee. Patients were prospectively evaluated preoperatively and after 2, 5, and 10 years of the surgery using multiple clinical scores: Lysholm, Tegner, International Knee Documentation Committee (IKDC), and the Knee injury and Osteoarthritis Outcome Score (KOOS); as well as with magnetic resonance imaging (MRI) T2-mapping at the same time points. Failure was defined as a reoperation because of symptoms caused by the primary repaired defect or a patient improvement of <10 points in the IKDC subjective score between the preoperative value and the final follow-up value.Results:Patients showed statistically significant clinical improvement in all PROM scores at 2, 5, and 10 years postoperative (PO) compared to their preoperative status. MRI T2-Mapping values of the repaired tissue decreased from 59.0 ± 14.6 ms preoperatively to 44.4 ± 15.6 ms at 10 years PO (P= 0.008), showing no statistical differences compared to the native cartilage values (39.1 ± 4.0 ms, P= 0.398). A surgical failure rate of 1.5% was documented, which was increased to 33% when clinical failures were also considered. Among all the analyzed factors linked to the likelihood of failure, lesions >4cm2 were the only ones to show statistical significance (P= 0.024).Conclusions:Patients treated with this arthroscopic MACT technique showed good and long-lasting clinical outcomes, as well as close to native cartilage characteristics on MRI T2-mapping. A limited number of failures were observed at 10 years PO, with most failures being in the first two years after treatment. Big chondral lesions (>4cm2) were found to have a greater likelihood of failing.UPLOAD-https://planion-client-files.s3.amazonaws.com/AOSSM/blobs/9e2d9f3a-b8a0-4921-9952-144a0de7acd7/1/Base_Px_AMECI_-_Clinica_2.pdf UPLOAD-https://planion-client-files.s3.amazonaws.com/AOSSM/blobs/e39a94d5-bbc5-4e27-8493-786a2237cef3/1/Patient-Reported_Outcome_Measures_1.pdf UPLOAD-https://planion-client-files.s3.amazonaws.com/AOSSM/blobs/aba360a2-961d-4b2e-a4fa-1049626e23d3/1/MRI_T2-Mapping_2.pdf UPLOAD-https://planion-client-files.s3.amazonaws.com/AOSSM/blobs/d9c78782-8a61-446f-b0e7-24873b631a5a/1/kaplan_meier.pdf

Matrix-assisted autologous chondrocyte transplantation for treatment of focal chondral lesions in the knee: the Hospital Israelita Albert Einstein experience.

ABSTRACTObjective Phase 1 clinical trial to determine feasibility, safety, and efficacy of a new advanced cell therapy product for treatment of knee articular cartilage injuries.Methods Three participants with knee focal chondral lesions were included, with no signs of osteoarthritis. Chondrocytes were obtained through knee arthroscopy, cultured in collagen membrane for 3 weeks at the laboratory, subjected to tests to release the cell therapy product, and implanted. All patients underwent a specific 3-month rehabilitation protocol, followed by assessments using functional and imaging scales. The main outcome was the incidence of severe adverse events.Results Three participants were included and completed the 2-year follow-up. There was one severe adverse event, venous thrombosis of distal leg veins, which was no associated with therapy, was treated and left no sequelae. The clinical and radiological scales showed improvement in the three cases.Conclusion The preliminary results, obtained with the described methodology, allow concluding that this product of advanced cell therapy is safe and feasible. ReBEC platform registration number: RBR-6fgy76

From Chondrocytes to Chondrons, Maintenance of Phenotype and Matrix Production in a Composite 3D Hydrogel Scaffold.

Osteoarthritis (OA) is a degenerative disease characterized by articular cartilage (AC) degradation that affects more than 30 million people in the USA. OA is managed with symptom-alleviating medications. Matrix-assisted autologous chondrocyte transplantation (MACT) is a tissue-engineered option, but current products are expensive and lack mechanical tunability or processability to match defect mechanical properties and anatomical shapes. Here, we explore the efficacy of a biocompatible hydrogel-based scaffold composed of sodium alginate, gelatin, and gum Arabic—referred to by SA–GEL–GA—to support bovine articular chondrocyte (bAChs) proliferation, pericellular matrix (PCM), and extracellular matrix (ECM) production. bAChs were grown for 45 days in SA–GEL–GA. Their viability, their live/dead status, histological staining, biochemical assays for glycosaminoglycans (GAGs) and collagen, atomic force microscopy (AFM) imaging, and immunofluorescence staining of collagen I, collagen II, aggrecan, and CD44 were assessed. We found that SA–GEL–GA was not cytotoxic, induced cellular proliferation by 6.1-fold while maintaining a round morphology, and supported ECM deposition by producing 3.9-fold more GAG compared to day 0. bAChs transformed into chondrons and produced a PCM enriched with collagen II (3.4-fold), aggrecan (1.7-fold), and CD44 (1.3-fold) compared to day 0. In summary, SA–GEL–GA supported the proliferation, ECM production, and PCM production of bAChs in vitro.

Early Efficacy of Type I Collagen-Based Matrix-Assisted Autologous Chondrocyte Transplantation for the Treatment of Articular Cartilage Lesions.

Background: Articular cartilage is a complex structure that allows for low frictional gliding and effective shock absorption. Various sports injuries and inflammatory conditions can lead to lesions in the articular cartilage, which has limited regenerative potential. Type I collagen combined with autologous chondrocytes in a three-dimensional culture were used to induce the regeneration of single-layer autologous expanded chondrocytes without chondrogenic differentiation. Purpose: To assess the clinical, radiological, and histological changes following collagen-based autologous chondrocyte transplantation (MACT) for chondral knee lesions. Methods: The study prospectively enrolled 20 patients with symptomatic knee chondral lesions (mean size lesion was 2.41 ± 0.43 cm2, range: 2.0–3.4 cm2) in the lateral femoral condyle and femoral groove who underwent type I collagen-based MACT between July 2017 and July 2019. knee injury and osteoarthritis outcome score (KOOS) was assessed before the procedure, and periodic clinical follow-up was conducted every 3 months for a maximum of 12 months following the procedure and at 1-year intervals thereafter. Magnetic resonance imaging (MRI) T2 mapping of repaired cartilage was also used for the quantitative analysis of regeneration. In one patient, second-look arthroscopy was performed to assess cartilage regeneration characteristics, and a portion of regenerated cartilage was harvested for histological evaluation 12 months after implantation. Results: At pre-operation and at three, six, 12, and 24 months after the operation, KOOS pain, symptoms, daily life activities, sports and recreation, as well as the quality of life were significantly improved between every two time points. Hematoxylin and eosin (HE) staining indicated that the newly formed cartilage was comprised of naive chondrocytes. Safranin O-fast (S-O) green staining of the regenerated tissue revealed fibroblast-like cells surrounded by glycosaminoglycans. Immunohistochemistry (IHC) analysis indicated that collagen type II was uniformly distributed at the deep zone of articular cartilage and type I collagen mainly depositing in the superficial cartilage layer. The T2 values for repaired tissue gradually decreased, eventually approaching near-average values. Conclusion: The present study demonstrated that type I collagen-based MACT is a clinically effective treatment for improving functionality and pain levels. Histological evidence confirmed hyaline cartilage induction and showed that repaired cartilage tended to emerge from the deep to the superficial layer. The quantitative MRI T2 mapping test indicated that there still was a difference between the transplanted cartilage and the surrounding hyaline cartilage. Taken together, the current method represents an efficient approach for the restoration of knee cartilage lesions.

Arthroscopic Matrix-Assisted Autologous Chondrocyte Transplantation Versus Microfracture: A 6-Year Follow-up of a Prospective Randomized Trial

Background: Few randomized controlled trials with a midterm follow-up have compared matrix-assisted autologous chondrocyte transplantation (MACT) with microfracture (MFx) for knee cartilage lesions. Purpose: To compare the structural, clinical, and safety outcomes at midterm follow-up of MACT versus MFx for treating symptomatic knee cartilage lesions. Study Design: Randomized controlled trial; Level of evidence, 1. Methods: A total of 48 patients aged between 18 and 50 years, with 1- to 4-cm2 International Cartilage Repair Society (ICRS) grade III to IV knee chondral lesions, were randomized in a 1:1 ratio to the MACT and MFx treatment groups. A sequential prospective evaluation was performed using magnetic resonance imaging (MRI) T2 mapping, the MOCART (magnetic resonance observation of cartilage repair tissue) score, second-look arthroscopic surgery, patient-reported outcome measures, the responder rate (based on achieving the minimal clinically important difference for the Knee injury and Osteoarthritis Outcome Score [KOOS] pain and KOOS Sport/Recreation), adverse events, and treatment failure (defined as a reoperation because of symptoms caused by the primary defect and the detachment or absence of >50% of the repaired tissue during revision surgery). Results: Overall, 35 patients (18 MACT and 17 MFx) with a mean chondral lesion size of 1.8 ± 0.8 cm2 (range, 1-4 cm2) were followed up to a mean of 6 years postoperatively (range, 4-9 years). MACT demonstrated significantly better structural outcomes than MFx at 1 to 6 years postoperatively. At final follow-up, the MRI T2 mapping values of the repaired tissue were 37.7 ± 8.5 ms for MACT versus 46.4 ± 8.5 ms for MFx (P = .003), while the MOCART scores were 59.4 ± 17.3 and 42.4 ± 16.3, respectively (P = .006). More than 50% defect filling was seen in 95% of patients at 2 years and 82% at 6 years in the MACT group and in 67% at 2 years and 53% at 6 years in the MFx group. The second-look ICRS scores at 1 year were 10.7 ± 1.3 for MACT and 9.0 ± 1.8 for MFx (P = .001). Both groups showed significant clinical improvements at 6 years postoperatively compared with their preoperative status. Significant differences favoring the MACT group were observed at 2 years on the KOOS Activities of Daily Living (P = .043), at 4 years on all KOOS subscales (except Symptoms; P < .05) and the Tegner scale (P = .008), and at 6 years on the Tegner scale (P = .010). The responder rates at 6 years were 53% and 77% for MFx and MACT, respectively. There were no reported treatment failures after MACT; the failure rate was 8.3% in the MFx group. Neither group had serious adverse events related to treatment. Conclusion: Patients who underwent MACT had better structural outcomes than those who underwent MFx at 1 to 6 years postoperatively. Both groups of patients showed significant clinical improvements at final follow-up compared with their preoperative status. MACT showed superiority at 4 years for the majority of the KOOS subscales and for the Tegner scale at 4 to 6 years. The MACT group also had a higher responder rate and lower failure rate at final follow-up. Registration: NCT01947374 (ClinicalTrials.gov identifier).

Long-term Results of Arthroscopic Matrix-Assisted Autologous Chondrocyte Transplantation: A Prospective Follow-up at 15 Years

Background: Matrix-assisted autologous chondrocyte transplantation (MACT) procedures have been developed to overcome some of the limits of first-generation autologous chondrocyte implantation. However, while good autologous chondrocyte implantation results have been documented over time, data are scarce on the long-term MACT results. Purpose: To evaluate long-term clinical results of a large cohort of patients treated with hyaluronic acid–based MACT for articular cartilage defects of the knee. Study Design: Case series; Level of evidence, 4. Methods: A long-term evaluation of 113 patients was performed (91 men, 22 women; mean ± SD age, 29.0 ± 10.6 years) for 115 knees affected by chondral and osteochondral lesions of the femoral condyles and trochlea. Of these, 61 knees had undergone previous surgery, while other procedures were combined during the same operation in 48 knees. These patients were prospectively evaluated before surgery and at 2, 5, and 10 years after surgery, as well as at a final mean follow-up of 15 years (range, 12-18 years), with various clinical scores: International Knee Documentation Committee (IKDC), EuroQol visual analog scale (EQ-VAS), and Tegner. Both surgical and clinical failures were documented. Results: The IKDC subjective score increased from the basal level of 39.9 ± 14.6 (mean ± SD) to 77.3 ± 20.5 (P < .0005) at 2 years; results remained stable up to the 15-year follow-up (76.9 ± 20.5). EQ-VAS and Tegner scores showed a statistically significant improvement up to 10 years, with a further significant improvement at the final follow-up. A failure rate of 15.0% was documented, which increased to 21.7% when clinical failures were also considered. A worse outcome was found for older age (P < .0005), female sex (P = .002), degenerative lesions (P < .0005), longer duration of symptoms (P = .005), and previous surgery (P < .0005). Conclusion: Arthroscopic MACT offered good and long-lasting results that were stable over time and resulted in a limited number of failures and reinterventions for up to 15 years of follow-up. Several factors were identified as having a prognostic value: a worse outcome could be expected in older patients, female patients, those affected by lesions with a degenerative cause, those having a longer duration of symptoms, and patients who underwent previous surgery.

Matrix-assisted chondrocyte transplantation with bone grafting for knee osteochondritis dissecans: stable results at 12years.

To document clinical and radiological results of arthroscopic matrix-assisted autologous chondrocyte transplantation (MACT) combined with bone grafting for the treatment of knee osteochondritis dissecans (OCD) at long-term follow-up. Thirty-one knees in 29 patients (20.4 ± 5.7years) were treated for symptomatic unfixable OCD lesions (2.6 ± 1.1 cm2) and prospectively evaluated at 2, 5, and 12years (average, minimum 10years). Patients were evaluated over time with IKDC subjective score, EQ-VAS, and Tegner scores. Failures were also documented. At the final follow-up, MRI evaluation was performed in 14 knees with the MOCART 2.0 score. Beside 4 early failures, an overall clinical improvement was documented: the IKDC subjective score improved from 39.9 ± 16.8 to 82.1 ± 17.0 and 84.8 ± 17.2 at 2 and 5years, respectively (p < 0.0005), and remained stable for up to 12years (85.0 ± 20.2). EQ-VAS and Tegner scores presented similar trends, but patients did not reach their original activity level. Worse results were obtained for lesions bigger than 4 cm2. At MRI evaluation, subchondral bone abnormalities were detected in over 85% of knees at long-term follow-up. Arthroscopic bone grafting followed by MACT for unfixable knee OCD can offer a promising and stable clinical outcome over time in lesions smaller than 4 cm2, with a low failure rate of 13%. Persistent subchondral alterations were documented at long-term MRI evaluation, suggesting the limits of this approach to regenerate the osteochondral unit in patients affected by knee OCD. IV.

Mosaicplasty versus Matrix-Assisted Autologous Chondrocyte Transplantation for Knee Cartilage Defects: A Long-Term Clinical and Imaging Evaluation

Different surgical procedures have been proposed over the past few years to treat cartilage lesions. The aim of this study was to compare mosaicplasty and matrix-assisted autologous chondrocyte transplantation (MACT) at long-term follow-up. Forty-three patients were included: 20 mosaicplasty and 23 MACT. Patients were evaluated before and 12 years after surgery with the International Knee Documentation Committee (IKDC) subjective and objective scores for symptoms and function, and with the Tegner score for activity level. Magnetic Resonance Imaging (MRI) was used to evaluate repair tissue with the MOCART 2.0 score. Mosaicplasty and MACT showed good clinical and MRI results (IKDC subjective score 75.3 ± 21.8 and 81.8 ± 13.0, both p &lt; 0.0005). Mosaicplasty presented a 10% reoperation rate and a 25% overall failure rate, while no failures were documented in MACT (p = 0.016). While size did not influence the results in the MACT group, mosaicplasty presented lower IKDC objective and Tegner scores in lesions bigger than 2 cm2 (p = 0.031 and p = 0.014, respectively). Mosaicplasty and MACT presented both satisfactory clinical and MRI results at long-term follow-up. However, for larger lesions, MACT presented better subjective and objective outcomes, as well as less failures, which should be considered when choosing the most suitable treatment for patients affected by knee cartilage lesions.

Failures, Reoperations, and Improvement in Knee Symptoms Following Matrix-Assisted Autologous Chondrocyte Transplantation: A Meta-Analysis of Prospective Comparative Trials.

Though multiple high-level comparative studies have been performed for matrix-assisted autologous chondrocyte transplantation (MACT), quantitative reviews synthesizing best-available clinical evidence on the topic are lacking. A meta-analysis was performed of prospective randomized or nonrandomized comparative studies utilizing MACT. A total of 13 studies reporting 13 prospective trials (9 randomized, 5 nonrandomized) were included (658 total study participants at weighted mean 3.1 years follow-up, range 1-7.5 years). Reporting and methodological quality was moderate according to mean Coleman (59.4 SD 7.6), Delphi (3.0 SD 2.1), and MINORS (Methodological Index For Non-Randomized Studies) scores (20.2 SD 1.6). There was no evidence of small study or reporting bias. Effect sizes were not correlated with reporting quality, financial conflict of interest, sample size, year of publication, or length of follow-up (P > 0.05). Compared to microfracture, MACT had greater improvement in International Knee Documentation Committee (IKDC)-subjective and Knee Injury and Osteoarthritis Outcome Pain Subscale Score (KOOS)-pain scores in randomized studies (P < 0.05). Accelerated weight-bearing protocols (6 or 8 weeks) resulted in greater improvements in IKDC-subjective and KOOS-pain scores than standard protocols (8 or 11 weeks) for MACT in randomized studies (P < 0.05) with insufficient nonrandomized studies for pooled analysis. Compared to microfracture, MACT has no increased risk of clinical failure and superior improvement in patient-reported outcome scores. Compared to MACT with standardized postoperative weight-bearing protocols, accelerated weight-bearing protocols have no increased risk of clinical failure and show superior improvement in patient-reported outcome scores. There is limited evidence regarding MACT compared to first-generation autologous chondrocyte implantation, mosaicplasty, and mesenchymal stem cell therapy without compelling differences in outcomes.

A critical review of the literature on arthroscopic autologous matrix-induced chondrogenesis and matrix-assisted autologous chondrocyte transplantation for acetabular chondral defects

Background/Aims Significant acetabular chondral defects are a common clinical finding during hip arthroscopy, for which the current surgical management approach may be falling short. Autologous matrix-induced chondrogenesis and matrix-assisted autologous chondrocyte transplantation are two novel cell-regenerative therapies that offer a way to repair acetabular chondral defects. Methods A literature search of Cochrane, CINAHL, AMED and Medline (2007–2017) databases revealed seven relevant articles, but only four involved a hip arthroscopic approach. Results All included studies demonstrated some significant improvements in patient-reported outcomes for autologous matrix-induced chondrogenesis and matrix-assisted autologous chondrocyte transplantation. There appears to be a practical advantage in terms of cost and convenience for using one-step autologous matrix-induced chondrogenesis. However, over-reliance on one particular research team and use of small-scale retrospective studies constitutes low-level, non-generalisable evidence. Conclusions The literature does not convincingly support either of these new applications over and above any other currently available treatments. Further research is needed and should involve different centres, longer follow-ups and place a higher emphasis on methodological rigour in order to maximise the trustworthiness of results.

High Rate of Failure After Matrix-Assisted Autologous Chondrocyte Transplantation in Osteoarthritic Knees at 15 Years of Follow-up

Background: Chondral and osteochondral lesions in osteoarthritic knees of young patients remain challenging for orthopaedic surgeons, due to a combination of high functional demands and limited indications for joint replacement in this population. The possibility of extending the indication of cartilage regenerative procedures to these patients may allow the delay of metal resurfacing. Purpose: To analyze the potential of a cartilage regenerative approach to provide clinical benefits in young patients with osteoarthritic knees, documenting outcomes in terms of clinical improvement as well as failures, in particular regarding knee replacement, at long-term follow-up. Study Design: Case series; Level of evidence, 4. Methods: A total of 41 patients (mean ± SD age, 43 ± 9 years) who had cartilage lesions (4 ± 2 cm2) in osteoarthritic knees (Kellgren-Lawrence grade 2 or 3) underwent matrix-assisted autologous chondrocyte transplantation (MACT) as a salvage procedure. Patients were evaluated with International Knee Documentation Committee (IKDC), EuroQol visual analog scale (EQ-VAS), and Tegner scores before surgery; at 1, 2, 5, and 9 years after surgery; and at a final follow-up at a mean of 15 years after surgery (range, 14-18 years). Failures were also recorded. Results: An improvement was observed in all scores after surgery, but a progressive worsening over time was noted. The mean ± SD IKDC score improved from 38.6 ± 16.2 to a maximum of 66.0 ± 18.6 at 2 years (P < .0005), with a subsequent deterioration until the final evaluation at 56.2 ± 21.7 (P = .024). A similar trend was confirmed by EQ-VAS scores. Tegner scores improved at all follow-up points but did not reach the preinjury level. Patients who underwent combined surgery obtained significantly lower results. Only 13 patients (32%) had an IKDC score higher than 70. During the follow-up period, 21 patients underwent reoperation (18 with knee replacement) and 3 more patients experienced clinical failure, for a total surgical and clinical failure rate of 59% at 15 years. Conclusion: The use of cartilage regenerative surgical procedures, such as MACT, as salvage procedures for young, active patients affected by chondral and osteochondral lesions in osteoarthritic knees led to a limited improvement, with the majority of patients experiencing failure at long-term follow-up. Although a minor subpopulation experienced favorable and stable improvement, the use of MACT for such a challenging indication remains questionable until responding patients can be profiled.

Redifferentiation of Articular Chondrocytes by Hyperacute Serum and Platelet Rich Plasma in Collagen Type I Hydrogels.

Matrix-assisted autologous chondrocyte transplantation (MACT) for focal articular cartilage defects often fails to produce adequate cartilage-specific extracellular matrix in vitro and upon transplantation results in fibrocartilage due to dedifferentiation during cell expansion. This study aimed to redifferentiate the chondrocytes through supplementation of blood-products, such as hyperacute serum (HAS) and platelet-rich plasma (PRP) in vitro. Dedifferentiated monolayer chondrocytes embedded onto collagen type I hydrogels were redifferentiated through supplementation of 10% HAS or 10% PRP for 14 days in vitro under normoxia (20% O2) and hypoxia (4% O2). Cell proliferation was increased by supplementing HAS for 14 days (p < 0.05) or by interchanging from HAS to PRP during Days 7–14 (p < 0.05). Sulfated glycosaminoglycan (sGAG) content was deposited under both HAS, and PRP for 14 days and an interchange during Days 7–14 depleted the sGAG content to a certain extent. PRP enhanced the gene expression of anabolic markers COL2A1 and SOX9 (p < 0.05), whereas HAS enhanced COL1A1 production. An interchange led to reduction of COL1A1 and COL2A1 expression marked by increased MMP13 expression (p < 0.05). Chondrocytes secreted less IL-6 and more PDGF-BB under PRP for 14 days (p < 0.0.5). Hypoxia enhanced TGF-β1 and BMP-2 release in both HAS and PRP. Our study demonstrates a new approach for chondrocyte redifferentiation.

Low rate of return to pre-injury sport level in athletes after cartilage surgery: a 10-year follow-up study

Although articular surface is frequently damaged in athletes, results in terms of return to sport and level of activity after cartilage surgery remain rather unpredictable and poorly documented. The aim of this study is to evaluate the clinical outcome in terms of rate and level of return to sport in a group of competitive athletes who underwent matrix-assisted autologous chondrocyte transplantation (MACT), as well as the impact on their athletic career. Thirty-one male patients (mean age 22.6 ± 6.3years) p racticing sport at competitive level, affected by focal chondral/osteochondral lesions of the distal femur, were enrolled and treated with arthroscopic hyaluronan-based MACT. Patients were evaluated prospectively at 1-year intervals with the IKDC subjective, Tegner, and EuroQol VAS scores during their pre-operative visit and subsequent follow-ups for up to 10years. Return to sport in terms of level, time and maintenance of the activity level was documented, together with surgical or clinical failures. A marked improvement in all scores was found: IKDC increased from 40.3 ± 13.4 to 81.7 ± 14.4 (p < 0.0005) at 12 months; a further improvement was observed at 2years (89.5 ± 11.3; p = 0.008), then results were stable for up to 10years (87.3 ± 13.6). The analysis of return to sport documented that 64.5% of patients were able to return at a competitive level, and 58.1% performed at the same pre-injury level, with activity rates decreasing over time. The rate of patients returning to competitive level was 84% in those without previous surgery (vs. 33% who had undergone previous surgery), 87% for those with traumatic lesions (vs. 33% and 50% for degenerative and OCD lesions, respectively), and 92.3% in younger patients (age < 20years). Among these factors, multivariate analysis demonstrated that previous surgery was the single most influencing factor for returning to the same sport level (p = 0.010). These long-term results showed that chondrocyte-based regenerative approach has some limitations in terms of sport-related outcomes. The level of high functional knee restoration needed for such high-demanding activity level can be challenging to achieve, especially in patients with a more compromised joint homeostasis. Return to sport rate varies significantly according to specific patient and lesion characteristics and best results are obtained in young patients with traumatic lesions without previous surgery, which should be considered when treating athletes affected by cartilage lesions. IV.

Biologic Reconstruction of Full Sized Cartilage Defects of the Hip: A Guideline from the DGOU Group "Clinical Tissue Regeneration" and the Hip Committee of the AGA

Background Symptomatic pre-arthritic deformities such as femoroacetabular impingement (FAI) or hip dysplasia often lead to localised cartilage defects and subsequently to osteoarthritis. The present review of the working group "Clinical Tissue Regeneration" of the German Society of Orthopaedics and Trauma (DGOU) and the hip committee of the AGA (German speaking Society for Arthroscopy and Joint Surgery) provides an overview of current knowledge of the diagnosis and surgical treatment of cartilage defects, in order to infer appropriate therapy recommendations for the hip. Methods Review of FAI and resultant cartilage damage in the hip as reported in published study findings in the literature and discussion of the advantages and disadvantages of different surgical procedures to preserve the joint. Results Most published studies on the surgical treatment of cartilage damage in the hip report defects caused by cam-type FAI at the acetabulum. Development of these defects can be prevented by timely elimination of the relevant deformities. At present, current full-thickness cartilage defects are mostly treated with bone marrow-stimulating techniques such as microfracture (MFx), with or without a biomaterial, and matrix-assisted autologous chondrocyte transplantation (MACT). Osteochondral autologous transplantation (OAT) is not the treatment of choice for isolated full-thickness chondral defects at the hip, because of the unfavourable risk-benefit profile. Due to the relatively short history of cartilage repair surgery on the hip, the studies available on these procedures have low levels of evidence. However, it is already becoming obvious that the experience gained with the same procedures on the knee can be applied to the hip as well. For example, limited healing and regeneration of chondral defects after MFx can also be observed at the hip joint. Conclusions The cartilage surface of the acetabulum, where FAI-related chondral lesions appear, is considerably smaller than the weight-bearing cartilage surface of the knee joint. However, as in the knee joint, MACT is the therapy of choice for full-thickness cartilage defects of more than 1.5 - 2 cm2. Minimally invasive types of MACT (e.g. injectable chondrocyte implants) should be preferred in the hip joint. In cases where a single-stage procedure is indicated or there are other compelling reasons for not performing a MACT, a bone marrow-stimulating technique in combination with a biomaterial covering is preferable to standard MFx. For treatment of lesions smaller than 1.5 - 2 cm2 the indication for a single-stage procedure is wider. As with defects in the knee, it is not possible to determine a definite upper age limit for joint-preserving surgery or MACT in the hip, as the chronological age of patients does not necessarily correlate with their biological age or the condition of their joints. Advanced osteoarthritis of the hip is a contraindication for any kind of hip-preserving surgery. Long-term observations and prospective randomised studies like those carried out for other joints are necessary.

Matrix-Assisted Autologous Chondrocyte Transplantation in the Knee: A Systematic Review of Mid- to Long-Term Clinical Outcomes.

Background:Matrix-assisted autologous chondrocyte transplantation (MACT) is a surgical treatment option for articular cartilage lesions of the knee joint.Purpose:To investigate mid- to long-term clinical outcomes of MACT in the patellofemoral (PF) and tibiofemoral (TF) joints.Study Design:Systematic review; Level of evidence, 4.Methods:A systematic review was performed by searching PubMed, Embase, and the Cochrane Library to find studies evaluating minimum 5-year clinical outcomes of patients undergoing MACT in the knee joint. Search terms used were knee, matrix, and autologous chondrocyte. Patients were evaluated based on treatment failure rates, magnetic resonance imaging, and subjective outcome scores. Study methodology was assessed using the Modified Coleman Methodology Score (MCMS).Results:Ten studies (two level 1, one level 2, one level 3, and six level 4 evidence) were identified that met inclusion and exclusion criteria, for a total of 442 TF patients and 136 PF patients. Treatment failure occurred in 9.7% of all patients, including 4.7% of PF patients and 12.4% of TF patients (P = .037). Weighted averages of subjective outcome scores, including Knee injury and Osteoarthritis Outcome Score, Short Form–36 Health Survey, and Tegner scores, improved from baseline to latest follow-up in both TF and PF patients. The mean MCMS was found to be 57.4, with a standard deviation of 18.5.Conclusion:Patients undergoing MACT in the knee show favorable mid- to long-term clinical outcomes. A significantly higher treatment failure rate was found in patients undergoing MACT in the TF joint compared with the PF joint.

Age Is Not a Contraindication for Cartilage Surgery: A Critical Analysis of Standardized Outcomes at Long-term Follow-up

Background: Age is commonly accepted as a negative prognostic factor in cartilage surgery, and cutoff values of 30 to 40 years have been previously suggested as treatment indication. However, the lower outcome scores documented in older patients do not take in consideration the decreasing requirements of an aging joint. Purpose: To analyze the real effect of age in terms of recovery with respect to the functional level expected for different age categories of patients treated for cartilage lesions. Study Design: Cohort study; Level of evidence, 3. Methods: Patients with International Cartilage Repair Society (ICRS) grade 3-4 defects, involving femoral condyles or trochlea without osteoarthritis, were treated with arthroscopic matrix-assisted autologous chondrocyte transplantation; 157 patients were evaluated with IKDC subjective and Tegner scores before surgery and then after 2 and 10 years. Results were first evaluated by dividing patients into 2 age groups according to the generally approved cutoff value of 40 years. The analysis was then repeated after the scores of each patient were standardized according to the score achievable per the normative data in healthy patients for the corresponding sex and age category. Results: A significant improvement in all scores was observed. IKDC subjective score improved from 38.9 ± 14.5 to 74.7 ± 21.8 at 10 years. When a cutoff value of 40 years was used, older patients reached a significantly worse IKDC subjective value at 10 years (65.8 ± 24.3 vs 77.2 ± 20.4, P = .007). However, different findings were obtained after the scores were standardized. Although optimal results were still found in younger patients (<30 years), patients older than 40 years also appeared to benefit from the treatment, and no significant differences were noted compared with the younger population. Conclusion: The benefit of cartilage treatments in patients with increasing age but without any sign of osteoarthritis was higher than previously reported in literature. In fact, when the decreasing functional level expected by an aging population was considered, standardized results showed an overall benefit after cartilage treatment in patients older than 40 years that was not significantly different from the outcome achieved in younger patients. Thus, age is not a strict contraindication as previously suggested, and future studies should consider standardization of data to prove the real age limit of cartilage treatments.

Failure of Autologous Chondrocyte Implantation.

Level IV.

Long-term Results After Hyaluronan-based MACT for the Treatment of Cartilage Lesions of the Patellofemoral Joint

Background: Cartilage lesions of the patellofemoral joint are a challenging condition. Hyaluronan-based matrix-assisted autologous chondrocyte transplantation (MACT) has been shown to offer a significant improvement in the short term but has a tendency to worsen at midterm follow-up. Hypothesis: Patients treated with MACT for lesions of the articular surface of the patellofemoral joint will present further clinical worsening at long-term follow-up. Study Design: Case series; Level of evidence, 4. Methods: Thirty-two patients with full-thickness chondral lesions in the patellofemoral joint were treated with hyaluronan-based MACT and were prospectively evaluated preoperatively and at 2-, 5-, and 10-year follow-up. The mean defect size was 4.45 cm2. There were 20 lesions located on the patella and 8 on the trochlea, and 4 patients had multiple lesions: 3 with patellar and trochlear lesions and 1 with patellar and lateral femoral condyle lesions. Results were evaluated using International Knee Documentation Committee (IKDC) subjective scores, EuroQol visual analog scale (EQ VAS) scores, and Tegner scores. Surgical and clinical failures were documented. Results: All scores showed a statistically significant improvement at 2-, 5-, and 10-year follow-up with respect to the preoperative level. No worsening was observed at the last follow-up, and results were stable up to 10 years. The improvement in mean (±SD) outcome scores from preoperatively to 2-, 5-, and 10-year follow-up was as follows: IKDC, from 46.0 ± 19.8 to 77.1 ± 17.4, 72.0 ± 20.4, and 78.6 ± 16.4, respectively; Tegner, from 2.5 ± 1.4 to 4.7 ± 1.8, 4.7 ± 1.6, and 4.4 ± 1.5, respectively; and EQ VAS, from 56.9 ± 18.4 to 81.7 ± 13.2, 79.2 ± 17.9, and 78.9 ± 1.7, respectively. Four patients did not achieve significant clinical improvement, and 1 of these patients required further surgical treatment. All failures were female patients with patellar defects, and 3 of them had degenerative lesions and underwent a previous or combined realignment procedure. Conclusion: The clinical results of hyaluronan-based MACT treatment of chondral lesions of the patellofemoral joint do not worsen over time but remain stable and show a low rate of failure at long-term follow-up.

Cartilage failures. Systematic literature review, critical survey analysis, and definition.

While midterm results of matrix-assisted autologous chondrocyte transplantation (MACT) are now available, less attention has been paid to the evaluation of failures of this surgical approach. Aim of this study was to analyse how "failures" are generally defined in cartilage surgery, in order to understand how the survival rate may change according to different definitions of failure. A systematic review on MACT in the knee was conducted to report failure rates as well as different failure definitions in the available literature. Afterwards, we analysed the survival curve at 8.5-year follow-up of a survey of 193 patients treated with MACT. Using different definitions to identify failures, we compared how the survival rate changed according to the different definitions of failure. The systematic review on 93 papers showed that the average failure rate reported on 3,289 patients was 5.2 % at a mean 34 months of follow-up. However, 41 studies (44.1 %) did not even consider this aspect, and failures were variously defined, thus generating confusing data that make a meta-analysis or a study comparison meaningless. The failure analysis of the MACT survey showed that the survival curve changed significantly depending on the definition applied; in fact, the failure rate ranged from 3.6 to 33.7 %. According to a critical literature and survey analysis, we proposed a combined surgical- and improvement-based definition which led to a failure rate of 25.9 % at midterm/long-term follow-up. Nowadays, failure definitions of cartilage treatments differ in scientific articles, thus generating confusion and heterogeneous data even when applied to the same cohort of patients. While the literature analysis shows a low number of failures, this study demonstrated that if properly addressed with a comprehensive definition, the real failure rate of cartilage surgical procedures in the knee is higher than previously reported. Recognizing failures would give a better understanding and a more realistic prognosis to patients and physicians seeking treatment for cartilage lesions. IV.