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).

Arthroscopic Treatment of Patellar and Trochlear Cartilage Lesions with Matrix Encapsulated Chondrocyte Implantation versus Microfracture: Quantitative Assessment with MRI T2-Mapping and MOCART at 4-Year Follow-up.

METHODS: Seventeen patients aged 18 to 55 years with symptomatic full-thickness cartilage lesions on either patella or trochlea were treated with matrix autologous chondrocyte implantation (MACI) or microfracture (MF). Both procedures combined with unloading/realigning techniques. Clinical assessment and T2-mapping were evaluated at 48-months. RESULTS: Clinically results from pre-op to 48-months improved significantly in MACI and MF for Lysholm (p = 0.001, p = 0.001), IKDC-S (p = 0.001, p = 0.002), KOOS-P (p = 0.000, p = 0.002), KOOS-DLA (p = 0.002, p = 0.003), KOOS-Sports/Rec (p = 0.000, p = 0.004), KOOS-QoL (p = 0.000, p = 0.003), KOOS-symptoms (p = 0.001, p = 0.020), and Kujala (p = 0.000, p = 0.01), respectively. Tegner was significant between baseline and 48 months only for MACI (p < 0.008) compared with MF (p = 0.25). No significant difference was observed between groups for any score at 3, 12, 24, and 48-months (p > 0.05). T2-mapping values improved significantly over time in MACI compared with MF at 24 months (39.35 vs. 50.44, p = 0.007) and 48 months (36.54 vs. 48.37, p = 0.005). When comparing control values to MACI at 12-m (p = 0.714), 24-m (p = 0.175), and 48-m (p = 0.097), no significant difference was found. MOCART (Magnetic Resonance Observation of Cartilage Repair Tissue) score comparison gave no statistical difference between groups. CONCLUSIONS: Clinically both techniques improved significantly over time. However, quantitative assessment showed that only newly formed tissue with MACI technique improves significantly since 12-months and maintains stable values compared with native cartilage until 48-month follow-up. MF results were never comparable to those native values. Level of evidence II.

First Clinical Application of Polyurethane Meniscal Scaffolds with Mesenchymal Stem Cells and Assessment of Cartilage Quality with T2 Mapping at 12 Months.

BACKGROUND: Complex meniscal lesions often require meniscectomy with favorable results in the short term but a high risk of early osteoarthritis subsequently. Partial meniscectomy treated with meniscal substitutes may delay articular cartilage degeneration. PURPOSE: To evaluate the status of articular cartilage by T2 mapping after meniscal substitution with polyurethane scaffolds enriched with mesenchymal stem cells (MSC) and comparison with acellular scaffolds at 12 months. METHODS: Seventeen patients (18-50 years) with past meniscectomies were enrolled in 2 groups: (1) acellular polyurethane scaffold (APS) or (2) polyurethane scaffold enriched with MSC (MPS). Patients in the MPS group received filgrastim to stimulate MSC production, and CD90+ cells were obtained and cultured in the polyurethane scaffold. The scaffolds were implanted arthroscopically into partial meniscus defects. Concomitant injuries (articular cartilage lesions or cartilage lesions) were treated during the same procedure. Changes in the quality of articular cartilage were evaluated with T2 mapping in femur and tibia at 12 months. RESULTS: In tibial T2 mapping, values for the MPS group increased slightly at 9 months but returned to initial values at 12 months (P > 0.05). In the APS group, a clear decrease from 3 months to 12 months was observed (P > 0.05). This difference tended to be significantly lower in the APS group compared with the MPS group at the final time point (P = 0.18). In the femur, a slight increase in the MPS group (47.8 ± 3.4) compared with the APS group (45.3 ± 4.9) was observed (P > 0.05). CONCLUSION: Meniscal substitution with polyurethane scaffold maintains normal T2 mapping values in adjacent cartilage at 12 months. The addition of MSC did not show any advantage in the protection of articular cartilage over acellular scaffolds (P > 0.05).

Arthroscopic Matrix-Encapsulated Autologous Chondrocyte Implantation: A Pilot Multicenter Investigation in Latin America.

Objective. To evaluate minimum biosecurity parameters (MBP) for arthroscopic matrix-encapsulated autologous chondrocyte implantation (AMECI) based on patients' clinical outcomes, magnetic resonance imaging (MRI) T2-mapping, Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) score, and International Cartilage Repair Society (ICRS) second-look arthroscopic evaluation, laying the basis for a future multicenter study. Design. Pilot clinical study. We analyzed the logistics to perform AMECI to treat focal chondral lesions in different hospitals following strict biosecurity parameters related to tissue and construct transportation, chondrocyte isolation, and cell expansion. Patient progress was analyzed with patient-reported outcome measures, MRI T2-mapping, MOCART, and ICRS arthroscopic second-look evaluation. Results. Thirty-five lesions in 30 patients treated in 7 different hospitals were evaluated. Cell viability before implantation was >90%. Cell viability in construct remnants was 87% ± 11% at 24 hours, 75% ± 17.1% at 48 hours, and 60% ± 8% at 72 hours after implantation. Mean final follow-up was 37 months (12-72 months). Patients showed statistically significant improvement in all clinical scores and MOCART evaluations. MRI T2-mapping evaluation showed significant decrease in relaxation time from 61.2 ± 14.3 to 42.9 ± 7.2 ms (P < 0.05). Arthroscopic second-look evaluation showed grade II "near normal" tissue in 83% of patients. Two treatment failures were documented. Conclusions. It was feasible to perform AMECI in 7 different institutions in a large metropolitan area following our biosecurity measures without any implant-related complication. Treated patients showed improvement in clinical, MRI T2-mapping, and MOCART scores, as well as a low failure rate and a favorable ICRS arthroscopic evaluation at a mid-term follow-up. Level of Evidence. 2b.

Evolución clínica y análisis del estado del cartílago articular por mapeo-T2 y segunda vista artroscópica a veinticuatro meses del trasplante de menisco medial / Meniscal transplantation. Clinical evolution of articular cartilage for T2-mapping and second-look arthroscopic at twenty-four months

Introducción: El objetivo de nuestro trabajo es evaluar la evolución clínica, la condroprotección y la reacción inmunológica del trasplante de menisco (TM) con aloinjerto gama irradiado (GI) versus fresco congelado (FC) a veinticuatro meses. Materiales y métodos: veinte TM mediales en veinte pacientes, se evaluaron escalas de rodilla, Mapeo-T2 y segunda vista artroscópica, así como identificación de reacciones inmunológicas con la medición de citocinas inflamatorias por PCR en sangre y líquido sinovial. Trece trasplantes con injerto FC y siete GI, edad promedio de treinta y dos años. Resultados: mejoría significativa en escalas a veinticuatro meses: KOOS (dolor 67.80/79.30; síntomas 60.80/82.10; AVD 8.05/92.40; deportes 37/63.35; CV 28.90/71.30), Lysholm (62.20/85.80), IKDCs (50.17/72.12), EVA (3.35/0.4). El cartílago del compartimento trasplantado se mantuvo dentro de valores normales, sin diferencia a los veinticuatro meses (fémur: 33.43 versus 33.50 ms, p = 0.16) (tibia: 33.57 versus 34.35 ms, p = 0.21). Todos los pacientes mostraron integridad del injerto a los doce meses en la segunda vista artroscópica. Solo se observó aumento en las citoquinas plasmáticas IL-6 e IL-17 en un paciente del grupo GI, sin repercusión clínica. Conclusiones: mejoría clínica, adecuada integración y condroprotección significativa a veinticuatro meses en ambos tipos de injertos

Introduction: Our objective is to evaluate the clinical course, chondroprotection and immunological reaction of meniscus transplantation (TM) with gamma irradiated (GI) versus fresh frozen (FC) allograft at twenty-four months. Materials and methods: twenty medial TMs in twenty patients, knee scales, T2-mapping and second arthroscopic view were evaluated, as well as identification of immunological reactions with the measurement of inflammatory cytokines by PCR in blood and synovial fluid. Thirteen transplants with FC graft and seven GI grafts, average age of thirty-two years. Results: significant improvement on scales at twenty-four months: KOOS (pain 67.80 / 79.30; symptoms 60.80 / 82.10; AVD 8.05 / 92.40; sports 37 / 63.35; CV 28.90 / 71.30), Lysholm (62.20 / 85.80), IKDCs (50.17 / 72.12), EVA (3.35 / 0.4). The cartilage of the transplanted compartment remained within normal values, with no difference at twenty-four months (femur: 33.43 versus 33.50 ms, p = 0.16) (tibia: 33.57 versus 34.35 ms, p = 0.21). Conclusions: all patients showed integrity of the graft at twelve months in the second arthroscopic view. An increase in plasma cytokines IL-6 and IL-17 was only observed in one patient in the GI group, without clinical repercussion. Clinical improvement, adequate integration and significant chondroprotection at twenty-four months in both types of grafts

D14 repeat polymorphism of the asporin gene is associated with primary osteoarthritis of the knee in a Mexican Mestizo population.

BACKGROUND: Asporin is a novel extracellular matrix protein (ECM) with an important role in the development of osteoarthritis (OA), because it has been reported that functional polymorphisms in the aspartic acid repeat (D) of the asporin gene (ASPN) are associated with susceptibility to OA. AIM: This study was planned to investigate the association of the ASPN polymorphism with primary OA of the knee in a Mexican population, including several countryside regions. METHODS: We conducted a case-control study in which 93 cases with primary OA of the knee and 118 controls were included. Cases included patients > 40 years of age, with a body mass index (BMI) ≤ 27 and a radiologic score for OA of the knee of ≥ 2. Controls were subjects > 40 years of age with a radiologic score of < 2. The D repeat polymorphism was genotyped and logistic regression was developed to evaluate risk magnitude. RESULTS: The D14 allele was more common in our cases and was associated with an increased risk for developing OA, while the frequencies of the remaining alleles did not exhibit differences. CONCLUSION: Our data suggest that the D14 allele of the ASPN polymorphism could exert an influence on primary OA of the knee etiology in a Mexican Mestizo population.

Knee muscle strength correlates with joint cartilage T2 relaxation time in young participants with risk factors for osteoarthritis.

The objective of this study is to correlate T2 relaxation time (T2RT), measured by magnetic resonance imaging (MRI) with quadriceps and hamstring strength in young participants with risk factors for knee osteoarthritis (OA). A descriptive cross-sectional study was conducted with participants between 20 and 40 years of age, without diagnosis of knee OA. Their T2 relaxation time was measured through MRI, and their muscle strength (MS) was measured with an isokinetic dynamometer. Seventy-one participants were recruited, with an average age of 28.3 ± 5.5 years; 39 (55 %) were females. Negative correlations were found between T2RT and quadriceps peak torque (QPT) in males in the femur r = -0.46 (p = 0.01), tibia r = -0.49 (p = 0.02), and patella r = -0.44 (p = 0.01). In women, correlations were found among the femur r = -0.43 (p = 0.01), tibia r = -0.61 (p = 0.01), and patella r = -0.32 (p = 0.05) and among hamstring peak torque (HPT), in the femur r = -0.46 (p = 0.01), hamstring total work (HTW) r = -0.42 (p = 0.03), and tibia r = -0.33 (p = 0.04). Linear regression models showed good capacity to predict T2RT through QPT in both genders. The present study shows that early changes in femoral, tibial, and patellar cartilage are significantly correlated with MS, mainly QPT, and that these early changes might be explained by MS, which could play an important role in pre-clinical phases of the disease.

Dedifferentiated giant-cell tumor of bone with an undifferentiated round cell mesenchymal component.

The dedifferentiated giant-cell tumor of the bone is a very rare variant of the giant-cell tumor (GCT). We report the clinical, radiographic and histological findings of a dedifferentiated GCT in which the dedifferentiated component consisted of small round cells. We also comment on previously reported cases of dedifferentiated GCT, discuss the clinical implications of this dual histology, and analyze the information published about the coexistence of similar genetic abnormalities in GCT and small round cell tumors of the bone.

Analysis of estrogen receptor alpha gene haplotype in Mexican mestizo patients with primary osteoarthritis of the knee.

The aim of this work was to test the association between estrogen receptor α gene (ERα) polymorphism and primary osteoarthritis (OA) of the knee in Mexican mestizo patients. A case-control study was conducted. Cases were patients >40 years of age, with a body mass index (BMI) ≤ 27 and radiologic score for OA of the knee of ≥2 according to Kellgren-Lawrence scale, and controls were subjects >40 years age with a radiologic score <2. Two restriction fragment length polymorphisms, PvuII (T/C; rs2234693), and XbaI (A/G; rs9340799), of the ERα were analyzed. Allelic haplotypes were constructed and non-conditional logistic regression was developed to evaluate risk magnitude through odds ratios (ORs) and 95% Confidence intervals (95% CI). Three different allelic haplotypes were identified: TA; CG, and CA. Unadjusted analysis of the haplotypes did not show significant associations; nonetheless, when data were adjusted for gender, age, and BMI, a significant decrease risk was observed for CG haplotype (OR [95% CI]) = 0.5 (0.3-0.9)] (P = 0.04). These results suggest that ERα gene CG haplotype could be associated with a reduced risk of primary knee OA in Mexican mestizo population.

A COL2A1 gene polymorphism is related with advanced stages of osteoarthritis of the knee in Mexican Mestizo population.

Primary osteoarthritis (OA) is a multifactorial disease with several genetics factors involved. The COL2A1 gene is of particular interest because it encodes for the most abundant protein in articular cartilage. The aim was to evaluate the association of COL2A1 gene polymorphism with OA of the knee in Mexican Mestizo patients. A case-control study was conducted; cases comprised patients with a radiologic scoring > or = 2 and controls with a radiologic scoring <2. DNA was extracted from a peripheral blood sample, the polymorphic site of the COL2A1 gene was submitted to polymerase chain reaction (PCR), and the products were digested using PvuII restriction enzyme. For statistical analysis, a non-conditional logistic regression was developed. There were no associations among alleles in the overall sample, nevertheless, a significant association was found with p (Pp/pp) allele and OA of the knee grade 4 [odds ratio (OR), 95% confidence interval (CI 95%) 4.1 (1.2-14.6)] adjusted by gender, age, and body mass index (BMI). These results suggest an association of a COL2A1 gene polymorphism with advanced stages of OA of the knee in Mexican Mestizo population.