International Cartilage Repair Society Research Articles

Efficacy and safety of CARTIGROW® in patients with articular cartilage defects of the knee joint: a four year prospective studys

IntroductionResearch shows autologous chondrocyte implantation (ACI) is a promising treatment for articular cartilage lesions. In this study, we assessed mid-term efficacy and safety of gel-based ACI or autologous adult live cultured chondrocytes (CARTIGROW®) implantation in patients with cartilage defects of the knee joint.MethodsIn this prospective, open-label study, patients (19–38 years) with focal, international cartilage repair society grade III or IV articular cartilage defects of the knee joint were enroled at four centres across India from April 2015 to September 2015. Punch biopsy was conducted to harvest cartilage, from which chondrocytes were isolated and cultured, and the characterised chondrocytes were implanted into the cartilage defect. Key efficacy outcomes were assessed by quantitative changes in international knee documentation committee (IKDC), visual analogue scale (VAS) scores, and qualitative changes in magnetic resonance imaging at six months and four years from baseline.ResultsOf the14 patients enroled in the study, all patients completed the six month follow-up and 11 completed the four year follow-up. The IKDC score improved significantly from 32.84 ± 9.25 at baseline to 67.49 ± 13.03 at six months (mean difference [MD] 34.66 ± 13.00, p < 0.0001) and to 60.18 ± 10.33 at four years (MD 28.21 ± 15.14, p = 0.0001). The VAS score reduced from 72.00 ± 14.40 at baseline to 16.64 ± 17.03 at six months (MD 55.36 ± 24.50, p < 0.0001) and further to 12.72 ± 9.05 at four years (MD 62.09 ± 10.66, p < 0.0001). All patients showed improvement on MRI of the knee joint. No adverse events were reported.ConclusionAutologous adult live cultured chondrocytes (CARTIGROW®) implantation showed good mid-term efficacy in patients with cartilage defects of the knee joint with no side-effects.

Diagnostics of Articular Cartilage Damage Based on Generated Acoustic Signals Using ANN-Part I: Femoral-Tibial Joint.

Osteoarthritis (OA) is a chronic, progressive disease which has over 300 million cases each year. Some of the main symptoms of OA are pain, restriction of joint motion and stiffness of the joint. Early diagnosis and treatment can prolong painless joint function. Vibroarthrography (VAG) is a cheap, reproducible, non-invasive and easy-to-use tool which can be implemented in the diagnostic route. The aim of this study was to establish diagnostic accuracy and to identify the most accurate signal processing method for the detection of OA in knee joints. In this study, we have enrolled a total of 67 patients, 34 in a study group and 33 in a control group. All patients in the study group were referred for surgical treatment due to intraarticular lesions, and the control group consisted of healthy individuals without knee symptoms. Cartilage status was assessed during surgery according to the International Cartilage Repair Society (ICRS) and vibroarthrography was performed one day prior to surgery in the study group. Vibroarthrography was performed in an open and closed kinematic chain for the involved knees in the study and control group. Signals were acquired by two sensors placed on the medial and lateral joint line. Using the neighbourhood component analysis (NCA) algorithm, the selection of optimal signal measures was performed. Classification using artificial neural networks was performed for three variants: I—open kinetic chain, II—closed kinetic chain, and III—open and closed kinetic chain. Vibroarthrography showed high diagnostic accuracy in determining healthy cartilage from cartilage lesions, and the number of repetitions during examination can be reduced only to closed kinematic chain.

Outcome-Affecting Parameters of Hip Arthroscopy for Femoroacetabular Impingement with Concomitant Cartilage Damage-Data Analysis from the German Cartilage Registry.

This study aims to report on a prospectively collected, multicenter database of patients undergoing hip arthroscopy for femoroacetabular impingement syndrome (FAI) and concomitant cartilage damage (according to the International Cartilage Repair Society) and to assess the outcome-affecting parameters. In the study, 353 hips with up to 24 months’ follow-up were assessed by iHOT-33 scoring and achievement of the minimal clinically important difference (MCID) and patient acceptable symptom state (PASS) levels. Multiple and binary regression analyses were performed to identify factors related to (un-) favorable outcomes and to assess their clinical relevance with regard to achieving the MCID and PASS. Multiple regression yielded the parameters of male sex (p = 0.022) and lower body mass index (BMI) (p = 0.019) at 6 months, lower BMI (p = 0.022) and younger age (p = 0.022) at 12 months, and younger age at 24 months (p = 0.039) to be significantly associated with higher iHOT scoring. Male sex (p = 0.019) and lower BMI (p = 0.018) were significantly correlated with achievement of the PASS in binary regression at 6 months, whereas at 12 (p = 0.010) and at 24 (p = 0.003) only younger age was shown to be significantly correlated. None of the parameters was statistically associated with achievement of the MCID. As the parameters of younger age, male sex, and lower BMI were identified as temporarily correlated with a preferable outcome in general and with achievement of the PASS in particular, these findings help to preoperatively identify factors associated with (un-) favorable therapy results.

Repair of experimentally induced femoral chondral defect in a rabbit model using Lyophilized growth promoting factor extracted from horse blood platelets (L-GFequina)

Lyophilized equine platelet derived growth factors (LGF) is a novel advanced platelet rich protein growth factor. It has been successfully applied in various fields of regenerative medicine to treat a variety of inflammatory and degenerative musculoskeletal conditions. Our study aimed to evaluate the efficacy of intraarticularly injected LGF for the remedy of articular cartilage injury, commonly characterized by progressive pain and loss of joint function in osteoarthritic rabbits. Full-thickness cylindrical cartilage defects were generated in both femoral condylar articular surfaces in twenty rabbits. The left joint of all animals was injected with the adjuvant as a self-control negative, while the right joint was injected by LGF. Four- and eight-weeks post-surgery, the femoral condyles were harvested, and assessed grossly, microscopically and immunohistochemically. Cytokines (TNF-α, IL-1β, PDGF and TGF-β1) contents of the chondral defects were quantified by ELISA as well as the gene expression of Col I and Col II via RT-qPCR. The LGF treated defects showed significant higher ICRS (International cartilage repair society) healing scores of cartilaginous regeneration with a significant higher histological healing score on using O'Driscoll histological scoring system. Additionally, LGF significantly lowered the levels of the pro-inflammatory cytokines TNF-α and IL-1β. It also significantly increased the anabolic and angiogenic growth factors (PDGF and TGF-β1), and significantly elevated the expression of chondrogenic-related marker genes; Col I and Col II. The current study reveals that LGF improves chondral healing and thus it can be a superior nominee as an adjunctive therapy to positively influence regeneration of chondral defects in osteoarthritic patients.

Autologous Osteochondral Grafts Result in Improved Clinical Outcomes in Patients With Early Knee Osteoarthritis

PurposeTo determine whether autologous osteochondral grafts improve clinical outcomes in early knee osteoarthritis (EKOA) and whether the grafts prevent progression of radiographic joint degeneration.MethodsIn this study, we identified patients older than 40 years with EKOA having no traumatic events, with grade 0, 1, or 2 on the Kellgren-Lawrence (KL) classification and more than grade 3 of cartilage degeneration according to the International Cartilage Repair Society scale. Recipient sites were as follows: 14 patellofemoral (PF3) joint, 18 medial femoral condyle (M1), and 6 lateral femoral condyle (L2). Japanese Orthopedic Association (JOA) score and International Knee Documentation (IKDC) subjective score (SUB) were examined as clinical outcomes.ResultsThe study included 31 knees in 31 patients who underwent autologous osteochondral grafts for EKOA and more than two years follow-up. The sample included 15 men and 16 women. The mean operative age was 56.0 years, and the mean follow-up period was 76 months (range, 24-170 months). In the preoperative period, JOA and SUB were 73.9 and 49.5, respectively. At follow-up, the JOA and SUB scores were 93.7 and 84.5, respectively. The differences were statistically significant. Progression of KL classification occurred in 0% of the PF3 group, 17% of the L2 group, and 33% of the M1 group. The outcomes of the M1 group significantly became worse (P = .0381) than those of the L2 and the PF3 groups, and the PF3 group significantly maintained good clinical outcomes (P = .0334).ConclusionAutologous osteochondral grafts for degenerated cartilage improved clinical outcomes of EKOA even if the recipient had cartilage degeneration, and not trauma. The PF3 group maintained significantly good clinical outcomes, and the M1 group became significantly worse.

Osteochondral regeneration of the femoral medial condyle by using a scaffold-free 3D construct of synovial membrane-derived mesenchymal stem cells in horses

BackgroundMedical interventions for subchondral bone cysts in horses have been extensively studied. This study investigated the regeneration of articular cartilage and subchondral bone with scaffold-free three-dimensional (3D) constructs of equine synovial membrane-derived mesenchymal stem cells (SM-MSCs) isolated from three ponies and expanded until over 1.0 × 107 cells at passage 2 (P2).ResultsSM-MSCs were strongly positive for CD11a/CD18, CD44, and major histocompatibility complex (MHC) class I; moderately positive for CD90, CD105, and MHC class II; and negative for CD34 and CD45 on flow cytometry and differentiated into osteogenic, chondrogenic, and adipogenic lineages in the tri-lineage differentiation assay. After culturing SM-MSCs until P3, we prepared a construct (diameter, 6.3 mm; height, 5.0 mm) comprising approximately 1920 spheroids containing 3.0 × 104 cells each. This construct was confirmed to be positive for type I collagen and negative for type II collagen, Alcian blue, and Safranin-O upon histological analysis and was subsequently implanted into an osteochondral defect (diameter, 6.8 mm; depth, 5.0 mm) at the right femoral medial condyle. The contralateral (left femoral) defect served as the control. At 3 and 6 months after surgery, the radiolucent volume (RV, mm3) of the defects was calculated based on multiplanar reconstruction of computed tomography (CT) images. Magnetic resonance (MR) images were evaluated using a modified two-dimensional MR observation of cartilage repair tissue (MOCART) grading system, while macroscopic (gross) and microscopic histological characteristics were scored according to the International Cartilage Repair Society (ICRS) scale. Compared to the control sites, the implanted defects showed lower RV percentages, better total MOCART scores, higher average gross scores, and higher average histological scores.ConclusionsImplantation of a scaffold-free 3D-construct of SM-MSCs into an osteochondral defect could regenerate the original structure of the cartilage and subchondral bone over 6 months post-surgery in horses, indicating the potential of this technique in treating equine subchondral bone cysts.

Comparison Between Arthroscopic and Histological International Cartilage Repair Society Scoring Systems in Porcine Cartilage Repair Model.

ObjectiveThe arthroscopic and histological International Cartilage Repair Society (ICRS) scores are designed to evaluate cartilage repair quality. Arthroscopic ICRS score can give a maximum score of 12 and the histological score can give values between 0% and 100% for each of its 14 subscores. This study compares these methods in an animal cartilage repair model. This study hypothesizes that there is a significant correlation between these methods.DesignA chondral defect was made in the medial femoral condyle of 18 pigs. Five weeks later, 9 pigs were treated with a novel recombinant human type III collagen/polylactide scaffold and 9 were left untreated to heal spontaneously. After 4 months, the medial condyles were evaluated with a simulated arthroscopy using the ICRS scoring system followed by a histological ICRS scoring.ResultsThis porcine cartilage repair model produced repaired cartilage tissue ranging from good to poor repair tissue quality. The mean arthroscopic ICRS total score was 6.8 (SD = 2.2). Histological ICRS overall assessment subscore was 38.2 (SD = 31.1) and histological ICRS average points were 60.5 (SD = 19.5). Arthroscopic ICRS compared with histological ICRS average points or its overall assessment subscore showed moderate correlation (r = 0.49 and r = 0.50, respectively). The interrater reliability with the intraclass correlation coefficients for arthroscopic ICRS total scores, histological ICRS overall assessment subscore, and ICRS average points showed moderate to excellent reliability.ConclusionsArthroscopic and histological ICRS scoring methods for repaired articular cartilage show a moderate correlation in the animal cartilage repair model.

The Effect of Single vs Serial Platelet-Rich Plasma Injection in Osteochondral Lesions Treated with Microfracture: An in Vivo Rabbit Model

Category:Ankle; Basic Sciences/BiologicsIntroduction/Purpose:Platelet-rich plasma (PRP) has gained increasing interest as a potential therapeutic augment for decreasing inflammation and enhancing healing after cartilage injury. However, it remains unknown whether osteochondral repair outcomes benefit from multiple PRP injections. We performed this animal study to investigate the effects of serial PRP injections on cartilage repair tissue, subchondral bone remodeling, and joint inflammation.Methods:Forty-eight adult New Zealand White rabbits were randomly assigned to receive either one (1P), two (2P), or three (3P) PRP injections. Cylindrical full-thickness cartilage defects with subsequent microdrilling were created on the central medial femoral condyle of both knees. PRP injections were provided on the day of surgery and every 2 weeks thereafter until the assigned number of injections was achieved for each group. Rabbits in each group were euthanized at 3, 6, or 12 weeks postoperatively. Cartilage repair tissue was assessed using the International Cartilage Repair Society (ICRS) macroscopic and modified ICRS histological scoring systems. Subchondral bone remodeling was evaluated by micro-computer tomography (µCT) analysis. Joint inflammatory cytokines including IL-1, IL-1ra, IL-6, IL-8, TNFα, and TGFβ were assessed by quantitative polymerase chain reaction.Results:Macroscopic assessment at 3 and 6 weeks demonstrated improved mean ICRS macroscopic scores in the PRP groups compared with the control group, although this difference was not significant. The mean ICRS macroscopic score at 12 weeks in Group 3P was significantly lower than the control, but there was no significant difference compared with Group 1P and Group 2P (Control: 6.1+-3.3, Group 1P: 3.4+-2.7, Group 2P: 4.2+-2.9, Group 3P: 0.7+-1.5). The mean modified ICRS histological score was significantly higher at each time point for the PRP groups compared with the control group, but there was no significant difference in the scores among PRP groups. There were no significant differences in outcomes for the characteristics evaluated by µCT nor inflammatory cytokine levels among each group at each time point.Conclusion:Serial PRP injections, as compared to a single PRP injection, do not have a significant impact on cartilage repair tissue nor inflammatory cytokine levels at 12 weeks after surgery in an in vivo animal model. Further work is necessary to determine the effect of single versus serial PRP injections on cartilage repair tissue in humans.

ACL Reconstruction Patients Have Increased Risk of Knee Arthroplasty at 15 Years of Follow-up: Data from the Norwegian Knee Ligament Register and the Norwegian Arthroplasty Register from 2004 to 2020.

Background:Anterior cruciate ligament (ACL) injury is considered a risk factor for osteoarthritis. The primary aim of the present study was to investigate the cumulative risk of, and risk factors associated with, a subsequent knee arthroplasty after an ACL reconstruction at up to 15 years of follow-up. The secondary aim was to compare the relative risk of knee arthroplasty after ACL reconstruction compared with that in the general population.Methods:Data were analyzed by combining data from 2 national registries, the Norwegian Knee Ligament Register and the Norwegian Arthroplasty Register. The cumulative risk of knee arthroplasty after undergoing ACL reconstruction was calculated as 1 minus the corresponding Kaplan-Meier estimate, and possible risk factors for knee arthroplasty after ACL reconstruction were assessed in a Cox regression model with hazard ratios (HRs) as estimated effect measurements. The relative risk of knee arthroplasty for patients managed with ACL reconstruction as compared with that in the general population was calculated in stratified age groups.Results:From the study population of 27,122 knees, 115 knees underwent knee arthroplasty. We found a 1.1% (95% confidence interval [CI], 0.9 to 1.4) cumulative risk of knee arthroplasty 15 years after ACL reconstruction. Deep cartilage injury, ICRS (International Cartilage Repair Society) grade 3 to 4 (HR, 4.8; 95% CI, 3.1 to 7.6), revision of the ACL (HR, 3.9; 95% CI, 2.2 to 7.1), and a 2-year postoperative KOOS Sport/Recreation subscore of <44 (HR, 3.1; 95% CI, 1.5 to 6.2) were important risk factors for knee arthroplasty. We found a higher risk of knee arthroplasty at the age of 30 to 39 years after a previous ACL reconstruction as compared with the general population (relative risk, 3.3; 95% CI, 1.6 to 6.7).Conclusions:Fifteen years after an ACL reconstruction, the overall cumulative risk of knee arthroplasty was 1.1%. Cartilage injury at the time of ACL reconstruction, revision ACL reconstruction, and a KOOS Sport/Recreation subscore of <44 (at 2 years postoperatively) were major risk factors for subsequent knee arthroplasty. We found a 3.3-times higher risk of knee arthroplasty at the age of 30 to 39 years after a previous ACL reconstruction as compared with that in the general population.Level of Evidence:Prognostic Level II. See Instructions for Authors for a complete description of levels of evidence.

A rabbit femoral trochlear defect model for chondral and osteochondral regeneration

Articular cartilage degeneration represents one of the main features of osteoarthritis. Recently, novel approaches based on biomaterials have been successfully applied to osteochondral regeneration. Our study was carried out on rabbits to assess a model of articular cartilage damage to test biomaterials for osteochondral regeneration. We created osteochondral defects on the surface of the trochlear groove area of the femurs in 15 white male New Zealand rabbits of the size of 3 mm × 3 mm (diameter × depth). Rabbits were then monitored and samples were collected 2 weeks, 4 weeks, and 6 weeks after the operation. The reconstruction of defects was assessed macroscopically according to the International Cartilage Repair Society (ICRS) scale and radiography (X-ray). For microscopic evaluation, haematoxylin-eosin staining and safranin O staining were used. The defects were repaired by regenerative tissue, and the recovery results gradually increased after 2 weeks, 4 weeks, and 6 weeks, showing both microscopically and macroscopically. However, the regenerative tissue was mainly fibrous connective tissue, not cartilage or bone. This is a model of articular cartilage damage that is suitable for early screening of preclinical studies related to osteochondral regeneration using biomaterials.

Second-Look Arthroscopic Findings and Clinical Outcomes after Adipose-Derived Regenerative Cell Injection in Knee Osteoarthritis.

BackgroundTo evaluate the clinical outcomes and second-look arthroscopic findings after intra-articular adipose-derived regenerative cell (ADRC) injection as treatment for knee osteoarthritis (OA).MethodsADRCs were administered to 11 patients (19 knees; mean age, 61.7 years) with knee OA. Subcutaneous adipose tissue was harvested by liposuction from both thighs, and arthroscopic lavage was performed, followed by ADRC injection (mean dose, 1.40 × 107 cells) into the synovial fluid. Outcome measures included the Knee Injury and Osteoarthritis Outcome Score, Lysholm score, and visual analog scale score. Arthroscopic examinations were performed to assess the International Cartilage Repair Society cartilage injury grade preoperatively and overall repair postoperatively. Noninvasive assessments were performed at baseline and at 1-, 3-, and 6-month follow-ups; arthroscopic assessments were performed at baseline and at 6 months.ResultsAll outcome measures significantly improved after treatment. This improvement was evident 1 month after treatment and was sustained until the 6-month follow-up. Data from second-look arthroscopy showed better repair in low-grade cartilage lesions than in lesions with a greater degree of damage. No patients demonstrated worsening of Kellgren-Lawrence grade, and none underwent total knee arthroplasty during this period.ConclusionsClinical outcomes were improved in patients with knee OA after ADRC administration. Cartilage regeneration was more effective in smaller damaged lesions than in bigger lesions.

Second-Look Arthroscopy after Surgery for Osteochondral Lesions of the Talus: A Systematic Review and Meta-Analysis

Category:AnkleIntroduction/Purpose:The primary aim was to assess and compare cartilage quality after different surgical interventions evaluated by second-look arthroscopy (SLA). Secondary aims were to report concomitant diagnoses found during SLA, and to correlate the cartilage quality with clinical- and radiological outcomes.Methods:A literature search was performed through PubMed, Embase (Ovid), and Cochrane Library. The primary outcome was the difference of cartilage quality as assessed with SLA between different surgical interventions. The Moderator analysis was used to calculate differences between treatment groups. Associated 95% confidence intervals (CI) were calculated with the Clopper- Pearson interval. Additionally, correlations between the cartilage quality and clinical- or radiological outcomes were calculated and percentages of concomitant diagnoses per treatment group were reported.Results:Nineteen studies comprising 447 ankles having undergone SLA 14 months after the initial surgery were included. The cartilage quality success rate for bone marrow stimulation (BMS) was 53% (95% CI 38-68%), for Retrograde Drilling (RD) 100% (95% CI 66-100%, for fixation (FIX) 92% (95% CI 70-89%), for Osteochondral Transplantation (OCT) 94% (95% CI 69-99%) and Chondrogenesis-Inducing Techniques (CT) this was 81% (95% CI 70-89%). The success rate of BMS was significantly lower than FIX, OCT and CIT. There were no significant differences in success rates between the other treatment options. The incidence of concomitant diagnoses found during second-look arthroscopy differed among different treatment strategies. For BMS, a positive correlation was found between the International Cartilage Repair Society score (ICRS) and AOFAS-scores (rc =.67, p <0.01). For OCT, no significant correlation was found between the MOCART score and the ICRS (rc =.36, p =.23).Conclusion:Bone marrow stimulation yields inferior cartilage quality as assessed with SLA in comparison to fixation, osteo(chondral) transplantation and cartilage implementation. The role of the quality of the subchondral bone and its repair must be highlighted concerning correlation with clinical outcomes and long-term success as well as prevention of development of osteo- arthritis.

Hypothermically Stored Amniotic Membrane for the Treatment of Cartilage Lesions: A Single-Arm Prospective Study with 2-Year Follow-Up.

ObjectiveThe purpose of this study was to determine the safety and efficacy of hypothermically stored amniotic membrane (HSAM) for the treatment of cartilage lesions of the knee using imaging, patient-reported outcomes (PROs), second-look arthroscopy, and histology. Patients were treated with HSAM and followed for 2 years.DesignSubjects with focal chondral lesions of the femur (International Cartilage Repair Society grade 3-4) were enrolled in this single-arm prospective study. Standard of care imaging was completed. PROs, including the Knee Injury and Osteoarthritis Outcome Score (KOOS), Marx Activity Scale, and Visual Analog Scale (VAS), were collected at baseline and at 3, 6, 12, 18, and 24 months. Three subjects underwent an optional arthroscopy and biopsy of the repair at 24 months.ResultsTen subjects were enrolled and completed the study. At 24 months, KOOS Sports & Recreation improved 173.3% and Quality of Life improved 195.3% from baseline. Marx Activity Scale increased 266.8% from 12 to 24 months. VAS scores improved 84.8% and 81.0% from baseline to 24 months for average and maximum pain. Modified Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) scoring showed that 7 of 10 subjects had complete defect repair and filling by 24 months. Biopsy staining for collagen II revealed integration and remodeling of HSAM into a mix of hyaline-like cartilage and fibrocartilage matrix.ConclusionThis study provides evidence supporting the safety and efficacy of HSAM for treating symptomatic cartilage lesions. Subjects showed a high degree of defect fill and integration with the native cartilage and reported improvements in pain and function post-treatment. Results provide important original data for future clinical trials.

Safety and Efficacy of Matrix-Associated Autologous Chondrocyte Implantation With Spheroids for Patellofemoral or Tibiofemoral Defects: A 5-Year Follow-up of a Phase 2, Dose-Confirmation Trial.

Background:Matrix-associated autologous chondrocyte implantation (ACI) is a well-established treatment for cartilage defects. High-level evidence at midterm follow-up is limited, especially for ACI using spheroids (spherical aggregates of ex vivo expanded human autologous chondrocytes and self-synthesized extracellular matrix).Purpose:To assess the safety and efficacy of 3-dimensional matrix-associated ACI using spheroids to treat medium to large cartilage defects on different locations in the knee joint (patella, trochlea, and femoral condyle) at 5-year follow-up.Study Design:Cohort study; Level of evidence, 2.Methods:A total of 75 patients aged 18 to 50 years with medium to large (4-10 cm2), isolated, single cartilage defects, International Cartilage Repair Society grade 3 or 4, were randomized on a single-blind basis to treatment with ACI at 1 of 3 dose levels: 3 to 7, 10 to 30, or 40 to 70 spheroids/cm2 of defect size. Outcomes were assessed via changes from baseline Knee injury and Osteoarthritis Outcome Score (KOOS), International Knee Documentation Committee score, and modified Lysholm assessments at 1- and 5-year follow-up. Structural repair was evaluated using MOCART (magnetic resonance observation of cartilage repair tissue) score. Treatment-related adverse events were assessed up to 5 years for all patients. The overall KOOS at 12 months was assessed for superiority versus baseline in a 1-sample, 2-sided t test.Results:A total of 73 patients were treated: 24 in the low-dose group, 25 in the medium-dose group, and 24 in the high-dose group. The overall KOOS improved from 57.0 ± 15.2 at baseline to 73.4 ± 17.3 at 1-year follow-up (P < .0001) and 76.9 ± 19.3 at 5-year follow-up (P < .0001), independent of the applied dose. The different defect locations (patella, trochlea, and weightbearing part of the femoral condyles; P = .2216) and defect sizes (P = .8706) showed comparable clinical improvement. No differences between the various doses were observed. The overall treatment failure rate until 5 years was 4%. Most treatment-related adverse events occurred within the first 12 months after implantation, with the most frequent adverse reactions being joint effusion (n = 71), arthralgia (n = 14), and joint swelling (n = 9).Conclusion:ACI using spheroids was safe and effective for defect sizes up to 10 cm2 and showed maintenance of efficacy up to 5 years for all 3 doses that were investigated.Registration:NCT01225575 (ClinicalTrials.gov identifier); 2009-016816-20 (EudraCT number).

Are the functional outcomes really inferior following unicondylar knee arthroplasty in patients with partial-thickness cartilage loss?

The main indication for medial Unicondylar Knee Arthroplasty (UKA) is Full-Thickness Cartilage Loss (FTCL) in the isolated medial compartment of the knee. However, controversial outcomes were reported in patients with Partial-Thickness Cartilage Loss (PTCL). The aim of this study is to compare PTCL and FTCL based on intraoperative findings in medial UKA in terms of functional outcomes and complication rates requiring reoperation and revision. Two hundred and fifteen knees of 174 patients who underwent mobile-bearing UKA between October 2014 and February 2018 for the diagnosis of symptomatic anteromedial osteoarthritis were evaluated retrospectively. A single senior surgeon evaluated the type of cartilage loss in the medial compartment intraoperatively according to the International Cartilage Repair Society classification system. Clinical outcomes were evaluated using Oxford Knee Score (OKS) and International Knee Documentation Committee (IKDC) score pre- and post-operatively at the last follow-up. Patients with PTCL and FTCL were compared in terms of their pre- and post-operative OKS and IKDC scores, and their improvements, as well as complication rates requiring reoperation and revision. The mean follow-up time was 33.1 ± 5.3 months. The PTCL (n = 80) and FTCL (n = 135) groups were statistically similar in terms of age (P = 0.41), gender (P = 0.921), body mass index (P = 0.165), bilaterality (P = 0.111), American Society of Anesthesiologists physical status (P = 0.218), Charlson Comorbidity Index (P = 0.74), and post-operative follow-up (P = 0.167). The mean pre-operative OKS and IKDC scores were improved from 24.5 ± 4.1 and 39.9 ± 5 to 40.3 ± 3.6 and 73.9 ± 7.7 at the last follow-up, respectively (P < 0.001). Pre-operative OKS and IKDC scores were superior in favor of the PTCL group. However, no significant difference was found between the groups in terms of post-operative OKS (P = 0.53) and IKDC (P = 0.975) scores, and their improvements (OKS, P = 0.953; IKDC, P = 0.536). The complication rates requiring reoperation was 5% (n = 11) in all patients. Of these, 9% (n = 7) from the PTCL group and 3% (n = 4) from the FTCL group were reoperated. Nevertheless, no significant difference was found between the groups (P = 0.105). In PTCL, medial UKA is a reliable surgery in terms of functional outcomes, the same as in FTCL; however, its complication rates requiring reoperation is higher without statistical significance. Level III, Therapeutic Study.

Preoperative Evaluation and Surgical Simulation for Osteochondritis Dissecans of the Elbow Using Three-Dimensional MRI-CT Image Fusion Images.

We used our novel three-dimensional magnetic resonance imaging-computed tomography fusion images (3D MRI-CT fusion images; MCFIs) for detailed preoperative lesion evaluation and surgical simulation in osteochondritis dissecans (OCD) of the elbow. Herein, we introduce our procedure and report the findings of the assessment of its utility. We enrolled 16 men (mean age: 14.0 years) and performed preoperative MRI using 7 kg axial traction with a 3-Tesla imager and CT. Three-dimensional-MRI models of the humerus and articular cartilage and a 3D-CT model of the humerus were constructed. We created MCFIs using both models. We validated the findings obtained from the MCFIs and intraoperative findings using the following items: articular cartilage fissures and defects, articular surface deformities, vertical and horizontal lesion diameters, the International Cartilage Repair Society (ICRS) classification, and surgical procedures. The MCFIs accurately reproduced the lesions and correctly matched the ICRS classification in 93.5% of cases. Surgery was performed as simulated in all cases. Preoperatively measured lesion diameters exhibited no significant differences compared to the intraoperative measurements. MCFIs were useful in the evaluation of OCD lesions and detailed preoperative surgical simulation through accurate reproduction of 3D structural details of the lesions.

Icariin accelerates cartilage defect repair by promoting chondrogenic differentiation of BMSCs under conditions of oxygen-glucose deprivation.

This study explored the role played by combined ICA and bone mesenchymal stem cells (BMSCs) in repairing rabbit knee cartilage defects. Firstly, rabbit BMSCs were isolated and used to construct an in vitro cellular model of oxygen‐glucose deprivation/reoxygenation (OGD/R). Subsequently, ICA processing, Alcian blue staining, immunofluorescence and Western blot studies were performed to evaluate the ability of BMSCs to display signs of chondrogenic differentiation. Furthermore, a rabbit knee cartilage injury model was established in vivo. International Cartilage Repair Society (ICRS) macroscopic evaluations, H&E, Alcian blue and EdU staining, as well as immunohistochemistry, were analysed cartilage repair and pathological condition of the knee cartilage tissue. Our in vitro results showed that ICA promoted the chondrogenic differentiation of BMSCs, as well as aggrecan (AGR), bone morphogenetic protein 2 (BMP2) and COL2A1 protein expression in BMSCs. In vivo experiments showed that rabbits in the BMSCs or ICA treatment group had higher ICRS scores and displayed a better restoration of cartilage‐like tissue and chondrocyte expression on the surface of their cartilage defects. In conclusion, ICA or BMSCs alone could repair rabbit knee cartilage damage, and combined treatment with ICA and BMSCs showed a better ability to repair rabbit knee cartilage damage.

Zonal-Layered Chondrocyte Sheets for Repairment of Full-Thickness Articular Cartilage Defect: A Mini-Pig Model

The cell sheet technique is a promising approach for tissue engineering, and the present study is aimed to determine a better configuration of cell sheets for cartilage repair. For stratified chondrocyte sheets (S-CS), articular chondrocytes isolated from superficial, middle, and deep zones were stacked accordingly. Heterogeneous chondrocyte sheets (H-CS) were obtained by mixing zonal chondrocytes. The expressions of chondrocytes, cytokine markers, and glycosaminoglycan (GAG) production were assessed in an in vitro assay. The curative effect was investigated in an in vivo porcine osteochondral defect model. The S-CS showed a higher cell viability, proliferation rate, expression of chondrogenic markers, secretion of tissue inhibitor of metalloproteinase, and GAG production level than the H-CS group. The expressions of ECM destruction enzyme and proinflammatory cytokines were lower in the S-CS group. In the mini-pigs articular cartilage defect model, the S-CS group had a higher International Cartilage Repair Society (ICRS) macroscopic score and displayed a zonal structure that more closely resembled the native cartilage than those implanted with the H-CS. Our study demonstrated that the application of the S-CS increased the hyaline cartilage formation and improved the surgical outcome of chondrocyte implication, offering a better tissue engineering strategy for treating articular cartilage defects.

Treatment of knee osteochondritis dissecans with autologous tendon transplantation: Clinical and radiological results.

BACKGROUNDDefect treatment with tendon autograft in osteochondral lesions has been published in the literature with an experimental study in dogs. To demonstrate that it is possible to treat knee osteochondral lesions with the technique of autologous tendon transplantation.AIMTo evaluate the clinical and radiological results of patients with knee osteochondral lesions who were treated with autologous tendon transplantation.METHODSTwenty patients (22 knees) with osteochondritis dissecans (OCD) lesions involving the knee were treated with autologous tendon transplantation between 2005-2018. All lesions were International Cartilage Repair Society grade IV. All patients were evaluated clinically at final follow-up with knee injury and osteoarthritis outcome score (KOOS); and radiologically with magnetic resonance observation and cartilage repair tissue (MOCART) and Kellgren-Lawrence (KL) classification.RESULTSA total of 20 patients (22 knees) with a mean age of 25.5± 6.8 years were included. The average defect size was 4.2 ± 2.1 cm2, and the average defect depth was 0.9 ± 0.4 cm. Total KOOS score was preoperatively 29.4 ± 5.5 and was later found to be 81.5 ± 5.9 after an average of 68.7 ± 37.7 mo follow-up. The mean MOCART score was 56.2 ± 10.7. Preoperatively, all of the patients had KL grades of 0–1; during the follow-up period, 80% of the patients showed no radiological progress of osteoarthritis. Patients with less than 4 cm2 lesion had statistically significantly better overall KOOS than patients whose more than 4 cm2 lesion, particularly in sport and quality of life subscales.CONCLUSIONThe autologous tendon transplantation is a single-step, safe, simple, cost-effective method for the treatment of knee OCD with satisfactory clinical and radiological outcomes, particularly in patients with less than 4 cm2 lesion.

Second-look arthroscopic cartilage status is related to intermediate-term outcomes after medial opening-wedge high tibial osteotomy.

To determine the relationship between articular cartilage status and clinical outcomes after medial opening-wedge high tibial osteotomy (MOHTO) for medial compartmental knee osteoarthritis at intermediate follow-up. We reviewed 155 patients (155 knees) who underwent MOHTO from January 2008 to December 2016 followed by second-look arthroscopy with a mean 5.3-year follow-up (2.0 to 11.7). Arthroscopic findings were assessed according to the International Cartilage Repair Society (ICRS) Cartilage Repair Assessment (CRA) grading system. Patients were divided into two groups based on the presence of normal or nearly normal quality cartilage in the medial femoral condyle: good (second-look arthroscopic) status (ICRS grade I or II; n = 70), and poor (second-look arthroscopic) status (ICRS grade III or IV; n = 85) groups at the time of second-look arthroscopy. Clinical outcomes were assessed using the International Knee Documentation Committee (IKDC) score, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and 36-Item Short Form survey. Significant improvements in all clinical outcome categories were found between the preoperative and second-look arthroscopic assessments in both groups (p < 0.001). At the latest follow-up, the mean IKDC and WOMAC scores in the good status group further improved compared with those at the time of second-look arthroscopic surgery (p < 0.001), which was not shown in the poor status group. The mean IKDC (good status, 72.8 (SD 12.5); poor status, 64.7 (SD 12.1); p = 0.002) and mean WOMAC scores (good status, 15.7 (SD 10.8); poor status, 21.8 (SD 13.6); p = 0.004) significantly differed between both groups at the latest follow-up. Moreover, significant correlations were observed between ICRS CRA grades and IKDC scores (negative correlation; p < 0.001) and WOMAC scores (positive correlation; p < 0.001) at the latest follow-up. Good cartilage status was found more frequently in knees with the desired range of 2° to 6° valgus correction than in those with corrections outside this range (p = 0.019). Second-look arthroscopic cartilage status correlated with clinical outcomes after MOHTO at intermediate-term follow-up, despite the relatively small clinical differences between groups. Cite this article: Bone Joint J2021;103-B(11):1686-1694.