Treatment Of Knee Cartilage Defects Research Articles

Clinical and Radiological Outcomes at ≥10-Year Follow-up After Matrix-induced Autologous Chondrocyte Implantation in the Patellofemoral Joint.

Matrix-induced autologous chondrocyte implantation (MACI) has demonstrated encouraging outcomes in the treatment of knee cartilage defects, although limited research is available on its longer term (≥10 years) sustainability in the patellofemoral joint. To report the clinical and radiological outcomes at ≥10 years in a prospectively recruited cohort of patients undergoing MACI in the patellofemoral joint and compare outcomes in patients undergoing MACI on the patella versus the trochlea. Case series; Level of evidence, 4. The current study prospectively enrolled 95 patients who underwent patellofemoral MACI, of whom 29 (13 patella, 16 trochlea) underwent concomitant tibial tubercle osteotomy. Patients were assessed preoperatively and at 2, 5, and ≥10 years using a range of patient-reported outcome measures (PROMs) including the Knee injury and Osteoarthritis Outcome Score, the 36-item Short Form Health Survey, and the frequency and severity of knee pain as well as patient satisfaction, full active knee flexion and extension, and peak isokinetic knee extensor and flexor torques. High-resolution magnetic resonance imaging (MRI) was performed to assess pertinent graft parameters, as well as determine an overall MRI composite score, per the Magnetic Resonance Observation of Cartilage Repair Tissue scoring system. Results were analyzed according to the graft location (patella or trochlea). Of the 95 patients recruited, 82 patients (41 patella, 41 trochlea) were available for a clinical review at ≥10 years after surgery (mean follow-up, 11.9 years [range, 10-15 years]). For the whole patellofemoral MACI cohort, all PROMs significantly improved over time (P < .05), with no significant changes (P > .05) observed in any MRI-based score from 2 to ≥10 years after surgery. At ≥10 years, 90.2% (n = 74) were satisfied with MACI in relieving their knee pain, and 85.4% (n = 70) were satisfied with the improvement in their ability to participate in sports. No differences (P > .05) were observed in PROMs between those undergoing patellar MACI and those undergoing trochlear MACI, although a significant group effect was observed for limb symmetry indices of knee extensor (P = .009) and flexor (P = .041) strength, which were greater in those undergoing patellar (vs trochlear) MACI. No statistically significant differences (P > .05) were observed between patellar and trochlear grafts on any MRI-based measure. In the cohort assessed at ≥10 years after surgery, 4 patients (2 patella, 2 trochlea) demonstrated graft failure on MRI scans, although a further 3 patients (all trochlea) were omitted from the ≥10-year review for having already progressed to total knee arthroplasty. Good clinical scores, high levels of patient satisfaction, and adequate graft survivorship were observed at ≥10 years after MACI on the patella and trochlea.

Hydrogel-Based Matrix-Associated Autologous Chondrocyte Implantation Shows Greater Substantial Clinical Benefit at 24 Months Follow-Up than Microfracture: A Propensity Score Matched-Pair Analysis.

To compare substantial clinical benefit (SCB) of a hydrogel-based, matrix-associated autologous chondrocyte implantation (M-ACI) method versus microfracture (MFx) in the treatment of knee cartilage defects. Propensity score matched-pair analysis, using the MFx control group of a phase III study as comparator for M-ACI treatment in a single-arm phase III study, resulting in 144 patients in the matched-pair set. Groups were comparable regarding baseline Knee Injury and Osteoarthritis Outcome Score (KOOS), sex, age, body mass index, symptom duration, smoking status, and previous knee surgeries. Defect sizes in the M-ACI group were significantly larger than in the MFx group (6.4 cm2 vs. 3.7 cm2). Other differences concerned location, number, and etiology of defects that were not considered to influence the interpretation of results. At 24 months, significantly more patients in the M-ACI group achieved SCB in KOOS pain (72.2% vs. 48.6%; P = 0.0108), symptoms (84.7% vs. 61.1%, P = 0.0039), sports/recreation (84.7% vs. 56.9%, P = 0.0008), and quality of life (QoL; 72.2% vs. 44.4%, P = 0.0014). The SCBs for KOOS activities in daily living and International Knee Documentation Committee score were higher for M-ACI but not significantly different from MFx. The SCB rates consistently favored M-ACI from 3 months onward. The highest improvements from baseline at 24 months in patients with SCB were observed for KOOS sports/rec. (M-ACI: 60.8 points, MFx: 55.9 points) and QoL (M-ACI: 58.1, MFx: 57.4). Hydrogel-based M-ACI demonstrated superior SCB in KOOS pain, symptoms, sports/rec., and QoL compared with MFx in patients with knee cartilage defects through 2 years follow-up.

One-stage cartilage repair using the autologous matrix-induced chondrogenesis combined with simultaneous use of autologous adipose tissue graft and adipose tissue mesenchymal cells technique: clinical results and magnetic resonance imaging evaluation at five-year follow-up

PurposeTo evaluate medium-term outcomes of knee cartilage defects repair by autologous matrix-induced chondrogenesis combined with simultaneous use of autologous adipose tissue graft and adipose tissue mesenchymal cells, defined as LIPO-AMIC technique.MethodsThe LIPO-AMIC technique has been used in ICRS degree III–IV knee defects. Eighteen patients have been prospectively evaluated during two and five years both clinically and by MRI.ResultsPatients showed progressive significant improvement of all scores starting early at six months, and further increased values were noted till the last follow-up at 60 months. Mean subjective pre-operative IKDC score of 36.1 significantly increased to 86.4 at 24 months and to 87.2 at 60 months. Mean pre-operative Lysholm score of 44.4 reached 93.5 at two years and 93.5 at five years. MRI examination showed early subchondral lamina regrowth and progressive maturation of repair tissue and filling of defects. The mean total MOCART score showed that a significative improvement from two year follow-up (69.1 points) to last follow-up was 81.9 points (range, 30–100 points, SD 24). Complete filling of the defect at the level of the surrounding cartilage was found in 77.8%.ConclusionsAdipose tissue can represent ideal source of MSCs since easiness of withdrawal and definite chondrogenic capacity. This study clearly demonstrated the LIPO-AMIC technique to be feasible for treatment of knee cartilage defects and to result in statistically significant progressive clinical, functional and pain improvement in all treated patients better than what reported for the AMIC standard technique, starting very early from the 6-month follow-up and maintaining the good clinical results more durably with stable results at mid-term follow-up.

Effect study of exosomes derived from platelet-rich plasma in the treatment of knee cartilage defects in rats

BackgroundThe repair of articular cartilage defects has always been a difficult problem. We aimed to investigate the therapeutic effect of intra-articular injection of platelet-rich plasma (RPR) and PRP-derived exosomes (PRP-Exos) on cartilage defects in rat knee joints and then provide experience for the use of PRP-exos in cartilage defect repair.MethodsRat abdominal aortic blood was collected, and PRP was extracted by two-step centrifugation. PRP-exos were obtained by kit extraction, and PRP-exos were identified by various methods. After the rats were anesthetized, a cartilage defect subchondral bone was created at the proximal end of the origin of the femoral cruciate ligament with a drill. SD rats were divided into 4 groups, including PRP group, 50 μg/ml PRP-exos group, 5 μg/ml PRP-exos group, and control group. One week after the operation, 50 μg/ml PRP, 50 μg/ml PRP-exos, 5 μg/ml PRP-exos and normal saline were injected into the knee joint cavity of rats in each group, once a week. A total of two injections were given. On the 5th and 10th week after drug injection, the serum levels of matrix metalloproteinase 3 (MMP-3) and tissue inhibitor of matrix metalloproteinase 1 (TIMP-1) were detected by each treatment method, respectively. The rats were killed at the 5th and 10th weeks, respectively, and the cartilage defect repair was observed and scored. The defect repair tissue sections were used for HE staining and type II collagen immunohistochemical staining.ResultsThe histological results showed that both PRP-exos and PRP could promote cartilage defect repair and type II collagen formation, and the promoting effect of PRP-exos was significantly better than that of PRP. In addition, enzyme-linked immunosorbent assay (ELISA) results showed that compared with PRP, PRP-exos could significantly increase serum TIMP-1 and decrease serum MMP-3 in rats. And the promoting effect of PRP-exos was concentration dependent.ConclusionIntra-articular injection of PRP-exos and PRP can promote the repair of articular cartilage defects, and the therapeutic effect of PRP-exos is better than the same concentration of PRP. PRP-exos are expected to be an effective treatment for cartilage repair and regeneration.

Treatment of knee cartilage by cultured stem cells and three dimensional scaffold: a phase I/IIa clinical trial.

Damage of the knee cartilage is a common condition manifesting itself mainly by pain and/or swelling that may substantially reduce the quality of life while ultimately leading to osteoarthritis in affected patients. Here, we aimed to evaluate the safety and efficacy of cultured autologous bone marrow mesenchymal stem cells (BM-MSCs) attached to the 3D Chondrotissue® scaffold by autologous blood plasma coagulation (BiCure® ortho MSCp) in the treatment of knee cartilage defects. The primary endpoint of this phase I/IIa clinical trial was to evaluate the safety of the treatment. The secondary objective was to determine the short-to-medium-term therapeutic outcomes by standardized scoring questionnaires including Lysholm Knee Scoring Scale (Lysholm score), Knee Injury and Osteoarthritis Outcome Score (KOOS), and pain Visual Analogue Scale (VAS) systems and imaging (X-ray and magnetic resonance imaging, MRI). A total of six patients were included and followed for 12months after the surgery. BiCure® ortho MSCp was well tolerated with no adverse events associated with the investigational medicinal product. Significant improvements were observed in Lysholm scores and KOOS while X-ray showed no deterioration of the arthritis and MRI revealed a persistent filling of the chondral defects by the implant. Overall, our data demonstrate the safety of the tested investigational medicinal product. The function of the treated knee improved within oneyear after surgery in all enrolled patients. EudraCT No.: 2018-004,067-31; October 18 2018.

Synthetic Biphasic Scaffolds versus Microfracture for Articular Cartilage Defects of the Knee: A Retrospective Comparative Study

The purpose of this study was to compare the results of a biphasic synthetic scaffold (TruFit, Smith & Nephew) to microfracture for the treatment of knee cartilage defects and identify patient- and lesion-specific factors that influence outcomes. Prospectively collected data from 132 patients (mean age, 41.8 years; 69% male) with isolated chondral or osteochondral femoral defects treated with biphasic synthetic scaffolds (n = 66) or microfracture (n = 66) were reviewed. Clinical outcomes were evaluated longitudinally over 5 years with the Short Form-36 (SF-36), Activities of Daily Living of the Knee Outcome Survey (KOS-ADL), International Knee Documentation Committee (IKDC), and Marx Activity Scale. Cartilage-sensitive magnetic resonance imaging (MRI) was performed to evaluate osseous integration and cartilage fill in a subgroup of patients. Multivariate regression analysis was used to identify predictors of clinical outcomes within the scaffold group. Both groups demonstrated clinically significant improvements in knee clinical scores over 5 years (P < 0.01). There were no significant differences in KOS-ADL and IKDC scores between groups up to 5 years postoperatively. Marx activity level scores in the microfracture group declined over time, while significant improvements in activity level scores were observed in the scaffold group over 5 years (P < 0.01). Good-quality tissue fill and cartilage isointensity were more often observed in the scaffold group compared with the microfracture group, particularly with longer time intervals. Increasing age, high body mass index, prior microfracture, and traumatic etiology were predictors for inferior outcomes in the scaffold group. Activity level and MRI appearance following treatment of cartilage lesions with the biphasic synthetic scaffold were superior to microfracture over time in this nonrandomized, retrospective comparison.

Focal metallic inlay resurfacing prosthesis in articular cartilage defects: short-term results of 118 patients and 2 different implants.

The goal of this study was to share our experience with two different inlay metallic implants in the treatment of knee cartilage defects and to analyze their effects on functional scores. This retrospective study included 118 patients operated on for focal full-thickness knee cartilage lesions, who were treated with a focal metallic inlay resurfacing prosthesis. A cobalt-chromium (Co-Cr) resurfacing implant was applied to 73 patients with a knee chondral lesion, and a biosynthetic implant was applied to 45. All patients were evaluated preoperatively and postoperatively using the KOOS, VAS, and Tegner activity scores. The group with the Co-Cr-resurfacing implant showed a significantly greater improvement (p < 0.001) in the Tegner and VAS scores at the 2-year follow-up examination. The KOOS scores were similar in both groups. Median patient age was similar in both groups. All patients had a follow-up of at least 2years. The preoperative and postoperative scores were compared and significant improvements (p < 0.001) were observed. The biosynthetic implant had a higher revision rate. In the univariate analysis, age and type of implant were significantly associated with revision surgery. In the multivariate Cox-regression analysis model, the type of implant was significantly associated with revision surgery. All the patients operated with the above-mentioned implants showed significant improvements in pain and activity scores. Despite the overall good clinical results, 17% of patients with a biosynthetic implant and > 6% of patients with Co-Cr-resurfacing implant required revision surgery. Age and implant type were the main risk factors associated with revision.

Efficacy and safety of autologous cell therapies for knee cartilage defects (autologous stem cells, chondrocytes or the two): randomized controlled trial design.

The main aim of this trial is to test the safety and efficacy of autologous stromal/stem cells, chondrocytes or the two combined in the treatment of knee cartilage defects. Patients with symptomatic chondral/osteochondral defects will be randomized to cell therapy treatment with one of three cell populations (1:1:1). The primary efficacy outcome is a functional knee score (Lysholm) at 15 months post-treatment and the primary safety outcome is the incidence of adverse events. Secondary objectives are to analyze repair tissues, quality of life and cost-utility assessments. Exploratory objectives are to identify predictors for success/potency and dose-response relationships. This trial has been carefully designed so that valuable scientific and clinical information can be gathered throughout and in the final analysis.

Autologous osteochondral transplantation for treatment of cartilage defects in osteoarthritic knee: preliminary results

Introduction: Osteoarthritis is a contributing factor for pain and loss of function of the knee. Osteoarthritis results in many damages to the knee; one of the most common damages that is difficult to recover is cartilage injury. This study aims to apply autologous osteochondral transplantation (OAT) under knee arthroscopy for the treatment of knee cartilage defects. Methods: This was a prospective, descriptive and non-controlled study. Patients were diagnosed as having osteoarthritis, as confirmed by 1cm2 – 3cm2 cartilage defects. Arthroscopic OAT was performed on each patient. Treatment efficacy and safety were evaluated based on Lysholm, Oxford Knee Scores (OKS) and pain scales (VAS) after 3, 6, 12 and 18 months. Results: From 3/2014 - 8/2016, 61 cases (54 women and 7 men) participated in the study. The average age was 55 ± 8 years old. Most cases had cartilage defects in the medial condyle. Results showed that Lysholm, OKS scores and VAS scales improved after 12 months of treatment. Of the cases, 33 of 61 were followed out to 18 months; these patients showed improvement in knee function and pain scores. There was 1 case with incomplete matching between the plug and receiving site and 1 case with a broken plug. At the final stage of monitoring, there were no patients who experienced complications, such as broken instruments or fracture of condyle, nor who experienced early postoperative complications, such as infection and bleeding. Conclusion: Autologous osteochondral transplantation via arthroscopy is a safe and promising method for the treatment of knee cartilage defects in patients with average osteoarthritis.

Microfracture for Treatment of Knee Cartilage Defects in Children and Adolescents

Even though operative microfracture is the most frequent method for treatment of limited knee joint cartilage lesions among adults, data about ouctome in children and adolescents are rare. We performed a retrospective chart review and telephone interview to analyze for the clinical outcome following knee joint cartilage defect microfracturing among 10 children. Mean postoperative Lysholm was 92.1±9.9 and Tegner was 7.0±1.9. Clinical outcome differed across knee joint regions, as well as in dependence of varying pre-operative symptom duration, although this was not significant. Regression analysis did not reveal a significant impact of patient or defect characteristics on clinical outcome. Arthroscopic microfracturing for treatment of limited size symptomatic knee joint cartilage defects among children and adolescents is considered a reasonable surgical option. However, long-term outcome and larger patient cohorts are required.

Microfracture plus autologous osteochondral paste transplantation to treat knee cartilage defects in rabbits

Objective To evaluate the effectiveness of microfracture plus autologous osteochondral paste transplantation in treatment of knee cartilage defects in rabbits. Methods Models of articular cartilage defects were established in 46 healthy adult male New Zealand rabbits which were divided into 3 groups:control group ( n =10),microfracture group ( n =18) and experiment group ( n =18).In the control group,the cartilage defects were left untreated.In the microfracture group,multiple grid-like mini-holes were made using the microfracture technique.In the experiment group,the defects were covered with autologous osteochondral paste after the grid-like mini-holes were made.At 4,8 and 12 weeks post-treatment,the knees were assessed grossly,histologically,and by glycosaminoglycan (GAG) content measurement and Wakitani scoring. Results After 12 weeks,the defects in the experiment gronp were filled with hyaline-like cartilage tissue,and both the cartilage and the subchondral bone were basically repaired.The repaired cartilage was superior to those in the other groups in terms of gross appearance and histomorphology.The Wakitani histological scores at 4,8 and 12 weeks post-treatment were respectively 5.0 ± 1.0,6.7 ± 1.5 and 13.0 ± 1.0 in the experiment group,2.3 ±0.6,5.0 ± 1.0 and 7.7 ± 1.2 in the microfracture group,and 0.0 ± 0.0,1.3 ± 0.6 and 1.7 ± 0.6 in the control group.The experiment group was significantly better then the other 2 groups in all the above indexes ( P ＜ 0.05 ).The GAG contents at 4,8 and 12 weeks post-treatment were respectively 6.25 ±0.31 μg/mg,13.11 ±0.21 μg/mg and 16.23 ±0.66 μg/mg in the experiment group,and 3.04 ±0.21 ug/mg,5.75 ±0.24 μg/mg and 7.03 ±0.21 μg/mg in the microfracture group,with significant differences between the 2 groups ( P ＜ 0.05). Conclusion Microfracture plus autologous osteochondral paste transplantation may be a promising treatment option for cartilage defects because it is much more effective than microffacture alone. Key words: Knee joint; Arthroplasty; Cartilage, articular; Transplantation, autologous; Wounds and injuries

Tissucol-based scaffold in the treatment of knee cartilage defects: Experimental resurfacing by embryonic stems cells

Tissucol-based scaffold in the treatment of knee cartilage defects: Experimental resurfacing by embryonic stems cells

Transplantation of chondrocytes seeded on collagen‐based scaffold in cartilage defects in rabbits

Recent success in tissue engineering by restoring cartilage defects by transplanting autologous chondrocyte cells on a three-dimensional scaffold has prompted the improvement of this therapeutic strategy. Here we describe a new approach investigating the healing of rabbit cartilage by means of autologous chondrocytes seeded on a biomaterial made of an equine collagen type I-based scaffold. Full-thickness defects were created bilaterally in the weight-bearing surface of the medial femoral condyle of both femora of New Zealand male rabbits. The wounds were then repaired by using both chondrocytes seeded on the biomaterial and biomaterial alone. Controls were similarly treated but received either no treatment or implants of the delivery substance. Histological examination of the reconstructed tissues at 1, 3, 6, and 12 months after transplantation showed that at 1 and 3 months there was no formation of reconstructed tissue in any of the groups evaluated; after 6 months there was evidence of a newly regenerated tissue with some fibrocartilaginous features only in the group treated with biomaterial-seeded cells, and at 12 months a more organized tissue was evident in the same group. With regards to the group transplanted with biomaterial alone and the untreated control group, there was no evidence of new tissue production. These results advocate the use of this collagen-based scaffold for further in vivo studies on large size animals and, finally, in human clinical trials for the treatment of knee cartilage defects.

Cellular aspects on treatment of cartilage injuries.

Cellular aspects on articular cartilage growth and development are discussed. Cells with chondrogenic potential are described and current treatment models for cartilage injuries are considered. A rabbit model for treatment of articular cartilage defects with autologous cultured and transplanted chondrocytes for treatment of knee cartilage defects in humans are discussed.