Validation of the Knee Injury and Osteoarthritis Outcome Score (KOOS) for the treatment of focal cartilage lesions

SummaryObjectiveTo validate the Knee Injury and Osteoarthritis Outcome Score (KOOS) for the treatment of focal cartilage lesions.MethodsA total of 40 patients (mean age 35±12 years,) treated for a focal cartilage lesion in the knee were included in this study. Test–retest data were collected with an intermediate period of 2 days. Patients were asked to complete the Dutch KOOS and complementary questionnaires [short form-36 (SF-36), Lysholm, EuroQol-5D (EQ-5D)] to evaluate the clinimetric properties of the KOOS in terms of internal consistency (Cronbach's alpha), reliability [intra-class-correlation (ICC) and Bland and Altman plots], construct validity (Spearman's rank correlation), floor and ceiling effects and responsiveness.ResultsThe Cronbach's alpha of the KOOS subdomains and total score ranged from 0.74 to 0.96. The overall ICC of the KOOS was 0.97 while the subscales ranged from 0.87 to 0.95. The Bland and Altman plots showed a small individual variance between the two assessments in time. Spearman's rank correlations between the subscales of the KOOS and representative subscales of the SF-36, Lysholm and EQ-5D were high to moderate ranging from 0.43 to 0.70. We observed no floor effect while the largest observed ceiling effect was 10.3%. The responsiveness was moderate to large with the effect size ranging from 0.70 to 1.32 and the standardized response mean 0.61 to 0.87.ConclusionThis study illustrates the validity and reliability of the KOOS in measuring the clinical condition of patients after treatment of focal cartilage lesions. This study provides a basis for the use of the KOOS for future clinical research in cartilage repair

Articular Cartilage Evaluation After TruFit Plug Implantation Analyzed by Delayed Gadolinium-Enhanced MRI of Cartilage (dGEMRIC)

Background: Quantitative MRI of articular cartilage has rapidly developed in recent years and provides the clinician with a noninvasive tool to determine the biological consequence of an intervention. Purpose: To evaluate the quality of intra-articular cartilage, using the dGEMRIC scanning technique, 1 year after TruFit implantation. The hypothesis was that implantation of a TruFit plug does not lead to damage at the opposing articular cartilage. Study Design: Case series; Level of evidence, 4. Methods: A total of 13 patients (age, 32 ± 8 years) were evaluated with dGEMRIC at 12 ± 4 months after treatment of an osteochondral lesion by implantation of 1 or multiple TruFit plugs. The dGEMRIC scanning protocol was applied 90 minutes after intravenous Magnevist (0.2 mmol/kg body weight) injection. Different regions of interest (ROIs) were defined: the femur cartilage, cartilage directly surrounding the implanted TruFit plug, the TruFit plug, and the articulating and nonarticulating tibia cartilage. The average dGEMRIC index (T1gd; magnetic resonance imaging relaxation time per ROI) was calculated by a pixel-by-pixel curve fitting using the Levenberg-Marquardt method. Differences between the mean T1gd of the individual ROI for all patients were tested using analysis of variance with post hoc Bonferroni correction. A P value <.05 was considered statistically significant. Results: The average T1gd of the TruFit ROI (385 ± 74 ms) was comparable with those in the femur (409 ± 49 ms) and surrounding (392 ± 64 ms) ROIs (P ≥ .339). The average T1gds for the articulating (578 ± 133 ms) and nonarticulating (516 ± 118 ms) ROIs were higher compared with the femur (409 ± 49 ms), surrounding (392 ± 64 ms), and TruFit (385 ± 74 ms) ROIs (P < .002), while no difference was observed between the tibia ROIs (P = .160). Conclusion: Implantation of the TruFit plug in osteochondral lesions does not damage the opposing or surrounding surface, and newly formed tissue inside the plug has cartilage-like dGEMRIC characteristics 12 months after implantation. The implantation of synthetic TruFit plugs is safe for the opposing cartilage, an item that is frequently discussed when using such materials to treat focal cartilage defects

Design and fabrication of standardized hydroxyapatite scaffolds with a defined macro-architecture by rapid prototyping for bone-tissue-engineering research

This investigation describes the production and characterization of calcium phosphate scaffolds with defined and reproducible porous macro-architectures and their preliminary in vitro and in vivo bone-tissue-engineered response. Fugitive wax molds were designed and produced using a rapid prototyping technique. An aqueous hydroxyapatite slurry was cast in these molds. After sintering at 1250°C and then cleaning, dimensional and material characterizations of the scaffolds were performed. The resulting scaffolds represented the design, and their dimensions were remarkably consistent. A texture inherent to the layer-by-layer production of the mold was impressed onto the vertical surfaces of the scaffolds. The surface roughness (Ra) of the textured surfaces was significantly greater than that of the nontextured surfaces. Material analyses revealed a β-TCP phase in addition to hydroxyapatite for the molded ceramics. Non-molded control ceramics exhibited only hydroxyapatite. Thirty scaffolds were seeded with culture-expanded goat bone-marrow stromal cells (BMSCs) and implanted subcutaneously in nude mice for 4 or 6 weeks. Histology revealed mineralized bone formation in all the scaffolds for both implantation periods. After 4 weeks, bone was present primarily as a layer on scaffold surfaces. After 6 weeks, the surface bone formation was accompanied by bone budding from the surface and occasional bridging of pores. This budding and bridging bone formation almost always was associated with textured scaffold surfaces. However, the area percentage of bone in pores was similar for the 4- and 6-week implantation periods

One-stage focal cartilage defect treatment with bone marrow mononuclear cells and chondrocytes leads to better macroscopic cartilage regeneration compared to microfracture in goats

SummaryObjectiveThe combination of chondrocytes and mononuclear fraction (MNF) cells might solve the expansion induced dedifferentiation problem of reimplanted cells in autologous chondrocytes implantation as sufficient cells would be available for direct, one-stage, implantation. Earlier in vitro work already showed a positive stimulation of cartilage specific matrix production when chondrocytes and MNF cells were combined. Therefore, this study aimed to evaluate cartilage regeneration using a one-stage procedure combining MNF cells and primary chondrocytes for the treatment of focal cartilage lesions in goats compared to microfracture treatment.DesignFreshly created focal cartilage defects were treated with either a combination of chondrocytes and MNF cells embedded in fibrin glue or microfracture treatment. After 6 months follow-up local regeneration as well as the general joint cartilage health were evaluated using validated scores and biochemical assays.ResultsMacroscopic (P = 0.015) scores for the cartilage surface at the treated defect were, after 6 months, significantly higher for the chondrocyteMNF treatment compared to microfracture-treated defects, but microscopic scores were not (P = 0.067). The articulating cartilage showed more (P = 0.005) degeneration following microfracture treatment compared to chondrocyteMNF treatment. Biochemical glycosaminoglycans (GAG) evaluation did not reveal differences between the treatments. Both treatments had resulted in a slight to moderate cartilage degeneration at other locations in the joint.ConclusionIn conclusion, treatment of focal articular cartilage lesions in goats using a combination of MNF cells from bone marrow and unexpanded chondrocytes leads to better macroscopic regeneration compared to microfracture, however needs further fine-tuning to decrease the negative influence on other joint compartments

Громадська робота як чинник повсякденного життя вчителя

Treatment and reconstruction of large bone defects, delayed unions, and nonunions is challenging and has resulted in an ongoing search for novel tissue-engineered therapies. Bone morphogenetic protein-2 (BMP-2) gene therapy is a promising strategy to provide sustained production of BMP-2 locally. Alginate polymer-based nonviral gene therapy with BMP-2 plasmid DNA (pBMP-2) in constructs with multipotent mesenchymal stromal cells (MSCs) has resulted in prolonged gene expression and bone formation in vivo. To further translate this technology toward larger animal models, important issues remain to be investigated, such as the necessity of seeded cells as a target for gene therapy. For that purpose, a large animal-screening model in an orthotopic location, with fully separated chambers, was investigated. Four cylinder-shaped implants were placed in the iliac crests of ten goats. Polycaprolactone tubes around each implant allowed bone ingrowth from the underlying bone and bone marrow and ensured separation of the experimental conditions. An empty tube showed low levels of spontaneous bone ingrowth, and implantation of autologous bone indicated proper bone function with respect to remodeling and resorption. Control ceramic scaffolds were compared to scaffolds containing pBMP-2 either or not combined with seeded MSCs. Fluorochrome incorporation evaluated at 3, 6, and 9 weeks and histomorphometry at 12 weeks after implantation revealed clear differences between the groups, with pBMP-2 combined with MSCs being the most effective. The BMP-2 was demonstrated in a variety of bone-residing cells through immunohistochemistry. Further analysis indicated that multinucleated giant cells might have an important role in transgene expression. Taken together, this work introduces a large animal model for studying bone formation at multiple sites simultaneously in an orthotopic location. The model appeared robust, showed no neighboring effects, and demonstrated effectivity of combined cell and gene therapy

Cytokine profiles in the joint depend on pathology, but are different between synovial fluid, cartilage tissue and cultured chondrocytes

__Introduction:__ This study aimed to evaluate whether profiles of several soluble mediators in synovial fluid and cartilage tissue are pathology-dependent and how their productio

Interleukin-6 is elevated in synovial fluid of patients with focal cartilage defects and stimulates cartilage matrix production in an in vitro regeneration model

Introduction: This study aimed to determine whether, as in osteoarthritis, increased levels of interleukin-6 (IL-6) are present in the synovial fluid of patients with symptomatic cartilage defects and whether this IL-6 affects cartilage regeneration as well as the cartilage in the degenerated knee.Methods: IL-6 concentrations were determined by ELISA in synovial fluid and in conditioned media of chondrocytes regenerating cartilage. Chondrocytes were obtained from donors with symptomatic cartilage defects, healthy and osteoarthritic donors. The effect of IL-6 on cartilage regeneration and on metabolism of the resident cartilage in the knee was studied by both inhibition of endogen