Human osteochondritis dissecans fragment-derived chondrocyte characteristics ex vivo, after monolayer expansion-induced de-differentiation, and after re-differentiation in alginate bead culture

Background Autologous chondrocyte implantation (ACI) is a therapy for articular cartilage and osteochondral lesions that relies on notch- or trochlea-derived primary chondrocytes. An alternative cell source for ACI could be osteochondritis dissecans (OCD) fragment-derived chondrocytes. Assessing the potential of these cells, we investigated their characteristics ex vivo and after monolayer expansion, as monolayer expansion is an integral step of ACI. However, as monolayer expansion can induce de-differentiation, we asked whether monolayer-induced de-differentiation can be reverted through successive alginate bead culture. Methods Chondrocytes were isolated from the OCD fragments of 15 patient knees with ICRS grades 3–4 lesions for ex vivo analyses, primary alginate bead culture, monolayer expansion, and alginate bead culture following monolayer expansion for attempting re-differentiation. We determined yield, viability, and the mRNA expression of aggrecan and type I, II, and X collagen. Results OCD fragment-derived chondrocyte isolation yielded high numbers of viable cells with a low type I:II collagen expression ratio ( 1. Conclusion OCD fragment derived human chondrocytes may hold not yet utilized clinical potential for cartilage repair. Keywords: Chondrocyte; Articular cartilage; De-differentiation Re-differentiation; Monolayer expansion; Alginate bead cultur

Manufacturing of new roughness standards for the linearity of the vertical axis – Feasibility study and optimization

AbstractIn order to provide an alternative for the vertical axis calibration of stylus instruments which is usually performed based on step height standards, a new measurement standard geometry for the calibration of the linearity and research on its manufacturing is needed. For the manufacturing of these geometric measurement standards there is, according to the type of the measurement standard, a broad range of manufacturing processes that can be applied. New measurement standards for the roughness calibration were developed at the University of Kaiserslautern and an ultra-precision turning process was chosen for its manufacturing. The paper presents a feasibility study of the chosen manufacturing process. The aim of the investigations is to present the development of the standard and the qualification of the ultra-precision turning process for the manufacturing of calibration standards. An examination was performed in order to characterize the influences of different process parameters on the quality of the manufactured roughness standard

Proliferative remodeling of the spatial organization of human superficial chondrocytes distant from focal early osteoarthritis

Objective Human superficial chondrocytes show distinct spatial organizations, and they commonly aggregate near osteoarthritic (OA) fissures. The aim of this study was to determine whether remodeling or destruction of the spatial chondrocyte organization might occur at a distance from focal (early) lesions in patients with OA. Methods Samples of intact cartilage (condyles, patellofemoral groove, and proximal tibia) lying distant from focal lesions of OA in grade 2 joints were compared with location-matched nondegenerative (grade 0–1) cartilage samples. Chondrocyte nuclei were stained with propidium iodide, examined by fluorescence microscopy, and the findings were recorded in a top-down view. Chondrocyte arrangements were tested for randomness or significant grouping via point pattern analyses (Clark and Evans Aggregation Index) and were correlated with the OA grade and the surface cell densities. Results In grade 2 cartilage samples, superficial chondrocytes were situated in horizontal patterns, such as strings, clusters, pairs, and singles, comparable to the patterns in nondegenerative cartilage. In intact cartilage samples from grade 2 joints, the spatial organization included a novel pattern, consisting of chondrocytes that were aligned in 2 parallel lines, building double strings. These double strings correlated significantly with an increased number of chondrocytes per group and an increased corresponding superficial zone cell density. They were observed in all grade 2 condyles and some grade 2 tibiae, but never in grade 0–1 cartilage. Conclusion This study is the first to identify a distinct spatial reorganization of human superficial chondrocytes in response to distant early OA lesions, suggesting that proliferation had occurred distant from focal early OA lesions. This spatial reorganization may serve to recruit metabolically active units as an attempt to repair focal damage.National Institutes of Health (U.S.) (grant P5O-AR39239)National Institutes of Health (U.S.) (grant R01-AR33236)Deutsche Forschungsgemeinschaft (DFG) (grant RO 2511/1-1)Deutsche Forschungsgemeinschaft (DFG) (grant RO 2511/2-1

Kinematic simulation to investigate the influence of the cutting edge topography when ball end micro milling

During the ball end micro milling of material measures, the cutting edge topography is imaged on the machined workpiece. The influence of the chipping on the resulting surface quality is much more dominant than other kinematic effects. In this simulative study, a model is built that is able to predict the correlation between the cutting edge topography and the resulting workpiece topography. Thus, the mentioned correlation can be investigated without overlaying effects of material separation or measurement uncertainties, which are unavoidable in an experimental study. The model has been validated based on four artificial chippings

Osteoarthritis-Induced Metabolic Alterations of Human Hip Chondrocytes

Osteoarthritis (OA) alters chondrocyte metabolism and mitochondrial biology. We explored whether OA and non-OA chondrocytes show persistent differences in metabolism and mitochondrial function and different responsiveness to cytokines and cAMP modulators. Hip chondrocytes from patients with OA or femoral neck fracture (non-OA) were stimulated with IL-1β, TNF, forskolin and opioid peptides. Mediators released from chondrocytes were measured, and mitochondrial functions and glycolysis were determined (Seahorse Analyzer). Unstimulated OA chondrocytes exhibited significantly higher release of IL-6, PGE 2 and MMP1 and lower production of glycosaminoglycan than non-OA chondrocytes. Oxygen consumption rates (OCR) and mitochondrial ATP production were comparable in unstimulated non-OA and OA chondrocytes, although the non-mitochondrial OCR was higher in OA chondrocytes. Compared to OA chondrocytes, non-OA chondrocytes showed stronger responses to IL-1β/TNF stimulation, consisting of a larger decrease in mitochondrial ATP production and larger increases in non-mitochondrial OCR and NO production. Enhancement of cAMP by forskolin prevented IL-1β-induced mitochondrial dysfunction in OA chondrocytes but not in non-OA chondrocytes. Endogenous opioids, present in OA joints, influenced neither cytokine-induced mitochondrial dysfunction nor NO upregulation. Glycolysis was not different in non-OA and OA chondrocytes, independent of stimulation. OA induces persistent metabolic alterations, but the results suggest upregulation of cellular mechanisms protecting mitochondrial function in OA

Functional improvement following direct interventional leaflet repair of severe tricuspid regurgitation

AIMS: Several new percutaneous tricuspid repair systems have recently been introduced as new treatment options for severe tricuspid regurgitation (TR). Clinical improvement following percutaneous tricuspid valve leaflet repair has been demonstrated by recent studies. A possible impact on exercise capacity has not yet been reported. METHODS AND RESULTS: Eleven patients with at least severe TR and successful tricuspid leaflet repair using the PASCAL Ace implant at our cardiology department were included in this analysis. All patients suffered from symptomatic right‐sided heart failure with compromised exercise capacity. Cardiopulmonary exercise testing (CPET), clinical, laboratory, and echocardiographic parameters were assessed at baseline and 3 months follow‐up. The primary endpoint was the change in maximal oxygen consumption [VO(2) max (mL/(min*kg))] at 3 months follow‐up. Secondary endpoints included improvement in TR, cardiac biomarkers, and other clinical outcomes. TR severity at 3 months follow‐up post‐PASCAL Ace implantation was significantly lower than at baseline (P = 0.004). Cardiac biomarkers including high‐sensitivity troponin T and N‐terminal pro‐brain natriuretic peptide as well as right ventricular diameter improved slightly without reaching statistical significance (P = 0.89, P = 0.32, and P = 0.06, respectively). PASCAL Ace implantation resulted in a significant improvement in cardiopulmonary exercise capacity at 3 months follow‐up compared with baseline. Mean VO(2) max improved from 9.5 ± 2.8 to 11.4 ± 3.4 mL/(min*kg) (P = 0.006), VO(2) max per cent predicted from 42 ± 12% to 50 ± 15% (P = 0.004), peak oxygen uptake from 703 ± 175 to 826 ± 198 mL/min (P = 0.004), and O(2) pulse per cent predicted from 67 ± 21% to 81 ± 25% (P = 0.011). Other CPET‐related outcomes did not show any significant change over time. CONCLUSIONS: In this single‐centre retrospective analysis, direct tricuspid valve leaflet repair using the transcatheter PASCAL Ace implant system was associated with a reduced TR severity and improved cardiopulmonary exercise capacity

Stress-vs-time signals allow the prediction of structurally catastrophic events during fracturing of immature cartilage and predetermine the biomechanical, biochemical, and structural impairment

Objective Trauma-associated cartilage fractures occur in children and adolescents with clinically significant incidence. Several studies investigated biomechanical injury by compressive forces but the injury-related stress has not been investigated extensively. In this study, we hypothesized that the biomechanical stress occurring during compressive injury predetermines the biomechanical, biochemical, and structural consequences. We specifically investigated whether the stress-vs-time signal correlated with the injurious damage and may allow prediction of cartilage matrix fracturing. Methods Superficial and deeper zones disks (SZDs, DZDs; immature bovine cartilage) were biomechanically characterized, injured (50% compression, 100%/s strain-rate), and re-characterized. Correlations of the quantified functional, biochemical and histological damage with biomechanical parameters were zonally investigated. Results Injured SZDs exhibited decreased dynamic stiffness (by 93.04 ± 1.72%), unresolvable equilibrium moduli, structural damage (2.0 ± 0.5 on a 5-point-damage-scale), and 1.78-fold increased sGAG loss. DZDs remained intact. Measured stress-vs-time-curves during injury displayed 4 distinct shapes, which correlated with histological damage (p < 0.001), loss of dynamic stiffness and sGAG (p < 0.05). Damage prediction in a blinded experiment using stress-vs-time grades was 100%-correct and sensitive to differentiate single/complex matrix disruptions. Correlations of the dissipated energy and maximum stress rise with the extent of biomechanical and biochemical damage reached significance when SZDs and DZDs were analyzed as zonal composites but not separately. Conclusions The biomechanical stress that occurs during compressive injury predetermines the biomechanical, biochemical, and structural consequences and, thus, the structural and functional damage during cartilage fracturing. A novel biomechanical method based on the interpretation of compressive yielding allows the accurate prediction of the extent of structural damage.National Institutes of Health (U.S.) (Grant R01-AR45779)Deutsche Forschungsgemeinschaft (Grant RO2511/1-1)Deutsche Forschungsgemeinschaft (Grant RO2511/2-1)Germany. Federal Ministry of Education and Research (Grant 01KQ0902B TP2

Abfall von Sauerstoffsättigung und Blutdruck sowie Anstieg des zentralen Venendrucks im Rahmen eines Mitralklappenclippings bei einer 81-Jährigen

BACKGROUND: Atrial septal defects (ASD) following endovascular mitral valve clipping are potentially hemodynamically relevant complications. Immediate closure with an occluder can represent a safe and effective treatment. CASE SUMMARY: An 81-year-old female patient suffering from severe dyspnea due to previously known severe mitral valve regurgitation was scheduled for elective mitral valve clipping. The clip was successfully implanted. Removal of the transseptal cannula resulted in a sudden drop in oxygen saturation and systolic blood pressure as well as an immediate increase in central venous pressure. An iatrogenic left-right shunt was observed at the atrial level with a relevant shunt volume. Immediate closure using an atrial septal occluder successfully restored the oxygen saturation and hemodynamic parameters. CONCLUSION: An increase in central venous pressure, reduction of systolic blood pressure or oxygen saturation after withdrawal of the transseptal cannula during mitral valve clipping should always be further investigated regarding a possible ASD

Evaluation des Bundesprogramms "Soziale Teilhabe am Arbeitsmarkt": Erster Zwischenbericht

Das Bundesprogramm "Soziale Teilhabe am Arbeitsmarkt" zielt auf die Verbesserung der sozialen Teilhabe von arbeitsmarktfernen Langzeitleistungsbeziehenden im SGB II, die entweder mit Kindern in einer Bedarfsgemeinschaft leben und/oder auf Grund von gesundheitlichen Einschränkungen besonderer Förderung bedürfen. Es ist im Jahr 2015 gestartet und läuft bis zum 31.12.2018. Bislang nahmen knapp 10.000 Personen aus 105 Jobcentern an dem Programm teil. Eine Ausweitung des Programms hat zum Jahreswechsel 2016/17 stattgefunden. Der vorliegende Zwischenbericht stellt erste Ergebnisse der programmbegleitenden Evaluation vor.The programme "Social Inclusion in the Labour Market" (Soziale Teilhabe am Arbeitsmarkt) is a Federal labour market programme aiming to support social inclusion of persons with severe placement obstacles who are long-time receivers of Arbeitslosengeld II (minimum income support). The programme runs from 2015 to 31.12.2018 and focusses on persons who live together with children and/or who need special support due to health limitations. Until now, almost 10,000 persons from 105 Jobcenters participate in this programme. The programme will be extended from January 2017 on. This intermediate report presents first findings from the evaluation research team