Züchtung primärer osteogener Zellen auf neuartigen Gerüststrukturen in Kleinfermentern zur Herstellung von Knochenimplantaten in vitro

Als Grundlage für die Herstellung von Knochengewebeersatz in vitro wurden in dieser Arbeit Konzepte zur Kultivierung von Knochenvorläuferzellen untersucht. Aus dem Knochenmark der Ratte isolierte Zellen wurden mit verschiedenen Basalmedien, Wachstumsfaktorkombinationen und Serumkonzentrationen kultiviert und auf ihr Proliferations- und Differenzierungspotenzial getestet. Hierbei zeigte sich, dass die Kombination Fibroblast Growth Factor 2 und Platelet-Derived Growth Factor-BB die Proliferation der Zellen am besten unterstützten. Aufgrund der verminderten Adhäsion und Ausspreitung der Zellen konnte auf einen Serumanteil im Kulturmedium nicht völlig verzichtet, dieser jedoch von ursprünglich 15 auf 1% reduziert werden. Bei der Kulturführung auf dreidimensionalen Trägergerüsten wurden sowohl Besiedlungskonzepte von unterschiedlichen Gerüststrukturen untersucht als auch Verfahren zur Langzeitkultur (>7 Tage) von Knochenvorläuferzellen etabliert und verglichen. Ein für diese Anwendung entwickelter Kleinfermenter wurde weiter optimiert und das Arbeitsvolumen von 80 auf 30 ml reduziert. Dieses System erwies sich als statischen Kulturen deutlich überlegen. Die Kultivierung der Zellen in Festbettperfusionsreaktoren mit kontinuierlichem Medienaustausch ermöglicht eine 30tägige Kulturführung auf porösen Calciumphosphatgerüsten mit einer im Vergleich zur statischen Kultur beschleunigten Proliferation, höheren Gesamtzellausbeute sowie verbesserten Matrixbildung und -mineralisierung.As a basis for the production of bone tissue implants in vitro different concepts for the cultivation of osteoprogenitor cells have been investigated in this work. Cells isolated from the bone marrow of rats have been cultivated with different basal media, combinations of cytokines and serum concentrations and tested for their proliferation and differentiation potential. Thereby it became evident that cellular proliferation was supported best by a combination of fibroblast growth factor 2 (FGF-2) and platelet-derived growth factor-BB (PDGF-BB). Because of a substantially reduced adhesion and spreading of cells a complete removal of serum from the culture medium was not accomplished but the serum percentage could be reduced from initially 15% down to 1%. Protocols for seeding as well as three-dimensional long-term cultivation of osteoprogenitor cells in different novel scaffold structures have been established and compared. A specially developed small-scale bioreactor (working volume 80ml) was further optimised and scaled down (30 ml). It showed superior performance in comparison to static cultures which were run in parallel. The cultivation of osteoprogenitors in these perfused fixed-bed bioreactors with a continuous exchange of medium allows a 30-days culture on porous calcium phosphate scaffolds with accelerated proliferation, higher cell yields, and improved formation, maturation and mineralisation of extracellular matrix when compared to static culture

Prognostic Abilities and Quality Assessment of Models for the Prediction of 90-Day Mortality in Liver Transplant Waiting List Patients.

Model of end-stage liver disease (MELD)-score and diverse variants are widely used for prognosis on liver transplant waiting-lists.818 consecutive patients on the liver transplant waiting-list included to calculate the MELD, MESO Index, MELD-Na, UKELD, iMELD, refitMELD, refitMELD-Na, upMELD and PELD-scores. Prognostic abilities for 90-day mortality were investigated applying Receiver-operating-characteristic-curve analysis. Independent risk factors for 90-day mortality were identified with multivariable binary logistic regression modelling. Methodological quality of the underlying development studies was assessed with a systematic assessment tool.74 patients (9%) died on the liver transplant waiting list within 90 days after listing. All but one scores, refitMELD-Na, had acceptable prognostic performance with areas under the ROC-curves (AUROCs)>0.700. The iMELD performed best (AUROC = 0.798). In pediatric cases, the PELD-score just failed to reach the acceptable threshold with an AUROC = 0.699. All scores reached a mean quality score of 72.3%. Highest quality scores could be achieved by the UKELD and PELD-scores. Studies specifically lack statistical validity and model evaluation.Inferior quality assessment of prognostic models does not necessarily imply inferior prognostic abilities. The iMELD might be a more reliable tool representing urgency of transplantation than the MELD-score. PELD-score is assumedly not accurate enough to allow graft allocation decision in pediatric liver transplantation

An Improved Actuation System for an Artificial Tongue Prostesis

A total glossectomy can cause communication, swallowing, and chewing issues for oral or oropharyngeal cancer patients. This project attempted to develop a self-contained prosthetic tongue that could assist in swallowing by transporting food from the front to the back of the oral cavity. Current tongue prostheses are used for cosmetic reasons, while there are few solutions that address feeding issues that glossectomy patients may face. One example is a glossectomy spoon that inhibits a user’s ability to swallow food in an efficient or natural way. Past iterations of the prosthetic used pneumatic, electromagnetic, or mechanical linkage actuation methods and experienced a number of limitations, including the ability to move the bolus, to fit within the oral cavity, and to require surgical implementation. The previous linkage design successfully moved the bolus, however, it lacked miniaturization. After several ideations of designs, it was determined that a fewer number of links supported by a return spring system with a silicone pad would be ideal to move the bolus from the front to the back of the oral cavity. This apparatus would then be housed inside a retainer along with the entire control board, the motor and gear system, and eventually the battery. To ensure the system was operating in an accurate environment, an oral cavity simulation was developed as well as a fatigue testing of over 250 iterations of all portions of the device to ensure that it would maintain usability over long periods of time. This paper will describe the developmental procedures, outcomes, challenges, and future work

Klinische Forschungsvorhaben mit Medizinprodukten: Vorgehen einer akademischen Institution

Barthold M, Fischer I, Schröder C, Albrecht U-V, Rohde B. Klinische Forschungsvorhaben mit Medizinprodukten: Vorgehen einer akademischen Institution. DKZF. 2015;(5):35-38

An empirical relationship for the seismic activity rate of the Groningen gas field

AbstractThe Groningen field is the largest onshore gas field in Europe. Continuous production since 1963 has led to induced seismicity starting in the early 1990s. Production measures aimed at lowering the level of seismicity have been implemented since 2014. In this paper we start from an empirical relationship between the cumulative number of seismic events and cumulative gas production. We show that a better way to analyse the data is to relate the ratio of activity rate over production rate versus the cumulative production, such that the model parameters and their uncertainty can be determined. This also allows us to make predictions including the confidence intervals.Using this model, we first performed regression analysis based on the larger seismic catalogue which includes all recorded events with a magnitude of 1.3 and larger, because we consider this value to be the magnitude of completeness since 1995. We have also performed regression analysis based on a smaller seismic catalogue consisting of all events with a magnitude of 1.5 and larger. This was done in order to be able to compare our forecast with forecasts performed by others. Our prediction for 2016, based on the seismic catalogue of all events with a magnitude of M≥1.5 (using only the events recorded before 2016), was 16±8 events. By the end of 2016, 13 such events had been recorded.We discuss a number of factors which may influence the predictive power of the derived relationship and which require further study. For instance, we consider the delay between production and earthquakes which increases with decreasing reservoir pressure. In addition, the effect of seasonal fluctuation in Groningen production should be considered. Future work can be done to include these effects in the empirical model. We also investigated the challenges related to the applicability of the analysis to sub-regions of the Groningen field.</jats:p

Quality Assessment of the nine investigated prognostic models as spider web illustration.

Each corner of the pentagonal spider web represents one category of the quality assessment tool (internal validity, external validity, practicality of the model, evaluation of the model, and statistical validity). Each color represents one evaluator. An optimal assessment result would be an outer line connecting the five corner points. The nearer the line is at the center of the spider web, the poorer is the category’s assessed quality.</p

Results of univariable and multivariable regression analyses to determine the odds ratios of variables for the risk of 90-day waiting list mortality.

<p>Results of univariable and multivariable regression analyses to determine the odds ratios of variables for the risk of 90-day waiting list mortality.</p