444 research outputs found
Philip R. Davies, Thomas Römer (éd.), Writing the Bible. Scribes, Scribalism and Script, Durham, Acumen, 2013
No full textHunziker-Rodewald Regine. Philip R. Davies, Thomas Römer (éd.), Writing the Bible. Scribes, Scribalism and Script, Durham, Acumen, 2013. In: Revue d'histoire et de philosophie religieuses, 94e année n°3, Juillet-Septembre 2014. p. 323
Der Einfluss von Oberflächendefekten auf das Abbauverhalten von Magnesiumlegierungen für medizinische Anwendungen
No full textThe degradation of Mg alloys is very sensitive to impurities and microstructure changes.
Thus, surface cleaning after manufacturing is essential for all applications under a corrosive
environment. In particular for biomedical applications, controlled degradation is crucial.
Several studies have turned out that HAc etching is a promising surface treatment to
decrease the degradation rate. To date, there have been no systematic investigations
concerning the effect of surface treatment on Mg-Gd alloys, which are of particular interest
in the field of biology. The aim of this work is to determine the relationship between different
HAc etching conditions and the morphology and microstructure of Mg-Gd alloys in the nearsurface
region as well as the impact on the degradation behaviour.Die Degradation von Mg Legierungen reagiert sehr empfindlich auf Verunreinigungen und
Mikrostrukturänderungen. Somit ist die Reinigung der Oberfläche nach der Herstellung für
alle Anwendungen in korrosiver Umgebung erforderlich. Insbesondere ist eine gleichmäßige
Degradation bei medizinischer Anwendung essentiell. In früheren Studien stellte sich eine
Ätzung mit Essigsäure (HAc) in Bezug auf Herabsetzung der Korrosionsrate als
vielversprechend heraus. Zur Oberflächenbehandlung mittels HAc-Ätzung von Mg-Gd
Legierungen, die speziell im biologischen Bereich interessant sind, gibt es bislang keine
systematischen Untersuchungen. Das Ziel dieser Arbeit ist es daher, den Zusammenhang
zwischen verschiedenen Ätzzuständen und der oberflächennahen Morphologie und
Mikrostruktur von Mg-Gd-Legierungen sowie deren Einfluss auf das Degradationsverhalten
zu bestimmen
In vitro investigation on the regenerative effect of Magnesium-based microparticles for osteoarthritis treatment
No full textOsteoarthritis (OA) is one of the degenerative and epidemic joint disorders occurring worldwide. Although the molecular mechanisms are poorly understood, aging, gender, heredity, joint injury, impaired joint movement, stress and obesity are the main OA etiology. Till now there are no benchmark medical therapies for preventing or delaying OA onset. This thesis investigates the possibility of using Magnesium (Mg)-based microparticles in aiding the treatment of OA. Mg-based materials are thought to be a suitable biomaterial candidate due to their cytocompatibility, ability to degrade and noteworthy is their osteopromotive quality. The main objective of this research was to demonstrate the positive link of Mg implant in preventing the occurrence of OA. To achieve the objective this thesis covered a series of experiments right from the degradation of Mg implant in physiological medium to the implant’s compatibility on SCP1 cells. The final part investigated the association of Mg implants in an OA in vitro model revealing the significance of Mg in reducing the progression of OA. The evidence collected in this thesis leads to the conclusion that Mg-based microparticles have the potential to slow the progression of in vitro OA and help restore the differentiation potential/repair mechanism in bone and cartilage, depending on the severity of the inflammation. The ability of Mg microparticles to safely degrade with minimal toxicity on cells and the capability to support bone/cartilage repair mechanisms in vitro, makes Mg a versatile material for bone and cartilage tissue applications. The degradation rate, cytocompatible characteristics, and the demonstrated support for bone and cartilage repair mechanisms in vitro highlight the potential of Mg microparticles as an intelligent bioimplant material for OA therapy
In vitro effects of degradable Magnesium- Lithium thin films on cells of the nervous system
No full textLithium (Li) is used as a medication for bipolar disorder (BD) since several decades and can potentially help with managing other neurodegenerative disorders. However, a longstanding hurdle has been the narrow therapeutic range of Li which leads to several side effects and chronic toxicity. Localized and consistent Li release from an implant could maintain therapeutic Li concentrations with a reduced dosage, thereby ameliorating the side effects. Therefore, this thesis explores Mg-Li alloys as Li-releasing implants by investigating cellular responses of glial cells at the cellular, metabolic and molecular levels. Mg-Li thin film structures were chosen as they are better suited for miniaturized and mechanically compliant neural implants. Two Mg-Li alloys, Mg-1.6Li and Mg-9.5Li, were used in the form of thin films and extracts. Cellular responses relevant to potential applications were investigated in in vitro models developed for neuroinflammation and nerve injury. Mg-Li alloys showed certain anti-inflammatory and neuroprotective effects similar to traditionally administered Li. Moreover, Mg as a carrier material had beneficial effects of its own and no clear antagonistic effects to Li were evident in this study. Therefore, Mg-Li alloys show promise as Li-releasing implants and for other regenerative applications in the nervous system. The results provide valuable insight for material optimization and regarding the application potential of Mg-Li alloys. They also provide a strong basis to support further studies with patient-derived material and in vivo models, innovation in implantation strategies and to expand the application of Mg-Li alloys as biomaterials
Magnesium Polyolefin Interaktionen während der thermischen Entbinderung im MIM Prozess mit Magnesium
No full textMetal injection moulding (MIM) of magnesium has been developed in the recent years with the aim to produce metallic implants for the biomedical sector with unique prop-erties such as a special microstructure which is independent of the part geometry. Powder metallurgy (PM) possesses the benefit of easy and fast alloy development by the mixing of elemental or pre alloyed powders. MIM of magnesium has the potential to combine the benefits of the metallic material, for example the strength and the ones of the plastic injection moulding such as cheap mass production of small and complex shaped parts. However, due to the reactive nature of magnesium a few challenges have to be overcome. Once the sinterability of magnesium was proven the MIM process could be introduced. First trials showed that polyethylene (PE) based polymers, typi-cally used for MIM of reactive materials such as titanium, cause a strong sintering inhibiting effect, while polypropylene (PP) based polymers do not show this effect. Within this work a fundamental understanding of the mechanisms taking place during the thermal debinding of PE and PP based polymers in combination with magnesium powder is developed by using literature and different experimental setups.Metallpulverspritzguss (MIM) von Magnesium wurde in den letzten Jahren mit dem Ziel entwickelt metallische Implantate für biomedizinische Anwendungen mit einzig-artigen Eigenschaften wie insbesondere einer speziellen, geometrieunabhängigen Mik-rostruktur herzustellen. Die Pulvermetallurgie (PM) bietet den Vorteil einfacher und schneller Legierungsentwicklung durch das Mischen von elementar oder vorlegierten Pulvern. MIM von Magnesium bietet das Potential die Vorzüge von metallischen Ma-terialien, unter anderem deren Festigkeit, mit denen des Spritzgussprozesses, insbe-sondere die günstige Herstellung von kleinen komplex geformten Teilen in hohen Stückzahlen, zu verbinden. Durch die reaktive Natur von Magnesium müssen jedoch einige Herausforderungen überwunden werden. Nach dem erfolgreichen Nachweis der Sinterbarkeit von Magnesium konnte dieses in den MIM Prozess eingeführt werden. Erste Versuche haben gezeigt, dass Polyethylen (PE) basierte Polymere, welche typi-scherweise für den MIM Prozess von reaktiven Metallen wie zum Beispiel Titan ge-nutzt werden, einen stark sinterhemmenden Effekt haben. Polypropylen (PP) basierte Polymere zeigen diesen Effekt nicht. Im Rahmen dieser Arbeit wird, durch den Ge-brauch von Literatur und diversen experimentellen Aufbauten, ein grundlegendes Ver-ständnis über die Mechanismen, welche während des thermischen Entbinderns von PP und PE basierten Polymeren in Kombination mit Magnesium auftreten, erarbeitet
Ein Simulationsmodell zur Identifikation von Diffusionskoeffizienten anhand charakteristischer Kenngrößen aus Sinterexperimenten
No full textNew modeling approaches open up ever more possibilities for the simulation of microstructure de-velopment in solid phase sintering. In order to take advantage of these, the validation and use of sin-tering models requires precise knowledge of the material properties, especially the diffusion coeffi-cients. However, hardly any reliable data are currently available for the surface and grain boundary diffusion of most sinter materials. Against this background, a sinter model is developed in the present work and, in order to determine the required but difficult to access material properties on the basis of experimentally determined characteristic parameters, it is used in a method for parameter identifica-tion.
As a simulation model, a two-particle model is developed, in which the material transport is realized using predetermined diffusion paths. The local differences in chemical potential along the diffusion paths are calculated by the derivatives of the interfaces according to the associated volumes. This novel approach allows, for the first time for this class of sinter models, to treat all diffusion mecha-nisms in a uniform way.
The behavior of the model is first validated using experimental data from the literature. It is observed that the diffusion coefficients, for which simulation results are in good agreement with the literature data, can be excellently approximated by an Arrhenius equation. This observation is seen as an im-portant confirmation of the plausibility of the model behavior.
The suitability of the model for parameter identification is demonstrated by determining the interfa-cial diffusion coefficients of titanium. The basis is formed by the characteristic quantities neck growth and shrinkage from experiments designed close to application. The parameter identification, where it is necessary to find the combination of diffusion coefficients that leads to the best agreement of the parameters in simulation and experiment, is formulated as a scalar optimization task and solved with a particle swarm algorithm. Potential for improvement is recognized in the experimental design, since the experiments for the -phase of titanium provide an ambiguous result. The sintering model itself, however, is again confirmed by the predictive behavior shown in comparative experiments.
The final comparison of the own model compared to a particle pair modelled with the phase field method reveals differences in the modelling and in the model behavior, which rather suggests the validation of phase field models based on experiments than to question the model developed here. For sintering models using the phase field method, the modelling of shrinkage in particular is per-ceived as insufficient. The need for precise knowledge of the diffusion properties for their validation once again illustrates the need for methods to determine diffusion coefficients, as developed in this thesis
Zellreaktionen auf biologisch abbaubare Magnesium-basierte Materialien : chondrogene Differenzierung
No full textBone growth in children is regulated by cartilaginous areas named growth plates, which are vulnerable to damage. Implant application and removal can cause damage of those areas and generate irreversible bone malformations. Biodegradable magnesium (Mg)-based materials are a potential alternative to permanent implants, avoiding implant removal. Nevertheless effects of those materials on growth plate
cartilage need to be evaluated.
In vitro chondrogenic differentiation of human umbilical cord perivascular (HUCPV) stem cells and ATDC5 chondrogenic cell line was evaluated under the influence of pure Mg (Mg), Mg with 10 wt% of gadolinium (Mg-10Gd) and Mg with 2 wt% of silver (Mg-2Ag) extracts. Specifically, gene expression, cell growth, morphology and
extracellular matrix (ECM) production were studied after seven, 14 and 21 days.
Additionally, proteomic studies allowed the identification of proteins regulated under the influence of the extracts. After seven days of direct culture on the materials, cell growth, distribution and ECM synthesis were investigated, together with the composition of the resulting degradation layer on the materials.
Results indicated that the three materials have chondrogenic potential, being stronger in Mg-10Gd, which induced chondrocyte maturation or hypertrophy. Cell coverage and ECM production in direct contact with the samples was influenced by the homogeneity of the degradation layer, being higher in Mg-10Gd and Mg-2Ag than in Mg samples. Furthermore, chondrogenesis of cells in direct contact with the materials was enhanced with both HUCPV and ATDC5 cells.
This study confirmed the tolerance of cells involved in bone growth to Mg-based materials, which shows its possible potential for treating children´s fractures.Das Knochenwachstum bei Kindern wird in knorpeligen Bereichen reguliert, die als Wachstumsplatten bezeichnet werden und anfällig für Schäden sind. Das Einfügen und Entfernen von Implantaten kann zu Schäden und irreversible Knochenfehlbildungen in diesen Bereichen führen. Biologisch abbaubare Magnesium (Mg)-basierte Materialien sind eine potentielle Alternative zu permanenten Implantaten, um eine Implantatentfernung zu umgehen. Allerdings müssen dafür zunächst mögliche negative Effekte dieser Materialien auf den
Wachstumsplattenknorpel bewertet werden.
Die chondrogene Differenzierung von perivaskulären Stammzellen der menschlichen Nabelschnur (HUCPV) und von einer chondrogenen Zelllinie (ATDC5) wurde in vitro unter dem Einfluss von Extrakten aus reinem Mg (Mg), Mg mit 10 % Gadolinium (Mg-10Gd) und Mg mit 2 % Silber (Mg-2Ag) - untersucht. Nach 7, 14 und 21 Tagen
wurde die Genexpression, das Zellwachstum, die Morphologie und die extrazelluläre Matrix (EZM)-Produktion bewertet. Zusätzlich erlaubten Massenspektrometrie Studien die Identifizierung von Proteinen, die unter dem Einfluss der Extrakte
reguliert wurden. Bei der direkter Kultur auf den Materialien wurden nach 7 Tagen das Zellwachstum, die Verteilung der Zellen und die EZM-Synthese zusammen mit der Zusammensetzung der Abbauprodukte auf der Oberflächenschicht der
Materialien untersucht. Die Ergebnisse zeigten, dass die drei Mg-Materialien ein chondrogenes Potential
aufweisen. Bei Mg-10Gd ist dieses am stärksten, da eine Chondrozytenreifung oder Hypertrophie induziert wurde. Die Zellabdeckung und die EZM-Produktion in direktem Kontakt mit den Proben wurde durch die Homogenität der Degradationsschicht beeinflusst, die bei Mg-10Gd und Mg-2Ag höher war als bei
Mg-Proben. Weiterhin wurde durch direkten Kontakt mit den Materialien sowohl bei HUCPV als auch ATDC5-Zellen die Chondrogenese der Zellen verstärkt. Diese Studie bestätigt die Toleranz der am Knochenwachstum beteiligten Zellenfür
Mg-basierte Materialien was ein mögliches Potenzial für die Behandlung von Frakturen bei Kindern zeigt
In Vitro Bewertung der Zytokompatibilität Magnesium-basierter Implantatmaterialien mit Osteoklasten
No full textGenetische Regulierung von osteoblastischen Zellen als Reaktion auf Magnesiumkorrosion
No full textMagnesium-based implants exhibit several advantages, such as biodegradability and the enhancement of in vivo bone formation. Nonetheless, the degradation of magnesium may induce cell type-specific modifications of metabolism, which still remain unclear. To examine the mechanisms of osteoinduction, the reaction of bone-derived cells (U2OS, MG63, and SaoS2 cells and primary human osteoblasts (OB)) to magnesium (Mg) was analysed. Magnesium salt (MgCl2) was used as the simplest model system. Additionally, magnesium-based extracts were then applied to create more realistic magnesium degradation conditions. In a third approach, the cells were incubated directly on magnesium metal to investigate the influence of direct contact on metabolism.
The relations between cell count, viability, and cell size and the presence of magnesium were investigated to analyse the effects on proliferation and differentiation. Additionally, the cells were seeded directly on top of pre-incubated magnesium samples, and the number of focal adhesions was analysed. Furthermore, the expression of genes involved in bone metabolism was determined by qPCR. The analysed conditions were verified with a proteomics approach analysing primary human osteoblasts.
As an in vitro model system, MgCl2 yielded very heterogeneous results. Magnesium-based extracts indicated no particular stimulus, depending on the selected cell line. In contrast to these results, the experiments performed using primary human osteoblasts were remarkably different. Some osteoinductive reactions were detected for primary human osteoblasts:
I. Increased cell counts after extract addition;
II. Increased cell sizes in combination with augmented adhesion behaviour after MgCl2 and extract exposure; and
III. Bone remodelling gene expression patterns were observed for nearly all analysed conditions.
Thus, it can be concluded that magnesium induces enhanced in vivo bone formation in combination with other degradation factors.
Proteomics revealed distinct differences in the patterns obtained under the various conditions. Osteoinductive features were confirmed at the protein level. Most striking was the frequent occurrence of calcium (Ca) binding proteins and proteins involved in cell metabolism or cell structure.
In conclusion, the results obtained using the cell lines were heterogeneous and showed no specific stimulation after magnesium exposure, whereas a distinct osteoinductive effect could be demonstrated with primary human osteoblasts.Magnesium-basierte Implantate weisen eine Reihe von Vorteilen, wie z. B. die biologische Abbaubarkeit und die Verbesserung der Knochenbildung in vivo, auf. Nichtsdestotrotz kann der Magnesiumabbau im Körper zelltypspezifische Änderungen des Stoffwechsels induzieren, welche nach jetzigem Stand der Forschung noch ungeklärt sind. Um die Mechanismen der Osteoinduktion zu untersuchen, wurde die Reaktion von Knochenzellen (U2OS, MG63, SaoS2, primäre humane Osteoblasten (OB)) nach Magnesiumexposition (Mg) analysiert. Magnesiumchlorid (MgCl2) wurde als das einfachste Modellsystem verwendet. Um Abbaubedingungen in vivo möglichst realistisch darzustellen, wurden zusätzlich magnesiumbasierte Extrakte verwendet. In einem dritten Schritt wurden die Zellen direkt auf dem Magnesium inkubiert, um den Einfluss des direkten Kontaktes auf den Stoffwechsel zu bestimmen.
Der Einfluss von Magnesium auf Zellzahl, Viabilität und Zellgröße wurde analysiert, um dessen Effekt auf die Proliferation und Differenzierung zu ermitteln. Die Zellen wurden direkt auf den vorinkubierten Magnesiumproben ausgesät und zusätzlich die Anzahl der fokalen Adhäsionen ermittelt. Zusätzlich wurde mittels qPCR die Expression von Genen bestimmt, die am Knochenstoffwechsel beteiligt sind. Die zuvor untersuchten Bedingungen wurden mit einem Proteomansatz und primären humanen Osteoblasten verifiziert.
MgCl2 als in vitro Modellsystem wies sehr heterogene Ergebnisse auf. Magnesium-basierte Extrakte zeigten keinen besonderen Stimulus auf die verwendeten Osteosarkomzelllinien. Im Vergleich konnte bei Verwendung von primären humanen Osteoblasten ein gegenläufiges Bild gezeigt werden. Die Ergebnisse zeigen folgende Hinweise auf Osteoinduktion bei Verwendung von primären humanen Osterblasten:
I. Eine erhöhte Zellzahl nach Extrakt-Exposition;
II. Erhöhte Zellgrößen in Kombination mit einem verstärkten Haftverhalten nach MgCl2 und Extrakt-Exposition;
III. Genexpressionsmuster, die den Knochenumbau unter fast allen analysierten Bedingungen begünstigen.
Diese Ergebnisse lassen den Schluss zu, dass Magnesium, in Kombination mit anderen Abbaufaktoren, die Knochenbildung in vivo induziert. Die Ergebnisse aus der Proteom-analyse zeigten deutliche Unterschiede in den Expressionsmustern unter den verschiedenen Bedingungen. Die osteoinduktiven Eigenschaften konnten auf Proteinebene bestätigt werden. Am Häufigsten zeigte sich ein erhöhtes Auftreten von Calcium (Ca)-bindenden Proteinen sowie von Proteinen, die am Zellstoffwechsel oder der Zellstruktur beteiligt sind. Zusammenfassend sind die Ergebnisse, die mit den Zelllinien erzielt wurden heterogen und zeigten keine spezifischen Stimuli nach Magnesiumexposition, während bei primären Osteoblasten ein eindeutiger osterinduktiver Effekt zu sehen ist
Ensuring the in vitro degradation reproducibility of powder metallurgy processed Mg 0.6Ca system
No full textMagnesium degradation is a complex phenomenon that is too difficult to be described by a single influential parameter. Magnesium degradation is often influenced by either overtaking or overlapping factors like the cell culture medium composition, physiological conditions, impurities, and material’s internal microstructure, etc. This poses a challenge in obtaining the reproducible degradation results. Hence, in the present work, microstructural features like porosity and grain size distributions in powder metallurgy (PM) Mg-0.6Ca system were discretely evaluated for their roles in altering the specimen in vitro degradation rates. Importance was also given to the specimen impurity and mechanical properties. Based on the results, the limitations in PM processing conditions towards obtaining robust degradation results or, in other words, the material parameter thresholds to be realized for obtaining reproducible degradation profiles in PM Mg-0.6Ca specimens were put forth. Additionally, using literature evidence, the mechanisms governing pore closure and grain growth during liquid phase sintering of Mg-0.6Ca specimens from the PM processing perspective were determined.
PM Mg-0.6Ca specimens were fabricated via powder blending of pure magnesium and master alloy Mg-10Ca powders. Specimens of seven different porosities, from 3% to 21%, were produced by varying sintering temperatures. Specimens with heterogeneous grain size distributions were obtained by surface modification of pure magnesium powders by means of a mechanical sieving treatment. Degradation profiles were analyzed in vitro using a semi static immersion test for 16 days under physiological conditions of 37 °C, 20% O2, 5% CO2, 95% relative humidity. Dulbecco’s modified Eagle’s medium was used as cell culture medium with Glutamax and 10% fetal bovine serum as supplements. Mechanical properties were determined using micro tensile specimens. The results indicate that low mean degradation rates (MDR 95% to ≤ 45% when falling below this value. Similarly, the pore interconnectivity sharply drops from > 95% to < 10% at this porosity, thereby enhancing the degradation reproducibility. From PM processing perspective, the sintering temperature of 570 °C is proven as beneficial to promote liquid fractions high enough to enhance specimen sinter density. The present work also showed that heterogeneous grain growth is prompted by the reduced oxide pinning effect at the grain boundaries during sintering of PM Mg-0.6Ca specimens. The heterogeneous grain growth additionally induced the formation of eutectic lamellar structure α-Mg + Mg2Ca at certain grain boundaries throughout the microstructure, which is otherwise not evident in specimens with a homogeneous grain size. Based on the literature and results of the present work, it is postulated that this eutectic structure is the major reason for a non-reproducible degradation in PM Mg-0.6Ca specimens possessing a heterogeneous grain structure. Though mechanical properties are not majorly affected, it is recommended that heterogeneous grain growth is to be avoided in PM Mg-0.6Ca specimens. The presented results also implicitly conveyed the flexibility of PM as a viable technique to design Mg-Ca materials with tailor made degradation and mechanical strengths
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