Development and assessment of in vitro simulation approaches to intracerebral haemorrhage

This current PhD Thesis in Neuropathology focuses on the development and assessment of in vitro simulation approaches to intracerebral haemorrhage. The PhD Thesis provides a clinical and experimental neuropathological overview of intracerebral haemorrhage as well as an account of the in vitro simulation approaches to the disease, before proceeding to the presentation of the experimental work designed and performed by the author. The development of the herein presented in vitro simulation approaches to intracerebral haemorrhage was based on the use of an immortalized embryonic murine hippocampal cell-line (mHippoE-14) and its response to oligomycin-A and ferrum or haemin under appropriately selected conditions (aiming to simulate the natural history of the disease in a more reliable manner). The PhD Thesis provides a characterization of the mHippoE-14 cell-line (through a real-time cellular response analysis and a cytomorphological characterization), before proceeding to the actual experimental justification of the conditions chosen for the development of the herein presented in vitro simulation approaches to intracerebral haemorrhage, and their assessment. The latter was performed through the undertaking of: (a) real-time cellular response analysis, (b) cytomorphological assessment, (c) profiling of neuronal markers’ expression, (d) neurochemical assessment, and (e) proteomic profiling. All experiments were performed at the University of Glasgow. The current PhD Thesis also provides a critical appraisal of: (a) the utility, novelty and limitations of the developed in vitro simulation approaches, and (b) the positioning of the developed in vitro simulation approaches within the neuropathopoietic context

Processing And Characterization Of Innovative Magnesium Alloys For Biodegradable Orthopaedic Implants

There is a need for innovation in medical implant devices through novel biomaterials that will improve the quality of life. The first step in the creation of a foundation of knowledge and technology to improve these implant devices is through the creation of new alloys with the capabilities of biodegradation and bioabsorption without a toxic effect that will pass through FDA regulatory procedures. In this study, unique heat treatment processing techniques coupled with innovation in elemental alloying produced distinctive magnesium (Mg) based alloy systems. The MgZnCa system was used as the underpinning system where four groups of novel alloys were developed, which include the as-cast Mg−xZn−0.3Ca system, the heat treated Mg−4.0Zn−0.3Ca system and as-cast and heat treated Mg−1.0Zn−0.3Ca system alloyed with 1.3% rare earth elements. All alloy groups were assessed through immersion corrosion tests utilizing 0.9% NaCl physiological solution and MEMα cell culture medium, tensile and compressive mechanical testing, and cytotoxicity assays. The increase of Zn content in the Mg−xZn−0.3Ca system had an effect on phase precipitation and grain size refinement, which caused an increase in mechanical strength and a reduction of corrosion resistance up to a Zn content of 4.0 wt.%. The cytotoxicity assays determined that the Mg−4.0Zn−0.3Ca system showed negative cytocompatibility with the MC3T3-E1 cell line which can be reduced or eliminated by diluting the interaction between the two. The addition of rare earth elements caused significant grain size refinement, increased corrosion resistance, increased mechanical strength compared to the MgZnCa system, and positive cytocompatibility. Through this research, novel Mg-based alloys were developed with the potential of being employed as orthopaedic biomaterials capable of supporting the mechanical and physical function of an injured tissue throughout the entire healing process