Magnesium-based supports for stem cell therapy of vascular disease

Monica Echeverry Rendon

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    Magnesium (Mg) is a widely used material in industrial applications due its low weight, ductility and good mechanical properties. For clinical applications such as non-permanent implants Mg is considered as a good option because it is biodegradable and its degradation products are not harmful for the human body. Moreover, Mg is essential element in the biology of mammals. However, Mg is chemically reactive and hydrogen gas is released as part of the oxidation i.e. degradation. Pockets of hydrogen gas may develop at implant sites and cause unwanted tissue necrosis. Fortunately, the degradation rate can be altered by physico-chemical modification of the material and may alleviate adverse biological responses. A successful procedure is plasma electrolytic oxidation (PEO) technique, which generates as a surface layer of MgO/Mg(OH)2 in a controlled way. Thus the degradation rate of the Mg can be carefully tuned and reduced. An additional advantage of PEO is that properly designed topographical surfaces can be produced that improve adhesion and function of e.g. therapeutic stem cells. The aims of this work was firstly to use PEO to modify the surface of c.p Mg (chemically pure Mg) in order to improve its degradation considering using this support to deliver therapeutic cells that augment healing of vascular lesions. A second major aim was to set off the development of therapeutic devices that synchronize the degradation of the material with the progress of the tissue healing in particular after balloon catheterization of atherosclerotic arteries and placing magnesium-based stents. This thesis contains in the different chapters a complete study of modified magnesium from both a material and a biological perspective. This work started with the production, optimization and characterization of the material. After that, a biological validation was performed based on in vitro and ex vivo assays, performed under static and dynamic conditions with different cell types related to blood vessels (arteries) including endothelial cells, smooth muscle cells, macrophages and fibroblasts. Additionally, cell-material interaction and therapeutically effect of adipose tissue-derived stromal/stem cells cultured on the surfaces was studied. This work yielded prototype coatings that reduce the degradation rate of the material, while improving biocompatibility, in particular under hemodynamic conditions. The complexity to develop the idea to a final product is large and requires further investment in time and investigation to achieve the final goal of a biofunctional, biodegradable cardiovascular stent, for which we made the first pioneering steps. We conclude that modification c.p Mg implants by PEO technique is promising for cardiovascular devices that support the healing of the vascular lesion by delivering of stem cells.
    Originele taal-2English
    KwalificatieDoctor of Philosophy
    Begeleider(s)/adviseur
    • Harmsen, Marco, Supervisor
    • Echeverria, F., Supervisor, Externe Persoon
    • Robledo, Sara, Co-supervisor, Externe Persoon
    • Krenning, Guido, Co-supervisor
    Datum van toekenning24-okt-2018
    Plaats van publicatie[Groningen]
    Uitgever
    Gedrukte ISBN's978-94-034-1112-5
    Elektronische ISBN's978-94-034-1111-8
    StatusPublished - 2018

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