Page 12 - Magnesium-based supports for stem cell therapy of vascular disease - Mónica Echeverry Rendón

CHAPTER 1
Metallic materials are used for fabrication of medical devices to alleviate clinical symptoms of a plethora of diseases and to improve the quality of life of patients. These diseases include cardiovascular disease (CVD), the prime global cause of death [1]. Arterial lesions and occlusions underlie a majority of CVD and have been the particular target of ‘metal-based’ interventions i.e. the use of stents to treat atherosclerotic plaque-related occlusion but also pathologi- cal dilatations i.e. aneurysms [2]. The long term persistence of undegradable materials in the body always elicits a bi- ological response called the foreign body reaction (FBR). The FBR generally causes the formation of a fibrous capsule around the implant, but may additionally cause a long term inflammation, albeit smoldering [3]. Stents implanted in arteries that are damaged by balloon catheterization, may induce a pathological medial hyperplasia that leads to a renewed occlusion of the lumen (restenosis) [4][5]. Currently, drug-eluting stents are highly fashionable to use. These elute mTor inhibitors such as analogs of FK506 and rapamycin, which inhibit proliferation of vascular smooth muscle cells (SMC) and thus prevent restenosis. However, these drugs also reduce endothelial proliferation and thus hamper re-endothelialization of stented lesions [6][7]. In other words, the drug inhibits intima formation which is essential to maintain an anti-coagulatory state. As a consequence, long term clinical studies reveal an increased risk for thrombo- sis. In addition, the elution of the drugs on obviously wears off in time after implantation and with it its therapeutic value. To address these caveats, biodegradable stents have been developed in the past decade, that are based on polymers or degradable metal alloys [8][9][10]. A favorable metal to fabricate biodegradable stents is magnesium (Mg), because magnesium ions are essential to proper functioning of several enzymes and thus essential to sustain human life [11][12]. Nevertheless, the oxidation of magnesium in aqueous solution is rather vigorous and thus Mg demands (surface) modification to control its degradation (corrosion) and resident time in the body at lesion sites.
Fig.1 General therapeutic concept of the present project
Over the past two decades an increasing number of studies reported on the development of magnesium-based de- vices with fine-tuned mechanical properties and increased corrosion resistance. On occasion, alloys of Mg and poten- tially toxic metals such as aluminum or rare earth metals, reduced the biocompatibity in a concentration-dependent fashion, albeit that alloys have a lower corrosion rate [13][14][15]. Thus novel methods to adjust corrosion while maintaining biocompatibility of Mg are warranted. A promising alternative to improve the corrosion resistance of Mg is though the surface modification of the material by using of conversion techniques that involve chemical or stry transformations (read: oxidation), in particular anodization methods [16][17][18].
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