Page 22 - Magnesium-based supports for stem cell therapy of vascular disease - Mónica Echeverry Rendón

CHAPTER 2
4. Why use magnesium as a biomaterial?
Elements such as magnesium (Mg), zinc (Zn), iron (Fe), calcium (Ca) and silicon (Si) are essential for the human body. In the case of Mg, the recommended adult daily dosage is 240-420 mg/day per body, for iron of 8-18 mg/day, for zinc 8-11 mg/day and for silicon 20-50 mg/day [7][36]. After potassium (K+), magnesium (Mg2+) is the second most abundant cation in the intracellular fluid of the human body. In general, 10% of Mg is in free ionized form while the remaining 90% is bound to proteins (e.g. as co-factor for enzymes), nucleic acids, phospholipids and ATP. In the body, 60% of Mg is accumulated in bone, 39% is in the intracellular space and only 1% remains in the extracellular space. In addition, less than one percent of the body’s Mg is in the blood. The exogenous administration of Mg is cardio protective because it reduces mitochondrial production of reactive oxygen species (ROS). Exogenous Mg, prevents also depletion of intracellular pools of magnesium, potassium and calcium, which supports mitochondrial function. Magnesium ions are important co-factors for several enzymes that require Mg for their activity. These enzymes are e.g. involved in transfer processes of phosphate groups including reactions that require energy production (ATP). Mg also interacts with carbohydrates, fats, proteins and the metabolism of electrolytes [37]. In the transport mecha- nisms of Mg, Na+/Mg2+ antiporter and the Ca2+/Mg2+ exchanger both are involved; in this latest case, Mg acts as a natural calcium-channel blocker increasing the levels of prostaglandin E which is both a vasodilator and a platelet inhibitor. In addition, the plasma concentration of Mg directly influence vascular tone [37,38].
Ingested food and supplements are the major source of Mg for the body, the required quantity is absorbed in the intestine by active and passive mechanisms, then transported to different tissues and finally transferred to the cells in the tissues. Excess of Mg is eliminated by the kidneys and expelled in the urine. As was mentioned before, the hu- man body can handle high concentrations of Mg, however, chronic exposure to serum levels above 1.2 mmol/L is toxic and a health risk. The corresponding disorder, hypermagnesemia and is associated with reduced clearance of Mg due to renal dysfunction. Patients with this complication present delays in the formation or thrombin and platelet aggregation; also high risk to contract other problems as neuromuscular toxicity, hypothyroidism and diabetes. On the other hand, a deficiency of Mg or reduction in its dietary intake may increase the risk for diabetes, thrombosis, arthrosclerosis, ischemia, myocardium infarction, hypertension and cardiac arrhythmias [26,37,39,40]. That is how, by the increasing of magnesium doses, the endothelial function and vascular smooth muscle cells contraction can be modulated which decrease the risk for cerebrovascular accidents (CVA) or CVD such as cardiac arrhythmias and hypertension. Mg stimulates the production of vasodilators by endothelium such as prostacyclin and nitric oxide and suppress the inhibitory activity of the sodium-potassium ATPase pump which prevents negative changes in the vascular tone and dysfunctional coagulation[37,41].
5. Biodegradable vascular implants of magnesium
Magnesium is the lightest of all structural metals, its density is 1.738 g/cm3 which is similar to cortical bone which is 1.75–2.1 g/cm3 [26]. Magnesium has a great capacity to absorb kinetic energy while it’s elongation is limited to 2-10% [26] and it has a Young’s modulus of 45 GPa. Its modulus of rigidity, is about 16 GPa which is relatively low when compared to other biomaterials such as titanium (Ti), titanium alloys or steel about 110.3, between 105-120 and 200 GPa respectively. However this is still far from the modulus of tissues such as for the human carotid artery which is around 300kPa (this value change for diastole and systolic pressure and also can change in case of vascu- lar diseases) [43,44]. Nevertheless, Mg is an interesting material for biomedical applications because it reduces the probability of having stress shielding in the material-tissue interface. An example of this is in bone replacement in which Mg has showed a good mechanical behavior because osseous tissue has an elastic modulus of 20 GPa which is relatively close to the elastic modulus of Mg [7,42]; additionally, Mg is easy to machine with high dimensional stability, which facilitates the manufacture of complex shaped parts. [26]. With respect to biological properties, Mg
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