Page 23 - Magnesium-based supports for stem cell therapy of vascular disease - Mónica Echeverry Rendón

BIODEGRADABLE MAGNESIUM-BASED SUPPORTS FOR THERAPY OF VASCULAR DISEASE A GENERAL VIEW
is considered biocompatible, non-toxic, and it is actively involved in the deposition process of biological apatite and consequently in the formation of bone [26]. Magnesium (Mg) is an important element for the body and daily doses are needed, rendering magnesium a promising material for cardiovascular applications. This relates to its proper me- chanical behavior and biological properties. As an alkaline earth metal its surface properties are uniquely suitable for modification and surface chemistry control. However, a major challenge for application of magnesium as biomaterial is its corrosion properties. The corrosion rate of Mg is about 2.89 mm/year in 0.9% NaCl in which hydrogen evolution reaction is involved. That is how per each atom of corroded Mg one molecule of hydrogen is produced. Although this gas is not toxic, it’s accumulation in cavities might be [7]. Over the last decade, more studies have been concentrated on improving the rates of degradability of this material by adding alloy elements and via surface modification of the material with a protective layer against corrosion. Moreover, the biomaterial interface can be quite sensitive to its bioactive environment and surface properties not only have intrinsic features but these can be dynamic and transform during exposure to complex, extreme bioactive environments [45]. The ability to design bioactive ma- terials that can respond favorably with enhanced surface properties yet maintaining effective bulk properties has opened opportunities for new biomaterials surface modification approaches that can with a high degree of selectiv- ity and control result in optimal bioresorbable materials and in particular Mg-based materials for the regeneration of damaged blood vessels [46,47]. One surface modification approach is the use of anodization as a viable option and strategy to modify surfaces [48,49]. Using this technique, the thickness, composition and morphology of the passive layer can be controlled through variation of parameters such as electrolyte composition, voltage, current density and time. An alternative and in some cases a complementary surface-modification technique is the use of plasma-irradiation driven treatments to modify the biomaterial surface. Plasma modification can provide a high fidelity and refined method to control the surface properties at physical scales that can dominate protein adhesion and cell proliferation [45]. With these alternatives, an effective and viable set of surface modification methodolo- gies could be envisioned for Mg-based biomaterials expanding its use for biomedical applications as in the case of cardiovascular diseases.
Magnesium was discovered in 1755 by Joseph Black and already within years after the discovery, researchers ex- plored the use of magnesium as biodegradable implants such as staples or screws. The characteristics of this material makes it an interesting option for orthopedic replacements of bone and for cardiovascular applications in the manu- facturing of stents [26]. For this last field, the pioneer was the physician Edward C. Huse who in 1878 used Mg wires in humans to bind blood vessels obtaining successful results [50–52]. Prior to that, the famous physician/surgeon, Erwin Payr, used magnesium implants to make wires, tubes pins, plates, cramps and nails, which were used in his clinical interventions in particular transplantations [50,51]. In these previous cases, Mg was successfully used in its pure metallic form (c.p Mg), where the element of Mg was in approximately 99.9 % and the rest small quantity of impurities, but progress was hampered due to its fast degradation and concurrent release of hydrogen. In general, the degradation behavior of c.p Mg negatively affects tissue healing and formation of new tissue. The high local concentration of Mg ions is cytotoxic and causes tissue necrosis. Formation of gas accumulations, due to acceler- ated degradation of material near to the implant, may also cause separation of the tissue and the implant due to production of gas cavities, delaying the healing process and in some cases inducing necrosis in the surrounding area [52,53]. However, the effect of hydrogen production can be more critical for bone applications in comparison with cardiovascular devices as the latter are usually part of a dynamic system were blood flow can remove and control the gas evolution by mass transport. On the other hand, blood clotting may increase with gas hydrogen production. Not- withstanding, if the H2 production is so high and depending of the anatomical location of the stent, the production of gas bubbles could mostly or completely “block blood” flow causing death however most due to the dissolution of the hydrogen in blood is fast this risk is low [42,50,54]. In addition, previous studies of composition of gas cavities in tissue produced after degradation of magnesium, show that also N2, O2 and CO2 are involved in this process were hydrogen is quickly exchanged for these other gases and consequently the problem associated with H2 evolution in Mg implants might not be so hard to solve [55]. In any case, as a consequence of this situation , Mg was severely
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