Page 124 - Magnesium-based supports for stem cell therapy of vascular disease - Mónica Echeverry Rendón

CHAPTER 7
accumulate over time saturating the medium resulting in an exaggerated cytotoxic effect far from the reality. Con- trary, under dynamic system, the mass transfer helps in the diffusion of the hydrogen and other corrosion products. Additionally in this V/A ratios the regulation of the pH by the buffer on the solution is efficient. However the effect of free Mg in the system remained similar under these conditions, implying that the damaging signal in vascular tissue is mainly caused by hypermagnesia.
According with our results from the functional assays, slight affectation of the cells treated with extracts from coated material was observed, however this effect could be temporal and cells were able to recuperate and recovered the function with time. The evaluation of the effect of Mg extracts on the integrity and functionality of the endothelium in coronary arteries from pig, allowed us to evaluate tissue reaction to the placement of the material in the blood vessel. The endothelium plays and crucial role in the vascular homeostasis, and the use of the coatings of Mg showed a decline in the release of the Mg2+, conserving the vasomotor response of the vessel. The production of nitric oxide (NO) are linked with the endothelial-dependent relaxation in which this free radical is produced showed an integrity in the endothelial layer [28]. This process is highly affected by the exposition of the tissue with extracts from pure Mg but not from the extracts from the coated material. Endothelial dysfunction is caused by an imbalance between the relaxation and contacting factors [28]. Damage in the structural configuration of the tissue may lead this kind of complication. The challenge for the stent application will be to repair the endothelium layer before the prolifera- tion of SMCs or fibroblast in the area avoiding structural and functional changes in the blood vessel because this can induce cardiovascular complications such as restenosis. Finally, from this study is possible to conclude that the underlying mechanism of the Mg degradation is still unclear and there a big gap between results obtained in vitro and its extrapolation in vivo.
5. Conclusions
- Modification of Mg by the technique of PEO allows to reduce the degradation rate of the material by obtaining a protective coating composed basically of oxide and magnesium hydroxide.
- In principle, bare Mg affects the viability of ECs and SMCs by the increments of levels of Mg in the surrounding area but not by pH changes where these cells showed to be more resistant.
- Coating obtained in presence of HMT and MAN showed a significant improvement in the biological performance in comparison with the untreated Mg.
- The use of a protective layer consisted of the oxide/hydroxide of the Mg allows to avoid the use of extra elements which could compromise more the compatibility of the material how is the case of some Mg alloys.
- The biological response changed depending of the cell type and the model used for its evaluation, for instance dynamic or static.
- ECs and SMC play and important role in the function of vascular tissue involved and may by directly affected by the placement of a Mg implant.
- Coatings of Mg obtained in this study efficiently reduce the Mg release resulting in better cell viability and vessel function.
- Under dynamic conditions the volume/area ratio is higher than in static model allowing to the buffered system to control the changes on the medium.
- Mass transfer process can be facilitated by the use of flow in the system which make of this a more reproducible method.
References
[1] L.G. Griffith, G. Naughton, Tissue engineering--current challenges and expanding opportunities, Science (80-. ). 295 (2002) 1009–1014.
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