Page 128 - Magnesium-based supports for stem cell therapy of vascular disease - Mónica Echeverry Rendón

CHAPTER 8
General discussion
Throughout this thesis, the problem of providing an alternative solution for the treatment of cardiovascular dis- eases (CVD) such as stenosis has been approached from different perspectives. The urgency to count with a new therapy is closely linked with the high impact that this project could have in society.
The WHO (World Health Organization), expects a 15% global increase of the prevalence of CVD 2010 and 2020. This is due to adverse lifestyle including smoking, high caloric nutrition, stress, physical inactivity and excessive alcohol intake to mention a few [1]. In contrast, global life expectancy has increased and thus also the possibility to contract CVD. Furthermore CVDs are more associated with aging with a higher frequency in people aged over sixty [2][3]. In addition, CVD is a co-morbidity from other diseases in particular type 2 diabetes (T2D) which currently is considered an ‘epidemic’ problem and which is expanding fast too [4]. The costs associated with prevention, diagnosis and treatment of CVD increase steadily. According to the CDC, by 2030 in the USA alone, more than $818 billion per year are spent on medical costs associated with CVD and around $275 billion on lost productivity [5]. Taking these facts into count, it is urgent to search for suitable therapeutic alternatives to impact this field and help to dampen the impact of CVD despite a series of pharmaceutical agents that at least partially, or better: no more than partially, alleviate the burden of CVD.
Currently, tissue engineering and regenerative medicine are disciplines that gain increasing recognition by indus- try, due to significant scientific and clinical progress and success. In the past decades, novel concepts and tech- nologies emerged while scientific research expands in this direction to develop new treatment modalities for CVD patients in need of reliable and fast solutions [6]. In historical perspective, implantable medical devices have been frequently used to functionally repair or replace damaged tissues and organs. In this case the interaction of bio- materials with the implant tissue microenvironment will induce specific biological responses, preferably with a sizeable therapeutic benefit [7]. In this context, bioactive interfaces play a crucial role: this is sensed from the first moment of implantation till integration or degradation. An appropriate bioactive surface or interface is critical for the regeneration or functional recovery of damaged tissue in terms of time, quality and cost [7].
For a long time, the use of magnesium (Mg) as implant material in the body was restricted due its high reactiv- ity, which produces a high alkalization of the surrounding environment accompanied by hydrogen accumulation, which was verified through all of our experiments from the point of view of the material as well as biologically [8]. Currently, those problems are more controlled due to the use of alloys or by surface modifications of the implant [9][10]. PEO is a simple, versatile, and low-cost technique in which the material is oxidized in a controlled way generating a protective layer that decrease the degradation rate of the material. The advantage of using pure Mg implants compared to Mg-based alloys, is that elements released from alloys such as aluminum and chromium might exert local cytotoxicity, while magnesium is not. Some elements in alloys are also nephrotoxic yet difficult to excrete from the body [11][12].
This thesis was established on the hypothesis that a degradable magnesium-based (Mg) vascular implant modified by plasma electrolytic oxidation (PEO) and combined with cell therapy promotes the regeneration of atheroscle- rotic vascular lesions. The process to obtain an implant with final use in humans is time-consuming and requires profound scientific knowledge. In this process, initially a study from a material perspective is required where me- chanical and physicochemical properties should be defined. Subsequently, biological characterization involving both,in vitro and in vivo experiments is needed to validate the hypothesis. Finally, it is important to investigate aspects related with the design of the device as well to approach to strategies for delivering the combination of cells and material in a successful way without compromising the therapeutic function at the place of interest. Our project was an important first approach to the idea while several new scientific questions emerged. A major result is that our research provides a better overview on the options of surface modification of c. p Mg for biological
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