Page 19 - 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
1. Introduction
Currently, cardiovascular disease (CVD) is a major problem in public health globally, it is the main cause of death [1]. The incidence of CVD strongly relates to ‘improved’ welfare of society, in particular the high caloric intake, high intake of nutrients rich in sugar and fat, while leading an increasingly sessile life. The societal burden both in clinical and economic perspective, rises accordingly. In spite of easy-to-take measurements on diet and lifestyle to reduce this burden, the demand for improved diagnostics and treatments for CVD requires large investments. A promising field for treatment is spawned from tissue engineering and regenerative medicine approaches. Much of the CVD relates to pathologies of the large transport conduits i.e. arteries. These pathologies are the consequence of athero- sclerosis and may present either as occlusive arterial disease e.g. coronary artery disease (CAD) or peripheral artery disease (PAD) or as dilating arterial disease known as aneurysm. This review focuses on occlusive arterial disease. This arterial disease is characterized by intimal (endothelial) dysfunction and by medial dysfunction, in particular compromising the medial smooth muscle cells (SMC). In the case of atherosclerosis and arterial occlusions (stenosis), endothelial dysfunction triggers excessive proliferation of SMCs and arterial stiffening due to excessive secretion of extracellular matrix (ECM) by these SMCs. Current treatment is based on balloon catheterization to open up the artery and placement of a stent to maintain lumen diameter. Stents are expandable tubular medical devices that are wrapped inside catheter in a folded state and unfold after withdrawal of the catheter [2,3]. Bare metal stents are permanent vascular implants that improve the structural integrity of the arterial wall [4–7]. The stent is usually fabricated of biocompatible metals. Conventional materials such as stainless steel, chromo-cobalt alloys, chrome platinum, nickel titanium alloy, among others, have been used to manufacture stents. These materials have been used for decades, however any implanted material that is foreign to the body, will elicit an inflammatory reaction known as the foreign body reaction (FBR). A FBR generally serves to eliminate the implant. The appearance and course of a FBR depends on the type of (bio)material and the tissue in which it is implanted [8,9]. In general, the onset of a FBR is the deposition of serum proteins on the implant, which attract, bind and active the first line of im- munological defense: neutrophilic granulocytes. These short lived leukocytes set the stage of influx of monocytes that differentiate to macrophage in situ. Simultaneously, implants are generally surrounded by a fibrous capsule that comprise of a single layer of fibroblasts to thick rigid capsules. From here on, the FBR differs depending on the implanted material. In case of stenting the fibrous capsule is contributed by medial SMCs. Almost half of the patients with implanted arterial stents, respond by progressive thickening of the media. This obviously causes a renewed narrowing, restenosis, of the vascular lumen.
The market for stents is extensive and a plethora of stents is on the market that differ with respect to structural design and material formulation [10–18]. Metals are frequently used to manufacture stents and a new generation of bioactive materials with resorbable properties gains attention in particular. The advantage of bioresorbable materi- als is the introduction of a temporary, rather than permanent, scaffold to provide the initial necessary mechanical strength that can sustain hemodynamic activity and vascular tissue reconstruction over time while resorbing in the body. In the group of the bioabsorbable materials, magnesium is promising due to its favorable biological and mechanical properties.
Treatment of vascular occlusions, may comprise of balloon angioplasty (BA) followed by placing a bare metal stent (BMS) or drug eluting stent (DES). The use of BA causes acute local damage to the arterial wall. The introduction of metal stents, irrespective of degradability, interferes with the wound healing process of the vascular wall after angioplasty. The aberrant proliferation of SMC warrants interventions such as DES. We anticipate that in the fore- seeable future, bioresorbable stents will be loaded with biologicals such as therapeutic cells to augment vascular healing and normalize the arterial media. In this review, we discuss current studies of magnesium-based alloys and methodologies to modify the surface with the purpose to improve the corrosion resistance and biological behavior.
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