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Gül, Burcu (2014): The qualitative assessment of biodegradable coronary stents with the use of intravascular ultrasound, optical coherence tomography and histology. Dissertation, LMU München: Faculty of Medicine



Percutaneous coronary intervention (PCI) is the most common treatment for coronary artery disease (CAD). The first form of PCI introduced was balloon angioplasty. After that, the advent of coronary stents (tubular wire mesh for intravascular mechanical support) led to a new era in interventional cardiology. Through the implantation of bare metal stents (BMS), all three limitations of balloon angioplasty – coronary artery dissection, elastic recoil and negative remodelling – are prevented. Unfortunately, bare metal stents have their own drawbacks: most significantly, in-stent stenosis as a result of deep focal vascular injury caused by stent struts, followed by excessive tissue proliferation. This drawback has since been addressed with the introduction of drug eluting stents (DES). Both BMS and DES are permanent stents. As foreign bodies implanted into coronary vessels, they cause the following adverse effects: hypersensitivity reaction, chronic inflammation, elimination of vasomotion, and stent thrombosis. Biodegradable stents have been set forth as a candidate to overcome the drawbacks of permanent stents through providing temporary mechanical stability for a vulnerable lesion before complete degradation without long-term impairment of vessel function. The two main materials used in biodegradable stents are poly-L-lactide and metal (or AMS, short for absorbable metal stents). One type of AMS is magnesium alloy. Before AMS become a standard in the treatment of CAD, more research is required to better understand their degradation kinetics and mechanical stability. In order to complete these studies, however, the stents must provide adequate opacity for visualization – wherein lies the challenge. It is not possible to visualize magnesium stents with coronary angiography. Newer imaging modalities such as optical coherence tomography (OCT) and intravascular ultrasound (IVUS) have been proposed as techniques to visualize these stents and their biodegradation. The aim of this study was twofold: first, to study the available in-vivo visualization techniques (OCT and IVUS) in order to identify their strengths and weaknesses in assessing the biodegradation process of AMS through comparison with histology; and secondly, to identify a new histological technique for studying the distribution of magnesium and its degradation products into surrounding tissue upon biodegradation. Four Gottingen mini pigs were implanted with AMS and BMS, and assessed with IVUS and OCT under fluoroscopic guidance at the time of implantation and prior to explantation (4 weeks later). Upon completion of the in-vivo studies, the hearts of the study objects were harvested for histological processing. Results showed that both IVUS and OCT are effective visualization techniques in studying the biodegradation process of AMS. IVUS is superior to OCT in capturing vessel morphometry thanks to its ease of use and consistently high image quality, thus enabling us to study vessel dimensions during biodegradation. OCT, however, is a better technique for detailed vessel assessment thanks to its higher resolution, and helps us to detect qualitative changes during biodegradation. The two methods correlate moderately during the morphometric analysis. The histological studies on the other hand showed a poorer correlation with the in-vivo techniques. This was likely due to strut integrity compromised during cryosectioning and subsequently washed away after staining, as in an adjunctive study we were able to show that staining did not affect morphometry. The measurements were consistently largest with IVUS, and the smallest with histology (IVUS > OCT > histology). Though IVUS and OCT together offer a gross understanding of AMS biodegradation, in order to complete this view at a cellular level one must employ a third technique. The technique investigated in this study was titan yellow staining, which proved to be a feasible method for capturing the biodegradation process and the distribution of magnesium within the vessel wall. This study showed for the first time that biodegradable magnesium stents and their degradation products can be visualized effectively ex-vivo, and that analysis of these images will allow us to better understand the changes due to degradation during in-vivo visualization. Its simplicity and speed make titan yellow preferred to the in-vitro corrosion techniques previously employed. The procedure, however, must be further modified in order to improve its effectiveness over a longer period of time. Once this is achieved, it will then be possible to measure the density of degradation products away from struts over time, so as to more thoroughly understand the degradation kinetics.