The qualitative assessment of biodegradable coronary stents with the use of intravascular ultrasound, optical coherence tomography and histology

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.