The document discusses the development of tissue engineered stents. It notes that stents are now being developed for uses beyond blood vessels, such as in the lungs, gastrointestinal tract, and heart. Early stents caused restenosis due to an inability to regenerate a healthy endothelial layer. Drug-eluting stents were developed to address this but can cause thrombosis if drug therapy is stopped. Newer designs aim to suppress smooth muscle proliferation while promoting endothelial regeneration using materials like nitric oxide donors. Polymer-free stents with microscale surface features also aim to optimize drug delivery and endothelial attachment.

1. Tissue Engineering of Stents
BY Dr. S.SREEREMYA
FACULTY OF BIOLOGY

2. •
• The adaptability of the stent concept has mainly opened horizons
beyond the vasculature, with stent technology now being
developed for, amongst others, pulmonary, gastro-intestinal and
structural heart applications. There were inter-woven themes that
mainly illustrate the complexity and multi-disciplinary character of
the modern medical stenting domain (Brown et al., 2009):
• The importance of the real-world clinical data in assessing stent
performance Mathematical modeling, both computational and
analytical, covering solid mechanics, fluid mechanics, fluid–
structure interaction (FSI) techniques, and diffusion and transport
modeling Modelling informed and validated by the experimental
information, including in vitro and in vivo data (pre-clinical and
clinical) Drug eluting the stents (DES),

3. • In-stent restenosis (ISR) is the paving cause of stent failure and is a
direct result of a dysfunctional vascular endothelium and
subsequent overgrowth of vascular smooth muscle tissue.
TiO2nanotubular (NT) arrays have been mainly found to affect
vascular endothelial cells (VECs) and vascular smooth muscle cells
(VSMCs) in vitro by accelerating VEC cell proliferation and
themigration while suppressing VSMCs. This study analyses for the
first time the potentially beneficial effects of TiO2 NT arrays on
vascular tissue in vivo. Drug-Eluting Stents
• The current clinically approved drug-eluting stents mainly release
drugs locally that suppress vascular smooth muscle cell
proliferation. These stents have the added pros of suppressing the
autocrine and paracrine mechanisms responsible for excessive
generation of extracellular matrix proteins. All currently available
drug-eluting stents also suppress local regeneration of the natural
endothelium.

4. • Consequently, the endothelial monolayer may not completely
regenerate much across the surface of the stent, paving to the loss
of a key homeostatic feature that regulates interactions of the
vessel wall with the circulating blood elements. For this reason,
stent-related thrombosis has mainly emerged as a life-threatening
side effect of the drug-eluting stent, primarily among patients who
have suspended any adjunctive antiplatelet or the anticoagulant
therapy. Stent thrombosis may result in the myocardial infarction or
death in up to 48% of cases. Accordingly, alternative agents for the
elution from the stent that have a more favorable profile (e.g., that
suppress vascular smooth muscle proliferation while enhancing
endothelial regeneration) are under investigation. Paradigmatic of
such agents are nitric oxide donors, which copious endothelial
regeneration while suppressing vascular smooth muscle
proliferation (Brown et al., 2009) .

5. • Typically, the biocompatibility constraint is applicable to specific
drug-eluting stents as well as stents having variable constitutional
and functional properties . The concept of utilizing stent coatings
was initially introduced as the means for trapping ions released
from the metal structure and keeping them from entering the body.
Since the inorganic materials availed for these applications have
demonstrated minimal drug-importing potential, nonbiodegradable
polymeric coatings, such as the polyhydroxyalkanoates (PHA) or
polyurethane, have been developed to transport and locally release
agents from the stent. Although PHA-coated stents have a tendency
to decrease intimal thickness relative to bare metal stents,
hemodynamic shear stresses have contributed to degradation of
the polymer stent surface structure, in turn leading to stent
thrombosis.

7. • Alternatively, biodegradable polymeric stents, while prone to foray
inflammation, are currently used in various phases of developmental and
market research. Novel solutions are being tested availing stents with
polymer-free macro- and nano features that provide a nonthrombogenic
surface to suppress in-stent restenosis and promote re-endothelialization.
The promise of such nanofeatures resides in their ability to mainly mimic
the natural nanofeatures of vascular tissue itself. Microporous and
Microstructured Surfaces
• The optimal stent is engineered to be much highly deliverable; to inhibit
vascular smooth muscle proliferation and generation of extracellular
matrix proteins; and to copious endothelial attachment, proliferation, and
restoration of a healthy endothelial surface. The stent must be composed
of metals or polymers that must satisfy biocompatibility constraints and
express adequate mechanical flexibility, strength, and dilatability. Stainless
steel, titanium, cobalt-chromium alloys, and titanium-nickel alloys have
been availed as principal structural elements.

8. • Bare-metal stents fabricated from a titanium-nickel alloy (e.g., Nitinol) are
preferred due to their excellent biocompatibility and structural versatility.
Nevertheless, in-stent restenosis is often attributed to bare-metal stents
having micron particle sizes that articulate and encourage neointimal
tissue formation. Additionally, the release of metal ions from the stent
might increase local inflammation (Sgura et al., 2002).
• Polymer-free microporous, microstructured, and slotted tubular stents are
a class of devices with surface features designed to optimize the stent
applicability. Such stents can be spray coated with the selected drugs that
are absorbed onto surface micropores to allow homogeneous drug
transfer.An alternative polymer-free technology encompasses selective
microstructuring of the abluminal surface of the stainless steel stent
through regulated microabrasion processes. This textured surface enables
coating with cytostatic drugs that can effectively suppress excessive
neointimal tissue formation (Unverdorben et al., 2003).

9. • In 1979, Gruentzig of Switzerland successfully executed percutaneous transluminal
coronary balloon angioplasty in stricture lesion to open up a new era of coronary
artery. This method dilates the balloon to typically widen the stricture lesion,
which brings about the improvement of blood flow with the dilatational balloon to
expand the narrowed coronary artery. Acute obliteration during or right after the
operation, however, may cause death or acute myo-cardial infarction, because 30%
- 42% of restenosis within 6 months occur from constriction and neointimal hyper-
plasia of coronary artery after the balloon dilatation(Mario et al.,2004). Coronary
thrombosis is one heart disease like myocardial infarction (Sreeremya, 2018)
• In the early 1980s, bare metal stent (BMS) was operated on the stricture lesion of
coronary artery with the stent on the balloon and wire mesh on the inner wall of
coronary artery to expand the coronary artery. The insertion of BMS had lower
restenosis occurrence rate than balloon expansion, and the stent played the key
role of supporting the blood vessel inner wall to prevent the contraction of the
coronary artery reducing the restenosis rate to 20% - 40%.

10. • Stent insertion reduced the critical shortfall of balloon expansion which
was the specific stricture of coronary artery with acute recoil, but
mechanical blood vessel damage was caused in the expansion process and
neointimal was formed to cause in stent restenosis. In order to prevent in
stent restenosis, many researches were conducted, and sirolimus
originally developed as immunosuppressant and paclitaxel used as
anticancer drug were reported to effectively suppress formation of
neointimal. The problem was, however, systemic injection of such drugs
interferes with the maintaining the local drug concentration in the stent,
and is prone to serious side effects. In order to overcome such problems
and its concerned traumas, the research to insert the drug on the stent
surface and locally release the drug was conducted. As the result, drug-
eluting stent (DES) was born, but this also has the issue of drug release
control and being unable to maintain appropriate drug concentration. In
order to overcome such limitations of the existing stents, the development
of biodegradable DES was suggested, which is expected to bring the
dramatic change in treatment of coronary arterial diseases.

11. • Journal of Research in Medical and Surgical
Nursing, Tissue Engineering of Stents,
Dr.S.Sreeremya , 2019.Vol 1(1):1-14