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I'm researching on neurovascular stents and I'm wondering why there is not much about drug-eluting neurovascular flow diverters in the literature? I read in an article that it's because of complex shape of cerebral arteries in comparison to cardiovascular system. But it doesn't look satisfactory to me. Any suggestion or idea is appreciated.

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Despite some superficial similarities, the design of coronary stents and neurovascular stents are quite different. Coronary stents are hard metal, made out of stainless steel. They are quite solid, and if you crush one, it will remain crushed. They are deployed by expanding a balloon at potentially very high pressures (10-20 atm). Coronary stents are relatively short, and are deployed in vessels that are relatively straight given the length of the stent.

Drug-eluting variants of coronary stents are additionally coated in a polymer (i.e., plastic) matrix that contains the active ingredient and releases ('elutes') it over time. The common commercially available drug-eluting stents release anti-proliferative agents to prevent neointimal growth.

The purpose is also somewhat different: you mention flow diverters, so you are likely thinking about the context of aneurysms, where they may be used alongside coils to seal off the aneurysm from the normal flow. They are not providing structural scaffolding to prevent vessel occlusion from atherosclerosis.

Neurovascular stents, including flow diverters, are often made of self-expanding metals like nitinol. They are more flexible, but try to keep their nominal shape. These stents are deployed by retracting a sheath and then they themselves pop out to their nominal diameter. Because of this different deployment strategy, they can also sometimes be retracted and repositioned. The way these stents deploy is a lot more gentle, and they are also typically longer than the coronary varieties. They also may be placed in vessels that can be accessed superficially, such as in the neck. A stainless steel stent in the neck would be a disaster: if you laid pressure on that part of the neck you could permanently collapse the stent. A self-expanding stent will bounce right back open.

Back to your actual question...

The actual purpose of coronary vs flow-diverting stents are different; the purpose of drug-eluting coronary stents, preventing neointimal hyperplasia, is not as relevant in the neurovascular context. Additionally, there are lots of good reasons to use self-expanding metals in the neurovasculature because of tortuous anatomy and superficial vessels in the case of the carotids. The hard plastics that are coated onto steel stents can't be easily placed onto self-expanding stents, so other techniques would need to be developed.

The article you read talking about the complex shape of cerebral arteries is in large part correct.

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  • $\begingroup$ I read in an another article (tandfonline.com/doi/abs/10.1179/016164105X35459) that another concern of using DES in the neurovascular interventions is that it is possible to have a therapeutic drug leakage into cerebrospinal fluid or more disastrously into the brain, which limited the applicability of DES to prevent neointima hyperplasia (i.e. in-stent restensosis) in the intracranial arteries. Any idea or suggestion about this claim? $\endgroup$ – Mehrdad Yousefi Sep 4 '18 at 16:51
  • $\begingroup$ @MehrdadYousefi It could be an issue of concern, just not one of the first I'd have on my list. I'm not aware of any neurological-specific worries with DES drugs like paclitaxel and rapamycin. Pharmacodynamic models that I am familiar with suggest that concentrations of DES drugs are low even in the media, let alone getting through the adventitia, and would be way less than the exposure when those drugs are taken systemically. The study you linked brings it up as an issue but then shows it did not occur in their study (at least not to an extent that they could detect drug in CSF). $\endgroup$ – Bryan Krause Sep 4 '18 at 17:02
  • $\begingroup$ So, I take the last reason that you mentioned in your answer as an interesting argument "The hard plastics that are coated onto steel stents can't be easily placed onto self-expanding stents, so other techniques would need to be developed." As a result, it's pretty much like that coating techniques are not capable to coat self-expanding stents (e.g. Nitinol) with polymeric drug coatings? Am I understanding this correctly? Do you have any reference to support this argument? I really appreciate your help because I need it for my PhD proposal. $\endgroup$ – Mehrdad Yousefi Sep 4 '18 at 17:16
  • $\begingroup$ My knowledge in the field might be outdated, and maybe it is now possible to do, but for example I do see the "Zilver PTX" stent is apparently a nitinol stent with paclitaxel, but it does not use a polymer. One of my concerns would be with how the flexibility of the material would be maintained when coated in plastic, or what would happen to the plastic during flexing (i.e., it could crack and release drug too fast, or produce a surface that is bad for hemocompatibility, etc). That also means that all of the drug is released within 72 hours, however, so not the same as polymer coated. $\endgroup$ – Bryan Krause Sep 4 '18 at 17:23
  • $\begingroup$ Thank you so much for your help! The Zilver PTX gave me a really good keyword to find useful references. Regarding the flexibility of drug coated stents I believe it will not change their flexibility so much because the coating thickness is thin in comparison to other stent's length scales. But for microscopic cracks I think it's possible to develop a polymeric coating with comparable mechanical properties to Nitinol to distribute bending stresses more homogeneously across the stent and its coating to prevent micro-cracks formation. $\endgroup$ – Mehrdad Yousefi Sep 4 '18 at 17:29

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