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The Development of Biodegradable Flow Diverters for Cerebral Aneurysm Treatment
Olivia Reid • Updated Jun 26, 2024 • 39 hits
The safe and effective treatment of cerebral aneurysms is a critical focus of research in the neurosurgical field. Traditionally, metal flow diverters have been utilized to redirect blood away from aneurysms, promoting clotting. However, neurosurgeon and biomedical engineer Dr. Alim Mitha has pioneered the development of biodegradable flow diverters as a promising alternative. These innovative devices provide comparable therapeutic benefits to metal flow diverters without the necessity for lifelong medication (e.g. long-term antiplatelet therapy). This advancement not only broadens treatment options but also enhances patient outcomes, marking a significant step forward in cerebral aneurysm care.
This article features transcripts for the BackTable Podcast. We’ve provided the highlight reel here, and you can listen to the full podcast below.
The BackTable Brief
• Advancements in flow diverters have improved delivery systems and can now be used to address posterior circulation aneurysms and fusiform aneurysms. However, these new technologies also increase the risk of blood clots due to the higher metal content in the vessels.
• Biodegradable flow diverters can address the challenges associated with long-term antiplatelet therapy; they offer comparable therapeutic benefits without the necessitating lifelong medication, as they gradually dissolve over time.
• Materials for biodegradable diverters are chosen based on degradation timelines that match the typical aneurysm occlusion period, generally around one to two years.
• Precise control over the degradation timeline ensures effective treatment duration while minimizing long-term risks, positioning biodegradable diverters as a promising innovation in cerebral aneurysm care.
Table of Contents
(1) The Role of Flow Diverters in Cerebral Aneurysm Treatment
(2) The Potential of Biodegradable Flow Diverters
(3) Clinical Advantages of Biodegradable Flow Diverters
The Role of Flow Diverters in Cerebral Aneurysm Treatment
Flow diverters are metal mesh devices placed in blood vessels to treat aneurysms by diverting blood flow away from the aneurysm, promoting clotting. They arose as a significant advancement in the treatment of aneurysms, and offer a safer alternative to traditional coiling methods. Flow diverters minimize the need to manipulate the aneurysm dome, reducing the risk of rupture.
Initially approved in 2011, flow diverters have seen improvements in delivery systems and visibility without major structural changes. Indications for their use have expanded from anterior circulation aneurysms to include posterior circulation and fusiform aneurysms. While they reduce procedural risks associated with direct aneurysm intervention, flow diverters do introduce an increased risk of thrombogenesis due to the higher metal content within the vessel.
[Dr. Diana Velazquez-Pimentel]
Great. Interventional neuroradiology might be new to a lot of our listeners, so why don't we take it right from the top? Can you just briefly explain to us what is a flow diverter and what is its role in interventional neuroradiology?
[Dr. Alim Mitha]
Yes. A flow diverter is a metal mesh that is placed inside the blood vessel to treat an aneurysm as opposed to traditional ways of treating an aneurysm through the blood vessels, which includes coiling and requiring the catheter to get into the weakest part of the aneurysm. A flow diverter is very different, in that it is placed in the main blood vessel but not into the aneurysm itself. It has enough material, typically metal, that allows it to divert blood flow away from the aneurysm, causing it to clot off.
[Dr. Diana Velazquez-Pimentel]
Awesome. Is this essentially like an endoluminal reconstruction? That is what's jumping into my mind.
[Dr. Alim Mitha]
Exactly. It's a two-phased approach to treating an aneurysm. The first phase is actually diverting the blood flow and causing the aneurysm to clot off. Then, the second phase is that endoluminal reconstruction that you mentioned, which includes endothelial cells from the patient's body, lining up over the aneurysm neck in order to completely exclude the aneurysm from the circulation.
[Dr. Diana Velazquez-Pimentel]
How have they evolved? Is this a relatively new technology or something that's now quite well-established?
[Dr. Alim Mitha]
Great question. Flow diverters started out as FDA-approved in around 2011. They haven't evolved very much over the past decade or so. They have improved in terms of things like their delivery systems, and in some of the materials that they are made with to make them more radio-opaque or visible for the interventional neuroradiologist or neurosurgeon implanting the device. Overall, the structure of the stent itself has not evolved very much over the last decade.
[Dr. Diana Velazquez-Pimentel]
What about its indications? From the experience I have in medical device development, one of the biggest challenges that we have with new uses of something like a stent, is making sure that we can use it in the patients where we think they might benefit. Has this been the case with flow diverters? What patients can you use these in? Any aneurysm or is it quite selective?
[Dr. Alim Mitha]
Flow diverters are typically used for patients with sidewall aneurysms or fusiform aneurysms. Initially, they were approved for aneurysms of the anterior circulation. Things like a superior hypothesial aneurysm, or a posterior communicating artery aneurysm, or an ophthalmic aneurysm, but that indication has expanded to aneurysms in the posterior circulation and also fusiform aneurysms in the posterior circulation.
[Dr. Diana Velazquez-Pimentel]
Can you just briefly explain what are the benefits of a flow diverter over, for example, a coiling, or an alternative treatment option in this population?
[Dr. Alim Mitha]
Yes. The benefits of flow diversion are that you put the stent inside the main blood vessel and don't actually have to go into the weakest part of the aneurysm, which is the dome. Manipulating devices or putting coils into the dome of the aneurysm is probably the highest risk of the procedure, and a practitioner typically would like to avoid that, if they can. There's a rupture rate of about 10% or so by putting devices into the aneurysm dome. Whereas a flow diverter, you stay in the main blood vessel. You simply deploy the flow diverter into the main blood vessel, without putting a catheter into the dome, and it is much safer from that perspective.
[Dr. Diana Velazquez-Pimentel]
It makes a ton of sense.
[Dr. Alim Mitha]
Yes. The downside of flow diverters, of course, is that you're putting something into the main blood vessel and something with quite a bit more metal than the blood vessel would be exposed to in the case of say, an aneurysm bridging stent. The thrombogenic risk is probably the biggest risk of a flow diverter.
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The Potential of Biodegradable Flow Diverters
The development of biodegradable flow diverters allows for avoidance of long-term antiplatelet therapy in younger cerebral aneurysm patients. Traditional stents, although effective, require long-term medication to prevent thrombosis, which is especially concerning for younger individuals due to the extended duration of treatment. Biodegradable stents aim to offer the same initial therapeutic benefits by diverting blood flow and promoting aneurysm clotting, but they dissolve over time, which eliminates the need for lifelong antiplatelet therapy.
This innovation leverages advanced materials capable of sustaining structural integrity for the necessary period before safely biodegrading. The materials are chosen based on their mechanical properties and degradation timelines;they aim to match the dissolution period with the typical aneurysm occlusion timeline which is generally around one year or more. This approach not only reduces the risk of thromboembolic events associated with discontinuing antiplatelet therapy but also broadens the treatment options for younger patients, who would otherwise face the long-term implications of permanent stents.
[Dr. Diana Velazquez-Pimentel]
Has this been the basis of your research and the idea behind biodegradable flow diverters? Maybe we should just jump straight in. Why don't you just describe what it is you're building and what are the key advantages of a biodegradable flow diverter?
[Dr. Alim Mitha]
We're getting at where did the idea for a bioabsorbable stent come from?
[Dr. Diana Velazquez-Pimentel]
Yes, let's start there
[Dr. Alim Mitha]
During my training, whenever we considered placing a stent, we always considered the age of the patient. I found it very interesting that we would always consider the age of the patient because we would be less likely to choose to put a stent in patients who are younger. Of course, all intravascular stents require antiplatelet agents. In the decision-making process for how to treat, for instance, a wide neck aneurysm in an older patient, stenting or stent-assisted coiling seems like a reasonable first choice. When you look at a younger patient, we would always put stenting lower down on the list, and often prioritizing surgical clipping in a younger patient over leaving anything behind in their blood vessel for a long period of time. This was, even more, an issue when flow-diverting stents came on the market around 2011, since these stents have so much more metal and they require even a longer duration of dual antiplatelet therapy compared to the aneurysm-bridging stent.
[Dr. Diana Velazquez-Pimentel]
Just to be explicit, your concern is them thrombosing off and causing a major stroke?
[Dr. Alim Mitha]
Exactly. We all know patients who have been on dual antiplatelet therapy and then they transition to single antiplatelet therapy after a flow-diverting stent, say even, six months later, which is when a lot of physicians recommend to stop one antiplatelet and just continue on the other antiplatelet, like aspirin. Then, they stop the aspirin at some point for whatever, a surgical procedure, and then they get a thromboembolic event. So they have to stay on the aspirin for the rest of their lives. When you want to subject a younger patient to the requirement of being on an antiplatelet for the rest of their lives, you always think twice about doing that.
[Dr. Diana Velazquez-Pimentel]
Just to bring you back to where the idea came from, you mentioned you're doing your neurosurgical residency, you're working as a neurosurgeon, and it's bizarre, you're in these MDT discussions, multidisciplinary discussions, and you're choosing not to treat young patients. What was the next inspiration? What made you think, "I've got to do something about this."
[Dr. Alim Mitha]
Thinking about how to make the technology more available and effective for younger patients without necessarily having them have the long-term repercussions of antiplatelet therapy. The most obvious thing is to actually create a stent that serves its purpose, for the time it needs to serve its purpose, and then just dissolve over time so the patient can then not worry about having to take the blood thinners.
At that time, newer materials were coming out, there were other fields that were incorporating absorbable components into their implants and devices, and so it was logical to try to make an absorbable stent. It would have been very difficult to try to get some of those stents up into the intracranial circulation through tortuous pathways. Then, we shifted our thinking a little bit and went to a braided design. With the help of very talented people and students along the way, we designed and prototyped a braided bioabsorbable stent.
[Dr. Diana Velazquez-Pimentel]
That's awesome, and tell me a little bit more about how it works. You have a young patient, they have an aneurysm, you're using this stent-flow diverter, like any other flow diverter. You're bridging the main vessel to block off the aneurysm. How long does it last? When you're consenting a patient, how long can they expect it to be there for?
[Dr. Alim Mitha]
Different materials can actually be tuned to last a different amount of time. What we were thinking about when we chose a material was how long it typically takes for an aneurysm to go away. We know that there's data out there that says aneurysms typically take about one year or more to actually occlude after you put in a flow-diverting stent, and that occlusion rate actually increases over the first couple of years.
We wanted our device to stick around for at least that long and then go away. That's how we approached choosing a material. These materials nowadays, as I mentioned, you can choose a host of different polymers that have different mechanical characteristics, and based on their processing and their molecular weight, they can dissolve at different time points.
Clinical Advantages of Biodegradable Flow Diverters
Biodegradable flow diverters offer significant advantages over metal stents, particularly in terms of imaging and clinical application. Without the metal, these stents avoid the artifact that can obscure CT and MRI scans, allowing for clearer, non-invasive imaging and reducing the need for invasive digital subtraction angiograms. This improvement is crucial for younger patients who may need lifetime imaging for various reasons.
Additionally, the softer, more conformable nature of polymers reduces risks like intimal hyperplasia and adverse blood flow alterations seen with stiffer metal stents. Current materials include poly-L-lactic acid, polyglycolic acid, and polycaprolactone, yet advances in material science are continuing to arise. These polymers enable precise control over the degradation timeline, ensuring the stent remains effective for the necessary period while minimizing long-term risks.
[Dr. Diana Velazquez-Pimentel]
Let's get into the imaging a little bit more because I find that really interesting. Talk us through, why is having a polymer more beneficial to CT and MRI imaging? You mentioned that it has advantages, but can you explain it a little bit more?
[Dr. Alim Mitha]
The bioabsorbable stent also has benefits in terms of imaging because there's much less, or in some cases, no metal in the bioabsorbable stent. You don't have that artifact that you typically see with metal stents showing up on a CT scan or an MRI scan. Typically a full metal stent, in order to get really good information about any residual aneurysm or the parent vessel, whether there's things like instant stenosis or thrombus, you need to do a digital subtraction angiogram, which is, of course, a more invasive procedure for the patient.
[Dr. Diana Velazquez-Pimentel]
Not to mention, if you put the stent in a young person, over their lifetime they may need brain imaging for any other reason. There's nothing here that's going to stop them from having that, which is amazing. Great to talk through some of the benefits of the biodegradable flow diverter.
You've briefly mentioned this first-in-human trial, and I'm always curious to learn more about your thoughts, what a founder's thoughts are on clinical adoption. There's tons of innovators. They have loads of great ideas, and then when you put it out in the market, people love to ask questions. Physicians are the same all over the world, always questioning, but why? What's the early feedback you've received from physicians? Do you think that there's going to be a big challenge to overcome in getting this out there to the world once it's regulated?
[Dr. Alim Mitha]
Early feedback is very promising in terms of deliverability to be, we want to make it the same as any other metal flow diverting stent on the market that physicians are used to deploying. To actually increase adoption, we really have to approve the value propositions, which we are currently in the process of doing. I think that message will be very important about the benefits of a polymeric bioabsorbable stent compared to the metal ones. That'll be very important for early adoption.
[Dr. Diana Velazquez-Pimentel]
We're not using metal, right? What materials can you use that are stiff enough and have an appropriate mesh density, length, deployability, such that they can function as a flow diverter?
[Dr. Alim Mitha]
I think newer materials will be developed over time that can serve the purpose even better than the materials we have available now. Currently, the materials that we're looking at now to create bioabsorbable stents include things like poly-L-lactic acid, polyglycolic acid, polycaprolactone, things like that, which are polymers that essentially degrade over time.
[Dr. Diana Velazquez-Pimentel]
Are they stiff enough to achieve what a flow diverter does?
[Dr. Alim Mitha]
Yes, that's a great question. Of course, you don't want too much stiffness because metal can sometimes cause bad things to blood vessels if they're too stiff. Things like intimal hyperplasia and changing the direction of blood flow because of their stiffness or causing the blood flow to adapt more to the stent's configuration as opposed to adapting more to the blood vessel. In general, the polymers are a little bit softer and they're a little bit more yielding, so they're less likely to put as much radial force on the inside of a blood vessel but more likely to conform to the blood vessel.
[Dr. Diana Velazquez-Pimentel]
I can imagine that's a huge benefit, especially in the small arteries that are in the brain. What about its deployability? Does using polymers create a problem with the delivery system or is it quite compatible?
[Dr. Alim Mitha]
Using polymers in terms of delivering them is interesting because you don't actually find that you need as stiff of a delivery catheter to get the polymeric stent into place. In general, today's catheters are over-engineered for bioabsorbable stents that may be coming out in the future.
[Dr. Diana Velazquez-Pimentel]
Awesome. In the preclinical lab experiments or any, in the experiments that you've been involved in, how long does it take to degrade? If you put this into, say, a 35-year-old, when can they expect this to be resorbed?
[Dr. Alim Mitha]
These stents can be made out of materials that are actually chosen based on the length of time it takes for them to degrade. Of course, that in turn is typically chosen based on the application of the stent. In the case of a flow-diverting stent for an aneurysm, you usually want the absorbable material to stick around for as long as it typically takes an aneurysm to heal, which is about a year, or up to two years, in that range.
At that point, you want the stent to dissolve or most of the stent to dissolve. If you choose a material that dissolves too quickly, then there can be issues with potentially aneurysms recurring or not being fully treated, meaning that the endothelial cells don't actually line up and create that new blood vessel wall or a parent vessel wall that you want to fully exclude the aneurysm from the circulation. I would think in this application, you would want the stent to stick around for at least a couple of years.
[Dr. Diana Velazquez-Pimentel]
Has material science advanced enough so that we can be confident that it is only going to last two years? Or is this something that is still to be answered?
[Dr. Alim Mitha]
Material science has actually come a long way and you can choose the same material and actually get a different molecular weight out of that material depending on how you process it. Then, that molecular weight actually in turn feeds into how long it will take for it to absorb. You can certainly choose materials and specifically their molecular weight to actually design when you want the stent to go away.
Podcast Contributors
Dr. Alim Mitha
Dr. Alim Mitha is a cerebrovascular / endovascular / skull base neurosurgeon at the Foothills Medical Centre in Calgary, Canada, and the co-founder, president, and CTO of Fluid Biomed Inc.
Dr. Diana Velazquez-Pimentel
Dr. Diana Velazquez-Pimentel is practicing physician and an NHS Clinical Entrepreneur in London.
Cite This Podcast
BackTable, LLC (Producer). (2024, January 17). Ep. 406 – Biodegradable Flow Diverters for Cerebral Aneurysms [Audio podcast]. Retrieved from https://www.backtable.com
Disclaimer: The Materials available on BackTable.com are for informational and educational purposes only and are not a substitute for the professional judgment of a healthcare professional in diagnosing and treating patients. The opinions expressed by participants of the BackTable Podcast belong solely to the participants, and do not necessarily reflect the views of BackTable.
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