You are here

Article Text

Article menu

Download PDFPDF

New Devices and Techniques
Original research
A novel self-expanding primarily bioabsorbable braided flow-diverting stent for aneurysms: initial safety results
  1. Mehdi Jamshidi1,
  2. Mahmoud Rajabian2,
  3. Michael B Avery3,
  4. Uttandaraman Sundararaj4,
  5. Janet Ronsky5,
  6. Brooke Belanger6,
  7. John H Wong6,
  8. Alim P Mitha1,6
  1. 1 Biomedical Engineering, University of Calgary Schulich School of Engineering, Calgary, Alberta, Canada
  2. 2 MIF Microscopy and Imaging Facility Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada
  3. 3 Clinical Neurosciences, University of Calgary, Calgary, Alberta, Canada
  4. 4 Chemical and Petroleum Engineering, University of Calgary, Calgary, Alberta, Canada
  5. 5 Mechanical and Manufacturing Engineering, University of Calgary, Calgary, Alberta, Canada
  6. 6 Clinical Neurosciences, University of Calgary Cumming School of Medicine, Calgary, Alberta, Canada
  1. Correspondence to Dr Alim P Mitha, Clinical Neurosciences, University of Calgary Cumming School of Medicine, Calgary, AB T2N 1N4, Canada; amitha{at}ucalgary.ca

Abstract

Introduction The advent of metal flow-diverting stents has provided neurointerventionalists with an option for treating aneurysms without requiring manipulations within the aneurysm sac. The large amount of metal in these stents, however, can lead to early and late thrombotic complications, and thus requires long-term antiplatelet agents. Bioabsorbable stents have been postulated to mitigate the risk of these complications. Here we present early data on the first self-expandable primarily bioabsorbable stent for aneurysms.

Methods Braided stents were developed using poly-L-lactic acid fibers with material surface area similar to metal flow diverters. Crush resistance force, hemolysis, and thrombogenicity were determined and compared with existing commercial devices. Stents were deployed in infra-renal rabbit aortas to determine angiographic side branch patency and to study neointima formation for a 1-month follow-up period.

Results Crush resistance force was determined to be on the order of existing commercial devices. Hemolytic behavior was similar to existing metal devices, and thrombogenicity was lower than metal flow-diverting stents. A smooth neointimal layer was found over the absorbable stent surface and all covered side branches were patent at follow-up.

Conclusion The design of self-expanding primarily bioabsorbable flow-diverting stents is possible, and preliminary safety data is consistent with a favorable profile in terms of mechanical behavior, hemocompatibility, side branch patency, and histological effects. Additional in vitro and long-term in vivo studies are in progress and will help determine aneurysm occlusion rates and absorption characteristics of the stent.

  • aneurysm
  • artery
  • blood flow
  • flow diverter
  • stent

https://doi.org/10.1136/neurintsurg-2019-015555

Statistics from Altmetric.com

    Request Permissions

    If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

    Introduction

    Despite the development and success of metal flow-diverting stents for aneurysm treatment, they are still associated with clinically significant long-term complications such as delayed thrombosis, in-stent stenosis, and inducing undesired inflammatory responses leading to neointimal hyperplasia.1 Once aneurysm occlusion occurs and complete blood vessel remodeling and neointima formation has been achieved, which typically occurs within 6–12 months, the stent is likely no longer required: however, stents cannot be removed.2 Their long-term presence may prevent normal arterial growth and vasomotion, limit access to side branches for future procedures, and interfere with radiographic visualization of neighboring structures or pathologies. Furthermore, they require the patient to remain on lifelong antiplatelet agents which results in increased treatment-associated costs, long-term risks of bleeding, and other medication side effects.

    Bioabsorbable stents are postulated as a strategy to mitigate these potential long-term complications by being absorbed after first achieving the short-term goals of stent placement. This can result in many advantages such as: eliminating the long-term rigidity of the stented artery; improving future treatment options by the lack of residual, obstructive materials in the case of aneurysm recurrence; allowing the use of non-invasive imaging techniques in the region without introducing artifact; and obviating the need for lifelong anti-thrombotic drugs after stent dissolution. Bioabsorbable stents and implants in different applications have also shown good biocompatibility and neointimal layer growth before complete absorption.3 4

    Of the bioabsorbable polymers, poly-L-lactic acid (PLLA) has shown promise for intravascular stenting applications.5 On degradation, the carboxyl and hydroxyl end groups of the PLLA produce non-toxic products, i.e. water and carbon dioxide, which themselves do not provoke an immune response or arterial wall inflammation.6 7 Furthermore, degradation is highly predictable, minimizing the risk of embolic complications. However, PLLA does not exhibit shape memory behavior and is thus unable to fully return to its original shape following large deformations. As a result, PLLA has only been widely used in designing non-self-expandable tube laser cut stents mounted on balloons for the coronary circulation.

    To date, there has been very little published on braided bioabsorbable polymeric stents used as flow diverters. In 2013, a report by Wang et al described the development of a partially biodegradable flow-diverting stent comprised of 24 metal fibers and 24 biodegradable polyglycolic acid fibers.8 In 2019, our group described the first self-expanding bioabsorbable flow-diverting stent for brain aneurysms, which was presented at the 2019 Joint Cerebrovascular Section Meeting.9 More recently, Nishi et al published their pilot data on a biodegradable flow-diverting PLLA stent requiring angioplasty for proper deployment.10

    In this article, we describe our novel self-expanding primarily bioabsorbable flow-diverting stent for brain aneurysms, report its physical and mechanical characteristics, initial safety data, and demonstrate the short-term scaffolding properties for neointimal growth. Our device is unique in that it is deliverable using conventional microcatheters, is self-expandable, and does not require angioplasty after deployment.

    Methods

    Three different designs of primarily PLLA stents were manufactured, including 44 PLLA fibers with four metal strands of tantalum-coated nitinol (44/4 stent), 46 PLLA fibers with two metal strands (46/2 stent), and 48 PLLA fibers with no metal strands (48/0 stent). Stents were designed with a 50 micrometer fiber thickness, an inner diameter of 4 mm, and a pitch angle to obtain at least a 60% porosity for in vivo testing in a 3 mm rabbit aorta. After braiding, samples were removed from the cylindrical mandrel and cut at 10–20 mm lengths.

    Stent porosity and pore density

    Magnified images of stents were acquired using a light microscope (Zeiss, Oberkochen, Germany). Porosity and pore density of all stents were measured over an area of 1 mm × 1 mm using ImageJ software (National Institute of Health, USA). Porosity was calculated as the measured empty area of the stent cells per mm2 of stent multiplied by 100%. Pore density was calculated based on the number of cells completely enclosed by stent struts in an area of 1 mm2.

    Crush resistance force comparisons

    Three different commercially available flow-diverting stents were used to compare crush resistance force (CRF) with our three types of manufactured bioabsorbable stents. These commercial stents included the Pipeline Embolization Device (PED) (Medtronic, Dublin, Ireland) (3.75 mm × 20 mm [n=3] and 4.25 mm × 20 mm [n=3]), the P64 stent (Phenox, Bochum, Germany) (4 mm × 18 mm [n=1]), and the Surpass stent (Stryker Neurovascular, Freemont, CA) (3.5 mm × 20 mm [n=1]). Crush resistance force, defined as the force exerted by the stent when exposed to radial compression in one direction, was determined using a BOSE ElectroForce 3200 Load Frame System instrument (TA Instruments, New Castle, DE) with a 5 N load cell. The lower plate was fixed and a reference point for the upper plate was determined in the instrument software to achieve an accurate distance between plates. The starting position was entered as the nominal stent diameter. Stents were then compressed between two plates to 50% of their original diameter and the required force was recorded.

    In vitro thrombogenicity tests

    To assess the hemolytic potential of the stent material, the direct contact methodology described in ASTM F756-17 was used. Briefly, blood for testing was prepared by diluting fresh New Zealand white rabbit blood (obtained from healthy experimental rabbits on Aspirin (10 mg/kg) and Plavix (10 mg/kg) orally, once per day for 1 week) using Dulbecco’s phosphate buffered saline (D-PBS, Millipore-Sigma, USA) to produce a hemoglobin concentration of 10 mg/mL. The (46/2) bioabsorbable stent, a PED, positive control (Buna-N-rubber, Aero Rubber Company, USA), and a negative control (glass) were incubated in tubes containing the blood in a 37°C water bath for 3 hours. At 30-min intervals, the tubes were gently inverted to ensure complete coverage of the samples. After incubation, the fluid was removed from the tube and centrifuged at 750 x g for 10 min. For each of the samples, a 1 mL sample of the supernatant was removed and mixed with 1 mL of Drabkin’s reagent (Millipore-Sigma, USA) and incubated at room temperature for 20 min. The absorbance was read at 540 nm using a Varioskan Lux plate reader (Thermo Fisher, USA). The hemoglobin concentration was determined from a hemoglobin standard curve. The percent mean hemolytic index was calculated for the bioabsorbable stent, the PED, and the negative and positive controls as follows:

    Embedded Image

    All samples were performed in triplicate. A hemolytic value above 5% is considered hemolytic according to ASTM F756-17.

    To assess the thrombosis potential of the test material, a static thrombosis test was used as detailed in ISO 10 993–4. Briefly, 1 cm-long sections of the positive control (non-medical grade silicone, Millipore-Sigma, USA), negative control (glass), competitor sample, and the bioabsorbable stents (n=3 for each group) were prepared and placed into whole rabbit blood (obtained from healthy experimental rabbits). All tubes were incubated in a 37°C water bath for 3 hours. At 30-min intervals, the tubes were gently inverted to ensure complete coverage of the samples. After incubation, samples were carefully removed from the tube and washed gently with D-PBS (Millipore-Sigma, USA). Samples were visualized using an Olympus SZ61 microscope (Olympus, USA) equipped with an Infinity HD camera (Lumenera, USA). The lumen and the outside of the samples were examined for the presence of clotting. Five random fields of view of each sample were captured and analyzed using ImageJ (National Institute of Health, USA) to calculate the percentage of lumen occlusion and percent thrombosis surface coverage of the samples.

    In vivo animal study

    Animal preparation and stent implantation

    All animal experiments were reviewed and approved by the Animal Care Committee at the University of Calgary (Animal Protocol #AC17-0106). Three female New Zealand white rabbits weighing 3±0.2 kg were used for the in vivo portion of the study. Animals were given Aspirin (10 mg/kg) and Plavix (10 mg/kg) orally, once per day, beginning 1 week prior to stent placement to prevent stent thrombosis, and continued daily until euthanasia. Rabbits were anesthetized with an intravenous injection of acepromazine (0.15 mg/kg) into the marginal ear vein and inhaled isofluorane (5% in 100% O2 by facemask). Animals were then intubated and maintained via 2.5% isofluorane in 100% O2 at 1 L/min. Subcutaneous injections of Anafen (1 mg/kg) and buprenorphine (0.03 mg/kg) were administered for analgesia, and Baytril (10 mg/kg) was given for antibiotic prophylaxis. Animals were monitored continuously with electrocardiography, arterial blood pressure, and transcutaneous oxygen saturation. Supportive care was provided using a heating pad to maintain euthermia and intravenous maintenance fluids (0.9% saline) were administered at 30 cc/hr.

    For the initial surgical procedure, the right femoral artery was exposed via cut down. The artery was suture-ligated distally, and a 4 F sheath (Merit Medical, USA) inserted proximal to the ligation. Digital subtraction angiography (DSA) was performed by administering Optiray 240 nonionic contrast dye boluses through the femoral sheath to obtain a baseline view of the aorta and its side branches. The 44/4 bioabsorbable stents were selected for in vivo placement due to their improved radiopacity compared with the 46/2 and 48/0 stents. Stents sterilized using ethylene oxide were loaded into 4F catheters and deployed in the infra-renal aortas of three New Zealand white rabbits, intentionally covering one or more lumbar segmental side branches (figure 3A). Post-stenting angiography was performed through the femoral sheath in the same manner previously described, in order to visualize stent wall apposition and rule out any early thrombus formation. The sheath was then removed, and the femoral artery was suture-ligated proximal to the insertion point. The wound was closed in anatomical layers using 4–0 Vicryl sutures. These subjects were then monitored in our animal housing unit with 12-hour light-dark cycles, and food and water ad libitum. The physical and behavioral conditions of the animals were observed twice on weekdays and once on weekends by trained core facility personnel. Rabbits were sacrificed at 1 month to determine parent vessel and side branch patency, and to characterize neointimal layer growth.

    Figure 3
    Figure 3

    Stent implantation and follow-up results (A) schematic of the stent deployment method into the rabbit aorta with branching lumbar arteries. (B) digital subtraction angiography (DSA) image of the bioabsorbable stent in the infrarenal aorta immediately after deployment. The crisscross pattern of the metal fibers can be identified in this image, and demonstrates the stent covering two lumbar arteries. (C) DSA image taken at 1-month post-stenting showing the patency of the aorta and its side branches covered by the stent. (D) gross image of harvested aorta after 1 month showing good stent wall apposition. (E) histological image of the cross-section of the stented aorta after 1 month showing a neointimal layer covering the stent struts. In the upper part of the figure, a mal-opposed stent strut can be seen with circumferential neointima formation. (F) scanning electron microscopy (SEM) image of the neointimal layer growth over the stent struts after 1 month. (G) high-magnification SEM image of the neointimal layer overlying the stent struts at 1 month. (H) SEM image showing patency of a side branch orifice after 1 month with partial endothelialization of the stent struts overlying the ostium.

    Follow-up and stent harvesting

    One month following stent implantation, rabbits were anesthetized and a 4F sheath was placed into the femoral artery. An angiogram through the femoral sheath was performed using the same technique described in order to confirm patency of the aorta, to again visualize stent wall-apposition, and determine patency of the jailed side branches compared with baseline images. Subsequently, rabbits were sacrificed with 3 mL intracardiac euthanyl. The aorta containing the bioabsorbable stent was delicately harvested and gently irrigated with formalin for 10 min, removing the remaining blood from the artery. The sample was then divided into two sections, one for histomorphological staining and the other for scanning electron microscopy (SEM). The samples were immersed in 20% formalin solution at room temperature for at least 24 hours.

    Histomorphological staining

    The sample was transferred from formalin to 70% ethanol prior to histologic processing. Gross photography of the fixed artery was first obtained using a SZ61 stereo microscope (Olympus). Samples were embedded in a methyl methacrylate resin and processed using a technique described by Rippstein et al.11 Photomicrographs were captured via bright field microscopy and assessed for extent and thickness of neointimal formation. The thickness of neointima formation was quantified by sampling eight radial positions over the stent struts on a representative image.

    Scanning electron microscopy

    SEM was performed on bare and implanted stents, and the latter to assess neointimal layer growth over the stent struts and to visualize the patency of the side branch orifice. Following immersion in formalin for 24 hours, the sample was sequentially dried in ethanol concentrations of 30%, 50%, 70%, 80%, 90%, 95%, then finally 100% ethanol twice. The sample was directly transferred from the second 100% ethanol solution into a 2:1 ethanol-hexamethyldisilazane (HMDS) solution for 20 min, followed by 20 min in a 1:2 ethanol-HMDS, and finally into 100% HMDS for 20 min. After the last step, the sample was transferred to a new 100% HMDS solution and left overnight in the fume hood. After drying, the sample was coated with platinum nanoparticles for SEM imaging.

    Results

    Physical/mechanical properties of stents

    The braiding parameters used to create the stents used in the experiments resulted in braided stents with a porosity of 60% and a pore density of 17 pores/mm2. Stents were deployable through conventional microcatheters with inner diameters of 0.027” while maintaining the ability to self-expand (figure 1). Our studies demonstrated the CRF of commercial intracranial stents to be between 0.56 N for the P64 stent and 2.3 N for the PEDs. By comparison, the mean CRF of our 48/0, 46/2, and 44/4 PLLA stents were 0.45N, 0.85N, and 1.23N, respectively (figure 2).

    Figure 1
    Figure 1

    Structural properties of a fully bioabsorbable self-expandable stent: (A) photograph of the bioabsorbable stent in a position that demonstrates the flexibility of the structure. (B) self-expansion of the stent while being deployed from a microcatheter with an inner diameter of 0.027”. (C) light microscopy image of the stent cells. (D) transferred and edited image (ImageJ software) showing porosity of the stent (~60%) with 40.771% referring to the area of the fiber strands in black color. (E) scanning electron microscopy (SEM) image of the stent structure.

    Figure 2
    Figure 2

    Crush resistance force of commercial stents vs bioabsorbable stents. Data showing crush resistance force of commercial stents compared with three different designs of bioabsorbable stents.

    Thrombogenicity testing

    The hemolytic index of the positive control showed a hemolytic effect (15.5%) while negative control showed a negligible effect (0.02%). The hemolytic indices of the bioabsorbable stents and the PED stent were 0.4% and 0.5%, respectively, the difference of which was not statistically significant (P=0.67, two-tailed unpaired t-test). With regards to static stent thrombosis, the bioabsorbable stent exhibited a significantly lower percent surface coverage of thrombus (2.3%) compared with the PED (3.6%) (P=0.005, mixed effects linear regression to account for potential clustering of measurements within each replicate) (table 1).

    View this table:
    Table 1

    Thrombogenicity and hemolysis results (n=3 for each group)

    In vivo testing

    No complications were encountered during stent placement, and all stents were well-opposed to the aorta on initial post-stenting angiography. Angiographic aortic and side-branch patency was found at the stented segment in all animals at follow-up, with no cases of stent migration (figure 3B and C). All stents demonstrated satisfactory angiographic wall apposition with no obvious endoleaks.

    On gross pathology, good wall apposition of the stent could be seen in the harvested aorta (figure 3D). The histological result illustrated in figure 3E demonstrates a neointimal layer over the stent struts after 1 month. In the upper part of figure 3E mal-opposed stent strut can be seen, but with neointima formation around the strut. The average neointimal layer thickness was 36 µm.

    Scanning electron microscopy confirmed formation of a smooth neointimal layer over the majority of the stent struts at 1 month (figure 3F and G). There were also areas of exposed stent struts that appeared to have broken through a previously developed neointimal layer, but this was believed to be an artifact of tissue processing. In some locations, the stent was noted to be less well opposed to the vessel wall, and thrombus could be seen primarily on the abluminal side of the stent struts. Side branches were also shown to be patent on SEM, with partial endothelialization of the stent struts overlying the ostia (figure 3H).

    Discussion

    Our goal was to develop a stent with the flow-diverting characteristics, thus we aimed to achieve a low porosity and high pore density. Pore density is proportional to fiber number, while porosity is inversely proportional. The range of optimal porosity for flow-diverting stents to divert the blood flow from the neck of aneurysm is 60% to 75%, with pore densities in the 18 to 32 pores/mm2 range.12–14 By our braiding parameters, the porosity and pore density of the stent was in the range of flow-diverting stents. Unpublished initial in vitro studies using the stent deployed in silicone models and performing high frame rate DSA to obtain the mean aneurysm flow amplitude ratio, as well as animal (rabbit and pig model) experiments in which we have deployed stents across aneurysms, have also clearly demonstrated the ability of the stent to divert blood flow, and will be the subject of a separate article.

    Crush resistance force measured by parallel plate fixtures is one of the standard and reliable tests of radial force for comparison purposes, along with chronic outward force and radial resistive force.15 Our studies demonstrated the CRF range of commercial intracranial stents to be between 0.56 N for the P64 stent and 2.0–2.2 N for the PEDs. By comparison, the CRF of our 48/0 PLLA stent was 0.45, which is lower than commercially available metal stents. The mechanical properties (ie, tensile strength and Young’s modulus) of PLLA fibers, however, are significantly lower than most metallic wires such as cobalt-chromium alloys or nitinol (NiTi) that are commonly used in commercially available flow-diverting stents such as the PED, Surpass, and P64. To improve mechanical properties of absorbable stents, others have coated stents with a bioabsorbable polyurethane elastomer and implemented an axial runner in the structure,16–18 although this requires curing and post-curing the rubber at elevated temperatures for extended periods of time which can be detrimental to the core biodegradable fibers. Wang et al developed a hybrid flow-diverting device made from a combination of absorbable and metal fibres.8 Unlike our device, however, their absorbable strands were made of PGA, and they added an equal number of PGA strands to an existing braid of metal fibers. No mention was made, however, of fiber thickness or the resulting mechanical properties. In order to improve the mechanical properties of our stent, as well as to make the bioabsorbable stent radiopaque, we opted to add metal wires in the structure, which likely has minimal impact on the potential advantages of otherwise fully absorbable stents. In doing so, the CRF of the stent increased to within the range of commercial stents. Additional studies on chronic outward force and radial resistive force are required to more completely characterize the mechanical properties of our stent.

    Clinical studies in humans have shown that commercially available bioabsorbable coronary stents (BCS) incur a higher risk of thrombosis.19 20 This may, however, be due to the significantly greater strut thickness of coronary stents compared with our stents. While increased strut thickness is associated with an elevated thrombotic risk, it is simultaneously beneficial by increasing the radial force of BCS sufficiently to provide the required scaffolding effects and to resist the counteracting vessel recoil, which is especially important for treating coronary artery stenosis.21 22 To investigate the hemocompatibility of our stent design, it was compared with the most commonly used commercial flow-diverting stent, the PED, and showed similar results in terms of hemolytic potential and thrombogenicity.

    Despite satisfactory results obtained for our stent in terms of the physical and mechanical properties, as well as initial hemocompatibility studies, in vivo trials are a critical step toward success. Uniform deployment and wall apposition are key factors in preventing complications such as thrombosis and late in-stent restenosis. Also, wall apposition of the stent is critical to formation of a neointimal layer over the stent struts. If the neointimal layer does not cover the bioabsorbable struts evenly, either the stent itself or small segments of PLLA fibers can potentially migrate during fragmentation of polymer in the absorption process, increasing the chance of stroke. The delivery conditions reported in our animal studies resulted in a significant temporary stent diameter reduction of more than four times, yet did not require angioplasty to obtain good wall apposition as opposed to other studies.10 We have since been using 0.027” catheters (as shown in figure 1B) to deploy the stents in our studies and achieving good self-expansion without the need for angioplasty. In the experiments reported here, we demonstrated growth of a neointimal layer over a 1-month period that can prevent subsequent thrombus formation and stabilize the stent to prevent migration in the parent vessel. The formation and growth of the neointimal layer over this short time period also indicates the potential ability of the stent to divert blood flow and result in aneurysm occlusion.

    Conclusion

    In summary, we have demonstrated the potential for braided bioabsorbable stents to be used for the treatment of aneurysms. Our stent shows good biocompatibility in in vitro and in vivo safety experiments. Further studies will determine the absorption characteristics as well as the long-term effectiveness of the stent porosity characteristics for treating blood vessel pathologies such as brain aneurysms.

    Acknowledgments

    The authors would like to thank Cheryl Hall for her assistance with the animal procedures.

    References

    1. ↵
      2. Indolfi C ,
      3. De Rosa S ,
      4. Colombo A
      . Bioresorbable vascular scaffolds — basic concepts and clinical outcome. Nat Rev Cardiol 2016;13:719–29.doi:10.1038/nrcardio.2016.151
      OpenUrl
    2. ↵
      2. Becske T ,
      3. Potts MB ,
      4. Shapiro M , et al
      . Pipeline for uncoilable or failed aneurysms: 3-year follow-up results. J Neurosurg 2017;127:81–8.doi:10.3171/2015.6.JNS15311
      OpenUrlCrossRefPubMed
    3. ↵
      2. Uurto I ,
      3. Mikkonen J ,
      4. Parkkinen J , et al
      . Drug-eluting biodegradable poly-D/L-lactic acid vascular stents: an experimental pilot study. J Endovasc Ther 2005;12:371–9.doi:10.1583/05-1525.1
      OpenUrlCrossRefPubMedWeb of Science
    4. ↵
      2. Vorpahl M ,
      3. Nakano M ,
      4. Perkins LEL , et al
      . Vascular healing and integration of a fully bioresorbable everolimus-eluting scaffold in a rabbit iliac arterial model. EuroIntervention 2014;10:833–41.doi:10.4244/EIJV10I7A143
      OpenUrlCrossRefPubMed
    5. ↵
      2. Agrawal C ,
      3. Haas K ,
      4. Leopold D , et al
      . Evaluation of poly(L-lactic acid) as a material for intravascular polymeric stents. Biomaterials 1992;13:176–82.doi:10.1016/0142-9612(92)90068-Y
      OpenUrlCrossRefPubMedWeb of Science
    6. ↵
      2. Arat A ,
      3. Daglioglu E ,
      4. Akmangit I , et al
      . Bioresorbable vascular scaffolds in interventional neuroradiology. Clin Neuroradiol 2018;28:585–92.doi:10.1007/s00062-017-0609-5
      OpenUrl
    7. ↵
      2. Sotomi Y ,
      3. Onuma Y ,
      4. Collet C , et al
      . Bioresorbable scaffold: the emerging reality and future directions. Circ Res 2017;120:1341–52.doi:10.1161/CIRCRESAHA.117.310275
      OpenUrlAbstract/FREE Full Text
    8. ↵
      2. Wang K ,
      3. Yuan S ,
      4. Zhang X , et al
      . Biodegradable flow-diverting device for the treatment of intracranial aneurysm: short-term results of a rabbit experiment. Neuroradiology 2013;55:621–8.doi:10.1007/s00234-013-1150-0
      OpenUrlCrossRefPubMed
    9. ↵
      2. Jamshidi M
      . Development of bioabsorbable braided vascular scaffolds for the intracranial circulation, 2019. Available: https://prism.ucalgary.ca/handle/1880/110472 [Accessed 20 Nov 2019].
    10. ↵
      2. Nishi H ,
      3. Ishii A ,
      4. Ono I , et al
      . Biodegradable flow diverter for the treatment of intracranial aneurysms: a pilot study using a rabbit aneurysm model. J Am Heart Assoc 2019;8:e014074.doi:10.1161/JAHA.119.014074
    11. ↵
      2. Rippstein P ,
      3. Black MK ,
      4. Boivin M , et al
      . Comparison of processing and sectioning methodologies for arteries containing metallic stents. J Histochem Cytochem 2006;54:673–81.doi:10.1369/jhc.5A6824.2006
      OpenUrlCrossRefPubMedWeb of Science
    12. ↵
      2. Joost DV ,
      3. Jeroen B ,
      4. Anouk VN , et al
      . New generation of flow diverter (Surpass) for unruptured intracranial aneurysms. Stroke 2013;44:1567–77.
      OpenUrlAbstract/FREE Full Text
    13. ↵
      2. Nelson PK ,
      3. Lylyk P ,
      4. Szikora I , et al
      . The pipeline embolization device for the intracranial treatment of aneurysms trial. AJNR Am J Neuroradiol 2011;32:34–40.doi:10.3174/ajnr.A2421
      OpenUrlAbstract/FREE Full Text
    14. ↵
      2. Tähtinen OI ,
      3. Manninen HI ,
      4. Vanninen RL , et al
      . The silk flow-diverting stent in the endovascular treatment of complex intracranial aneurysms: technical aspects and midterm results in 24 consecutive patients. Neurosurgery 2012;70:617–24.doi:10.1227/NEU.0b013e31823387d4
      OpenUrlCrossRefPubMedWeb of Science
    15. ↵
      2. García A ,
      3. Peña E ,
      4. Martínez MA
      . Influence of geometrical parameters on radial force during self-expanding stent deployment: application for a variable radial stiffness stent. J Mech Behav Biomed Mater 2012;10:166–75.doi:10.1016/j.jmbbm.2012.02.006
      OpenUrlPubMed
    16. ↵
      2. Zhao F ,
      3. Xue W ,
      4. Wang F , et al
      . Braided bioresorbable cardiovascular stents mechanically reinforced by axial runners. J Mech Behav Biomed Mater 2019;89:19–32.doi:10.1016/j.jmbbm.2018.09.003
      OpenUrl
    17. ↵
      2. Sharma U ,
      3. Concagh D ,
      4. Core L , et al
      . The development of bioresorbable composite polymeric implants with high mechanical strength. Nat Mater 2018;17:96–103.doi:10.1038/nmat5016
      OpenUrl
    18. ↵
      2. Ginsberg G ,
      3. Cope C ,
      4. Shah J , et al
      . In vivo evaluation of a new bioabsorbable self-expanding biliary stent. Gastrointest Endosc 2003;58:777–84.doi:10.1016/S0016-5107(03)02016-9
      OpenUrlPubMed
    19. ↵
      2. Räber L ,
      3. Brugaletta S ,
      4. Yamaji K , et al
      . Very late scaffold thrombosis: intracoronary imaging and histopathological and spectroscopic findings. J Am Coll Cardiol 2015;66:1901–14.doi:10.1016/j.jacc.2015.08.853
      OpenUrlFREE Full Text
    20. ↵
      2. Kang S-H ,
      3. Chae I-H ,
      4. Park J-J , et al
      . Stent thrombosis with drug-eluting stents and Bioresorbable scaffolds: evidence from a network meta-analysis of 147 trials. JACC Cardiovasc Interv 2016;9:1203–12.doi:10.1016/j.jcin.2016.03.038
      OpenUrlCrossRefPubMed
    21. ↵
      2. Waksman R ,
      3. Lipinski MJ ,
      4. Acampado E , et al
      . Comparison of acute thrombogenicity for metallic and polymeric bioabsorbable scaffolds: Magmaris versus absorb in a porcine arteriovenous shunt model. Circ Cardiovasc Interv 2017;10:e004762:1–10.doi:10.1161/CIRCINTERVENTIONS.116.004762
      OpenUrlAbstract/FREE Full Text
    22. ↵
      2. Kolandaivelu K ,
      3. Swaminathan R ,
      4. Gibson WJ , et al
      . Stent thrombogenicity early in high-risk interventional settings is driven by stent design and deployment and protected by polymer-drug coatings. Circulation 2011;123:1400–9.doi:10.1161/CIRCULATIONAHA.110.003210
      OpenUrlAbstract/FREE Full Text

    Footnotes

    • Contributors MJ was responsible for conception and design, acquisition, analysis, interpretation of data, drafting, revising, and final approval of the work. MR was responsible for design, acquisition, analysis, interpretation of data, drafting, revising, and final approval of the work. MBA was responsible for analysis, interpretation of data, drafting, revising, and final approval of the work. US was responsible for design, analysis, interpretation of data, revising, and final approval of the work. JLR was responsible for design, analysis, interpretation of data, revising, and final approval of the work. BLB was responsible for interpretation of data, revising, and final approval of the work. JHW was responsible for conception, analysis, interpretation of data, revising, and final approval of the work. APM was responsible for conception and design, acquisition, analysis, interpretation of data, drafting, revising, and final approval of the work. All authors agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

    • Funding US was funded by a Natural Sciences and Engineering Research Council of Canada Discovery Grant #05503-2015.

    • Competing interests APM, JHW, and MJ are listed as inventors on patents related to technology described in this article. APM and JHW are founders and shareholders of Fluid Biotech Inc., to which the patents related to technology described in this article are assigned.

    • Patient consent for publication Not required.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Data availability statement Data are available upon reasonable request.