Thrombogenicity of the p48 and anti-thrombogenic p48 hydrophilic polymer coating low-profile flow diverters in an in vitro human thrombin generation model.

OBJECTIVES: The implantation of flow diverters, or stents in general, necessitates the use of dual anti-platelet treatment with typical regimes including aspirin and a P2Y12 inhibitor. This carries an inherent risk of haemorrhage. We sought to compare the thrombogenicity of the anti-thrombogenic p48 hydrophilic polymer coating compared to the standard uncoated p48 flow diverter using an in vitro thrombogenicity assay. METHODS: To evaluate the thrombin generation influenced by the different stent types the stents were placed in wells of a 24-well plate with the addition of plasma from healthy volunteers the thrombin calibrator respectively the PPP-reagent was added. Subsequently, the thrombin substrate was added and the thrombin generation was analysed every 60 s using a thrombinoscope. The assay is calibrated using samples containing a known amount of active thrombin in PPP. Thrombin activity is proportional to the change in fluorescence. RESULTS: The p48 hydrophilic polymer coating shows a significantly lower peak thrombin concentration (1.13 ± 0.21 vs. 1.41 ± 0.22) and longer time to peak thrombin concentration (0.96 ± 0.04 vs. 0.74 ± 0.07) compared to the uncoated p48 device (p < 0.01). The responses of the p48 hydrophilic polymer coating were similar to that of the negative control. CONCLUSION: The hydrophilic polymer coating surface modification significantly reduces the thrombogenicity of the p48 flow diverter. These results corroborate the findings from previous in vitro studies.

Prospective study to assess the tissue response to HPC-coated p48 flow diverter stents compared to uncoated devices in the rabbit carotid artery model.

BACKGROUND: Flow diverters (FDs) are widely used in the treatment of intracranial aneurysms, but the required medication increases the risk of haemorrhagic complications and limits their use in the acute setting. Surface modified FDs may limit the need for dual antiplatelet therapy (DAPT). Hydrophilic polymer coating (HPC) may reduce the need of medication. METHODS: This explorative study, approved by the local authorities and the local welfare committee, compared stent behaviour and overall tissue response between HPC-coated FDs and uncoated FDs, both implanted into the common carotid arteries of eight New Zealand white rabbits. Endothelialisation, inflammatory response, and performance during implantation were assessed. Angiographic follow-up was performed to observe the patency of the devices after implantation and after 30 days. Histological examinations were performed at 30 days to assess foreign body reaction and endothelialisation. Kruskal-Wallis and Wilcoxon tests were used to compare non-parametric variables. RESULTS: Angiography showed that both coated and uncoated FDs performed well during implantation. All devices remained patent during immediate follow-up and after 30 days. Histopathology showed no significant difference in inflammation within the vessel wall between the two cohorts (2.12 ± 0.75 vs. 1.96 ± 0.79, p = 0.7072). Complete endothelialisation of the stent struts was seen with very similar (0.04 ± 0.02 mm vs. 0.04 ± 0.03 mm, p = 0.892) neoendothelial thickness between the two cohorts after 30 days. CONCLUSION: Taking into account the limitation in sample size, non-significant differences between the HPC-coated and uncoated FDs regarding implantation, foreign body response, and endothelialisation were found.

The pCONUS HPC: 30-Day and 180-Day In Vivo Biocompatibility Results.

BACKGROUND: Endovascular stents are commonly used during neurointerventional procedures; however, the concomitant use of dual anti-platelet treatment (DAPT) can limit their use. There is a need to develop stent coatings that mitigate requirement for DAPT. METHODS: The hydrophilic polymer coating is a novel glycan-based multilayer polymer that inhibits platelet adhesion. After Institutional Animal Care and Use Committee approval, 18 New Zealand white rabbits (mean weight 4.02 ± 0.51 kg) were commenced on DAPT (ASA 10 mg/kg/day and clopidogrel 10 mg/kg/day). A bare nitinol pCONUS and coated pCONUS HPC were implanted into the common carotid arteries of each rabbit. Histological examinations were performed at 30 days (n = 9) and 180 days (n = 8) to assess the acute and chronic inflammatory reactions to the pCONUS HPC. Wilcoxon/Kruskal-Wallis and ANOVA were used with p value < 0.05 considered as significant. RESULTS: There is no statistically significant difference in inflammation within the intima/media or adventitia at 30 days (p = 0.3901 and p = 1, respectively) or at 180 days (p = 0.144 and p = 1, respectively) between pCONUS and pCONUS HPC cohorts. There is no significant difference in the presence of granulomas or giant cells between the cohorts at either 30 days (p = 1 and p = 0.8363) or 180 days (p = 1.00 and p = 0.149). At 30 days and 180 days, there was near-complete endothelialisation of the stent struts and no significant difference between the pCONUS or pCONUS HPC (p = 0.7832 and p = 0.334, respectively). CONCLUSION: pCONUS HPC stents do not elicit an acute or chronic inflammatory response in vivo with no significant difference in the tissue response to bare nitinol pCONUS stents or pCONUS HPC stents.

In vivo canine study of three different coatings applied to p64 flow-diverter stents: initial biocompatibility study.

BACKGROUND: Flow-diverter stents (FDSs) have revolutionised the treatment of intracranial aneurysms. However, associated dual antiplatelet treatment is mandatory. We investigated the biocompatibility of three proprietary antithrombogenic coatings applied to FDSs. METHODS: After Institutional Animal Care and Use Committee approval, four domestic juvenile female dogs (weight 19.9 ± 0.9 kg, mean ± standard deviation) were commenced on three different oral antiplatelet regimes: no medication (n = 1), acetylsalicylic acid (n = 2), and acetylsalicylic acid and clopidogrel (n = 1). Four p64 FDSs were randomly implanted into the subclavian, common carotid, and external carotid arteries of each dog, including both uncoated p64 stents and p64 stents coated with three different antithrombogenic hydrophilic coating (HPC). Angiography and histological examinations were performed. Wilcoxon/Kruskal-Wallis and ANOVA were used with p value < 0.05 considered as significant. RESULTS: Minimal inflammatory cell infiltration and no device-associated granulomatous cell inflammation were observed. No significant difference in adventitial inflammation (p = 0.522) or neointimal/medial inflammation (p = 0.384) between coated and uncoated stents as well as between the different stent groups regarding endothelial cell loss, surface fibrin/platelet deposition, medial smooth muscle cell loss, or adventitial fibrosis were found. Acute self-limiting thrombus formed on 6/16 implants (37.5%), and all of the thrombi were noted on devices implanted in the common or external carotid artery irrespective of the surface coating. Two of 12 p64 HPC-coated stents (16.7%) and 1/4 uncoated p64 stents (25%) showed severe or complete stenosis at delayed angiography. CONCLUSIONS: In these preliminary in vivo experiments, HPC-coated p64 FDSs appeared to be biocompatible, without acute inflammation.

Comparative in vitro study of five mechanical embolectomy systems: effectiveness of clot removal and risk of distal embolization.

INTRODUCTION: We report an in vitro study comparing the effectiveness of clot removal and clot fragmentation of five embolectomy systems. METHODS: A flow model was embolized with fresh and old thrombi, occluding an inner diameter of 2-5 mm simulating internal carotid artery (ICA), basilar artery (BA) and middle cerebral artery (MCA) branch occlusion. Embolectomy was performed using five retrieval systems: CATCH (Balt), Merci retriever (Concentric), InTime and Attracter (Boston Scientific), and the Phenox Clot Retriever (Phenox). Clot removal and evidence and type of thrombus fragmentation and distal embolization were recorded. RESULTS: There were no observable differences attributable to thrombus age. The Merci, CATCH and Phenox Clot Retriever were equally able to mobilize and remove thrombi with the exception of one particularly firm clot. There were marked differences in terms of thrombus fragmentation and distal embolization. All devices produced micro- and macrofragments during penetration and retrieval. The Phenox Clot Retriever was able to filter fragments. The InTime and Attracter devices failed to retrieve thrombi in this model and achieved partial removal at best with a tendency towards thrombus displacement and fragmentation. CONCLUSION: Within limits, the experimental setup was appropriate for generating occlusions of diameter 2-5 mm of various lengths, simulating ICA, BA and MCA thromboembolism. In this model, thrombus mobilization appeared to be less dependent upon the individual design of the retrieval system than on thrombus fragmentation. The ability to prevent distal embolization is, however, strongly dependent on the ability of a thrombectomy device to capture fragments that are generated during removal of the device.