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

Abstract

BackgroundFlow-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.MethodsAfter 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.ResultsMinimal 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.ConclusionsIn these preliminary in vivo experiments, HPC-coated p64 FDSs appeared to be biocompatible, without acute inflammation.

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

“…No other benefits of the HPC coating, for example, the efficacy of the pCONUS HPC under single anti-platelet treatment (SAPT), can be gleaned from this study. However, these results, taken together with our previously published in vitro [ 26 ] and in vivo [ 28 ] results, suggest that the pHPC coating has strong anti-thrombogenic properties and does not promote an inflammatory reaction.…”

Single-Center Experience With the Bare p48MW Low-Profile Flow Diverter and Its Hydrophilically Covered Version for Treatment of Bifurcation Aneurysms in Distal Segments of the Anterior and Posterior Circulation

“…In November 2018, a coated variant of the p48MW obtained CE mark and has been made available for European patients. The HPC has been tested extensively in vitro and ex vivo, and the first clinical experiences have been reported (16)(17)(18)(19)(20)(21). Basically, the coating consists of a covalently bonded pentasaccharide layer at the surface of the device, which prevents platelet and leukocyte adhesion at the surface of the nitinol mesh.…”

Use of the pCONus HPC as an adjunct to coil occlusion of acutely ruptured aneurysms: early clinical experience using single antiplatelet therapy

“… 7 In vivo studies have shown that the pHPC has no pharmaceutical effect and is biocompatible in both dogs and rabbits, with no evidence of acute inflammatory response. 27–29 These in vivo studies comparing coated and uncoated devices showed no difference in the rate of neo-endothelialization, which implies that pHPC reduces the thrombogenicity of the device but does not inhibit its endothelialization. Until now, only one series has reported the clinical use of pHPC.…”

“…It is designed to mimic the biological properties of the glycocalyx, the coverage that can be found on the luminal surface of the endothelium of the arterial wall, making the coated surface hydrophilic and, consequently, less thrombogenic 7. In vivo studies have shown that the pHPC has no pharmaceutical effect and is biocompatible in both dogs and rabbits, with no evidence of acute inflammatory response 27–29. These in vivo studies comparing coated and uncoated devices showed no difference in the rate of neo-endothelialization, which implies that pHPC reduces the thrombogenicity of the device but does not inhibit its endothelialization.…”