Longitudinal healing flow diverting stents with phosphorylcholine surface modification.

BACKGROUND: Flow diversion has become a standard treatment for cerebral aneurysms. However, major drawbacks include the need for dual antiplatelet therapy after implant and delayed complete occlusion of the aneurysm, which occurs when new tissue growth excludes the aneurysm from the parent artery. Biomimetic surface modifications such as the phosphorylcholine polymer (Shield surface modification) represent major advances in reducing thrombogenicity of these devices. However, in vitro studies have raised concerns that this modification may also delay endothelialization of flow diverters. METHODS: Bare metal Pipeline, Pipeline Shield, and Vantage with Shield devices were implanted in the common carotid arteries (CCAs) of 10 rabbits (two in the left CCA, one in the right CCA). Following implant and at 5, 10, 15, and 30 days, the devices were imaged with high-frequency optical coherence tomography and conventional angiography to evaluate tissue growth. At 30 days the devices were explanted and their endothelial growth was assessed with scanning electron microscopy (SEM) at five locations along their length using a semi-quantitative score. RESULTS: The average tissue growth thickness (ATGT) was not different between the three devices. Neointima was apparent at 5 days and all devices demonstrated similar ATGT at each time point. On SEM, no difference was found in the endothelium scores between the device types. CONCLUSION: In vivo, neither the Shield surface modification nor the device design (Vantage) altered the longitudinal healing of the flow diverter.

Surface modification of neurovascular stents: from bench to patient.

Flow-diverting stents (FDs) for the treatment of cerebrovascular aneurysms are revolutionary. However, these devices require systemic dual antiplatelet therapy (DAPT) to reduce thromboembolic complications. Given the risk of ischemic complications as well as morbidity and contraindications associated with DAPT, demonstrating safety and efficacy for FDs either without DAPT or reducing the duration of DAPT is a priority. The former may be achieved by surface modifications that decrease device thrombogenicity, and the latter by using coatings that expedite endothelial growth. Biomimetics, commonly achieved by grafting hydrophilic and non-interacting polymers to surfaces, can mask the device surface with nature-derived coatings from circulating factors that normally activate coagulation and inflammation. One strategy is to mimic the surfaces of innocuous circulatory system components. Phosphorylcholine and glycan coatings are naturally inspired and present on the surface of all eukaryotic cell membranes. Another strategy involves linking synthetic biocompatible polymer brushes to the surface of a device that disrupts normal interaction with circulating proteins and cells. Finally, drug immobilization can also impart antithrombotic effects that counteract normal foreign body reactions in the circulatory system without systemic effects. Heparin coatings have been explored since the 1960s and used on a variety of blood contacting surfaces. This concept is now being explored for neurovascular devices. Coatings that improve endothelialization are not as clinically mature as anti-thrombogenic coatings. Coronary stents have used an anti-CD34 antibody coating to capture circulating endothelial progenitor cells on the surface, potentially accelerating endothelial integration. Similarly, coatings with CD31 analogs are being explored for neurovascular implants.

A novel intrasaccular aneurysm device with high complete occlusion rate: initial results in a rabbit model.

BACKGROUND: Intrasaccular flow-disrupting devices are a safe and effective treatment strategy for intracranial aneurysms. We utilized high-frequency optical coherence tomography (HF-OCT) and digital subtraction angiography (DSA) to evaluate SEAL Arc, a new intrasaccular device, and compare the findings with the well-established Woven EndoBridge (WEB) device in an animal model of saccular aneurysms. METHODS: In a rabbit model, elastase-induced aneurysms were treated with SEAL Arc (n=11) devices. HF-OCT and DSA were performed after implant and repeated after 12 weeks. Device protrusion and malapposition were assessed at implant time and scored on a binary system. Aneurysm occlusion was assessed at 12 weeks with the WEB Occlusion Scale and dichotomized to complete (A and B) or incomplete (C and D) occlusion. The percentage of neointimal coverage after 12 weeks was quantified using HF-OCT. We compared these data to previously published historical controls treated with the gold-standard WEB device (n=24) in the same model. RESULTS: Aneurysm size and device placement were not significantly different between the two groups. Complete occlusion was demonstrated in 80% of the SEAL Arc devices, which compared favorably to the 21% of the aneurysms treated with WEB devices (P=0.002). Neointimal coverage across SEAL Arc devices was 86±15% compared with 49±27% for WEB (P=0.001). Protruding devices had significantly less neointimal coverage (P<0.001) as did incompletely occluded aneurysms (P<0.001). Histologically, all aneurysms treated with SEAL Arc devices were completely healed. CONCLUSION: Complete early aneurysm occlusion was frequently observed in the SEAL Arc treated aneurysms, with significant neointimal coverage after 12 weeks.