In vitro assessment of vascular injury following stent retriever retraction in clinically-relevant endothelialized silicone models.

Mechanical thrombectomy devices have potential to injure the vessel during treatment of acute ischemic stroke. The goal of the current work was to tailor in vitro endothelialized silicone models for stent retriever assessment and to evaluate endothelial injury following treatment by various stent retriever designs and sizes. Clinically-relevant neurovascular geometries were first modeled out of silicone, then sterilized, coated with fibronectin, placed in bioreactors, seeded with human endothelial cells, and cultivated under flow. Several sizes of two different commercially available stent retrievers were then deployed in, and retracted through, vessels. Vessels were immediately harvested and stained. Endothelial injury, identified as denudation, was quantified using ImageJ. Results illustrated that endothelial injury ranged from 16-18% in wire/microcatheter-only treated vessels, 37-61% in 1-pass treatments, and 52-70% in 2-pass treatments. Overall this work showcases an in vitro approach for early stage assessment of the extent and location of vascular injury following stent retriever retraction.

Evaluation of vessel injury after simulated catheter use in an endothelialized silicone model of the intracranial arteries.

PURPOSE: Neurothrombectomy catheters can disrupt or injure the vessel wall. This potential injury is often studied in animal or cadaver models, but prior work suggests that endothelialized silicone models may be an option for early in vitro assessment. The purpose of this work was to create a complex, clinically-relevant endothelialized neurovascular silicone model, and to determine the utility of the model for evaluating vessel injury due to catheter simulated use. METHODS: Models of the ICA and MCA were fabricated out of silicone, sterilized, coated with fibronectin, placed in bioreactors, and endothelialized with HUVECs. These silicone vessels were maintained under flow for 3 and 7 days, and cellular linings were assessed. Subsequently, 24 silicone vessels were created and treated with neurovascular catheters. Vessels were accessed with a guidewire, microcatheter, and/or aspiration catheter, either once (1-pass) or three times (3-pass). Vessels were then fixed, and injury was evaluated through quantitative image analysis and a visual scoring system. RESULTS: Complex silicone models were successfully endothelialized and maintained with consistent cell linings. The transparent silicone permitted catheter simulated use without fluoroscopy, and injury to the vessel wall was observed and successfully imaged and characterized. Vessels subjected to 3-passes exhibited more injury than 1-pass, and injury increased with the number and size of devices. These results illustrated expected trends and support use of these models for early assessment of vessel injury. CONCLUSION: Complex silicone neurovascular models can be endothelialized and used in vitro to assess and compare injury due to the use of neurovascular catheters.

Endothelialized silicone aneurysm models for in vitro evaluation of flow diverters.

OBJECTIVE: The goal of this work was to endothelialize silicone aneurysm tubes for use as in vitro models for evaluating endothelial cell interactions with neurovascular devices. The first objective was to establish consistent and confluent endothelial cell linings and to evaluate the silicone vessels over time. The second objective was to use these silicone vessels for flow diverter implantation and assessment. METHODS: Silicone aneurysm tubes were coated with fibronectin and placed into individual bioreactor systems. Human umbilical vein endothelial cells were deposited within tubes to create silicone vessels, then cultivated on a peristaltic pump and harvested at 2, 5, 7, or 10 days to evaluate the endothelial cell lining. A subset of silicone aneurysm vessels was used for flow diverter implantation, and evaluated for cell coverage over device struts at 3 or 7 days after deployment. RESULTS: Silicone vessels maintained confluent, PECAM-1 (platelet endothelial cell adhesion molecule 1) positive endothelial cell linings over time. These vessels facilitated and withstood flow diverter implantation, with robust cell linings disclosed after device deployment. Additionally, the endothelial cells responded to implanted devices through coverage of the flow diverter struts with increased cell coverage over the aneurysm seen at 7 days after deployment as compared with 3 days. CONCLUSIONS: Silicone aneurysm models can be endothelialized and successfully maintained in vitro over time. Furthermore, these silicone vessels can be used for flow diverter implantation and assessment.

Quantifying the mechanical and histological properties of thrombus analog made from human blood for the creation of synthetic thrombus for thrombectomy device testing.

BACKGROUND: Untreated ischemic stroke can lead to severe morbidity and death, and as such, there are numerous endovascular blood-clot removal (thrombectomy) devices approved for human use. Human thrombi types are highly variable and are typically classified in qualitative terms - 'soft/red,' 'hard/white,' or 'aged/calcified.' Quantifying human thrombus properties can accelerate the development of thrombus analogs for the study of thrombectomy outcomes, which are often inconsistent among treated patients. METHODS: 'Soft'human thrombi were created from blood samples ex vivo (ie, human blood clotted in sample vials) and tested for mechanical properties using a hybrid rheometer material testing system. Synthetic thrombus materials were also mechanically tested and compared with the 'soft' human blood clots. RESULTS: Mechanical testing quantified the shear modulus and dynamic (elastic) modulus of volunteer human thrombus samples. This data was used to formulate a synthetic blood clot made from a composite polymer hydrogel of polyacrylamide and alginate (PAAM-Alg). The PAAM-Alg interpenetrating network of covalently and ionically cross-linked polymers had tunable elastic and shear moduli properties and shape memory characteristics. CONCLUSIONS: Due to its adjustable properties, PAAM-Alg can be modified to mimic various thrombi classifications. Future studies will include obtaining and quantitatively classifying patient thrombectomy samples and altering the PAAM-Alg to mimic the results for use with in vitro thrombectomy studies.