Characterization of strut indentation during mechanical thrombectomy in acute ischemic stroke clot analogs.

BACKGROUND: Although it is common practice to wait for an 'embedding time' during mechanical thrombectomy (MT) to allow strut integration of a stentriever device into an occluding thromboembolic clot, there is a scarcity of evidence demonstrating the value or optimal timing for the wide range of thrombus compositions. This work characterizes the behavior of clot analogs of varying fibrin and cellular compositions subject to indentation forces and embedding times representative of those imparted by a stentriever during MT. The purpose of this study is to quantify the effect of thrombus composition on device strut embedding, and to examine the precise nature of clot integration into a stentriever device at a microstructural level. METHOD: Clot analogs with 0% (varying densities), 5%, 40%, and 80% red blood cell (RBC) content were created using ovine blood. Clot indentation behavior during an initial load application (loading phase) followed by a 5-min embedding time (creep phase) was analyzed using a mechanical tester under physiologically relevant conditions. The mechanism of strut integration was examined using micro-computed tomography (µCT) with an EmboTrap MT device (Cerenovus, Galway, Ireland) deployed in each clot type. Microstructural clot characteristics were identified using scanning electron microscopy (SEM). RESULTS: Compressive clot stiffness measured during the initial loading phase was shown to be lowest in RBC-rich clots, with a corresponding greatest maximum indentation depth. Meanwhile, additional depth achieved during the simulated embedding time was most pronounced in fibrin-rich clots. SEM imaging identified variations in microstructural mechanisms (fibrin stretching vs rupturing) which was dependent on fibrin:cellular content, while µCT analysis demonstrated the mechanism of strut integration was predominantly the formation of surface undulations rather than clot penetration. CONCLUSIONS: Disparities in indentation behavior between clot analogs were attributed to varying microstructural features induced by the cellular:fibrin content. Greater indentation was identified in clots with higher RBC content, but with an increased level of fibrin rupture, suggesting an increased propensity for fragmentation. Additional embedding time improves strut integration, especially in fibrin-rich clots, through the mechanism of fibrin stretching with the majority of additional integration occurring after 3 mins. The level of thrombus incorporation into the EmboTrap MT device (Cerenovus, Galway, Ireland) was primarily influenced by the stentriever design, with increased integration in regions of open architecture.

Multiscale Experimental and Computational Modeling Approaches to Characterize Therapy Delivery to the Heart from an Implantable Epicardial Biomaterial Reservoir.

Delivery of therapeutic-laden biomaterials to the epicardial surface of the heart presents a promising method of treating a variety of diseased conditions by offering targeted, localized release with limited systemic recirculation and enhanced myocardial tissue uptake. A vast range of biomaterials and therapeutic agents using this approach been investigated. However, the fundamental factors that govern transport of the drug molecules from the biomaterials to the tissue are not well understood. Here, the transport of a drug analog from a biomaterial reservoir to the epicardial surface is characterized using experimental techniques and microscale modeling. Using the experimentally determined parameters, a multiscale model of transport is developed. The model is then used to study the effect of important design parameters such as loading conditions, biomaterial geometry, and orientation relative to the cardiac fibers on drug delivery to the myocardium. The simulations highlight the significance of the cardiac fiber anisotropy as a crucial factor in governing drug distribution on the epicardial surface and limiting factor for penetration into the myocardium. The multiscale model can be useful for rapid iteration of different device concepts and for determination of designs for epicardial drug delivery that may be optimal and most promising for the ultimate therapeutic goal.