Development of physiologically relevant synthetic thrombus for use in visual analysis of in vitro mechanical thrombectomy device testing

BACKGROUND: Ischemic stroke is a leading cause of death and significant long-term disability worldwide. Mechanical thrombectomy is emerging as a standard treatment for eligible patients. As clinical implementation of stent retrieval and aspiration thrombectomy increases, there is a need for physiologically relevant in vitro device efficacy testing. Critical to this testing is the development of standardized 'soft' and 'hard' synthetic blood clots that mimic the properties of human thrombi and are compatible with imaging technologies. Synthetic clots allow researchers to extract information regarding clot integration, model hemodynamics, and quantify the physics of thrombectomy. METHODS: This work develops polyacrylamide and alginate-based synthetic clots that are compatible with particle image velocimetry (PIV) and radiographic imaging techniques while maintaining mechanical properties of 'soft' and 'hard' human clots. Dynamic mechanical analysis testing using an HR2-Rheometer demonstrates comparable mechanical properties to human clots previously tested by this research group and provided in existing literature. RESULTS: The synthetic clots are formulated with either 0.5% w/v polyethylene microspheres for PIV visualization or 20% w/v barium sulfate for angiographic visualization, enabling real-time imaging of clot behavior during thrombectomy simulations. The soft formulation shows compressive and shear properties of ~12 kPa and 2-3 kPa, respectively. The hard clots are 3-4 times stiffer, with compressive and shear properties of 41-42 kPa and 8-9 kPa, respectively. CONCLUSION: Standardized synthetic clots offer a platform for reproducible device testing. This provides a greater understanding of mechanical thrombectomy device efficacy, which may lead to quantifiable advances in device development and eventual improved clinical outcomes.