Standardized Fabrication Method of Human-Derived Emboli with Histologic and Mechanical Quantification for Stroke Research.

ABSTRACT

BACKGROUND: As access to patient emboli is limited, embolus analogs (EAs) have become critical to the research of large vessel occlusion (LVO) stroke and the development of thrombectomy technology. To date, techniques for fabricating standardized human blood-derived EAs are limited in the variety of compositions, and the mechanical properties relevant to thrombectomy are not quantified. METHODS: EAs were made by mixing human banked red blood cells (RBCs), plasma, and platelet concentrate in 10 different volumetric percentage combinations to mimic the broad range of patient emboli causing LVO strokes. The samples underwent histologic analysis and tensile testing to mimic the pulling action of thrombectomy devices, and were compared to patient emboli. RESULTS: EAs had histologic compositions of 0-96% RBCs, 0.78%-92% fibrin, and 2.1%-22% platelets, which can be correlated with the ingredients using a regression model. At fracture, EAs elongated from 81% to 136%, and the ultimate tensile stress ranged from 16 to 949 kPa. These EAs' histologic compositions and tensile properties showed great similarity to those of emboli retrieved from LVO stroke patients, indicating the validity of such EA fabrication methods. EAs with lower RBC and higher fibrin contents are more extensible and can withstand higher tensile stress. CONCLUSIONS: EAs fabricated and tested using the proposed new methods provide a platform for stroke research and pre-clinical development of thrombectomy devices.