Abstract 157: Micromechanics of Blood Clots

Abstract

Understanding clot biomechanics is critical for the treatment of cardiovascular diseases. Based on our recent observation that that the structural configuration of the clot network correlates well with the mechanical properties such as stiffness, we hypothesized that the heterogeneity in the mechanical response of the microstructure dictates clot micromechanics and hence the macroscopic behavior. To test this hypothesis, we have custom-developed a microextensometer device coupled to a microscope to probe and image microstructural changes and micromechanical behavior of fibrin and blood clots. 20 μL clots were pulled at a prescribed strain rate of 60 μm/s using a programmable nano-positioner, and the force was measured using a 10 g load cell and acquired at 500 Hz. From the stress-strain measurements, we observed that both FFP and blood clots showed non-linear and abrupt changes in resistive tensile force in response to constant strain rate (Fig. 1A). Using fiduciary markers, we observed that cross-linked, but not uncrosslinked, fibrin clots showed a microscopically non-uniform deformation in response to macroscopically constant strain rate. Further, computational analysis of the mechanical response of clot microstructure to an applied stress revealed heterogeneity in strain energy distribution dictated by the network properties (Fig. 1B). Together, our results suggest that the heterogeneity in microscale translates to the non-linear response at the macroscale, and will ultimately dictate the pathophysiology of thrombosis.

Novel Human Acute Ischemic Stroke Blood Clot Analogs for In Vitro Thrombectomy Testing

“…There is a growing awareness of the importance of clot phenotypes, mechanical properties, clot-device interactions, and the interactions of clots with the surrounding vessel, factors that influence revascularization rates. 1,27,[31][32][33][34] However, clinicians largely continue to treat patients using their preferred treatment strategy rather than tailoring their treatment strategy to suit the suspected clot composition because there have been few clinical studies comparing various thrombectomy techniques in their ability to retrieve different phenotypes of thrombi from patients with AIS. 35 The histologic composition of the clot analog phenotypes created in this study is in line with the range of clot compositions typically seen in AIS.…”