CAREER: Toward a Fundamental Understanding of Why Thrombus Dissolves, Persists, or Breaks Off

点击翻译按钮获取中文摘要

This Faculty Early Career Development (CAREER) award will use experimental and computational strategies to quantify fundamental biophysical properties of blood clot. The research work will study why blood clot sometimes dissolves, sometimes persists, and sometimes embolizes (breaks off.) To this end, the research work will use a clot mimic system that is highly controllable and of realistic composition. Using both experimental and computational strategies, the work will enable mechanistic insight into a what determines blood clot’s fate. Future extensions of this work may enable improved diagnostic and therapeutic strategies for patients that suffer from clot-related disease such as heart attacks, stroke, or deep vein thrombosis. This scientific approach may also be applicable to other soft and biological materials, as blood clot is very similar to these. Thus, this research project will contribute to the progress in many areas of science. Finally, the work integrates its research objectives with educational objectives and broader impact goals that will directly translate our advancements in health and science to public value. The specific goal of this research is to use deep vein thrombus as a model system to fundamentally understand and learn to predict how thrombus microstructure gives rise to its biophysical properties, how these properties change during thrombus maturation and with treatment, and how maturation and treatment determine thrombus fate. To accomplish this goal, the research work will first quantify thrombus’ micro- and macroscopic biophysical properties during maturation and lysis using classic mechanical testing modalities such as simple shear testing, confined compression testing, and mode I fracture tests. Additionally, it will make use of strategies to conduct these experiments under confocal observation. Second, this work will calibrate and validate multiscale models to understand and predict thrombus fate. To this end, two types of models will be used: an investigative, microstructural model and a predictive, continuum model. Both models will be calibrated and validated against the experimental data and then used to investigate the mechanisms that lead to thrombus dissolution, persistence, and embolization. Additionally, these models will provide a framework that, in the future, will aid in optimizing deep vein thrombus treatment and therapeutic technologies.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.