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In this talk, I will present my previous and current research on artificial heart/lung devices and brain biomechanics. First, I will discuss blood-contacting medical devices such as artificial hearts and lungs, which provide cardiopulmonary support for patients with heart or lung failure. I will describe how I developed and applied mathematical models integrated with computational fluid dynamics (CFD) to guide the design and optimization of these devices. Prototypes generated through this simulation-based approach were evaluated using in vitro blood loop testing and demonstrated superior hemolytic performance compared to existing commercial devices. Next, I will highlight our integrative approach to studying brain biomechanics across multiple length scales by combining mechanical testing, biomedical imaging, and theoretical modeling. Our model captures complex brain tissue mechanical behaviors—such as loading rate sensitivity, fiber orientation dependence and damage accumulation—and has been incorporated into a full-scale human head model to visualize fiber tract damage under head impact conditions. Finally, I will discuss ongoing efforts to extend the model to account for tissue-fluid interactions, enabling a more comprehensive understanding of brain mechanics in in both healthy and diseased states.