Minghui Cheng (Civil & Architectural Engineering, Architecture), Zhao-Jun Liu (Surgery), Omaida Velazquez (Surgery)
Summary
Peripheral arterial disease (PAD) resulting in limb ischemia represents a critical clinical challenge, affecting millions and causing significant morbidity. The murine hind limb ischemia model is a gold-standard preclinical tool for studying vascular regeneration, disease progression, and therapeutic response, including gene therapy and stem cell therapy approaches. Seminal studies established surgical ligation and excision of the femoral artery as standard methods for inducing ischemia, enabling the evaluation of therapies like E-selectin/adeno-associated virus (AAV) gene therapies, which promote neovascularization and tissue repair [1,2, 3, 4]. However, reliance on animal models is increasingly constrained by inter-animal variability, limited longitudinal resolution, and the ethical imperative to reduce animal use in line with recent NIH policies encouraging non-animal alternatives for biomedical research. The overarching goal of this project is to develop and validate a comprehensive digital twin of the mouse limb ischemia model that will transform preclinical PAD research by enabling accurate predictions of disease progression and therapeutic interventions. The digital twin has the potential to serve as a computational surrogate to conduct virtual experiments, thereby reducing the number of animals required for preclinical studies
Team
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