Modeling Lymphatic System Dynamics: Experimental and Computational Approaches to Lymphedema Treatment

Lymphedema is a debilitating condition caused by impaired lymphatic drainage, leading to chronic swelling and tissue damage. Despite its widespread prevalence, effective treatment options remain limited due to an incomplete understanding of the lymphatic system’s physiological responses to injury and treatment interventions. This thesis aims to bridge this knowledge gap by integrating experimental and clinical approaches with computational modeling to explore lymphatic function and remodeling. This work is structured around three specific aims. Aim 1 focuses on a large-animal study using a sheep model to characterize the growth and remodeling of lymphatic vessels following injury. By combining in-vivo imaging, ex-vivo vessel analysis, and mechanical modeling, this study will provide critical insights into the contractile dynamics and adaptive responses of lymphatic vessels under mechanical stress. Aim 2 develops a lumped parameter model to simulate lymphaticovenous anastomoses (LVA), a microsurgical intervention for lymphedema, assessing how different configurations influence lymphatic transport efficiency. Aim 3 integrates growth and remodeling responses into the computational model to predict long-term LVA adaptations under varying mechanical loads. By linking experimental observations with computational simulations, this research aims to advance our understanding of lymphatic adaptation mechanisms and inform the development of LVA treatment for lymphedema. The findings will contribute to the refinement of LVA techniques and provide a foundation for future studies on lymphedema interventions.