Project Summary/Abstract
Lymphedema, a condition characterized by swelling and impaired lymphatic flow, affects a significant
portion of the global population, particularly individuals undergoing cancer treatments involving
lymphadenectomy and radiotherapy. Despite its prevalence, there is still a lack of comprehensive understanding
of the underlying mechanisms driving lymphedema progression and the most effective treatment strategies. This
project seeks to address these challenges through a multidisciplinary approach that combines biomechanics,
computational modeling, and experimental data.
The primary focus of this research is to study the lymphatic flow dynamics and adaptations in response
to lymphaticovenous anastomoses (LVA), a surgical intervention commonly used to treat lymphedema. By
collaborating with Chang-Gung Hospital, we have gained access to invaluable clinical data, including declassified
patient data, which allows us to investigate the outcomes and impacts of both antegrade and retrograde
anastomoses in treating lower limb lymphedema. This novel analysis platform provides unique insights into
lymphatic function in vivo in humans, and we employ non-invasive imaging techniques to quantify lymphatic
pump dynamics.
Our research leverages a theoretical framework that integrates a lumped parameter model for
lymphangion function and lymph transport, a microstructurally-motivated constitutive model for the mechanical
behavior of isolated lymphatic vessels, and innovative models for acute mechanically-mediated vasoreactive
adaptations and long-term volumetric growth. We simulate changes in muscle contractility and geometry of a
single isolated lymphatic vessel in response to sustained elevation in afterload to understand the acute and long-
term adaptations to mechanical loading.
Furthermore, we develop computational models to investigate the effects of growth and remodeling
(G&R) processes in the lymphatic vessel network in response to elevated loading conditions caused by LVA.
This multi-scale approach considers the biomechanics at the tissue and cellular levels, aiming to determine the
causative factors behind lymphatic failure and the potential impact of LVA on lymphangion loading.
Through this project, we aim to gain deeper insights into the mechanosensitivity of the lymphatic
vasculature and the implications of shear stress and pressure on lymphatic contractility. The findings from our
research have the potential to advance our understanding of lymphatic flow regulation and the adaptation
process in response to various loading conditions. Ultimately, this knowledge could lead to improved treatment
strategies for lymphedema patients and potentially pave the way for more effective biomedical engineering
interventions.
