Human‑Scale Lymphatic Modeling to Guide Lymphatic Interventions: Application to a Soft Robotic Assist Device

PURPOSE: The lymphatic system is essential for maintaining tissue-fluid homeostasis. In conditions of elevated venous pressures (e.g., congestive heart failure or congenital single-ventricle heart disease after Fontan palliation), increased capillary filtration and impaired lymphatic drainage disrupt this balance, predisposing patients to lymphatic overload and edema. The lack of human-scale computational models capturing lymphatic pumping and coupled tissue-fluid exchange limits the development of effective interventions. METHODS: We developed a human-scale lumped-parameter model that combines multi-lymphangion thoracic duct pumping with a Starling-based tissue-fluid balance model, enabling integrated simulation of central lymphatic function and tissue-fluid homeostasis. The framework was used to evaluate surgical and device-based lymphatic interventions. Model predictions were combined with virtual fitting using MR-derived anatomy from three Fontan patients to demonstrate translational applicability and design an extravascular soft robotic lymphatic assist sleeve, whose performance was characterized in hydraulic benchtop experiments. RESULTS: The model reproduced physiologic thoracic duct flow (~3.1L/day) and predicted interstitial fluid accumulation under venous hypertension (up to ~ 18 mL/min net accumulation). Surgical (lymphatic decompression) and device-based (extravascular sleeve) interventions increased thoracic duct flow and reduced simulated tissue-fluid accumulation (47% and 76.5% reduction, respectively), with the sleeve providing frequency-dependent augmentation. Virtual fitting confirmed anatomical feasibility of device implantation in all three Fontan patients. Benchtop testing demonstrated pressure step-ups from 5.5 to ~ 17 mmHg and flow augmentation from 2.5 to ~ 18 mL/min at actuation frequencies of 20-60 bpm. CONCLUSION: Our human-scale computational framework offers mechanistic insights into lymphatic dysfunction under elevated venous pressure and provides a platform for the design and evaluation of lymphatic interventions.