Abstract:
Introduction: In tissue engineering for lung applications, understanding and controlling fluid
dynamics within engineered constructs is paramount. Agent-based modeling (ABM) offers a powerful
framework to simulate complex physiological systems, yet its application to pulmonary edema (PE) in
this context remains underexplored. This study presents an innovative ABM, built in NetLogo, to
simulate cardiogenic PE (CPE) by modeling extravascular lung water dynamics under hydrostatic
pressure (HP) and oncotic pressure (OP). This model can serve as a tool to inform the design of tissueengineered lung constructs by providing insights into fluid management strategies.
Materials and Methods: The ABM was developed using NetLogo, employing a simplified Starling
equation: Q = k (HP - OP). The model's spatial environment includes capillary, alveolar-capillary
membrane (ACM), and alveoli, with agents representing water molecules and macromolecules. Two
scenarios were simulated: (1) Normal: HP = 18 mmHg, OP = 25 mmHg, (2) CPE: HP = 22 mmHg,
OP = 24 mmHg.
Results: In the normal scenario, the model achieved a physiological balance with approximately 200
ml of extravasation cleared. In the CPE scenario, there was significant fluid accumulation (>400 ml by
~40 ticks). Adjusting parameters, such as reducing OP, amplified the edema, demonstrating the model's
flexibility. The model is available at:
https://modelingcommons.org/browse/one_model/5103#model_tabs_browse_info.
Conclusions: This ABM provides a valuable platform for tissue engineers to understand and
manipulate fluid dynamics in lung constructs. By simulating the effects of different pressure gradients
and permeability, it can guide the development of biomaterials and scaffolds that optimize fluid
handling in engineered lung tissues. The model's extensibility allows for future incorporation of
additional complexities, such as gas exchange and variable tissue properties, enhancing its utility in
both research and practical applications.
