(E-165) Establishing a Fluid-Structure Interaction Model for Examining Structural Deformations in Decellularized Mouse Lungs During Re-endothelialization

Introduction:: Endothelialization of acellular lung scaffolds remains a significant challenge hindering the generation of bioengineered lungs. Specifically, there is little known of the interactions between delivered cells and the scaffold microenvironment. Herein, we employ fluid-structure interaction (FSI) to investigate the structural changes of lung vasculature during the re-endothelialization process of a decellularized lung scaffold with the objective to optimize the re-endothlialization procedure. Addressing the limitations of rigid wall assumptions in conventional computational fluid dynamics (CFD) studies, this research incorporates deformable and porous structures to more accurately model re-endothelialization. The model offers valuable insights into the delivery of cells to distal vessels, a critical challenge in the field of tissue engineering and regenerative medicine for bioengineered lungs. Additionally, this study provides a CFD analysis to evaluate variables such as wall shear stress and perfusion rate through the acellular lung scaffold vasculature walls during re-endothelialization.


Materials and Methods:: This study utilized COMSOL Multiphysics for analysis. In the geometry generation phase, intact pulmonary systems from 12-week-old adult mice (C57Bl/6) were employed to create three lung geometries. The systems underwent cannulation and cleansing through a detergent-based decellularization process to remove cellular material. A contrast agent (Microfil) was then injected into the vasculature for micro-CT X-ray imaging. Image processing involved MATLAB and ImageJ for vasculature isolation and segmentation, and 3D Slicer for rendering. The fluid domain was established within the vasculature, while the solid domain was assigned to the porous parenchyma. An interface at the fluid-solid contact point was designated, enabling fluid property extraction for finite element analysis (FEA). Consequently, both vasculature and parenchyma experienced deformation during recellularization due to fluid pressure and flow of cells through porous layer. In the mesh generation phase, a dynamic mesh was used for the parenchyma to measure vasculature deformation arising from fluid-solid interactions during the recellularization process. The dynamic mesh was optimized with COMSOL using 107,892 tetrahedral elements, balancing computational efficiency and precision in fluid-structure interaction scenarios. A laminar flow condition was assigned for the modeling of the fluid. This condition was confirmed by verifying that the flow resulted in a Reynolds number of less than 1000. The pulmonary artery functioned as the fluid flow inlet, while the pulmonary vein and parenchyma surface served as outlets. COMSOL's CFD and structural mechanics modules were employed to determine structural deformation resulting from fluid-induced stresses, assuming linear elastic behavior and isotropic material properties.


Results, Conclusions, and Discussions:: In this research, three distinct re-endothelialization conditions were investigated, comprising of positive pressure seeding, negative pressure seeding, and dual pressure seeding (Mohammadali Ahmadipour, 2021). Positive pressure seeding involved the direct infusion of the cell suspension fluid into the cannulated lung scaffold through the pulmonary artery. Negative pressure seeding was executed by applying a vacuum around the parenchyma and the pulmonary vein while maintaining atmospheric pressure in the pulmonary artery; this action draws the cell media from the pulmonary artery into the scaffold. Lastly, the dual pressure approach employed the same conditions as negative pressure seeding, with the key difference being that the cell media fluid was directly introduced through the pulmonary artery, akin to the positive pressure scenario. The computational fluid dynamics (CFD) model for porous flow enables the examination of region-specific flow across the vascular walls. This measure is crucial to characterize, as it influences the cellular path during the re-endothelialization process. In every re-endothelialization instance, the arterial walls exhibited the greatest flow rate, followed by the venous and then distal vessel walls. This is primarily attributed to the fact that the pulmonary artery (flow field inlet) experienced maximum flow dynamic pressure. Conversely, the pulmonary vein exhibited a reduced flow rate due to the resistances it faced, as the fluid flow lost some momentum when traversing the distal vessels. The average wall shear stress (WSS) experienced by the vascular walls was subsequently analyzed. In all cases, the distal vessels consistently displayed the highest WSS values across all geometries. This is presumably a result of microfluidic flow's influence within smaller vessels, where shear viscous forces prevail. By implementing a more accurate fluid-structure interaction model for the re-endothelialization process, this research has the potential to significantly impact the development of bioengineered lungs, paving the way for more effective and efficient tissue engineering strategies, ultimately improving patient outcomes in the field of regenerative medicine.


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References (Optional): : Mohammadali Ahmadipour, P. D. (2021). Negative Pressure Cell Delivery Augments Recellularization of Decellularized Lungs. Tissue Eng Part C Methods.