Towards constructing a generalized structural 3D breathing human lung model based on experimental volumes, pressures, and strains

PLoS Comput Biol. 2025 Jan 13;21(1):e1012680. doi: 10.1371/journal.pcbi.1012680. eCollection 2025 Jan.

Abstract

Respiratory diseases represent a significant healthcare burden, as evidenced by the devastating impact of COVID-19. Biophysical models offer the possibility to anticipate system behavior and provide insights into physiological functions, advancements which are comparatively and notably nascent when it comes to pulmonary mechanics research. In this context, an Inverse Finite Element Analysis (IFEA) pipeline is developed to construct the first continuously ventilated three-dimensional structurally representative pulmonary model informed by both organ- and tissue-level breathing experiments from a cadaveric human lung. Here we construct a generalizable computational framework directly validated by pressure, volume, and strain measurements using a novel inflating apparatus interfaced with adapted, lung-specific, digital image correlation techniques. The parenchyma, pleura, and airways are represented with a poroelastic formulation to simulate pressure flows within the lung lobes, calibrating the model's material properties with the global pressure-volume response and local tissue deformations strains. The optimization yielded the following shear moduli: parenchyma (2.8 kPa), airways (0.2 kPa), and pleura (1.7 Pa). The proposed complex multi-material model with multi-experimental inputs was successfully developed using human lung data, and reproduced the shape of the inflating pressure-volume curve and strain distribution values associated with pulmonary deformation. This advancement marks a significant step towards creating a generalizable human lung model for broad applications across animal models, such as porcine, mouse, and rat lungs to reproduce pathological states and improve performance investigations regarding medical therapeutics and intervention.

MeSH terms

  • Animals
  • COVID-19* / virology
  • Computational Biology
  • Computer Simulation
  • Finite Element Analysis*
  • Humans
  • Imaging, Three-Dimensional / methods
  • Lung* / physiology
  • Models, Anatomic
  • Models, Biological
  • Pressure
  • Respiration
  • Respiratory Mechanics / physiology
  • SARS-CoV-2

Grants and funding

This study was supported in part by a Dassault Systèmes U.S. Foundation Grant and as part of the Living Lung Project (AB, ME), the Opportunity to Advance Sustainability Innovation and Social Inclusion (OASIS) UCR and State of California Climate Action Through Resilience Program (AB, GOR, MS, ME), the Eugene Cota Robles Fellowship (GOR), and the National Science Foundation Graduate Research Fellowship (CAM). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.