Mechanics of pulmonary airways: Linking structure to function through constitutive modeling, biochemistry, and histology.

Breathing involves fluid-solid interactions in the lung; however, the lack of experimental data inhibits combining the mechanics of air flow to airway deformation, challenging the understanding of how biomaterial constituents contribute to tissue response. As such, lung mechanics research is increasingly focused on exploring the relationship between structure and function. To address these needs, we characterize mechanical properties of porcine airways using uniaxial tensile experiments, accounting for bronchial orientation- and location- dependency. Structurally-reinforced constitutive models are developed to incorporate the role of collagen and elastin fibers embedded within the extrafibrillar matrix. The strain-energy function combines a matrix description (evaluating six models: compressible NeoHookean, unconstrained Ogden, uncoupled Mooney-Rivlin, incompressible Ogden, incompressible Demiray and incompressible NeoHookean), superimposed with non-linear fibers (evaluating two models: exponential and polynomial). The best constitutive formulation representative of all bronchial regions is determined based on curve-fit results to experimental data, accounting for uniqueness and sensitivity. Glycosaminoglycan and collagen composition, alongside tissue architecture, indicate fiber form to be primarily responsible for observed airway anisotropy and heterogeneous mechanical behavior. To the authors' best knowledge, this study is the first to formulate a structurally-motivated constitutive model, augmented with biochemical analysis and microstructural observations, to investigate the mechanical function of proximal and distal bronchi. Our systematic pulmonary tissue characterization provides a necessary foundation for understanding pulmonary mechanics; furthermore, these results enable clinical translation through simulations of airway obstruction in disease, fluid-structure interaction insights during breathing, and potentially, predictive capabilities for medical interventions. STATEMENT OF SIGNIFICANCE: The advancement of pulmonary research relies on investigating the biomechanical response of the bronchial tree. Experiments demonstrating the non-linear, heterogeneous, and anisotropic material behavior of porcine airways are used to develop a structural constitutive model representative of proximal and distal bronchial behavior. Calibrated material parameters exhibit regional variation in biomaterial properties, initially hypothesized to originate from tissue constituents. Further exploration through biochemical and histological analysis indicates mechanical function is primarily governed by microstructural form. The results of this study can be directly used in finite element and fluid-structure interaction models to enable physiologically relevant and more accurate computational simulations aimed to help diagnose and monitor pulmonary disease.