title: Elastosis during airway wall remodeling explains multiple co-existing instability patterns.
abstract: Living structures can undergo morphological changes in response to growth and alterations in microstructural properties in response to remodeling. From a biological perspective, airway wall inflammation and airway elastosis are classical hallmarks of growth and remodeling during chronic lung disease. From a mechanical point of view, growth and remodeling trigger mechanical instabilities that result in inward folding and airway obstruction. While previous analytical and computational studies have focused on identifying the critical parameters at the onset of folding, few have considered the post-buckling behavior. All prior studies assume constant microstructural properties during the folding process; yet, clinical studies now reveal progressive airway elastosis, the degeneration of elastic fibers associated with a gradual stiffening of the inner layer. Here, we explore the influence of temporally evolving material properties on the post-bifurcation behavior of the airway wall. We show that a growing and stiffening inner layer triggers an additional subsequent bifurcation after the first instability occurs. Evolving material stiffnesses provoke failure modes with multiple co-existing wavelengths, associated with the superposition of larger folds evolving on top of the initial smaller folds. This phenomenon is exclusive to material stiffening and conceptually different from the phenomenon of period doubling observed in constant-stiffness growth. Our study suggests that the clinically observed multiple wavelengths in diseased airways are a result of gradual airway wall stiffening. While our evolving material properties are inspired by the clinical phenomenon of airway elastosis, the underlying concept is broadly applicable to other types of remodeling including aneurysm formation or brain folding.
authors.affiliation: Department of Mechanical Engineering, Stanford University, Stanford, CA 94305, USA.
authors.forename: Mona
authors.initials: M
authors.lastname: Eskandari
authors.affiliation: Department of Civil and Environmental Engineering, Stanford University, Stanford, CA 94305, USA.
authors.forename: Ali
authors.initials: A
authors.lastname: Javili
authors.affiliation: Department of Mechanical Engineering, Stanford University, Stanford, CA 94305, USA; Department of Bioengineering, Stanford University, Stanford, CA 94305, USA; Department of Cardiothoracic Surgery, Stanford University, Stanford, CA 94305, USA. Electronic address: ekuhl@stanford.edu.
authors.forename: Ellen
authors.initials: E
authors.lastname: Kuhl
mesh_terms: D056151:Airway Remodeling; D001249:Asthma / Q000150:complications / Q000473:pathology / Q000503:physiopathology*; D001696:Biomechanical Phenomena; D003198:Computer Simulation; D006801:Humans; D007249:Inflammation / Q000150:complications / Q000473:pathology; D013314:Stress, Mechanical
keywords: Airway; Elastosis; Finite element analysis; Folding; Growth and remodeling; Instability