טכניון מכון טכנולוגי לישראל
הטכניון מכון טכנולוגי לישראל - בית הספר ללימודי מוסמכים  
Ph.D Thesis
Ph.D StudentTenenbaum-Katan Janna
SubjectPulmonary Alveolar Flow Physiology: From Fetal to Childhood
Airways
DepartmentDepartment of Biomedical Engineering
Supervisor Professor Josue Sznitman
Full Thesis textFull thesis text - English Version


Abstract

At the onset of life in utero, the respiratory system begins as a tubular, liquid-filled organ that undergoes dramatic morphological and functional transformations, before crossing over to an air-filled organ. In the span from fetal life to early childhood, the pulmonary morphology exhibits significant changes that affect pulmonary acinar flows. Prenatally, such flows are acknowledged to impact lung development, influencing critical milestones towards autonomous breathing at birth; postnatally, airway remodeling and varying ventilation patterns during the first years of life are anticipated to alter aerosol deposition, an essential component for inhalation therapy and drug delivery considerations. In this context, recreating physiologically-realistic features of the pulmonary acinar environment in vitro through experiments or in silico through computational simulations is typically challenging. Not only must intricate acinar architectures be mimicked under ever-changing ventilation parameters, complex physiological functions of the underlying cellular makeup must be reconstituted. In the present work, we have combined experimental and numerical methods to address various aspects of pulmonary acinar fluid flows (liquid and air) during pre- and postnatal life. To investigate how such flows evolve through lung development in utero, we have devised true-scale biomimetic microfluidic models of fetal alveolated airways and integrated an alveolar epithelium that secretes pulmonary surfactant. Following the prenatal stage, ongoing efforts are carried out to design robust, anatomically-inspired platforms mimicking postnatal acinar structures, whereby air-filled microchannels are integrated with epithelial monolayers to reconstitute the air-liquid interface, a characteristic of pulmonary alveoli  ex utero. Finally, we have used computational Fluid Dynamics (CFD) to investigate inhaled therapeutic transport and deposition in the acinar regions during childhood. By modeling the dynamics of inhaled aerosols acknowledged to reach the alveolar regions, we shed new light on transport characteristics that may affect therapy and deposition outcome in young populations. Overall, our in vitro and in silico efforts attempt to bridge the gap in our understanding of the respiratory flows that characterize the pulmonary environment during lung development.