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Digital archive of theses discussed at the University of Pisa


Thesis etd-05062015-181832

Thesis type
Tesi di dottorato di ricerca
Thesis title
Development of a dynamic model of the alveolar interface for the study of aerosol deposition
Academic discipline
Course of study
commissario Moroni, Lorenzo
commissario Raiteri, Roberto
commissario Scilingo, Enzo Pasquale
tutor Prof.ssa Ahluwalia, Arti Devi
  • Air-liquid Interface
  • ALI
  • Alveolar
  • Bioreactor
  • Breathing
  • Lung
Graduation session start date
Release date
The aim of this project was to develop an in vitro model for contractile interface tissues for investigating the role of mechanical stretching on the permeability of epithelial cells to soluble and airborne nanoparticles. The
work was divided in two parts: first a prototype of an in vitro system for the alveolar interface for application to aerosol and drug deposition models was realised and validated. In the second part an innovative actuated cell chamber, based on the Electro-Active Polymer (EAP) technology was designed and tested.
The fi rst in vitro model consists of a compliant membrane enclosed in a double chamber system, named MALI (Moving Air-Liquid Interface) bioreactor. To mimic natural breathing, an external compressed air system is used to stretch the elastic membrane where alveolar epithelial cells are grown.
In the final chapter of the thesis an embedded actuator bioreactor system mimicking a vibrating physiological interface in vitro model was designed and tested. First innovative electrodes, named ionogels, were characterized and their performance compared with the traditional carbon grease electrodes. This step was necessary to overcome the sterility and handling problems of standard carbon grease electrodes in cell culture environments. The actuator was realised, mounting a commercial dielectric membrane mounted on a rigid frame with an annular electrodes deposited on both side. Subsequently, a two chamber system was designed and added to the actuator to generate an in vitro model of a vibrating interface. Once the system was able to provide the desired stimuli, the biocompatibility of the EAP was tested using an epithelial cell line.
The methods and tools presented in this thesis are a step forward towards the development of vibrating in vitro models of physiological interfaces.
The modularity and essential design is crucial because it eases the transition from old technology to new dynamic, three dimensional devices, and accelerates their acceptance into mainstream research. This is an important step for future improvements in in vitro studies such as drug development and toxicity testing, and emerging fields like personalized therapies.