Lifeline: Ex Vivo Lung Ventilation and Perfusion Experimental Platform for Pkpd Studies of Inhaled Therapeutics

A PhD student position will be available in the INSERM U1059-SAINBIOSE, University of Saint Etienne and
Ecole des Mines de Saint-Etienne, France, on the topic:
“LIFELINE: ex vivo Lung ventIlation and perFusion Experimental pLatform for PKPD studies of INhaled
thErapeutics”

From: October 2025 to October 2028

Environment: This doctoral position will be located in the thriving environment of the INSERM Unit U1059
portfolio of academic and industry funding, at the School of Medicine campus in Saint Etienne (Jean Monnet
university), and in direct proximity with the University Hospital and the Center for Biomedical and Healthcare
Engineering of Ecole Nationale Supérieure des Mines de Saint-Etienne, one of the top 10 French graduate
schools for science and technology. The team has over 10 years of international expertise in various ventilated
ex vivo models (Figure 1), and has already developed a ventilated-perfused (V-P) ex vivo model for 2 years.

Figure 1: Illustrations of the ventilated ex vivo models developed by the laboratory for the study of inhaled particles. (A)
Schematic of a porcin lung model ventilated under negative pressure with 1: stereolithographed human ENT tract; 2: one
- way valves; 3: artificial trachea; 4: filter to collect the exhaled dose; 5: ex vivo respiratory system of an animal; 6:
instrumented hypobaric chamber; 7: modulatable vacuum generator. (B) Photo of the porcin model. (C) Application for
mechanical ventilation. (D) Neonatal model with rabbit thorax.

The team is inherently multidisciplinary, and will bring the specific skills needed for each WP to ensure the
have the opportunity to participate to national and international meetings. Thanks to this expertise in the field
of ex vivo ventilation, the first prototype enabling ex vivo ventilation and perfusion of porcine lungs was
designed and developed in our laboratory (Figure 2).

Figure 2: Ex vivo V-P model developed for lung transplantation. (A) Perfusion circuit; (B) negative pressure ventilation and
perfusion housing of porcine lungs; (C) perfusion flow regulation system; (D) adjustment of negative pressure ventilation
parameters.

Indeed, the addition of perfusion to our previous model presents a major technological challenge as “fresh”
respiratory tracts must be harvested and used immediately after the animal's death, imposing surgical
restrictions, changes to supply chains and additional ethical constraints. After initial validation tests several
technological challenges were overcome by adding mobilization, rewarming, modulation of specific negative
pressure ventilation and recycling of perfusion fluids.

Lead and collaborations: the scientific objective of the LIFELINE project is to develop the first ventilation
- perfusion ex vivo platform for the pharmacokinetic and pharmacodynamic (PK/PD) study of inhaled
treatments. It will make possible to study the quantitative effects of different parameters on the absorption
of inhaled drug in order to improve and personalize therapies and diagnostic contrast agents according to the
different respiratory conditions. In order to achieve the success of this technological innovation, the work will
be divided into 4 work packages (WP), which are described below (Figure 3):
The objective of this doctoral thesis is to achieve the WP of the LIFELINE project with publication at different
stages of the project (Figure 3). This 3-year position will be co-supervised by Pr Sophie Perinel Ragey, MD-PhD,
intensivist and pulmonologist, who leads the research topic on ex vivo models in the laboratory and Pr Jérémie
Pourchez, PhD, senior researcher at Ecole des Mines de Saint Etienne, expert in biomedical engineering and
lead to local cooperation with the University Hospital of Saint Etienne and other teams working on the topic.
The team has developed multiple collaboration with national and international teams to study aerosolized
particles and models.

to ex vivo modeling, engineering, and finally pharmacokinetics. By the start of the position (~October 2025),
the applicant must hold a Master 2 in biological or pharmaceutical sciences. Basic knowledge in aerosol
research and healthcare, be a team player, and willing to progress in English and French, whichever
nationality.

indicating your motivation, experience, and research interests. Join a CV, an upto-date master graduate
transcript, at least one support/recommendation letter, and past communications if applicable (contribution
to a scientific article, review, poster ).

Application deadline: 5/04/2025
Keywords: anatomical model, aerosol therapy, respiratory physiology, pharmacology.

REFERENCES
Montigaud et al (DOI: 10.1038/s41598-023-38281-9) ; Montigaud et al (DOI: 10.2147/IJN.S260640) ;
Montigaud et al (DOI : 10.1038/s41598-019-42103-2) ; Perinel et al (DOI : 10.1038/srep43121) ; Perinel
et al (DOI : 10.1186/s12931-016-0395-7)