Integrating three-dimensional printing and bioprinting technologies to develop a stretchable in vitro model of the human airway

Bio-Design and Manufacturing, vol. 8, pp. 595–608

Abstract

Abstract The global demand for in vitro respiratory airway models has surged due to the coronavirus disease 2019 (COVID-19) pandemic. Current state-of-the-art models use polymer membranes to separate epithelial cells from other cell types, creating a nonphysiological barrier. In this study, we applied three-dimensional (3D) printing and bioprinting to develop an in vitro model where endothelial and epithelial cells were in direct contact, mimicking their natural arrangement. This proof-of-concept model includes a culture chamber, with an endothelial bioink printed and perfused through an epithelial channel. In silico simulations of the air velocity within the channel revealed shear stress values ranging from 0.13 to 0.39 Pa, aligning with the desired in vivo shear stress observed in the bronchi regions (0.1–0.4 Pa). Biomechanical movements during resting breathing were mimicked by incorporating a textile mesh positioned away from the cell–cell interface. The epithelial channel demonstrated a capacity for compression and expansion of up to −14.7% and +6.4%, respectively. Microscopic images showed that the epithelial cells formed a uniform monolayer within the lumen of the channel close to the bioprinted endothelial cells. Our novel model offers a valuable tool for future research into respiratory diseases and potential treatments under conditions closely mimicking those in the lung.

Authors 8

1. Julian Gonzalez‐Rubio Aachen Institute of Applied Medical Engineering Biohybrid and Medical Textiles

   RWTH Aachen University

   Affiliation as printed

   Biohybrid & Medical Textiles (BioTex), Institute of Applied Medical Engineering (AME), Helmholtz Institute for Biomedical Engineering, RWTH Aachen University, Aachen, 52074, Germany

2. Oscar O'Dwyer Lancaster-Jones

   Heidelberg University

   Affiliation as printed

   Bioprinting & Tissue Engineering, Center for Molecular Biology of Heidelberg University (ZMBH), Heidelberg, 69120, Germany

3. Charlotte Büchter Aachen ITA Institute for Textile Technology

   RWTH Aachen University

   Affiliation as printed

   ITA Institute for Textile Technology, RWTH Aachen University, Aachen, 52074, Germany

4. Stefan Jockenhoevel Aachen Institute of Applied Medical Engineering Biohybrid and Medical Textiles

   RWTH Aachen University

   Affiliation as printed

   Biohybrid & Medical Textiles (BioTex), Institute of Applied Medical Engineering (AME), Helmholtz Institute for Biomedical Engineering, RWTH Aachen University, Aachen, 52074, Germany

5. Laura De Laporte Aachen Institute of Technical and Macromolecular Chemistry DWI - Leibniz Institute for Interactive Materials Center for Biohybrid Medical Systems (CBMS) Advanced Materials for Biomedicine (AMB) Institute of Applied Medical Engineering

   RWTH Aachen University · Universitätsklinikum Aachen · DWI – Leibniz Institute for Interactive Materials

   Affiliation as printed

   Advanced Materials for Biomedicine (AMB), Institute of Applied Medical Engineering (AME), Center for Biohybrid Medical Systems (CBMS), University Hospital RWTH Aachen, Aachen, 52074, Germany

   DWI – Leibniz Institute for Interactive Materials, Aachen, 52074, Germany

   Institute of Technical and Macromolecular Chemistry (ITMC), RWTH Aachen University, Aachen, 52074, Germany

6. Mirko Trilling

   Essen University Hospital · University of Duisburg-Essen

   Affiliation as printed

   Institute for Virology, University Hospital Essen, University of Duisburg-Essen, Essen, 45147, Germany

   Institute for the Research on HIV & AIDS-associated Diseases, University Hospital Essen, University of Duisburg-Essen, Essen, 45147, Germany

7. Anja Lena Thiebes Aachen Institute of Applied Medical Engineering Biohybrid and Medical Textiles

   RWTH Aachen University

   Affiliation as printed

   Biohybrid & Medical Textiles (BioTex), Institute of Applied Medical Engineering (AME), Helmholtz Institute for Biomedical Engineering, RWTH Aachen University, Aachen, 52074, Germany

8. Daniela F. Duarte Campos corresponding Aachen Center for Biohybrid Medical Systems (CBMS) Advanced Materials for Biomedicine (AMB) Institute of Applied Medical Engineering

   RWTH Aachen University · Universitätsklinikum Aachen · Heidelberg University

   Affiliation as printed

   Advanced Materials for Biomedicine (AMB), Institute of Applied Medical Engineering (AME), Center for Biohybrid Medical Systems (CBMS), University Hospital RWTH Aachen, Aachen, 52074, Germany

   Bioprinting & Tissue Engineering, Center for Molecular Biology of Heidelberg University (ZMBH), Heidelberg, 69120, Germany