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Establishment of a 3D-Printed Tissue-on-a-Chip Model for Live Imaging of Bacterial Infections
Albert Fuglsang-Madsen1,2, Janus Anders Juul Haagensen1,2, Charlotte De Rudder1,2,3
1Department of Clinical Microbiology, Rigshospitalet, Copenhagen, Denmark.
Abstract:
Despite advances in healthcare, bacterial pathogens remain a severe global health threat, exacerbated by rising antibiotic resistance. Lower respiratory tract infections, with their high death toll, are of particular concern. Accurately replicating host-pathogen interactions in laboratory models is crucial for understanding these diseases and evaluating new therapies. In this communication, we briefly present existing in vivo models for cystic fibrosis and their limitations in replicating human respiratory infections. We then present a novel, 3D-printed, cytocompatible microfluidic lung-on-a-chip device, designed to simulate the human lung environment, and with possible use in recapitulating general infectious diseases.Our device enables the colonisation of fully differentiated lung epithelia at an air-liquid interface with Pseudomonas aeruginosa, a key pathogen in many severe infections. By incorporating dynamic flow, we replicate the clearance of bacterial toxins and planktonic cells, simulating both acute and chronic infections. This platform supports real-time monitoring of therapeutic interventions, mimics repeated drug administrations as in clinical settings, and facilitates the analysis of colony-forming units and cytokine secretion over time. Our findings indicate that this lung-on-a-chip device has significant potential for advancing infectious disease research, in optimizing treatment strategies against infections and in developing novel treatments.
Insights
A new 3D-printed lung-on-a-chip model accurately simulates bacterial infections like Pseudomonas aeruginosa, offering a better way to study respiratory diseases and test new antibiotic treatments.
Area of Science:
- Biomedical Engineering
- Infectious Diseases
- Microfluidics
Background:
- Bacterial pathogens and antibiotic resistance pose significant global health threats, particularly in lower respiratory tract infections.
- Existing in vivo models for diseases like cystic fibrosis have limitations in accurately replicating human respiratory infections.
- Developing advanced models is crucial for understanding host-pathogen interactions and evaluating novel therapies.
Purpose of the Study:
- To introduce a novel 3D-printed, cytocompatible microfluidic lung-on-a-chip device.
- To simulate the human lung environment for studying infectious diseases.
- To overcome limitations of current in vivo models for respiratory infections.
Main Methods:
- A 3D-printed microfluidic device was developed to create a lung-on-a-chip model.
- Fully differentiated lung epithelia were colonized with Pseudomonas aeruginosa at an air-liquid interface.
- Dynamic flow was incorporated to simulate clearance of toxins and bacterial cells, mimicking acute and chronic infections.
Main Results:
- The device successfully enabled colonization and infection with Pseudomonas aeruginosa.
- Dynamic flow simulated clearance mechanisms, applicable to both acute and chronic infection models.
- The platform allowed real-time monitoring of therapeutic interventions and analysis of bacterial load and cytokine secretion.
Conclusions:
- The developed lung-on-a-chip device shows significant potential for advancing infectious disease research.
- This model can optimize treatment strategies for bacterial infections.
- The platform facilitates the development of novel therapeutic approaches against infections.
