Fraunhofer Institute for Material and Beam Technology IWS
Fraunhofer Institute for Material and Beam Technology IWS

Vibro3D

Human Infection Model for Vibrio cholerae as an Alternative to Animal Testing

Project Description

As part of the Micro-Physiological Systems (MPS) joint project, Fraunhofer Institute for Material and Beam Technology IWS is developing innovative intestine-on-chip models that combine perfusion, realistic simulation of intestinal peristalsis, and defined hypoxic environments.

Project Objective

The aim is to replace classic animal models such as the infant rabbit model with a standardized, clinically compatible alternative.

In combination with the subprojects of the other partners UKJ (immunocompetent intestinal model), FSU Jena (microbiological characterization), HKI (systems biology data integration), and PEI (regulatory validation), this project enables realistic investigation of infection dynamics, immune responses, and therapeutic interventions in vitro. The project makes a direct contribution to the 3R principles and lays the foundation for a sustainable reduction in animal testing in infection research.

Illustration of the concept and joint interdisciplinary preliminary work by the applicants in the consortium.
© Friedrich-Schiller-Universität Jena
Illustration of the concept and joint interdisciplinary preliminary work by the applicants in the consortium.

Explanations regarding the illustration of the concept:

  • a) Schematic structure of the proposed intestine-on-chip model for investigating V. cholerae infections.
  • b) Cross-section through the intestinal tissue model and 10 immunofluorescence staining (endothelial cells: von Willebrand factor (green), epithelium: E-cadherin (orange), F-actin (red), membrane (dotted white lines).
  • c) Chip prototype for biomechanical stimulation.
  • d) Light microscopic image of endothelial cells on nylon mesh with collagen-elastin hydrogel.
  • e) OCT measurements of membrane deflection in the chip prototype.
  • f) Evidence of stable colonization of the epithelial layer of the intestine-on-chip model over 6 hours without transfer into the endothelium (CFU assay of endothelial and epithelial perfusate).
  • g) Cytokine profiles of the epithelial perfusate without (w/o) infection and 2, 6, and 12 hours after infection. * p<0.01 ANOVA 1-way testing with correction for multiple testing (Tukey)
  • h) Co-cultivation of two different V. cholerae strains with different reporter genes (GFP (green) and mKate (red)). Clonal expansion and biofilm formation are clearly visible.
  • i) 3D reconstruction of microscopy images for analysis of V. cholerae biofilms (green) and their colocalization with epithelial cell structures (cell nuclei blue) V. cholerae biofilms (green) and colocalization with epithelial ZO-1 (magenta).