Project 062

3D Bioprinting of ex vivo Liver Models

Prof. Dr. Jens Kurreck & Prof. Dr. Hartmut Schwandt
TU Berlin

03/2017 - 02/2019

3D printers can produce organ models that can help to test new pharmacological substances with respect to their efficiency and toxicity without the need to carry out animal experiments.

Current drug development is usually based on the principle to test new substances in two-dimensional (2D) cell culture and subsequently characterize them in an animal model. This procedure, however, has several drawbacks. Cells in a 2D cell culture do not represent the physiology of cells in a three-dimensional (3D) tissue, as they, for example, differ in their gene expression patterns. Animal models have the disadvantage that the animal cells differ from human cells. In addition, in vivo experiments are usually associated with unethical suffering of the animals.

To solve these problems, 3D organ models are being developed. In these models, cells are cultivated in the natural 3D environment. It is possible to employ human cells, and the use of animal models can be avoided. Great advancements were made with the development of additive manufacturing (3D bioprinting) technologies. The aim of the project is to produce a liver model by 3D printing. The liver is the main organ for the metabolization of exogenous substances. In addition, it is the target of numerous viruses of high medical relevance (e.g. hepatitis B and C viruses and adenoviruses).

In the project, the three-dimensional vascular structure of the liver will be printed and repopulated with human cells. To this end, a liver was explanted from a mouse. For the sake of animal welfare, it was explanted from a mouse that was left over from another animal experiment and was sacrificed anyway, so that no additional animal was needed. The explanted liver was decellularized (Figure 1A) and plastinated (Figure 1B) for spatial digitalization by CT scan (Figure 1C).

Fig. 1:
A decellularized mouse liver (A) was plastinated (B) and subsequently analyzed by CT scan (C).

As currently available 3D printing technologies do not immediately allow to generate the complex structure of an extracellular matrix of the liver, an intermediate model will be produced that is composed of tubes of the biopolymer polylactid-co-glycolid (PLGA). This scaffold can then be repopulated with cells and will be a preliminary version of the liver model (Figure 2).

Fig. 2:
Schematic representation of the intermediate mode. A) Perfusable PLGA tubes (green) with an adapter (turquois) for the media flow (red arrows) and fixation in the bioreactor. The cells (blue) will grow on the surface of the tubes. B) Modell with multiple tubes arranged in parallel (four horizontal and four vertical).

The 3D liver model will eventually be used to test substances and to develop antiviral strategies against hepatotropic viruses.

Institution

Prof. Dr. Jens Kurreck
Technische Universität Berlin
Institut für Biotechnologie, Fachgebiet Angewandte Biochemie, TIB 4/3-2
Gustav-Meyer-Allee 25
13355 Berlin, Germany

Prof. Dr. Hartmut Schwandt
Technische Universität Berlin
Institut für Mathematik, 3D Labor, MA 6-4
Straße des 17. Juni 136
10623 Berlin, Germany

Duration

03/2017 - 02/2019