Synthetic model system to study embryo implantation

The image shows a mouse blastocyst stained for cell membrane marker (red) and cell nuclei (blue).
© Ivan Bedzhov

Project title: A biomimetic platform mimicking the implantation niche of mouse embryos
Principal investigators: Ivan Bedzhov, Britta Trappmann
Project time: 11/2017 - 12/2018
Project code: FF-2017-04

Not much is currently known about how exactly embryos are implanted in the uterine wall – although the implantation is often decisive for the success or failure of a pregnancy. In 49 percent of all miscarriages, the embryos do not manage to settle successfully in the uterine wall. In their research project, Dr. Britta Trappmann, a biomedical engineer, and biologist Dr. Ivan Bedzhov want to develop a synthetic model which will enable them for the first time to observe the entire implantation process and thus analyse its dynamics.

Currently, the implantation of an embryo can only be investigated to a limited extent. This is because the process takes place hidden away, right inside the uterus – so researchers cannot observe and analyse it directly. Nor is there any tissue model with a comparable cellular environment and an opportunity to influence the parameters, depending on the experiment being carried out.

This is the point at which the Flexible Funds Project kicks in. Ivan Bedzhov supplies the basis for the biological part. Using mice as a model system, he analyses the mechanisms which take place before and after the implantation of the embryo. His research team has already developed a culture medium in which mouse embryos can grow on plastic plates. It is not, however, possible to mimic and analyse the implantation of the embryo using hard, impermeable plastic.

Here, Britta Trappmann and her research team will complement the analysis, as her laboratory focuses on the development of synthetic, three-dimensional extracellular matrices. Using these synthetic tissue models, on the basis of a new type of hydrogel, it is possible to examine how cells interact with the tissue around them. What is special about this model is that, as a result of the materials being used, researchers can influence many of the parameters individually. The hydrogel, for example, can have exactly the same degree of softness as the tissue of the lining of the uterus.

The researchers now want to work together to develop a synthetic tissue model which mimics the dynamics of the implantation in the uterus. In this way, they can follow the process by which the embryo is implanted in the uterine wall, and how the embryo cells interact with the mother’s blood vessels. With their new model the researchers will, for the first time, be able to observe and capture the entire process by time-lapse microscopy. This will critically enable a thorough analysis of the first interactions between the embryo and the mother.