Summary

A successful pregnancy is the result of a series of complex events involving an interaction between a receptive womb and a competent early embryo. Failure of the embryo to embed in the lining of the womb (endometrium) is a major cause of infertility and IVF failure. Perturbed implantation inevitably causes miscarriage, the commonest complication of pregnancy, affecting approximately 250,000 couples in the UK each year.

In this interdisciplinary project, we will develop vascularised polymer scaffolds that can be used to create an advanced in vitro 3D model of human endometrium using an organ-on-a-chip approach as a research platform to study normal and pathological embryo implantation events that cannot be studied directly in humans.

3D printing technology will be combined with the emulsion-templating process to generate polymer scaffolds with complex internal geometries (networks of channels and interconnected chambers) as novel microfluidic platforms to encourage vascularisation and later facilitate embryo implantation. The pore diameter, mechanical properties and surface functionality of these polymer scaffolds will be tailored to a high extent, making them suitable for 3D cell culture. The utility of the scaffolds will be tested by the culture of human endometrial stem cells, organoids and trophoblasts and endothelial cells within the channels. Once produced, the devices will be used to better understand the endometrial niche and its role in embryo implantation. Contact between the early embryo and endometrial cells is anticipated to induce paracrine cross-talking and enable coordinated trophoblast invasion, mimicking the natural process of the first stage of successful implantation.

A series of short pilot studies will be performed to investigate the functionality of the device in the co culture model. This research will ultimately allow the development of novel treatment strategies for persistent implantation failure and female infertility.

Key Outputs

Seminar at the University of Warwick’s Multidisciplinary Centre for Early Life with clinicians and medical scientists - translational research.
PhD presented recent results in the World Congress of the Tissue Engineering and Regenerative Medicine International Society (TERMIS 2021)