New bioengineering approach to fix fetal membranes

October 12, 2020

New research led by Queen Mary University of London and UCL has shown that small bioengineered molecules can be used to repair defects in the fetal membranes that surround and protect babies developing in the womb.

The study, published in the journal Prenatal Diagnosis, found that these molecules, known as peptide amphiphiles (PAs) self-assemble to form a 'plug' that seals holes within the fetal membranes, and could potentially help repair any damage.

The integrity of the fetal membranes during pregnancy is vital for normal development. The premature rupture of fetal membranes, known as preterm prelabour rupture of the membranes (PPROM), is a major cause of preterm birth accounting for around 40 per cent of early infant death.

Currently there are no clinical approaches available to repair or improve healing in the fetal membranes.

For the study, the researchers established a fetal membrane defect model, which mimics the creation of a defect site within the fetal membrane as a result of keyhole surgery. They assembled donated human fetal membrane tissue onto cell culture dishes and injected human amniotic fluid, the protective fluid which surrounds the developing fetus, underneath. The injection creates a small hole within the membrane to which the PAs were then added.

The research team found that PAs spontaneously assembled together seconds after coming into contact with the human amniotic fluid. Within two minutes, a dense mesh of fibres formed a plug, which sealed the hole created at the injection site after 24 hours.

When they combined this novel use of PAs with protein sequences known to promote adhesion and healing, the researchers observed an enhanced sealing and regenerative effect.

The findings follow on from previous work from the research team, which showed that reducing the levels of a protein called connexin 43 (Cx43) encouraged rebuilding of the fetal membranes, and enhances the processes of tissue healing and repair.

Whilst PPROM can occur spontaneously, it can also result from fetal surgery and prenatal diagnosis procedures such as amniocentesis that require doctors to make a hole in the fetal membrane sac.

Fetal medicine specialists are increasingly offering surgery to babies in the womb before birth, to treat abnormalities of the spine, diaphragm or placenta. PPROM complicates around one third of these cases, reducing the clinical effectiveness of fetal surgery.

Dr Tina Chowdhury, Senior Lecturer in Regenerative Medicine at Queen Mary, said: "The next step in this research is to understand whether these molecular 'plugs' are able to withstand the mechanical forces such as tension or pressure induced by the developing fetus and the amniotic fluid. We also need to explore the wound healing mechanisms in more detail, and the safety of using the peptides for expectant mothers and babies during pregnancy."

Professor Anna David, Professor of Obstetrics and Fetal Medicine at UCL Elizabeth Garrett Anderson Institute for Women's Health and a co-author of the study, said: "Finding a method to heal the amniotic membranes and prevent preterm birth after PPROM is a vital step to improving the outcomes of babies where the membranes rupture. The sealing and regeneration that we saw is very encouraging for our bioengineering approach."
The research was supported by funding from Sparks Children's Medical Charity (17QMU01), Rosetrees Trust (M404), KU Leuven University Fund, NIHR UCLH Biomedical Research Centre, Little Heartbeats and the Prenatal Therapy Fund, University College London Hospital Charity.

Head of Research at Rosetrees Trust, Dr Vin Rajkumar, said: "Rosetrees Trust is delighted to have supported Dr Tina Chowdhury's research on the molecular mechanisms that can cause PPROM. We hope that these findings will be the first steps to identifying potential treatments for this condition."

Kiki Syrad, Director of Grants and Impact at Sparks, the children's medical research charity, commented: "We're delighted to see the progress made on this vital project to understand more about how to reduce the risks of PPROM and preterm birth to babies. We hope these findings and further research in this area will one day help more children to enjoy a healthy start in life. This research demonstrates the importance of early funding and we're thrilled to support Dr Chowdhury and her team's important work."

Notes to editors

* Research publication: 'Potential sealing and repair of human FM defects after trauma with peptide amphiphiles and Cx43 antisense' Barrett DW, Okesola BO, Costa C, Thrasivoulou C, Becker DL, Mata A, Deprest J, David AL, Chowdhury T, Prenatal Diagnosis.

* For more information and a copy of the paper, please contact:

Sophie McLachlan
Faculty Communications Manager (Science & Engineering)
Queen Mary University of London
Tel: 020 7882 3787

About Queen Mary

Queen Mary University of London is a research-intensive university that connects minds worldwide. A member of the prestigious Russell Group, we work across the humanities and social sciences, medicine and dentistry, and science and engineering, with inspirational teaching directly informed by our world-leading research. In the most recent Research Excellence Framework we were ranked 5th in the country for the proportion of research outputs that were world-leading or internationally excellent. We have over 25,000 students and offer more than 240 degree programmes. Our reputation for excellent teaching was rewarded with silver in the most recent Teaching Excellence Framework. Queen Mary has a proud and distinctive history built on four historic institutions stretching back to 1785 and beyond. Common to each of these institutions - the London Hospital Medical College, St Bartholomew's Medical College, Westfield College and Queen Mary College - was the vision to provide hope and opportunity for the less privileged or otherwise under-represented. Today, Queen Mary University of London remains true to that belief in opening the doors of opportunity for anyone with the potential to succeed and helping to build a future we can all be proud of.

UCL - London's Global University

UCL is a diverse community with the freedom to challenge and think differently.

Our community of more than 41,500 students from 150 countries and over 12,500 staff pursues academic excellence, breaks boundaries and makes a positive impact on real world problems.

We are consistently ranked among the top 10 universities in the world and are one of only a handful of institutions rated as having the strongest academic reputation and the broadest research impact.

We have a progressive and integrated approach to our teaching and research - championing innovation, creativity and cross-disciplinary working. We teach our students how to think, not what to think, and see them as partners, collaborators and contributors.

For almost 200 years, we are proud to have opened higher education to students from a wide range of backgrounds and to change the way we create and share knowledge.

We were the first in England to welcome women to university education and that courageous attitude and disruptive spirit is still alive today. We are UCL.| Follow @uclnews on Twitter | Watch our YouTube channel | Listen to UCL podcasts on SoundCloud | Find out what's on at UCL Minds | #MadeAtUCL

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