Correcting an historical failure in women’s health

How did you become interested in applying materials science to challenges in women’s health?

When I was a PhD student in orthopaedic biomechanics, I took a phone call from an obstetrician who wanted to know if there was anyone in my lab who could measure forces. He was interested in preterm birth, and he wanted to know whether a medical procedure he was doing might change the properties of the foetal membrane to make it prone to rupturing prematurely. We collaborated on a study to examine that question, then started collaborating more generally, and by the time I finished my PhD, I was funded and working in the obstetrics and gynaecology (OB/GYN) department and doing my PhD in bone and biomaterials on the side.

We can tailor everything we’re doing from a materials standpoint to gives us the chance to test what’s important

How do you use materials science in your research today?

My current focus is on reproduction, so I’m interested in premature birth and how to prevent it, how to diagnose it, how to get away from the fact that one in 10 babies worldwide are born early, which can lead to a whole bunch of knock-on effects. One of the challenges with human pregnancy is that there are no good animal models for studying it, because placentas have evolved to be weirdly different in different mammalian species. This means that in vitro models, where we combine human cells with biomaterials, and in silico models, where we make computer models of material systems, are vital because they allow us to study things like the early development of the placenta that would otherwise be impossible due to the ethical issues of studying vulnerable populations.

What types of biomaterials are involved?

Natural tissues consist of cells plus an extracellular matrix (ECM), which is made up of things like collagen, proteins and sugars in a complex network involving molecules that communicate with the cells. If we make an artificial ECM out of, say, hydrogels or polymeric materials, then we can put the cells into an environment where we can control things like the stiffness of the material or its pore size, which affects diffusion. We can tailor everything we’re doing from a materials standpoint to try to make a system that interacts with the cells in a way that doesn’t just replicate the natural system, but also gives us the chance to test what’s important. For example, is the stiffness of the matrix important? Is diffusion important? Are there chemical signals we can get by adding molecules to our artificial ECM that are important?

What are the applications of this research?

We’re interested in a couple of things. One is pre-term rupture of foetal membranes, which happens in about 3% of all pregnancies, but is becoming more prevalent due to the rise of foetal surgery. Procedures to correct malformations in the foetus prior to delivery, or to fix something about the placenta, necessarily involve cutting through the bag of “waters” containing amniotic fluid that grows in both pressure and volume throughout pregnancy. This leads to a greater risk of the waters rupturing prior to term, so we’ve been looking at making a patch, using a tissue engineering approach to mechanically bolster the region where the surgeon has cut through.

We’re also interested in the early development of the placenta. We’ve been making hydrogel materials that mimic the internal lining of the uterus, materials that can act as an ECM for the cells of the early placenta as we try to understand how that development happens. Things that go wrong at this early stage, in the first trimester of pregnancy, tend to show up in the third trimester in conditions such as preeclampsia and foetal growth restriction. Both can lead to significant foetal morbidity and mortality, and preeclampsia can also lead to maternal morbidity and mortality. Basically, the placenta’s trying to kill you when you’re pregnant, and the placenta belongs to the foetus. It doesn’t come from the mother’s tissue; it’s completely the foetus’s, but it has all these endocrine signalling functions that can affect the mother’s blood pressure. This is what happens in preeclampsia, where the woman’s blood pressure can become dangerously high.

What are some other ways that materials science and women’s health overlap?

Women’s health is a very large, diverse field. I work on pregnancy, but there are also areas connected to non-pregnancy aspects of the female reproductive system (such as certain cancers), and areas that relate to medical issues that are more prevalent in women (such as osteoporosis) or that present differently due to a hormonal component (such as heart disease).

Diseases and conditions that primarily or exclusively occur in women have been underfunded relative to their burden on society

The ways that materials science comes into this are multifold. One of the most mature areas, although people don’t necessarily think of it that way, is contraception. Condoms are made of materials, diaphragms are made of materials, intra-uterine devices and implants like Norplant that release hormones – all these things are made of materials.

Another way that materials science and women’s health interact that’s been in the news recently involves vaginal mesh implants used to treat urinary incontinence and pelvic floor issues. The materials in these implants had been successfully used for hernia surgeries, but when they were repurposed for use in the vagina, they did not match the properties needed. They were too stiff, and in a number of high-profile cases, the implants caused a great deal more pain than they corrected.

But the problem is that the original condition is a horrible one. Many women, not just those who’ve given birth, experience prolapse of the pelvic organs as they get older, and in some cases the uterus drops down into the vagina to the point where it actually starts to exit the body and you can see and feel it. This is an appalling thing that used to not be discussed, and part of shining the light on women’s health issues is talking about things we used to think of as icky. It’s about getting people to say, “Actually, this probably happened to my grandmother and she didn’t talk about that because of the shame and because this was ‘women’s problems’ and we kept that in the closet.” Bringing these things into the light and talking about them is a big part of the solution.

Today, new approaches to pelvic floor problems are being considered, mostly using materials that have very different mechanical properties and geometries than the ones that had been developed for hernias. So I think there is a very hopeful future for this field, but on top of all of the other challenges to do with regulation and medical devices and getting new products to market, the people working in it are going to have to overcome the stigma of the previous failures. In addition to the material sciences and the engineering side, there’s a whole social aspect to it.

You’ve recently been named the inaugural director of Washington University’s new Center for Women’s Health Engineering. Why is it important to have a centre like this?

Women’s health is really understudied. This is partly because, historically, scientists were mostly men, but there’s also ethical challenges related to studying people who could be pregnant. As a result, for a very long time there were no mandates to require medical research to include female participants, female tissues, or even female cells. Practically the whole professional study of biology over the last 100 years has focused on male cells and male tissues, and the excuse for this was, “Oh, well, females are too complicated” because we have hormonal signals that change over the course of a 28-day cycle. The research establishment decided to keep it “simpler” by using men’s cells – that was the gold standard until quite recently.

This meant that certain things, like the fact that women present different symptoms when they have cardiovascular disease than men do, were not very well known. Osteoporosis is another under-studied topic; this isn’t my area of expertise, but there are interactions between hormones and what’s known as bone equilibrium (bone is constantly “remodelling”, creating new bone and removing the old) that make women more prone to osteoporosis. Women also tend to load their bones less. One of the best pieces of advice I ever gave to my mother was that when she got into her 60s, I told her it was a good idea to start lifting weights. She looked at me like I was crazy, but she’s now a very buff, nearly 70-year-old woman with arms I would absolutely die for because she has been lifting weights and trying to bulk up in order to help fight against osteoporosis.

What are some consequences of this failure to study women’s health?

There was a fantastic paper that came out last year in Science showing that because most inventors are men, whereas people who invent things to do with women’s health are mostly women, there have been fewer medical devices targeted at women’s health. Another paper that came out about two years ago found that if you take away all other factors, diseases and conditions that primarily or exclusively occur in women have been underfunded relative to their burden on society, while those in men have been vastly overfunded.

To fix this, you need research funding, you need companies to invent and market new devices, and you need people. The Center for Women’s Health Engineering is focusing on the last of these. We’re aiming to train the next generation, so that whereas once you might have had an entire group of young engineers who didn’t realize they could have a career in women’s health engineering, now we’ll have people doing research, working in companies and overall just bolstering this new and developing field.

What does success look like, either for the new centre or for the overall effort to get materials scientists to focus more on problems related to women’s health?

I hope that by shining a light on this topic, we get everybody interested in it. What I don’t want to happen is to end up with a field that’s exclusively female, such that it gets put into a box of “Oh, those are women’s problems and only women are interested in solving them.” Because pregnancy affects everybody. Reproduction affects everybody. Women’s health affects everybody. Regardless of whether you are male or female, you should care deeply about this subject, and that is why we want to really invest in this in a new and exciting way for the 21st century. My long-term goal is to have more people working in this area, because obviously, the more people we have, the more likely we are to find solutions.

• You can listen to Michelle Oyen in conversation with Margaret Harris in the Physics World Weekly podcast.