‘Ex-Utero’ project uses art, science to explore regenerative medicine

UNIVERSITY PARK, Pa. — On a sunny spring day at Penn State, Cristin Millett, professor of art in the College of Arts and Architecture’s School of Visual Arts, inserted a catheter needle into the umbilical vein of a placenta.

Wearing a white lab coat and dark-rimmed protective glasses, the sculptor by trade and longtime visual arts educator, peeled apart the plastic wrapping of the two-inch long needle and skillfully inserted it into the umbilical vein — called cannulation, the process is one she has done dozens of times as part of the Ex-Utero Project, an interdisciplinary global research project situated at the intersection of art and human reproductive sciences.

For the last five years, the project has brought together collaborators from the College of Arts and Architecture, Huck Institutes of the Life Sciences, the College of Engineering, all at Penn State, and the University of Western Australia’s School of Human Sciences. Together, the project participants are opening an artistic and scientific inquiry into the future of human reproduction that probes the biological and sociopolitical possibilities of ectogenesis, the as-of-yet unrealized development of an embryo outside the uterus.

Along the way, and with the help of biomedical engineering students and scientists from the College of Engineering and Huck’s Sartorius Cell Culture Facility, the team has developed a system to convert a section of umbilical cord into a biological scaffolding material that could eventually be used in tissue regeneration, pushing the frontiers of regenerative medicine.

Employing decades of skills learned as an artist, Millett is creating and exhibiting sculptures that explore ectogenesis, building a bridge between the scientific and artistic aspects of the project. By her side throughout the journey has been Cindy White, an award-winning documentary filmmaker who is a researcher affiliated with the College of Arts and Architecture as well as the Huck Institutes of Life Sciences.

Together, using approved scientific protocols, the duo studies the human placenta to create multimedia installations including visual documentation of the scientific and artistic process, sculptural elements and experimental films. They often present their work at scientific and artistic conferences, where they discuss the unique biological traits, scientific importance and cultural significance of the placenta — and the potential of such a currently critical reproductive organ becoming a vestigial organ as technologies advance.

“Although ectogenesis exists in the realm of the impossible, in a rapidly evolving world its ethical, cultural, political and philosophical implications are worth exploring,” Millett said.

Possibilities arise at the College of Arts and Architecture’s ADRI

Founded in 2014, the College of Arts and Architecture’s Arts and Design Research Incubator (ADRI) was established to support high-impact arts and design research projects with seed funding, workspace and technical support. While ADRI has supported dozens of individual projects, Millett said the incubator’s existence as a think tank is one of its enduring contributions to the college and University more broadly.

“It is a place where people in the college can come together to share ideas and think beyond their disciplines,” Millett said. “On any given day, you can strike up a conversation with amazing people doing incredible work, and in doing so perhaps discover fresh ways of thinking about your own work.”

One of those conversations occurred between Millett and White shortly after White joined ADRI in 2016 as a research associate.

White had recently moved from Australia, where she produced multimedia packages that documented research and arts projects at SymbioticA. This laboratory in the School of Anatomy and Human Biology at The University of Western Australia facilitates artistic research residencies, enabling artists to engage in wet biology practices in a biological science department.

On a parallel path, Millett had been incorporating elements of medicine and the human body into her sculpture work. Much of her research after graduate school was centered on medical instruments and medical texts. Combined with visits to anatomy theatres across Europe, the research informed her ideation process, but she wanted to dig deeper.

A turning point came in 2017 when Millett read about researchers at the Children's Hospital of Philadelphia (CHOP) who developed a unique “womb-like” device, or biobag, tested on prenatal lambs. The lambs, physiologically equivalent to about a 23-week-old human fetus, successfully grew, opened their eyes and developed normally within the artificial environment for up to four weeks.

“Because of the research at CHOP, I became very keenly interested in the current science of reproductive health, at the beginning of gestation all the way through to birth, and what the implications those technological breakthroughs could mean for humanity,” Millett said. “It was a pivotal moment in my career and the inspiration for the project.”

With an iteration of the project in mind, Millett approached White, who suggested connecting with Ionat Zurr, a researcher at SymbioticA and the Chair of the Fine Arts Discipline at the University of Western Australia’s School of Design who is considered to be a pioneer in the field of biological arts.

Zurr’s artist studio is a laboratory where she works with living cells as an artistic palette. Since the 1990s, she has critically explored the aesthetic, ethical and cultural implications of using life as a technology and its effects on bodies and ecologies. SymbioticA, which Zurr co-founded with researcher Oron Catts, is the first research laboratory of its kind that enables artists to critically engage in wet biology practices.

Within their lab, Zurr and Catts lead the Tissue Culture & Art Project, using tissue engineering and regenerative biology to create, or “grow,” semi-living sculptures, which have been exhibited internationally.

Millett visited SymbioticA in 2018, and after conversations with Zurr, she submitted a Fulbright application. Millett was awarded a Fulbright Senior Scholar Award for spring 2020, during which time she served as a resident artist at SymbioticA.

“The time at SymbioticA was transformative,” Millett said. “It was amazing how generously they shared their expertise in the wet lab. As soon as I landed, they said, ‘We will teach you, Cristin,’ and they did.”

During her time at SymbioticA, Millett learned the basics of culturing cells, which included passaging, or splitting, cells and cryopreservation. The exchange of ideas and knowledge was a mutual exercise, according to Zurr.

“Cristin brings strong sculptural expertise, along with a keen sense of spatial thinking and aesthetics,” Zurr said. “It was a great deal of fun working together through the technical challenges we encountered. We shared a rich conceptual exchange, often accompanied by plenty of laughter, as we quite literally got our hands wet in the process of making art.”

The residency, however, was cut short due to the COVID-19 pandemic, and Millett had to return home months ahead of what was scheduled.

“Thankfully, they gave me hands-on experience that opened opportunities for me to continue that work at Penn State,” Millett said.

Millett and Zurr saw an opportunity to broaden the collaboration with White, and the Ex-Utero Collective was formed.

Over the last six years, and across the globe, the collective has studied the human placenta, created multimedia installations, including visual documentation of the scientific and artistic process, and formed a partnership at Penn State with the Huck Institutes of the Life Sciences and the College of Engineering to advance the science of regenerative medicine. One recent exhibit, called “Placen-Tech,” produced by the collective consisted of an interactive mixed media acrylic sculpture with a live-feed of a corrosion-case placenta, merging “scientific inquiry with artistic methodologies to investigate the human placenta as a transient and temporary organ,” according to Millett.

Molding a network at Penn State

With the Ex-Utero Collective formed, Millett knew she wanted to continue the wet lab work, but the project needed a home. She began to network within the science community at Penn State and connected with Jonas Rubenson, professor of kinesiology who had worked with SymbioticA on several residencies. He offered lab space for the project, which received initial funding from the College of Arts and Architecture Dean's Research Fund — an initiative administered by the college’s Office of Research and Creative Activity.

That funding allowed Millett and White to equip the lab space and complete the training required for conducting wet lab research, including with the Institutional Biosafety Committee (IBC). The IBC approved Millett’s initial protocol in 2022 for what was then called “The Placenta Project,” and reviews the project protocol anew every year.

With all necessary trainings successfully completed and protocols approved, Millett worked with Penn State’s Office of General Council to develop a “Consent Form for Use of Tissue,” which is signed by the midwives who oversee homebirths and obtain verbal consent from the parents.

Within 48 hours after birth, the placentas are transferred to Millett following biosafety protocols. To date, Millett has received almost 40 donated placentas.

“We are incredibly grateful to parents who have donated,” Millett said. “I know that each placenta I work with was vital to creation of a new human life. I never lose sight of that, and I take great care with each donation to ensure that the placentas are handled not only safely but ethically.”

Refining the process leads to deeper scientific inquiry

When a placenta is received, Millett will visually inspect the specimen while taking notes on its condition and structure. Numerous photos and videos — mostly by White — are taken throughout the perfusion process, which is the process of inserting a catheter needle into the umbilical vein to allow for fluid transfer.

With the needle inserted, a solution made of saline and the anticoagulant Heparin is pumped through the placenta to remove blood clots from its vascular system. After the placenta is perfused, it is frozen.

From there, Millett’s work takes one of three tracks depending on the results from the perfusion process, which can occasionally reveal abnormalities in the umbilical cord or within the vascular structure.

The first, and most common, track is a corrosion cast of the placenta. After thawing the placenta, the process requires Millett to perfuse the specimen a second time and then inject a colored monomer resin through the catheter that hardens to reveal the details of the placenta’s vascular system.

“A corrosion cast allows us to visually study the placenta, but once I inject resin, the tissue, for biomedical research purposes, is rendered useless,” Millett said.

Although biomedically unusable, artistically Millett has incorporated the corrosion casts as elements in sculptures. This application, she explained, has tangible benefits as corrosion casts are durable and do not require freezing, Formaldehyde or ethanol.

The second is the more commonly known scientific process of immersion fixation, which requires the placenta to be submerged in Formaldehyde to prevent decay and maintain cellular structure for future study of the organ.

A third track that Millett has followed alongside Thomas Neuberger, research professor and director of the High-Field Magnetic Resonance Imaging Facility at Penn State, is to study the placenta using magnetic resonance imaging (MRI). Scanning the placenta in an MRI machine can reveal in detail the dense capillary networks within the organ, where the exchange of oxygen and nutrients between maternal and fetal blood takes place.

With a process established, and after conducting about six months of research, Millett and White gave their first major presentation on the project in September of 2022 at the opening event for the FEMeeting (women in art, science and technology) in Portugal as part of the Leonardo Art Science Evening Rendezvous (LASER) held at the University of Lisbon.

As the work progressed, the presentations continued in 2023 when Millett and White presented the project as part of a panel at the 28th International Symposium on Electronic Art in Paris; the FEMeeting in Taos, New Mexico; the Automation Culture conference in Australia; and at the 2023 Alliance for the Arts in Research Universities (a2ru) conference at Penn State.

The project received additional funding in 2023 when it was awarded the Joint Projects in Life/Medical Sciences, Arts and Humanities Grant from Penn State’s Huck Institutes of the Life Sciences with the College of Arts and Architecture serving as a co-sponsor of the grant.

As part of the grant, Dan Hayes, head of the Department of Biomedical Engineering and Dorothy Foehr Huck and J. Lloyd Huck Chair in Nanotherapeutics and Regenerative Medicine, connected Millett with Randy Rossi, director of Sartorius Cell Culture Facility (SCCF) and the next phase of the project took shape.

“Throughout the early years of the project, we were making progress, but I felt like more was possible,” Millett said.

Each line of inquiry she followed focused on the placenta, which led to artistic exploration and expression, but it was the sections of umbilical cord that piqued the interest of the scientists and delivered the “more” Millett was looking for.

Collaboration, scientific advancement and the future

For more than 45 years, Rossi has focused on mammalian cell culture, which is the in vitro process of growing and maintaining cells extracted from mammalian tissues. This work is a cornerstone of biomedical research, essential for developing vaccines, screening drugs and manufacturing therapeutic proteins.

Through the SCCF, Rossi offers support to numerous researchers, which yields work that is wide ranging, from producing proteins for antibody tests during COVID-19 to providing cells for a livestock laboratory focused on cultured meat. Within regenerative medicine — using stem cell technology and tissue engineering to replace or regenerate human tissues and organs and restore their functions — Rossi’s efforts are part of a greater effort to push the bounds of what might be possible.

“The challenge is that within regenerative medicine, anything that you’re trying to grow needs a scaffolding,” Rossi said, referring to a structure that provides a physical framework for cells to attach, migrate and proliferate in vitro.

Research in the field has led to synthetic or 3D-printed scaffolding, Rossi explained, but the easiest way is to take tissue and decellularize it. That process, he said, leaves behind the extracellular matrix, or the connective material that supported the cells. The result is the sought-after scaffolding.

“On the research end, there are innumerable purposes for the scaffolding,” Rossi said.

With regenerative medicine in mind, the team asked what they believed is a novel question: Can we decellularize an entire placenta and umbilical cord to offer an unusually large area of biological scaffolding?

To find out, the team formed in 2025 “Ex-Utero: Designing a Living System for In-Vitro Tissue Engineering,” which is now a semester-long project for a senior capstone course taken by biomedical engineering undergraduate students in the College of Engineering. The course was funded in 2025 by the Huck Institutes of Life Sciences Sartorius Cell Culture Facility and in 2026 by the College of Arts & Architecture and the Michael J. and Aimee Rusinko Kakos Dean’s Chair.

The long-term goal of the capstone course is for students to develop a system of decellularizing the entire placenta and umbilical cord and to seed it with other cell types. The project aims to preserve the tissue’s structure while preparing it for successful recellularization with living cells, pushing the frontiers of regenerative medicine.

Taught for the first time in the spring of 2025, students within the capstone course have developed a system for decellularizing part of the umbilical cord, which Rossi said surprised almost everyone.

“We were skeptical in the beginning, but we have made tremendous progress,” Rossi said. “We successfully decellularized a small section of the umbilical cord in the first capstone class. This year, we can do it routinely and keep it [the section of umbilical cord] intact.”

Rossi explained that a fundamental deficit of cell culture is scale. This is where the work in the Ex-Utero capstone course has made significant strides, he added.

“Lots of labs can decellularize tissue and make a little bit of scaffolding, but we’re talking about two square centimeters being as big as they can go. Because of this project, the students can produce six to eight inches of decellularized tissue,” Rossi said. “If we can get this to work with the whole placenta, that’s a huge amount of area and a more natural setting to observe the effects of what a researcher is trying to do.”

A few days before the Capstone Showcase in May of 2026, Millett sat back in a chair in her office and smiled.

“This is all so unexpected,” Millett said. “The fact that we’re about to exhibit work that could lead to breakthroughs in regenerative medicine is something that is beyond words.”

The team knows that the scientific advancement doesn’t reveal a means for generating human life outside of the body, but it does deliver on the core mission of Ex-Utero Project: Conversations are happening and collaboration is driving discovery.

“If we stopped now, I would think this is a wild success,” Millett said. “But the way we see it, we’re just getting started.”