Engineers and cancer researchers develop tunable biomaterials to treat lymphedema

A gloved hand holds a clear petri dish containing a translucent green hydrogel shaped like the ND monogram, representing the University of Notre Dame, used in Professor Donny Hanjaya-Putra's lab for research on lymphatic vessel growth.

The lymphatic system plays a vital role in many health issues, such as heart disease, neurodegenerative conditions, inflammation, metabolic disorders, cancer, and lymphedema. Despite its importance, scientists still lack many details about how the lymphatic system grows and functions, and this prohibits the development of effective treatments.

Controlling the growth of new lymphatic vessels, either in the body or through lab-grown methods, could be a promising long-term treatment for various diseases connected to the lymphatic system.

In a study forthcoming in Communications Biology, bioengineers and cancer researchers at the University of Notre Dame have discovered a new way to grow lymphatic vessels—small channels that help move fluid in the body—in a lab setting. This could be helpful for treating diseases like cardiovascular problems and lymphedema, a swelling, usually in the arms or legs, caused by a buildup of lymph fluid.

“We used tunable biomaterials to promote lymphatic regeneration, which can be used to treat lymphedema in children with rare diseases, as well as patients with breast cancer,” said Donny Hanjaya-Putra, assistant professor of aerospace and mechanical engineering. “This new method may help researchers study lymphatic diseases more effectively and could someday enable breakthrough approaches to treat lymphedema.”

Donny Hanjaya-Putra, with short black hair and glasses, smiles at the camera while wearing a blue plaid blazer over a white patterned shirt. The lab setting in the background includes scientific equipment and a blurred figure.
Donny Hanjaya-Putra

Scientists used a gel made from hyaluronic acid—a natural substance found in the body—to create a controlled environment where human adult stem cells can form these vessels. By adjusting the gel’s stiffness and adding growth molecules, they managed to make the cells assemble into vessels on their own in just a few days.

These lab-grown vessels could survive for weeks in the lab and even successfully integrated when implanted in an animal model that mimics the conditions of patients with breast cancer.

Donny Hanjaya-Putra stands beside Bioengineering Ph.D. student Donghyun Paul Jeong, who is seated at a computer analyzing lymphatic cell images on a large monitor. The screen displays colorful microscopic images, and the lab setting includes a black curtain, pipes, and equipment.
Donny Hanjaya-Putra and Bioengineering Ph.D. student Donghyun Paul Jeong
Bioengineering Ph.D. student Dominique Gramm, wearing a white lab coat and gloves, examines a sample under a high-tech microscope in a laboratory. A screen attached to the microscope displays a magnified image of the sample.
Bioengineering Ph.D. student Dominique Gramm

This new hydrogel system offers a flexible and efficient way to study lymphatic vessel growth without relying on complex and costly animal models. Instead of using many mice for testing responses to growth factors or drugs, researchers can make multiple hydrogel samples with precise amounts of these substances to quickly see their effects.

“We are very eager to work with companies who are interested in using these lab-grown lymphatic vessels in their drug screening pipeline, as well as with local community hospitals, who are excited to translate this relatively simple method as a surgical alternative for patients with lymphedema,” said Hanjaya-Putra.

Bioengineering Ph.D. students Keilany Lightsey and Sanjoy Saha discuss their research with Donny Hanjaya-Putra in a laboratory. Sanjoy Saha, seated on a stool and wearing gloves, holds a petri dish while explaining. Keilany Lightsey stands to the left, and Donny Hanjaya-Putra listens on the right, wearing a blue plaid blazer. The lab features scientific equipment, including a biosafety cabinet with pipettes and samples in the background.
Bioengineering Ph.D. students Keilany Lightsey and Sanjoy Saha talk with Donny Hanjaya-Putra in the lab.

Laura Alderfer and Sanjoy Saha, former and current Ph.D. students in Hanjaya-Putra’s lab, served as the paper’s first authors. Notre Dame researcher Laurie Littlepage, Campbell Family Associate Professor of Cancer Research in the Department of Chemistry and Biochemistry, led the chemical synthesis and animal aspects of the study. This research was supported by a Career Development Award from the American Heart Association, National Science Foundation, and National Institutes of Health as well as the Harper Cancer Research Institute.

— Karla Cruise, Notre Dame Engineering; Photos by Wes Evard, Notre Dame Engineering