Restore dysfunctional lymphatic networks to enable the body to fight disease

The human body is an amazingly designed machine, and mechanical processes such as those in the lymphatic system play a major role in maintaining healthy tissues and organs.

Donny Hanjaya-Putra is an assistant professor whose work lies at the intersection of engineering and medicine. He studies the lymphatic system -; the part of the immune system that rids the body of toxins and other unwanted materials. He examines how to restore dysfunctional lymphatic networks, which are associated with a wide range of diseases, including cancer, cardiovascular disease, diabetes, neurological conditions, and metabolic syndromes.

Now Hanjaya-Putra and his team -; Laura Alderfer, PhD student in bioengineering, with Elizabeth Russo, 2019 graduate; Adriana Archilla, student at Syracuse University; and Brian Coe, class of ’19 -; demonstrated how the stiffness of the extracellular matrix affects lymphatic vessel function.

The team combines this knowledge with polymer science and mechanical engineering to build new lymphatic cord-like structures, which help restore normal behavior to dysfunctional lymphatic systems and enable the body to fight disease.

Cells can sense mechanical stimuli, such as stiffness of the matrix, which activates certain genes to promote lymphatic formation. We used hyaluronic acid hydrogels (a natural sugar molecule) to enhance the cell binding pattern with appropriate mechanical stimuli (matrix stiffness) in a 2D model of lymphatic vessels and were able to stimulate new ones. lymphatic vessel formations. “

Donny Hanjaya-Putra, Assistant Professor

The team published their results in the FASEB Journal of the Federation of American Societies for Experimental Biology.

This type of research is only possible, Hanjaya-Putra said, because of advances in imaging and stem cell biology.

“Traditionally, medical students spent hours studying the cardiovascular system, but the emphasis was less on the lymphatic system,” Hanjaya-Putra said. “The reason, in large part, was due to the difficulty in visualizing the lymphatic vessels, which are transparent.

“Recent advances have allowed us to use specific cell markers to distinguish between blood endothelial cells and lymphatic endothelial cells, so we can now see and study these very important networks in vitro and in vivo.”

Hanjaya-Putra and her team are currently developing hydrogels that can be implanted under the skin to promote wound healing as well as gels that can be injected into the body at the site of the injury.

Alderfer, the lead author of the FASEB article, received a Fulbright US Student Program scholarship to study at the University of Helsinki. She will study lymphatic vessel formation in vivo in models of heart wounds and lesions with Kari Alitalo, a world leader in lymphatic vessel research and translational cancer biology.