A five-year NSF grant will fund research investigating methods to harness the regenerative potential of stem-cell-secreted proteins that could improve treatments for musculoskeletal injuries and other conditions.

Stem cells hold tremendous promise for treating injury after tissue loss, but their short lifespan has limited their potential after transplantation. Marian Hettiaratchi, an assistant professor in the Department of Bioengineering in the Phil and Penny Knight Campus for Accelerating Scientific Impact, aims to develop biomaterials to prolong the therapeutic effects of stem cell-secreted proteins, thanks to a five-year, $600,000 CAREER Award from the National Science Foundation.

Hettiaratchi’s lab combines chemical and biomedical engineering expertise to design biomaterials to control protein delivery to injured tissues. The new research has the potential to inform treatments for many diseases and injuries, including musculoskeletal injuries, cardiovascular disease, and spinal cord injuries.

“The promise of stem cells has not been fully realized, as most stem cells transplanted into the body after injury die rapidly after transplantation. Despite their fate, these stem cells still often have a small positive impact on the damaged tissues into which they are transplanted,” Hettiaratchi said.

“Our goal is to capture and concentrate these potent, cell-secreted proteins to enhance and prolong their therapeutic effects beyond the initial period of stem cell survival.”

To accomplish their goal, Hettiaratchi and her team seek to develop a library of affinity-based biomaterials that selectively sequester and present therapeutic proteins secreted by Mesenchymal stem/stromal cells (MSCs). The biomaterials will be engineered only to capture specific proteins of interest from a complex mixture of cell-secreted proteins, thereby allowing them to act as sieves – enriching therapeutic proteins without trapping ineffective proteins.

“As these cells are dying, they produce waste products and proteins that could have negative effects on the healing process, and so we're interested in creating these protein binders that will very specifically latch on to proteins that may enhance the healing process,” Hettiaratchi said.

Figuring out which proteins are of interest for regenerative purposes is something that her collaborator Nick Willett, associate professor of bioengineering, is particularly interested in, and Hettiaratchi’s team will be tapping into that expertise by collaborating with his Musculoskeletal Regenerative and Rehabilitation Engineering Lab.

“We’re working with the Willett Lab and combining what they’ve learned about proteins involved in tissue repair with what we're continuing to learn about engineering protein-trapping biomaterials to further refine our understanding of which proteins may have the biggest impact on tissue repair,” Hettiaratchi said.

The CAREER Award also builds upon the Hettiaratchi lab’s expertise in polymer chemistry, protein engineering, and bio-transport modeling, in which a system of equations is created to describe the movement of proteins through biomaterials, cells, and the body. Highly interdisciplinary in nature, the new research will require participation by students interested in bioengineering, chemistry, biology and human physiology. It will engage students across multiple departments at the University of Oregon in bioengineering research and education.

Hettiaratchi plans to make her research more accessible to a broad audience through education and outreach. She has a head start on outreach thanks to her BIOE 251 course, in which students created activities for K-12 students as part of their classwork last year. The class is the first of three required “fundamentals of bioengineering” courses that introduce students to foundational principles in bioengineering. Topics include dimensional analysis, mass, and energy balances, conservation of mass and energy, chemical reactions and introductory biomechanics.

Hettiaratchi credits the strong outreach efforts already in place at the UO, including Bryan Rebar’s work with STEM Careers through Outreach, Research, and Education (STEM CORE), as essential in building the outreach portion of her CAREER Award.

“I’m really excited about the connection between bioengineering research and education,” Hettiaratchi said. “With the Knight Campus Department of Bioengineering, I feel we’re in the perfect place to combine those two things.”

NSF CAREER Awards are one of the agency’s most prestigious awards, supporting early career researchers who have the potential to drive advances in their fields and to serve as academic role models in their departments and beyond. Hettiaratchi joined the Knight Campus in January 2020. Before that, she was a post-doctoral fellow at the University of Toronto. Her research focused on combining chemical and biomedical engineering approaches to create biomaterials that can precisely deliver proteins for central nervous system tissue repair. She holds a bachelor’s degree in chemical engineering with a biomedical specialization from the University of Calgary and a doctorate in biomedical engineering jointly from Georgia Tech and Emory University.

“Marian epitomizes the type of principal investigator and research focus we are developing in the Knight Campus Department of Bioengineering,” said Danielle Benoit, Lorry Lokey Chair of the Department of Bioengineering. “She’s revolutionizing therapeutic strategies with an eye to translation for clinical practice to improve human health and is leveraging amazing collaborators and rich resources and environment. We are ecstatic, although not surprised, that her research program is being recognized with the prestigious NSF CAREER Award and look forward to her research findings' continued success and impact.”

 — December 22, 2022