Biomedical engineer develops himself into ‘hybrid scientist’

Using electrospinning — a technology developed in 1934 for weaving fiber into textiles — Wan-Ju Li spins intricate webs of biodegradable nanofibers. These scaffolds, which mimic the size and layout of human collagen, enable him to culture stem cells and grow cartilage, bone, ligaments and other tissue.

“Environmental setup affects the cells dramatically, just like housing atmosphere and architecture affect the human beings living there,” says Li. “We want to make sure the humans living in the house are happy. That is the way to think about designing a scaffold — to make the cells sitting in the scaffold happy and able to respond and produce the matrix. That’s the whole idea of tissue engineering scaffold design.”

Li joined UW–Madison last spring as an assistant professor of biomedical engineering and orthopedics and rehabilitation. His research has generated two patents and produced nearly 25 publications, including one cited more than 340 times in six years.

A native of Taiwan, Li became interested in biology and medicine as a boy and earned his undergraduate degree in biomedical engineering.

For his master’s degree, he attended Drexel University in Philadelphia. With Drexel Biomedical Engineering, Science and Health Systems and Materials Engineering professor Frank Ko as his mentor, Li began exploring electrospinning as a tool for building cell scaffolds. In fact, Li built his first electrospinning prototype, still in use at Drexel today, in a faculty member’s garage with $30 of lumber from Home Depot. “It looks simple and not high-tech, but it functions well,” says Li.

After he earned his master’s degree in biomedical engineering, Li made a decision he calls a turning point in his life.

“I often felt limited by the lack of cell biology training when doing tissue engineering experiments,” he says. “Many biomaterials guys, including myself, focus on how to do the scaffold. We don’t have detailed ideas about how the cell responds to the scaffold chemistry and structure. And biologists doing tissue engineering have another way of thinking. They say, ‘The cell is the most essential part,’ and they don’t really pay attention to how the engineer designs the scaffold. It is obvious that either side only gets half of the story.”

To be an effective tissue engineer, Li knew he would need to be “fluent” in both engineering and biology.

Through a serendipitous conversation with a medical student at Thomas Jefferson University in Philadelphia, Li eventually met professor Rocky Tuan, now chief of the National Institutes of Health (NIH) cartilage biology and orthopedics branch. Tuan established the nation’s first cell and tissue engineering Ph.D. program, at Thomas Jefferson.

Li enrolled Tuan and began taking intensive biology courses. He slept little, spent hours at the library and studied constantly. “A couple of years later, I felt so grateful about that decision I made, because I am truly a hybrid scientist,” he says.

When Tuan accepted the position at NIH, Li accompanied him, writing his thesis there as a Ph.D. student. Li calls moving to Bethesda, Md., to work with Tuan one of the most important decisions of his life. “I had the chance to see the top research institute in the nation, as a graduate student,” he says.

In another bit of serendipity, Li heard through a friend that UW–Madison was searching for a tenure-track faculty member with his research capabilities. After his first interview here, Li was hooked. “I can tell you, from day one, I loved this city,” he says.

He also loves the support and encouragement he’s received from faculty in both biomedical engineering and orthopedics and rehabilitation. Ray Vanderby, a professor who also holds appointments in both departments, is his mentor.

“I really appreciate everything he has done for me so far,” says Li. “When he told me how he was going to help a young faculty member (when I was here for the interview), I knew this was the school. Here, the university is invested in the faculty success.”

And, Li says, the UW–Madison culture of collaboration is a good fit for him. “I have interactions with my engineering colleagues and find out their expertise,” he says. “I have them to collaborate with me, and I can serve as a bridge to the medical school. I can use advanced technologies in engineering to solve any medicine- or biology-related question or problem.”

In particular, Li hopes to continue optimizing the process for growing mature, functional tissue using stem cells, as well as studying how scaffold structure affects cell activity.

In the former area, Li is collaborating with veterinary medicine professor Mark Markel. For arthritis repair, Li and Markel are testing engineered cartilage function in a sheep model. They also plan to use the model for testing engineered tendon and intervertebral disc. The holy grail of tissue engineering, says Li, is to use a human patient’s own adult stem cells to grow bone, cartilage or other tissue that can be implanted to repair or replace damaged or diseased tissue. He has shown this method works in pig bone and cartilage.

To improve how he manipulates stem cells, Li also is investigating how the physical environment — the scaffold microstructural shape or dimension, such as nanofiber sizes — affects the cell, which cell receptors and signaling pathways are activated, and what genes turn on in response to the environment. He has cultured stem cells in both 2-D and 3-D scaffolds, and then extracted the cells and globally profiled 65,000 genes in microarrays to learn which genes are turned on and off in the 2-D and 3-D groups.

Li currently is investigating which genes are involved in the biological regulation controlled by the scaffold geometry. As a result, he also can use his engineering training to apply what he learns from the cells in modifications to the scaffold.

“I am very grateful that I have the training that allows me to investigate such questions that traditionally were investigated by biologists,” he says.