McGowan Institute for Regenerative Medicine
faculty member Rocky Tuan, PhD (pictured), is the director of the Center for Cellular and Molecular Engineering, Department of Orthopaedic Surgery, University of Pittsburgh School of Medicine, and the executive vice chairman for orthopaedic research at the University of Pittsburgh. Dr. Tuan’s research focuses on the development, growth, function, and health of the musculoskeletal system, the biology of adult stem cells, and the utilization of this knowledge to develop technologies that will regenerate and/or restore function to diseased and damaged musculoskeletal tissues. In 2009, he came to Pitt from the National Institutes of Health, National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), with a research portfolio with one major thrust: Use the body’s own regenerative power—augmented with biomaterials, nanomaterials, and/or stem cells—to make musculoskeletal tissue exactly as the body would.
“The ultimate goal is cell-based therapy or cell-based tissue regeneration,” Dr. Tuan said, as reported by PittMed’s Joe Miksch. “But in order to regenerate tissue, you need to understand the building blocks, the cells—they’re the real tissue engineers.”
While studying at Rockefeller University he had decided to pursue how the calcium that makes up a chicken’s eggshell becomes chicken bone. In his resulting PhD thesis, Dr. Tuan established the manner in which calcium is transported from the shell to the embryo. He was the first to do so, which, naturally, was exciting and prompted a whole new series of questions centered on bone.
Dr. Tuan is more concerned with how to create cartilage, tendon, and ligament tissues to replace those ravaged by injury or age. When these tissues are injured or worn by overuse, the result is often osteoarthritis—a painful, chronic, and difficult-to-treat condition that affects some 27 million Americans, according to the NIAMS.
“I realized that the skeleton has to repair itself, that it’s constantly undergoing turnover. Ossification is an active process. I asked myself, ‘How is this happening and why?’ I started thinking about stem cells, precursor cells, progenitor cells,” Dr. Tuan says. “That’s how I got into [orthopaedics].”
At present, osteoarthritis is managed through pain medication, physical therapy, and, in severe cases, surgery to repair the damaged tissue or replace joints. The problem with surgery is that the mended tissue—scar tissue, essentially—cannot bear the same weight as the native, healthy tissue. Further, it has a tendency to erode over time, necessitating follow-up procedures.
Replacement joints, as sophisticated as they have become, don’t hold up well over time. Dr. Tuan says we can do better, and we can do so by mimicking nature. Making man-made, or rather, “man-assisted” tissue in vitro from adult stem cells, particularly mesenchymal stem cells that are drawn from bone marrow, muscle, or fat, is the easy part—not that it’s particularly easy. The real difficulty arises, Dr. Tuan says, in making something that looks like muscle, cartilage, or a spinal disc function like muscle, cartilage, or a spinal disc.
A cell’s best friend, to Dr. Tuan, is a scaffold matrix. Without a space-filling guide the mesenchymal stem cells can glom onto, there’s a high risk that they’ll be swept away before they can become tissue. “When you’re dealing with tissues whose main function is to bear weight, I think it’s good to have a scaffold that can take care of that aspect of it,” he says.
In high-resolution microscopy, an “original matrix” appears as a bunch of nanometerscale fibers. Dr. Tuan takes a liquid polymer and, using a technique borrowed from the textile industry, spins the stuff rapidly in the presence of a strong electrical field. As the polymer attempts to diffuse the charge, it forms into a bunch of nanometer-scale fibers.
“The goal is to use these fibers for structural tissue regeneration and for therapeutic applications,” says Dr. Tuan.
With a goal of improving quality of life using modern technology, Dr. Tuan hopes his current tests make human clinical trials possible in 2 years. He also says he’s glad to be at Pitt to pursue this stage of his work. “For the kind of work I am interested in, Pittsburgh is a powerhouse,” Dr. Tuan says. “I don’t have to come in here and build anything, which is actually nice. Here, science is truly multidisciplinary, and I think it’s a lot more fun when you have different kinds of people thinking about these problems. It’s great to be in a place with that kind of interaction.”
Illustration: McGowan Institute for Regenerative Medicine.
PittMed (Spring 2010)
Bio: Dr. Rocky Tuan