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Tufts University researcher develops living tissue

MEDFORD/SOMERVILLE, Mass. A new approach to studying tissue development has earned Catherine K. Kuo, Ph.D., an assistant professor of biomedical engineering in Tufts University's School of Engineering, the Basil O'Connor Starter Scholar Award from the March of Dimes Foundation.

Kuo's research could yield insight into factors that contribute to orthopedic birth defects that occur in utero, such as clubfoot, which requires multiple surgeries to enable normal standing and walking. These defects occur as a result of abnormal musculoskeletal tissue development of the embryo.

In her experiments, Kuo will use living engineered embryonic tendon tissue to see how muscle movement by the developing fetus -- for example, kicking -- might influence abnormal musculoskeletal tissue development in the embryo.

"Currently we don't know the extent to which muscle activity contributes to birth defects," says Kuo. "I chose the tendon as a model tissue to study because of its critical roles in force transmission and joint stabilization in a normal musculoskeletal system."

Kuo will engineer tendon tissue in the lab from cells from chick and mouse embryos. "It's very difficult to study developing tissue, in this case, tendon, inside the body, and especially in utero," she says.

Kuo will seed living embryonic cells into a porous, biodegradable synthetic scaffold. Placed into a nutrient-rich bioreactor, the cell-seeded scaffold will grow into living engineered tissue.

Kuo will subject the tissue-engineered tendon to forces that mimic muscle movement, such as flexing, which occurs during kicking. Using this approach, Kuo will study what happens when cells are forming into tendons while being constantly exposed to stretching, twisting, and other forces.

"At the end of the day, we want to have the answers to the questions: How does tissue stiffness affect the developing cells? How does movement such as kicking affect them? And what are the combined effects of stiffness and movement?" says Kuo.

In addition, Kuo plans to intentionally engineer a developing tissue with abnormal stiffness to investigate its effect on embryonic development. These studies could potentially lead to learning which interventions could restore normal functioning after birth.

"By engineering and testing normally and abnormally developing tissues in the lab, we can perform large, systematic studies to screen the effects of different therapies that we couldn't easily do otherwise," she says.

Among her research goals is to discover if she can "retrain" embryonic or fetal cells. "During embryonic development, could we treat the cells and tissues in utero, or could we even take them out, treat them in a bioreactor to recondition them to behave normally, and then put them back in and help develop the normal function of that tissue?" she asks.

The Basil O'Connor Starter Scholar Research Award, $150,000 over two years, is designed to support young scientists and engineers embarking on their research careers with a particular focus on the prevention or treatment of birth defects.

Contact: Alex Reid
Tufts University

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