Melissa Pappas
Scientists have been studying bones and how they break for over a century, but they’ve primarily been doing so on the large scale, examining entire femur fractures through x-rays. To accurately model the dynamic, living system of bone and cells, scientists must examine and understand these structures on the fundamental length scale of the tissue: the nanoscale.
Ottman Tertuliano, AMA Family Assistant Professor in Mechanical Engineering and Applied Mechanics, is the recipient of a 2024 National Science Foundation (NSF) CAREER Award for his work studying the characteristics of bones and external forces that affect their likelihood of breaking by examining fractures on the nanoscale.
“We all have a bone story,” says Tertuliano. “Whether it be through fractures, osteoporosis or repeated wear and tear, bones bear the brunt of our active lives. Models built from the bottom on nanoscale observations will give us insight into the fundamental mechanics involved in bone fracture and repairs, fueling innovations to improve health and quality of life for everyone.”
In order to initiate this work, Tertuliano and his lab had to first assemble a system that enables them to observe dynamic cracks at the nanoscale in 3D, then they got to work performing experiments with real human bone from organ donors and and those received from collaborating biologists and surgeons working with patients undergoing total joint replacements.
“One of the major goals of this work is to define the fundamental differences between healthy and unhealthy tissue,” says Tertuliano. “By working with these two types of bone, we can examine how healthy tissue from donors with no history of bone diseases versus diseased tissue from surgery patients respond to exogenous stresses.”
The team’s experiments are set to answer two questions. They first expose the bones to time varying pressures that mimic walking, running or jumping to understand how the nanostructure of collagen and mineral adapts to prevent and slow down fractures. Next, inspired by this resilient bone nanostructure, they use nanoscale 3D printing to create engineered playgrounds for live bone cells. When they apply pressure to these engineered, living bone structures they can learn how the living cells adapt and remodel their local microenvironments to prevent larger macroscopic fractures. It’s a dynamic bottom up approach.
What makes these two dynamic processes distinguishable at the nanoscale? Separate time scales.
“Examining a crack forming on the nanoscale is like slowing down time to watch a zoomed-in version of what we typically think of as an instantaneous fracture,” Tertuliano says. “A crack may grow at about 1 micrometer/second, but there are obstacles in bone at various length scales to mitigate crack growth. We can watch cracks navigate those obstacles in real time with ultrafast synchrotron x-ray imaging.”
Once a fracture occurs, there is another time scale that Tertuliano is examining: the one of cellular response and repair. Cells can feel forces instantaneously, but don’t start to change tissues and repair structures until many days later.
“To fix a broken bone, cells first must clean up the site and then deposit new material,” says Tertuliano. “It’s like cleaning up a demolition site and then rebuilding a building; it’s a lengthy process.”
But it is this process that motivates Tertuliano’s future research goals in understanding the mechanics of repair and regeneration. His long term vision is to use an understanding of how mechanics affect dynamic, living systems and advance the regeneration of tissues, even entire limbs.
“You cannot separate the mechanics from biology here, they shapes the form and function of our bodies’ systems from musculoskeletal to cardiovascular and even neurological,” he says. “Understanding the fundamental mechanics of musculoskeletal systems on the nanoscale is our current focus but only a small part of the vision to regenerate tissue. There are so many important questions in tissue morphogenesis, development and disease that other researchers are working to answer and I am excited to be learning from the other experts at Penn and across the scientific community.”
Funding from the NSF CAREER Award will help to reach that goal and will support graduate student research and a larger initiative to make Tertuliano’s work more accessible. Through the The Laboratory for Research on the Structure of Matter, the LRSM, Tertuliano will host a local high school teacher who will work within his lab to translate the group’s research into a curriculum that can be accessible to K-12 students.
Additionally, for the next five summers, Tertuliano will fund and host a high school student from the Philadelphia Mütur Museum’s STEM program, which engages local students from underserved communities in science.
“In graduate school, my advisor received an email from a high school student wanting to do research in our lab for free,” says Tertuliano. “That moment opened my mind to the kind of privileges certain students have. I want to make those opportunities more accessible, especially to those who wouldn’t normally be able to use their summer in this way. I’m very excited to use this grant to remove the financial burdens these students can face and enable them to explore their curiosity.”
“When I ask myself how I can make an impact on some of our pressing engineering problems,” he continues, “I come back to my background in mechanics for advancing healthcare, but also my efforts in bringing more students who look like me into a space where they have historically been underrepresented. I think active inclusivity gets us closer to the answers we need that can only come from diverse perspectives.”
To learn more, please visit the Tertuliano Lab.