The National Institute of General Medical Sciences, an arm of the National Institutes of Health (NIH), has awarded Yubing Sun, associate professor of mechanical and industrial engineering at the University of Massachusetts Amherst, a $1.9 million Researcher Maximization Award to support his exploration of fundamental behind the process that closes the gaps caused by injury or growth between cells. This research has the potential to advance advances in our understanding of wound healing, cell regeneration therapies, and embryonic development.
The gaps under investigation are 0.5-5 mm in size, which is more physiologically relevant and comparatively large in this field.
Usually, when people study these gap-closing processes, they leave a very small gap – only a few cells in size. This is bigger than that – not just a few cells, but thousands or more.”
Yubing Sun, Associate Professor, Mechanical and Industrial Engineering, University of Massachusetts Amherst
“Our biggest goal here is to have a really good theoretical understanding of: what is the individual contribution from individual agents to this process?” he says. “When many factors are involved at once, who regulates the others?”
As an example of a gap closure process, he points to the closure of the neural tube during embryonic development. “It’s a well-studied process in animal models, but as an engineer, we want to introduce a more controlled environment to study how individual factors regulate this process,” he says. Normally, in animal studies, the researcher would manipulate different genes to see how it affects development. “But everything changes at the same time,” he explains. “It’s really hard to control individual factors.”
Instead, Sun and his team plan to create controlled mechanical and biochemical environments so they can investigate one agent at a time. These factors include things like forces, gap geometry, and matrix and tissue stiffness.
While the research itself is focused on understanding the fundamental processes of closing the gap, Sun points to several areas where this research could support future progress.
A future application is wound healing. Sun says there’s already a device that uses a vacuum cup to stretch the skin to speed up the closure process — but they don’t fully understand how it works. “Right now, a lot of parameters are determined empirically, but if you understand the process, you can design based on the principle and things become more efficient,” he says.
Another direction that this research can give is cellular regeneration. Sun points out that newborn mice and zebrafish have hearts that can regenerate after injury. “Imagine closing that gap or wound, and the cells on the surface of a heart can differentiate into those muscle cells in the heart,” he says. “But humans don’t have that ability.” A deep understanding of the gap-closing process could inspire future treatments for heart cell regeneration.
Sun points to mechanomedicine, drugs capable of mimicking the mechanical cues he aims to recreate in his lab, as a potential outcome informed by his current, fundamental research. “You’re not directly applying mechanical cues, but you’re using a drug to mimic that effect,” he says.
