The Rhythm of Healing
Cathal Kearney, assistant professor in the Biomedical Engineering Department, and his research team are developing tools to investigate the role of 24-hour circadian rhythms in tissue engineering using microtissues grown in the lab.
Circadian rhythms are a crucial part of biological systems—impacting nearly every physiological process in our body—yet they have traditionally been overlooked when it comes to growing new tissue. When cells and tissues are studied outside the body without the signaling cues provided by the body, individual cells rapidly fall out of sync with each other, thereby erasing rhythmic processes that should occur in natural systems. The lack of these processes leads to findings that do not capture the full complexity of biological systems.
With the support of a $1.91 million grant from the National Institutes of Health, Kearney and his team have been tackling this issue. From a biological perspective, they are interrogating the role of circadian rhythms in tissue regeneration processes so that it can be harnessed as a tool for optimizing healing. In studying this, however, they have realized that there is a lack of tools for performing these analyses, especially on microtissues (think organ-on-a-chip) grown in the lab.
To address the lack of tools, the team is developing automated devices in collaboration with Meghan Huber, assistant professor in the Mechanical and Industrial Engineering Department, which will provide synchronizing signals at designated circadian times to reinstate rhythmic processes in cell and tissue studies.
The first of these devices, thermoClock, is now complete and induces circadian rhythms by mimicking our body’s daily temperature cycles. In work led by BME graduate student Kelly (Kaiyin) Zhang, the team has demonstrated the device’s ability to synchronize healthy and disrupted circadian rhythms in cells and tissues. Notably, the device was able to match studies run by BME graduate student Chanelle Moise showing that disrupted circadian rhythms in the body slowed wound healing.
The Kearney Lab is also investigating how coordinating therapeutic delivery with distinct circadian phases affects tissue growth, and, in a first-of-its-kind approach, the lab is testing the possibility of driving circadian rhythms at regeneration sites through a triggered drug delivery system.
In describing this work and its ultimate goals, Kearney notes: “To our knowledge, nobody has examined the role of circadian rhythms—how our body behaves during our sleep and wake cycles—in tissue engineering. We know that disruption to our circadian rhythms affects many aspects of our health, including the ability to grow and heal tissue.
“But, what if we want to engineer systems that direct growth of tissue inside and outside the body? Can we use circadian rhythms to our advantage, or do we need to work around them? Our data so far points to an effect of circadian rhythms and timing on healing, and we want to fully understand that. What’s exciting for us is that we think this will unveil another mechanism that engineers can use in designing systems that regrow tissue for patients.”
By investigating this temporal aspect, Kearney and his team are filling in a new area in the broader picture of tissue engineering. Recreating the fullest possible picture of our bodies in the lab is crucial, as tissue engineering is used not only as a medical intervention to help patients restore damaged tissue, but also as a valuable research tool, notably in cancer research. It allows researchers to create functional tissue substitutes in the laboratory, allowing for the controlled study of diseases and the development and testing of potential treatments.
Another promising opportunity for Kearney’s work to make an impact is through introducing circadian rhythms in tissues outside of the body. These microtissues are used by a vast number of laboratories and industries that aim to understand human biology and replace animal experiments. Adding circadian rhythms to such tissues would increase their physiological relevance, and the interest that the Kearney Lab is seeing in their devices suggests that the community is increasingly recognizing the need for further understanding of circadian rhythms. In this way, through both tissue engineering and microtissue models, Kearney’s work can have profound implications for the research community as well as for patients themselves.