Precise, personalized medicine requires nanoscale research and insight into the human cell to better understand disease and healing — the prerequisite for developing targeted therapies for specific pathologies and individual patients. But researchers cultivate cells in “wet” cultures hostile to electronic instrumentation, making it difficult to monitor cell function and behavior for a long period of time.
We unpacked this problem by developing an electronic “scaffold” that floats on the surface of the cell medium so sensors can monitor biosignals while the cells reside and grow underneath. This lets researchers track key biological signposts to model diseases and develop treatments.
A key application is tissue engineering: combining cells, the scaffolding where they grow, and biologically active molecules into functioning tissue — like artificial skin, cartilage and bone — to improve or replace damaged tissue. Cells are the essential elements of tissue, and in the body, they construct support structures for themselves called extracellular matrix. This scaffold not only braces the cells, but it also is a signaling station for indicators of cell development and well-being.
The National Institute of Biomedical Imaging and Bioengineering at the National Institutes of Health perhaps describes this best. “Each signal can start a chain of responses that determine what happens to the cell. By understanding how individual cells respond to signals, interact with their environment, and organize into tissues and organisms, researchers have been able to manipulate these processes to mend damaged tissues or even create new ones.”
The challenge is to observe these signals while not interfering with cell growth. Long-term, reliable recording of cellular functions is impeded by the conditions required for culturing biological cells, such as maintaining a cell medium culture solution at 37°C with Co2 — a setting utterly incompatible with electrical recording.
Our breakthrough is a unique, sponge-like material with rubber-like properties that is so buoyant that the entire scaffold system floats on the surface of cell medium. The electrical measurement settings are placed on the top surface of this “ultrabuoy,” in the air while the cells thrive on the bottom of the scaffold, which is submerged in the cell medium solution.
This provides a hospitable environment for both biological cells and electrical measurement settings, so the signals coming from the cells can be recorded reliably and in a stable environment for longer intervals. These measurements at the interface between the biological cells and the recording electrodes can convey vital information — how well cells are adhering to one another, how successfully they are proliferating, the effects of introducing various drugs, and so forth.
This, in turn, creates a research platform for analyzing cell biology in a controlled environment — for example, to analyze properties of cardiac or neural cells to better understand heart or brain activities. Another potential use is to collect information on the interaction between invading cancer cells and their adjacent cells.
There also is potential for using the embedded-instrument scaffolding for long-term monitoring of tissue function during and after transplant into a patient. It might be possible to construct a naturally dissolving form of the scaffolding so its materials could degrade harmlessly in the body following implantation and post-implant monitoring, eliminating post-surgical extraction.
In short, the accurate, real-time, long-term recording of cell development signals can have a profound impact on fundamental studies of the underlying biophysics and disease modeling of cells and tissues. And in so doing, it can further advance healthcare in general, as well as precision medicine, in which therapies are customized to the personalized features of each individual.
Chi Hwan Lee
Assistant Professor of Biomedical and Mechanical Engineering
College of Engineering, Purdue University