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Exploring the frontier between innate immunity and materials design

INNATE IMMUNITY AND MATERIALS: "As the lab becomes more established, we would love to collaborate with industry characterizing device-specific responses, and developing strategies to achieve a desired host response,” says Queen’s engineering professor Lindsay Fitzpatrick.
LONGER LASTING: Continuous glucose monitoring sensors like this one need to be changed and re-sited often because the body’s immune system degrades their function. Fitzpatrick aims to design materials that change all that.
TINY RESEARCH PARTNERS: Zebrafish are becoming increasingly popular among biomedical researchers as human analogue test subjects. Fitzpatrick is using their unique attributes to learn more about how materials interact with living tissues.

 

One of the best modern techniques in the treatment of diabetes is continuous glucose monitoring (CGM): the real-time, around-the-clock measurement of a patient’s blood sugar levels. It allows doses of insulin to be administered via a small insulin pump precisely as needed, rather than in system-shocking doses every few hours. It also helps doctors and patients to build a better understanding of how diet, exercise, and stress affect blood sugar levels on a moment-by-moment basis.

There’s at least one big limitation though. The CGM sensors used to measure glucose levels must penetrate the skin, or even be implanted within the body, and they just aren’t very long-lasting. They need to be changed and moved, in most cases, every few days. It’s a repetitive process that can be uncomfortable, even painful, for patients. It’s all because the CGM sensors below the skin trigger the body’s immune response. The very inflammation and encapsulation processes our bodies employ to protect us from disease quickly degrade a sensor’s ability to make accurate measurements. And it’s not just CGM sensors. Almost any soft-tissue implant carries with it the risk that the body’s immune response will alter its function or render it useless.

It’s a problem medical science has wrestled with for decades and it’s just the kind of puzzle – where inflammation, innate immunity, and materials intersect – that Queen’s assistant professor Lindsay Fitzpatrick aims to help solve with her research work.

“People have been looking at how to control the foreign body reaction since doctors started implanting materials more than 50 years ago,” says Fitzpatrick. “We’re trying to look at this old problem by pulling in new information from the world of immunology as well as bringing in new models that will allow us to look mechanistically at what’s going on at the cell-material interface. Our goal is to design materials that cause minimal immune response and use them to build devices that can last much longer in the body.”

Imagine, a CGM sensor, or any implant, that works nominally for months, years, or perhaps one day even indefinitely. These materials will be a huge contribution to medical science and engineering and will almost certainly improve the daily lives of millions of people.

So, how are Fitzpatrick and her research group proceeding?

“We’re trying to tackle this by looking at the involvement of pattern recognition pathways that are used by our bodies to defend against pathogens,” says Fitzpatrick.

One way to do that is by testing new materials on Zebrafish. It turns out the ubiquitous aquarium fish, Danio rerio, is a great laboratory analogue for human physiological systems. Though they seem so different from people, about 70 percent of human genes are found in the zebrafish genome. There are zebrafish lab strains, bred specifically for different types of experimentation, including examining the pattern recognition pathways in which Fitzpatrick is interested. Zebrafish also breed quickly, have human-analogous tissue and organ systems, produce embryos that are relatively easy to collect and modify, love to live with lots of other zebrafish in compact places, and are much cheaper to care for than, for example, lab mice.

“We really haven’t used zebrafish much yet in biomaterials because it’s very challenging to implant material into them due to their small size,” says Fitzpatrick. “We’re developing techniques to overcome that. We’ll be able to do a lot of work at the embryo stage using microscopy that will help us to understand biomaterial interactions at a deeper level.”

It’s still early days though. Fitzpatrick has been building her lab and research group at Queen’s for three years now. In the future, she says, she’d like to add more graduate students, bring in a polymer chemist and possibly someone expert in zebrafish biology.

“I think the material host response  is a really big puzzle,” says Fitzpatrick. “The immune system is fascinating and complex, and we are constantly learning new things about it. There is so much potential for working where materials and living tissues meet and I’m able to make use of my engineering background to tackle some of these big medical problems.”