Bio-hybrid Device Acts as “Thermostat” to Control Systemic Inflammation in Sepsis

Bio-hybrid Device Acts as “Thermostat” to Control Systemic Inflammation in Sepsis

In a pre-clinical study by McGowan Institute for Regenerative Medicine faculty members (pictured top left clockwise)

Yoram Vodovotz, PhD, professor, Departments of Surgery, Immunology, Computational and Systems Biology, Clinical and Translational Science, and Communication Science and Disorders at the University of Pittsburgh, and director, Center for Inflammation and Regenerative Modeling at the McGowan Institute, and

Jörg Gerlach, MD, PhD, professor, Department of Surgery, University of Pittsburgh, and director, The Bioreactor Group at the McGowan Institute, and affiliated faculty members

Gregory Constantine, PhD, professor of mathematics and statistics at the University of Pittsburgh, and

Ruben Zamora, PhD, research assistant professor at the University of Pittsburgh in the Department of Surgery, and

researchers from the University of Pittsburgh School of Medicine, a small, external bioreactor holding human cells pumped out an anti-inflammatory protein to prevent organ damage and other complications in a model of sepsis caused by bacterial products. The findings were published in the inaugural issue of Disruptive Science and Technology.

Inflammation is a necessary biological response that brings cells and proteins to the site of tissue injury to contend with foreign agents, such as bacteria and the products they produce, and to begin the healing process, explained senior author Dr. Vodovotz. But sometimes, the inflammatory response escalates to create damage on its own, triggering more inflammation in a self-sustaining and dangerous cycle.

“In sepsis, for example, the inflammatory response evolves almost too quickly, but the available treatment strategies aim to prevent inflammation entirely,” he said. “A better approach would be to turn down the response when it’s too strong, yet still have appropriate inflammation signaling to promote tissue repair.”

During inflammation, the body makes a protein called tumor necrosis factor-alpha, or TNF-α. It also makes its counterpart, soluble TNF-α receptor, or sTNFR, which binds to and reduces the level of TNF-α. In some situations, such as sepsis, not enough sTNFR is made to limit the inflammatory response.

“This bio-hybrid device acts as a kind of inflammation thermostat,” Dr. Vodovotz said. “By loading it with cells that produce different amounts of sTNFR, or other inflammatory blockers, we may soon be able to tailor our interventions to carefully balance inflammation and immune responses based on the patient’s medical situation.”

His team now is exploring the effectiveness of cells engineered to produce sTNFR based on the individual production of TNF-α, rather than continuously, in order to create a disease-specific response for each patient. Such a personalized medicine therapy platform could be extended based on emerging knowledge regarding the biology of inflammation.

The Vodovotz group also is creating computer models of inflammation, which could be used to engineer the next generation of this device. The portability of the device could be particularly useful on the battlefield, where early intervention to control systemic inflammation after injury might improve the chances of survival.