Scientists create skin graft health monitor that glows in response to inflammation

Researchers in Japan are exploring a future where the body itself becomes a health monitor, no screens or batteries required. A joint team from Tokyo City University and the University of Tokyo, working with scientists at RIKEN and engineers from Canon Medical Systems Co., has developed an experimental skin graft that visibly responds to inflammation inside the body. The work, published in the journal Nature Communications, describes a living sensor made from engineered human skin cells that glow when specific immune signals rise.

The project is led by Distinguished Professor Hiroyuki Fujita of Tokyo City University, who is also a professor emeritus at the University of Tokyo, alongside Professor Shoji Takeuchi of the University of Tokyo. Their goal was to move beyond wearable devices that sit on the skin and instead build a monitoring system that becomes part of the body.

“Conventional approaches are often invasive or provide only snapshots in time,” Fujita said. “Our goal was to explore a biologically integrated system that enables continuous sensing and intuitive interpretation, even at home.”

Most internal biomarkers, such as proteins linked to inflammation or disease, are measured through blood tests. Those tests are accurate but invasive and cannot track changes continuously. Wearable devices can sample sweat or other fluids, but they often work for short periods and struggle with sensitivity.

The researchers focused on skin because it sits between the body and the outside world and renews itself constantly. In the outer skin layer, epidermal stem cells divide and replace old cells roughly every 50 days in humans. If those stem cells are engineered to sense biological signals, the sensing function can persist as the skin renews.

"Using this idea, our team genetically modified human epidermal keratinocytes, including stem cells, to respond to inflammation. We targeted a signaling route called the NF-κB pathway, which becomes active when inflammatory molecules such as tumor necrosis factor alpha, or TNF-α, are present. When this pathway switches on, it triggers immune-related genes," Fujita explained to The Brighter Side of News.

The researchers designed the cells so that NF-κB activation would also turn on production of enhanced green fluorescent protein, known as EGFP. When inflammation-related signals appear, the engineered cells glow green.

In laboratory tests, the engineered cells responded to increasing amounts of TNF-α with stronger fluorescence. Very low levels produced little change, while higher concentrations led to brighter signals. The response grew over time and tracked with TNF-α dose, showing that the system could reflect changes in inflammatory strength.

Selectivity tests showed that the cells reacted to molecules tied to NF-κB signaling but not to unrelated immune signals. When immune cells were added to the system, the engineered skin still lit up in response to inflammatory cues released by those cells.

The team then built a three-dimensional patch of tissue-engineered skin. They combined the engineered epidermal cells with normal human dermal fibroblasts, creating a layered structure that resembled real skin. When exposed to TNF-α, this living patch also produced a measurable fluorescent response, though weaker than flat cell cultures due to light scattering through tissue.

To test long-term function, the researchers transplanted the engineered skin onto immune-deficient mice. Over time, the graft integrated with the animals’ tissue and matured. The epidermal layer thickened and developed structures similar to human skin, even forming surface patterns not found in mice.

“Unlike conventional devices that require power sources or periodic replacement, this system is biologically maintained by the body itself,” Takeuchi said. “In our experiments, the sensor functionality was preserved for over 200 days, as the engineered stem cells continuously regenerated the epidermis.”

After the transplant healed, baseline fluorescence faded, which allowed the patch to act as a clean readout. When TNF-α was injected near the graft, the skin lit up within a day, peaked shortly after, and then dimmed as inflammation subsided. Weeks later, a second injection triggered the same response again. The repeated cycles showed that the sensor could detect inflammation multiple times over long periods.

The team also tested lipopolysaccharide, or LPS, a bacterial molecule that causes inflammation indirectly through immune cells. LPS did not activate the engineered skin directly in lab dishes, but in living mice it led to fluorescence as immune cells released inflammatory cytokines. The response was slower and varied with injection method, but the glowing signal consistently appeared only in the transplanted human skin.

The study shows that engineered skin stem cells can act as durable biological sensors and displays. By turning internal molecular events into visible signals on the body surface, the system bypasses the need for blood draws or electronic wearables.

Detecting TNF-α is especially challenging because it appears briefly and in small amounts during inflammation. Traditional tests require careful timing and sample handling. In contrast, living cells amplify signals through natural processes and maintain sensitivity over time.

The researchers note that challenges remain. Even in immune-deficient mice, some immune responses formed around the graft. The fluorescent protein itself may also trigger immune reactions in normal animals. Future work will need to address safety, long-term compatibility, and whether similar systems can be built using a person’s own cells.

If refined for human use, living sensor skin could change how chronic inflammation and disease are monitored. Patients with autoimmune disorders, infections, or inflammatory conditions might one day track disease activity through visible changes rather than frequent tests.

Researchers could gain new tools for studying immune responses over long periods. Beyond human medicine, similar systems could help monitor animal health in research or veterinary settings, especially when symptoms are hard to observe.

By blending biology and engineering, the approach opens a path toward health monitoring that works continuously and intuitively.

Research findings are available online in the journal Nature Communications.

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