Wearable health devices, such as smartwatches, have become commonplace, enabling the continuous monitoring of physiological signals at the skin's surface. Recently, a research team in Japan has developed a biohybrid approach that works inside the body--transforming engineered skin to a visible indicator of internal biological states.

A joint research group, led by Tokyo City University and the University of Tokyo, in collaboration with RIKEN and Canon Medical Systems Co., has unveiled a living sensor display: an engineered skin graft that fluoresces in response to specific biomarkers, such as inflammation. Reported in Nature Communications, the system leverages the body's natural skin regeneration to support long-term biomarker monitoring, providing a visual readout without blood sampling after implantation and enabling intuitive assessment by observation.

More Than Skin Deep

The monitoring of internal biomarkers--proteins that indicate inflammation, stress, or disease--typically relies on blood sampling or externally attached sensors that operate only for limited durations. "Conventional approaches are often invasive or provide only snapshots in time," Distinguished Professor Hiroyuki Fujita of Tokyo City University (Professor Emeritus, The University of Tokyo)."Our goal was to explore a biologically integrated system that enables continuous sensing and intuitive interpretation, even at home."

To achieve this, the researchers used epidermal stem cells, which naturally maintain and renew the skin throughout life. By genetically engineering these cells to respond to inflammatory signaling--more specifically, the activation of the NF-κB pathway--the team generated skin tissue that expresses enhanced green fluorescent protein (EGFP) in response to inflammation-related signals.

When the Sensor Is a Part of the Body

When transplanted onto mice, the engineered skin engrafted and functionally integrated with the host tissue. Upon the induction of inflammation, the grafted area emitted green fluorescence, translating internal molecular signals to an external optical signal.

Because the sensor comprises living epidermal stem cells, it is maintained through the skin's natural turnover.
"Unlike conventional devices that require power sources or periodic replacement, this system is biologically maintained by the body itself," said Professor Shoji Takeuchi of the University of Tokyo. "In our experiments, the sensor functionality was preserved for over 200 days, as the engineered stem cells continuously regenerated the epidermis."

Toward Visible, Long-Term Biomarker Monitoring

This study demonstrates a proof of concept for long-term, biologically integrated sensing without batteries, wiring, or active user operation. Although this work focused on inflammatory signaling, the underlying strategy is adaptable. By modifying the molecular targets, similar engineered skin constructs could be designed to respond to other physiological or metabolic cues.

The researchers note that such technology could have applications beyond human healthcare, including those in animal research and veterinary medicine, where visual indicators of health status may aid the early detection of disease in animals unable to communicate symptoms.

Although still at an early preclinical stage, this work offers a biologically grounded approach for interfacing living tissues with sensing functions, blurring the boundary between biological systems and engineered devices.

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The article, "Living sensor display implanted on skin for long-term biomarker monitoring" was published in Nature Communications at DOI:10.1038/s41467-025-67384-2.

Authors:
Jun Sawayama, Makoto Takeo, Yuki Takayama, Miki Takase, Hoshimi Aoyagi, Aki Takimoto, Saki Mizutani, Maiko Onuki, Satoshi Ikeo, Shogo Nagata, Miho Ogawa, Koji Yano, Takashi Tsuji, Shoji Takeuchi, and Hiroyuki Fujita*

Research Contact

Hiroyuki Fujita
Distinguished Professor, Tokyo City University
Professor Emeritus, the University of Tokyo
E-mail: hfujita(Please add "@tcu.ac.jp" to the end)

Shoji Takeuchi
Professor, Grad. School of Information Science and Technology, the University of Tokyo
Project Professor, Institute of Industrial Science, the University of Tokyo
E-mail: takeuchi(Please add "@hybrid.t.u-tokyo.ac.jp" to the end)