Engineered Skin “Living Sensor Display” Lights Up for Biological Monitoring

Wearable health devices, such as smartwatches, have become commonplace and enable continuous monitoring of physiological signals at the skin’s surface. A research team led by scientists at Tokyo City University and at The University of Tokyo, collaborating with researchers at RIKEN and at Canon Medical Systems Co., now reports on the development of a biohybrid approach that works by transforming engineered skin to a visible indicator of internal biological states.

The ”living sensor display” is an engineered skin graft that fluoresces in response to specific internal biomarkers, such as those associated with inflammation. The system leverages the body’s natural skin regeneration to support long-term biomarker monitoring, providing a visual readout without blood sampling after implantation. Headed by Hiroyuki Fujita, PhD, distinguished professor of Tokyo City University (professor emeritus, The University of Tokyo), the scientists carried out tests in live mice, demonstrating that the transplants were able to continually monitor inflammatory cytokines.

Development of the tissue engineered skin living sensor is described in a paper in Nature Communications, titled, “Living sensor display implanted on skin for long-term biomarker monitoring.” In their report investigators concluded, “This living sensor display holds promise for advancing health monitoring and disease prevention strategies by enabling continuous, sensitive, and specific in vivo biomarker tracking.”

Measuring biomarkers, such as blood glucose levels or presence of inflammatory cytokines, can play an important role in early disease prevention, provide insights into disease progression and personal health, and in the managing lifestyle of related diseases, the authors noted. Monitoring such internal biomarkers has traditionally relied on blood sampling, or externally attached sensors that operate only for limited duration. “Conventionally, biomarker detection has primarily been achieved through intermittent blood sampling, which allows for accurate measurements,” the team noted. “However, it is not suitable for long-term continuous monitoring owing to its invasive nature.”

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

Wearable devices can enable long-term, continuous monitoring of health-related biomarkers using sweat, saliva, tears or interstitial fluid, the scientists pointed out. “However, no method is able to monitor biomarkers within the body with high selectivity and sensitivity over long durations.”

To develop the living sensor display technology the researchers used epidermal stem cells known as skin keratinocyte stem cells (KSCs), which naturally maintain and renew the skin throughout life. By genetically engineering these cells to respond to inflammatory signaling, the team generated skin tissue that expresses enhanced green fluorescent protein (EGFP) in response to specific inflammation-related signals.

They focused on monitoring the inflammatory cytokine tumor necrosis factor-α (TNF-α). “To detect TNF-α, we first genetically engineered human epidermal keratinocytes (NHEK), including KSCs to express NF-κB-EGFP, which is activated by TNF-α stimulation,” they wrote. “Next, we used these cells to construct a tissue-engineered skin model and verify its concentration-dependent responsiveness to TNF-α stimulation.”

The researchers showed that, when transplanted onto mice, the engineered skin engrafted and functionally integrated with the host tissue. When inflammation was induced, the grafted area emitted green fluorescence, translating internal molecular signals to an external optical signal. “The fluorescent protein expressed within the transplanted cells emitted high intensity light that was visible from outside the skin,” the scientists commented. Because the sensor comprises living epidermal stem cells, it is maintained through the skin’s natural turnover. “Furthermore, the internal movement and differentiation of cells within the skin due to cellular turnover allows for long-term continuous monitoring without altering the illuminated area,” they added.

The study confirmed that the area of skin demonstrating the fluorescent response was maintained for more than 200 days after grafting. Co-author professor Shoji Takeuchi, PhD, at The University of Tokyo, noted, “Unlike conventional devices that require power sources or periodic replacement, this system is biologically maintained by the body itself. In our experiments, the sensor functionality was preserved for over 200 days, as the engineered stem cells continuously regenerated the epidermis.”

The 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. “By changing the receptors, it is conceivable to detect various target substances similarly in the future,” the scientists stated.

They further suggest that such technology could have applications beyond human healthcare, in areas including veterinary medicine, where visual indicators of health status may aid the early detection of disease in animals unable to communicate symptoms. “Unlike conventional wearable sensor technologies, this method enables the long-term, real-time acquisition of minute biochemical signals, with potential applications ranging from health management and early disease detection to veterinary medicine and livestock monitoring,” the authors reported.

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. While noting remaining challenges, the researchers wrote, “In conclusion, our Living Sensor Display leverages the characteristics of receptors to detect unstable and minute biomarkers in vivo with high sensitivity and continuity. By further investigating their invasiveness and safety, engineered cells can be implanted into the body, paving the way for a paradigm in healthcare that includes long term disease monitoring and health management through early detection.”