Engineered Human Skin Acts as a Living Biosensor for Inflammation

By Pooja Toshniwal PahariaReviewed by Lauren HardakerJan 21 2026

By turning human skin into a self-renewing biological display, researchers show how implanted living tissue can continuously report inflammatory signals without repeated blood tests.

Image credit: Guguart/Shutterstock.com

In a recent study published in Nature Communications, researchers developed and implanted living skin-based biosensors for long-term, surface-visible monitoring of inflammation, a hallmark of many human diseases.

Engineered Human Skin Enables Visible, Long-Term Inflammation Sensing

Using genetically engineered normal human epidermal keratinocytes (NHEKs), including keratinocyte stem cells (KSCs), engineered to fluoresce upon exposure to inflammatory signals such as tumour necrosis factor-alpha (TNF-α), the sensor enables longitudinal, hours-to-days–scale visual tracking of biomarker-associated signalling in vivo following implantation. The findings highlight the potential of living sensors for implantable, maintenance-free health surveillance and preventive care.

Fluctuations in biomarker levels, including blood glucose and inflammatory cytokines, indicate physicochemical and biological alterations in the body. Monitoring these changes enables early detection of developing pathologies and their prompt management, improving individual health and reducing the overall disease burden. Conventional practices are accurate but require blood sampling, which makes them less preferable for long-term health monitoring and disease tracking. Wearable devices enable non-invasive monitoring but have limited sensitivity and specificity in biomarker tracking over extended periods.

Genetically Modified Epidermal Cells Form Implantable Sensing Skin

In the present study, researchers implanted tissue-engineered human skin constructs onto the skin for sensitive, specific, long-term biomarker tracking using engineered NHEKs containing KSCs (from normal human epidermal keratinocytes) that express fluorescent proteins in response to environmental stimuli.

The team generated skin using tissue engineering with genetically modified NHEKs. They performed Hematoxylin and Eosin (H&E) and immunostaining to verify skin reconstruction. They also verified its concentration-dependent responsiveness to TNF-α stimulation in vitro. Subsequently, they transplanted it onto immunodeficient (SCID) mice for performance evaluation. After allowing at least four weeks post-transplantation to permit resolution of graft-associated inflammation, they investigated inflammatory responses by measuring changes in biomarker expression of Ly6g (neutrophil marker), F4/80 (pan-macrophage), CD86 (M1 macrophages), and CD163 (M2 macrophages).

To determine effectiveness, they administered an inflammatory agent subcutaneously near the transplanted skin. They assessed changes in fluorescence intensity using external fluorescence imaging and image-based quantification normalised to the graft area. The engineered keratinocytes within the sensor have transgenes fused with response elements (REs) for gene transcription. The cells express enhanced green fluorescent proteins (EGFP) as a visual readout based on changes in nuclear factor kappa B (NF-κB) signaling upon stimulation with 0.2 ng/mL and 20 ng/mL TNF-α in vitro, while in vivo stimulation involved subcutaneous injection of TNF-α adjacent to the graft, producing peak fluorescence approximately 1–2 days after dosing.

To assess cross-selectivity, the researchers examined responses to interleukin-1 beta (IL-1β), a cytokine regulated by NF-κB. They also evaluated changes in response to lipopolysaccharide (LPS) and IL-2, which are not directly involved in the NF-κB pathway in keratinocytes. To verify cell response in a more complex human immune environment, they developed co-cultures with human-derived peripheral blood mononuclear cells (PBMCs), used as a source of cytokine-mediated immune signalling.

Implanted Human Skin Remains Stable While Sensing Inflammatory Signals

In mice, the transplanted skin underwent natural turnover by the engineered NHEKs containing KSCs, engrafting long-term, mature human skin-like structures. The engineered skin model displayed skin biomarkers, including cytokeratin 14 (CK14, an epidermal basal layer marker), collagen type IV (a basal layer marker), and vimentin (a fibroblast marker).

An initial epidermal thickness of 20 µm in the tissue-engineered skin increased to 100 µm post-transplantation, similar to that of the human epidermis. In addition, the engineered skin tissue demonstrated papillary structures, which are absent in murine skin. Furthermore, the skin area showing fluorescent responses remained largely unchanged even after more than 200 days post-engraftment. These findings suggest successful skin reconstruction using genetically modified cells and the stable maintenance of the sensing display despite epidermal turnover.

After four weeks of transplantation, the engrafted epidermal keratinocytes displayed EGFP signals in response to TNF-α-induced alterations in the NF-κB pathway, indicating inflammation. The team found stronger fluorescence following in vivo TNF-α administration (peaking at approximately 1–2 days) than that observed with lower-dose in vitro stimulation. The authors attribute this stability and sensitivity to columnar epidermal organisation and long-lived progenitor cells within basal papillary ridges, which functioned as the living display for long-term, maintenance-free inflammation monitoring. Signal amplification through multiple transcriptional and translational processes within the cells facilitated sensitive detection.

The team observed a similar increase in fluorescence intensity upon IL-1β stimulation (but not IL-2). The findings indicate high selectivity of the genetically modified cells. Further, the fluorescence intensity remained unaltered with PBMCs alone but increased after PBMC activation with LPS. The findings suggest that the cells can track inflammation-driven immune signalling, with LPS acting as an indirect inflammatory trigger rather than a direct ligand sensed by the engineered keratinocytes, and the response reflecting cytokine-driven NF-κB activation in the skin graft.

Living Skin Sensors Enable Minimally Invasive Inflammation Monitoring

The study findings demonstrate that the living sensor can effectively and minimally invasively (following implantation) track biomarker-associated inflammatory signaling over biologically relevant timescales with high specificity and sensitivity.

The technology overcomes the limitations of conventional detection methods, such as enzyme-linked immunosorbent assays (ELISA) and mass spectrometry, which require whole blood samples. Importantly, the sensor can precisely detect changes in TNF-α–associated NF-κB signaling without preprocessing requirements, which is especially advantageous for molecules present in minute amounts and with short half-lives in the human body.

By using different receptors, the technology may detect markers of oxidative stress and hypoxia and track hormonal changes, potentially advancing healthcare monitoring and veterinary medicine practices. While the experimental mice lacked mature lymphocytes, the stronger secondary inflammatory response observed after repeat LPS challenge is discussed as potentially arising from SCID mouse immune “leakiness,” rather than confirmed adaptive immunity.

Future studies should use more immunocompetent models incorporating autologous cells and reporter protein molecules with reduced immunogenicity for broader applicability, alongside consideration of biosafety and societal aspects of deploying genetically modified living sensors.

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Journal Reference

Sawayama, J., Takeo, M., Takayama, Y. et al. (2026). Living sensor display implanted on skin for long-term biomarker monitoring. Nature Communications, 17, 56. DOI: 10.1038/s41467-025-67384-2. https://www.nature.com/articles/s41467-025-67384-2