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Peer-reviewedCC BY 4.0Advanced Science

An Innervated Human Skin Equivalent that Electrically Encodes Mechanical and Thermal Stimuli

  • Daniele Bellantoni1,2,3
  • Costantino Casale1,2
  • Marika Sperduti4
  • Nevio L. Tagliamonte4
  • Giorgia Imparato2
  • Loredana Zollo4
  • Paolo A. Netti1,2,3
4 affiliations
  1. 1Centro di Ricerca Interdipartimentale sui Biomateriali CRIB University of Napoli Federico II Napoli Italy
  2. 2Istituto Italiano di Tecnologia‐IIT Center for Advanced Biomaterials for Healthcare Napoli Italy
  3. 3Department of Chemical Materials and Industrial Production Engineering‐DICMAPI University of Naples Federico II Naples Italy
  4. 4Research Unit of Advanced Robotics and Human‐Centred Technologies – CREO Lab Universitá Campus Bio‐Medico di Roma Rome Italy
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Abstract

Understanding how peripheral sensory circuits encode mechanical and thermal stimuli requires an experimental system that combines native tissue architecture with high‐resolution electrophysiological readouts. Existing innervated in vitro skin models typically rely on chemical stimulation and optical measurements, limiting their ability to interrogate sensory encoding dynamics. Here, we present an innervated full‐thickness human skin equivalent that electrically encodes both mechanical and thermal stimuli. The construct integrates a differentiated epidermis and dermis with sensory neurons and Schwann cells forming free nerve ending‐like structures, from which the recorded activity originates, and is interfaced with high‐density microelectrode arrays. Controlled mechanical indentation and localized thermal stimulation evoke consistent, stimulus‐dependent firing patterns whose waveform morphology and temporal dynamics reveal distinct electrical signatures for mechanical and thermal inputs. To our knowledge, this represents the first demonstration of thermally and mechanically evoked electrophysiological activity in an engineered innervated human skin construct. This model enables controlled investigation of sensory encoding and establishes a biologically grounded and experimentally controllable interface between engineered tissues and electrophysiological sensing technologies with potential application in bioinspired tactile sensing, neural interfaces, and sensory restoration.

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Cite

BibTeXRIS
BibTeX
@article{bellantoni2026innervated,
  title = {{An Innervated Human Skin Equivalent that Electrically Encodes Mechanical and Thermal Stimuli}},
  author = {Daniele Bellantoni and Costantino Casale and Marika Sperduti and Nevio L. Tagliamonte and Giorgia Imparato and Loredana Zollo and Paolo A. Netti},
  journal = {Advanced Science},
  year = {2026},
  month = aug,
  doi = {10.1002/advs.77105},
  url = {https://doi.org/10.1002/advs.77105},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - An Innervated Human Skin Equivalent that Electrically Encodes Mechanical and Thermal Stimuli
AU  - Daniele Bellantoni
AU  - Costantino Casale
AU  - Marika Sperduti
AU  - Nevio L. Tagliamonte
AU  - Giorgia Imparato
AU  - Loredana Zollo
AU  - Paolo A. Netti
PY  - 2026
DA  - 2026/08/15
JO  - Advanced Science
DO  - 10.1002/advs.77105
UR  - https://doi.org/10.1002/advs.77105
AB  - Understanding how peripheral sensory circuits encode mechanical and thermal stimuli requires an experimental system that combines native tissue architecture with high‐resolution electrophysiological readouts. Existing innervated in vitro skin models typically rely on chemical stimulation and optical measurements, limiting their ability to interrogate sensory encoding dynamics. Here, we present an innervated full‐thickness human skin equivalent that electrically encodes both mechanical and thermal stimuli. The construct integrates a differentiated epidermis and dermis with sensory neurons and Schwann cells forming free nerve ending‐like structures, from which the recorded activity originates, and is interfaced with high‐density microelectrode arrays. Controlled mechanical indentation and localized thermal stimulation evoke consistent, stimulus‐dependent firing patterns whose waveform morphology and temporal dynamics reveal distinct electrical signatures for mechanical and thermal inputs. To our knowledge, this represents the first demonstration of thermally and mechanically evoked electrophysiological activity in an engineered innervated human skin construct. This model enables controlled investigation of sensory encoding and establishes a biologically grounded and experimentally controllable interface between engineered tissues and electrophysiological sensing technologies with potential application in bioinspired tactile sensing, neural interfaces, and sensory restoration.
SN  - 2198-3844
ER  -