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

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.