High-resolution spatiotemporal mapping of transient Joule heating and skin tissue responses during microneedle electroporation.

Microneedle electroporation holds promise for enhancing dermal gene and drug delivery, yet the biophysical consequences of millisecond exponential-decay pulses remain incompletely characterized. We employed mid-wave infrared temperature mapping, three-dimensional electromagnetic modeling, cell viability staining, and histological analysis to systematically characterize the thermal, electrical, and biological responses of skin during microneedle electroporation. Millisecond pulsed electric fields induced pronounced, spatially heterogeneous Joule heating, with peak temperatures governed by pulse voltage and duration. A consistent voltage- and pulse-duration dependent thermal asymmetry was observed, with the anode hotter than the cathode; the anode-cathode temperature difference reached a maximum ΔT of 37.8 °C at 200 V (∼40 ms). Numerical simulations indicated that localized electric field enhancement at microneedle tips and edges contributes to these thermal effects. Biologically, anode-focused heating caused thermal charring, coagulative necrosis, and sustained inflammation, whereas electroporation-induced acute cell death remained symmetric around both electrodes. High-voltage microneedle electroporation (≥100 V) thus produces substantial localized thermal injury, particularly at the anode. These findings establish a link between transient electro-thermal dynamics and tissue injury, delineating the distinct spatial contributions of electroporation-mediated and thermal damage, and provide a biophysical basis for understanding localized Joule heating and tissue responses during millisecond-scale microneedle electroporation.