A Novel Microfluidic System for 3D Epidermis and Full‐Thickness Skin Growth for Nanoparticle Safety Assessment

TL;DR

A new microfluidic system mimics human skin to better assess nanoparticle safety, showing how they can harm skin function and trigger inflammation.

Contribution

A dynamically perfused, modular microfluidic system for epidermis and full-thickness skin models with enhanced physiological relevance for nanoparticle toxicity testing.

Findings

Exposure to TiO2 nanoparticles reduced skin barrier integrity by 32.4% and metabolic activity by 12.1%.

The system showed increased permeability (2.9%) and histological signs of tissue damage.

Chemokine upregulation indicates an early inflammatory response to nanoparticle exposure.

Abstract

Chronic skin exposure to nanoparticles (NPs) from air pollution, cosmetics, tattoo inks, and smart textiles is linked to adverse effects such as accelerated aging, dermatitis, eczema, and increased melanoma risk. However, the limited predictive power and physiological relevance of conventional in vitro models, combined with the absence of standardized protocols for assessing NP toxicity, remain a major challenge. To address these limitations, the development of skin‐on‐chip (SoC) systems provides a more physiologically relevant solution, surpassing the constraints of static skin cultures. Here, a novel SoC model with dynamic perfusion and a modular architecture suitable for epidermis‐only (EoC) and full‐thickness (FT) skin models isdeveloped. Under dynamic conditions, both models are metabolically active, exhibit enhanced barrier function, and display a morphology resembling native human skin. Exposure to titanium dioxide (TiO2) NPs led to a 32.4% decrease in barrier integrity, a 12.1% reduction in metabolic activity, a 2.9% increase in permeability, and histological evidence of tissue damage. These alterations are associated with an early moderate inflammatory response, as indicated by the upregulation of chemokines. Collectively, these findings demonstrate that the microfluidic device functions as a versatile toxicological tool, with the biological complexity of the FT SoC enhancing its sensitivity for nanotoxicology studies.

This work presents a novel, dynamically perfused, configurable microfluidic system for epidermis‐only (E and full‐thickness skin (FT SoC) growth, emulating human skin structure and barrier function. Upon TiO2 nanoparticle exposure, the system reveals compromised barrier integrity, reduced metabolic activity, increased permeability, and chemokine‐driven immune signaling, positioning it as a predictive nanotoxicology tool.

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