# Innovations in skin microphysiological systems for nonclinical testing and FDA modernization

## TL;DR

This paper reviews new skin models that mimic human skin for testing, aiming to replace animal testing and support FDA modernization.

## Contribution

The paper introduces and evaluates three innovative skin models for nonclinical testing and regulatory applications.

## Key findings

- 3D bioprinting, skin organoids, and skin-on-a-chip replicate human skin functions like barrier formation and immune interactions.
- These models can simulate diseases such as psoriasis, atopic dermatitis, and melanoma for therapeutic evaluation.
- Automation and machine learning can enhance high-content screening of skin models for scalable applications.

## Abstract

Recent innovations in skin microphysiological systems (MPSs) have gained momentum following regulatory advances such as the FDA Modernization Act 2.0 and the global shift toward alternatives to animal testing. This review highlights the development of three major technologies—3D bioprinting, skin organoids, and skin-on-a-chip—and their roles in replicating human skin physiology for research and preclinical applications. We examine how these platforms model complex skin functions, including epidermal barrier formation, vascular and immune interactions, and disease phenotypes such as psoriasis, atopic dermatitis, melanoma, and viral infections. In addition to summarizing their utility in toxicological screening and therapeutic evaluation, we explore how current OECD test guidelines may guide future validation efforts. Finally, we discuss emerging strategies for integrating automation and machine learning-based image analysis to enable scalable, high-content screening of skin MPS models across diverse applications.