Innovations in skin microphysiological systems for nonclinical testing and FDA modernization

Comprehensive Summary

The following study provides a comprehensive review of recent advances in skin microphysiological systems (MPS), highlighting their growing importance following regulatory changes such as the FDA Modernization Act 2.0 and global efforts to reduce animal testing. The review focuses on three major technology platforms–3D bioprinted skin, skin organoids, and skin-on-a-chip(SoC) systems–and evaluates how each recapitulates key aspects of human skin physiology, including epidermal barrier formation, vascular perfusion, immune interactions, and long-term tissue dynamics. Drawing on extensive schematic figures (e.g., Figs. 1-7), the authors compare these advanced in vitro models with traditional OECD-recommended assays, detailing how MPS platforms overcome limitations such as the absence of vascularization, immune components, and chronic-exposure modeling. The review also surveys fabrication technologies, bioink design, organoid differentiation strategies, and emerging machine-learning-based image-analysis tools for high-content assessment.

Outcomes and Implications

The review positions skin MPS as a critical bridge between regulatory science, biomedical research, and industry, offering human-relevant alternatives to animal models for toxicology, disease modeling, and therapeutic testing. By integrating vascular, immune, and, in some cases, neural components, advanced skin-on-a-chip and organoid systems enable more predictive assessment of inflammatory diseases (e.g., psoriasis, atopic dermatitis), skin cancers, and chronic toxicity. Importantly, the authors emphasize both the promise and current limitations of MPS–such as reproducibility, standardization, and incomplete tissue maturation–arguing for cautious but strategic adoption in regulatory workflows. The review highlights future directions, including automation, scalable manufacturing, standardized validation metrics, and AI-driven quantitative analysis, which together could accelerate FDA and OECD acceptance. Overall, the work underscores how next-generation skin MPS may modernize nonclinical testing, improve translation accuracy, and support ethical, human-centered approaches in dermatology, cosmetics, and pharmaceutical development.