ArticleScience advances2025
Hydrodynamically generated multilayer skin spheroids enable in vitro screening of biologically active ingredients and toxicity tests.
Article in Science advances, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed.
- Silibinin-Loaded Proniosomal Gel for Cutaneous Application: Pharmaco-Technical Characterization and In Vitro-In Ovo Biocompatibility.Gels (Basel, Switzerland) · 2026Article
- A Microwell Array Embedded Microfluidic Gradient Platform for Drug Screening on Tumor Spheroids.Small (Weinheim an der Bergstrasse, Germany) · 2026Article
- High-Throughput Generation of Tumor Spheroids via Droplet Microfluidics for siRNA-Loaded Nanomedicine Assessment.Advanced healthcare materials · 2026Article
- Organoids in drug development: from predictive models to regulatory integration.Drug discovery today · 2026Review
- Combining advanced 3D spheroid-based skin models with deep-learning-based image analysis enables in-depth investigation of keratinocyte differentiation and barrier function.Frontiers in bioengineering and biotechnology · 2026Article
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Authors and funding
9 authors.
Funding
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Abstract
Human tissues often have a multilayer structure, with each layer performing a distinct physiological task. Reconstructing layered tissue structures with their respective functions is crucial for disease modeling, screening biologically active ingredients, and performing toxicology tests; however, multicellular spheroids used for these purposes generally lack a well-defined multilayer architecture. Here, to recapitulate a multilayer structure of the skin, we developed a hydrodynamically mediated approach to the generation of large arrays of fibroblast spheroids (a dermal core) that were engulfed with an epidermal layer of keratinocytes. These spheroids expressed biomarkers of the epidermis, epidermal-dermal junction, and dermis, and exhibited skin-like barrier properties. Screening of the synergistic effect of vitamins and peptides on protein synthesis by the spheroids and evaluation of skin toxicity with chemical agents showed a correlation with clinical results or existing standards. This approach offers enhanced control over spatial cell distribution in spheroids for advanced in vitro models of multilayer tissues.
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Registered trials
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