Elena RADU 1*, Laura-Elena ANDREI 1*, Ana-Maria ZAMFIRESCU 1**, Grațiela Grădișteanu-PÎRCĂLĂBIORU 1, Ming NI3, Yi ZHANG4, Ciprian ILIESCU 1,2,5**,
Bianca-Maria TIHĂUAN 1,2
Abstract. Developing new and effective therapeutics relies on using robust preclinical models that can closely mimic human physiological and immunological responses. Two-dimensional (2D) cell culture systems fail to replicate the complex tissular architecture and specialized microenvironments, which limits their ability to translate early findings into clinical success. Three-dimensional (3D) organoid models have also several drawbacks, such as handling complexity, variability in growth and differentiation, scalability issues, and reliability concerns, particularly in the context of high-throughput drug screening. This review provides a critical examination of skin related 2D and 3D models in the context of drug testing and disease modeling, evaluating their respective strengths and limitations. We also explore emerging technologies (e.g. immune-competent skin organoids) designed to overcome current barriers in organoid research, particularly those aimed at enhancing throughput, standardization, and data reproducibility in drug screening and toxicity testing.
Keywords: skin 3D organoids, 2D cell culture, drug discovery, diseases modelling, toxicity testing
DOI 10.56082/annalsarscibio.2025.2.181
1eBio-hub Center of Excellence in Bioengineering, National University of Science and Technology Politehnica Bucharest;
2 Academy of Romanian Scientists, 3, Ilfov Street, 050045 Bucharest, Romania;
3GenScript, Zhenjiang, Jiangsu Province, P. R. China;
4School of Integrated Circuit Science and Engineering, University of Electronic Science and Technology of China, Sichuan, China.
5 National Institute for Research and Development in Microtechnologies- IMT Bucharest, Romania
* Share first author – equal contribution
** Corresponding authors: anazamfirescu0803@upb.ro; ciprian.iliescu@upb.ro
PUBLISHED in Annals Academy of Romanian Scientists Series on Biological Sciences, Volume 14 no 2, 2025