170986 20260430151736.0 doi 10.1002/smsc.202500567 sideral 149050 ART-2026-149050 eng Guerrero-López, Paula Universidad de Zaragoza (orcid)0000-0003-3661-7718 Ultrastructural study of microphysiological systems of the tumor microenvironment 2026 The importance of studying the ultrastructure is underwritten by decades of research. Ultrastructural features help to understand pathological processes or inform disease diagnosis. However, ultrastructural studies in the promising cancer‐on‐a‐chip models are practically nonexistent because of the complexity of sample preparation for electron microscopy techniques, which is particularly aggravated with these miniaturized models. Our aim was to study ultrastructural features of microphysiological systems (MPS) of the tumor microenvironment consisting of 3D multicellular tumor structures that were grown in hydrogel‐based cancer‐on‐a‐chip models. To this end, we selected two different MPS from our lab as examples and devised a sample preparation technique for their observation under dual‐beam focused ion beam scanning electron microscopy (FIB‐SEM) and transmission electron microscopy (TEM). The proposed methodology allowed high‐resolution visualization of both external and internal organization of 3D multicellular tumor structures, including cell–matrix interactions, cell–cell junctions, spheroid–spheroid contacts, matrix deposition, and extracellular vesicle‐mediated intercellular communication. This study demonstrates the feasibility of using advanced electron microscopy techniques to observe ultrastructural features of miniaturized cancer models, thus revealing a new dimension in the use of these models to study tumor processes and find new therapeutic targets. Access copy available to the general public Unrestricted info:eu-repo/grantAgreement/EC/H2020/101018587/EU/Individual and Collective Migration of the Immune Cellular System/ICoMICS This project has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No H2020 101018587-ICoMICS info:eu-repo/grantAgreement/ES/MICINN/RYC2021-033490-I info:eu-repo/grantAgreement/ES/UZ/LMA-ELECMI ICTS info:eu-repo/semantics/openAccess by https://creativecommons.org/licenses/by/4.0/deed.es info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Pele, Karinna Georgiana Universidad de Zaragoza Barrado, Mariano Universidad de Zaragoza Alamán-Díez, Pilar Universidad de Zaragoza (orcid)0000-0003-1958-4432 García-Aznar, José Manuel Universidad de Zaragoza (orcid)0000-0002-9864-7683 García-Gareta, Elena Universidad de Zaragoza (orcid)0000-0001-7062-9099 0 X Universidad de Zaragoza Institutos Univ. de Investig. Área RPT Laboral INMA 1002 060 Universidad de Zaragoza Dpto. Bioq.Biolog.Mol. Celular Área Bioquímica y Biolog.Mole. 5004 605 Universidad de Zaragoza Dpto. Ingeniería Mecánica Área Mec.Med.Cont. y Teor.Est. 5001 065 Universidad de Zaragoza Dpto. Ciencia Tecnol.Mater.Fl. Área Cienc.Mater. Ingen.Metal. 6, 4 (2026), [16 pp.] Small Science 2688-4046 9912724 http://zaguan.unizar.es/record/170986/files/texto_completo.pdf Versión publicada 2404174 http://zaguan.unizar.es/record/170986/files/texto_completo.jpg?subformat=icon icon Versión publicada oai:zaguan.unizar.es:170986 articulos driver 2026-04-30-13:58:29 ARTICLE