RT Journal Article T1 Biomimetic core-shell breast cancer models using alginate, gelatin, and collagen I: simulating the tumor matrix for drug evaluation A1 Gato Díaz, Uxía A1 Castro Alves, Lisandra de A1 Concheiro Nine, Ángel Joaquín A1 Piñeiro Redondo, Yolanda A1 Álvarez Lorenzo, Carmen A1 Blanco Fernández, Bárbara A1 Rivas Rey, José K1 3D in vitro cancer model K1 Core-shell hydrogel K1 Doxorubicin resistance K1 Drug screening K1 Invadopodia AB Breast cancer remains among the most prevalent cancers in women worldwide. During tumor development, the extracellular matrix is altered to support tumor progression and therapy resistance. Therefore, there is a need to develop breast cancer models that replicate the complex tumor extracellular matrix to accurately mimic the mechanisms by which it influences drug resistance and cancer cell malignancy. In this study, we fabricated an innovative breast cancer 3D in vitro model consisting of core-shell hydrogel beads from alginate, gelatin, and collagen I by extrusion through a coaxial needle. Breast cancer cells proliferated in the core of all prototypes designed, forming spheroids and cell aggregates with a high resistance to doxorubicin. The addition of Collagen I to the developed model enabled the upregulation of malignancy markers (Col1A1, Ki67, FOXC2, SNAI1, NFKB1, WWTR1), invasion markers (WASL, ACTA1, MYO1E, TPM4, PODXL, ITGA2, ITGA5, MENA, EGFR, CDC42), and drug resistance markers (ABCG2, CYP1A1, BAX, HSP90AA1) occurring in vivo. The developed 3D in vitro model can clarify the contribution of the extracellular matrix to the tumor outcome and drug efficacy by replicating some key characteristics of breast tumors, establishing a novel tool for chemotherapeutic agents and drug screening. PB Elsevier YR 2026 FD 2026-01 LK https://hdl.handle.net/10347/46931 UL https://hdl.handle.net/10347/46931 LA eng NO Gato-Diaz, U., de Castro-Alves, L., Concheiro, A., Piñeiro, Y., Alvarez-Lorenzo, C., Blanco-Fernandez, B., & Rivas, J. (2026). Biomimetic core-shell breast cancer models using alginate, gelatin, and collagen I: simulating the tumor matrix for drug evaluation. International journal of biological macromolecules, 335(Pt 1), 149205. https://doi.org/10.1016/j.ijbiomac.2025.149205 NO This work was supported by the Strategic State Plan for Scientific, Technical, Innovation 501100011033, European Research Union MICIU/AEI/10.13039/ NextGenerationEU/PRTR (PLEC2022–009217) by the Ministry of Science, Innovation, and Universities of Spain (to L.A., Y. P., and J.R.) and by ISCII through CERTERA, the State Network Consortium for the Development of Advanced Therapy Medicines (PERTE for Cutting-Edge Health, Recovery, Transformation and Resilience Plan, Proyect CERT22/00015). The work was also funded by the Xunta de Galicia (ED431F 2024/19 to B.B.F.; ED431C 2024/09: to B.B.F., C.A.L., A.C.); Ministry of Science, Innovation, and Universities of Spain MICIU/AEI/ 10.13039/50110001103 (PID2023- 150422OB-I00 to A.C. and C.A.L.; PID2023-147892OA-I00 to B.B.F.), ERDF A way of making Europe, and the European Union; and MICIU/ AEI/10.13039/501100011033 MICIU/AEI (RYC2022–037421-I to B.B.F.). DS Minerva RD 22 may 2026