{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T16:32:09Z","timestamp":1786120329570,"version":"build-2736575974"},"reference-count":71,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2026,11,1]],"date-time":"2026-11-01T00:00:00Z","timestamp":1793491200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,11,1]],"date-time":"2026-11-01T00:00:00Z","timestamp":1793491200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T00:00:00Z","timestamp":1781827200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100013276","name":"Interreg Europe","doi-asserted-by":"publisher","award":["S1\/1.1\/P0033"],"award-info":[{"award-number":["S1\/1.1\/P0033"]}],"id":[{"id":"10.13039\/100013276","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008530","name":"European Regional Development Fund","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008530","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Foundation for Science and Technology","doi-asserted-by":"publisher","award":["PTDC\/BTA-BTA\/0696\/2020"],"award-info":[{"award-number":["PTDC\/BTA-BTA\/0696\/2020"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Foundation for Science and Technology","doi-asserted-by":"publisher","award":["UID\/PRR\/06407\/2025"],"award-info":[{"award-number":["UID\/PRR\/06407\/2025"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Foundation for Science and Technology","doi-asserted-by":"publisher","award":["UID\/06407\/2025"],"award-info":[{"award-number":["UID\/06407\/2025"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Biomaterials Advances"],"published-print":{"date-parts":[[2026,11]]},"DOI":"10.1016\/j.bioadv.2026.215022","type":"journal-article","created":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T07:00:07Z","timestamp":1781852407000},"page":"215022","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":0,"special_numbering":"C","title":["Impact of silk-derived sericin on the formation and metformin sensitivity of breast cancer-fibroblast heterotypic spheroids"],"prefix":"10.1016","volume":"188","author":[{"given":"Luis E.","family":"Calvo-Chica","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u00f3nia P.","family":"Miguel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maximiano P.","family":"Ribeiro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paula","family":"Coutinho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andr\u00e9 F.","family":"Moreira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"3","key":"10.1016\/j.bioadv.2026.215022_bb0005","first-page":"229","article-title":"Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA A Cancer J. Clin."},{"issue":"19","key":"10.1016\/j.bioadv.2026.215022_bb0010","doi-asserted-by":"crossref","first-page":"5701","DOI":"10.3390\/jcm11195701","article-title":"Addressing drug resistance in cancer: a team medicine approach","volume":"11","author":"Kulkarni","year":"2022","journal-title":"J. Clin. Med."},{"issue":"18","key":"10.1016\/j.bioadv.2026.215022_bb0015","article-title":"3D biomimetic models to reconstitute tumor microenvironment in vitro: spheroids, organoids, and tumor-on-a-Chip","volume":"12","author":"Li","year":"2023","journal-title":"Adv. Healthc. Mater."},{"issue":"1","key":"10.1016\/j.bioadv.2026.215022_bb0020","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1186\/s12929-024-00997-9","article-title":"Modelling the complex nature of the tumor microenvironment: 3D tumor spheroids as an evolving tool","volume":"31","author":"Rodrigues","year":"2024","journal-title":"J. Biomed. Sci."},{"issue":"11","key":"10.1016\/j.bioadv.2026.215022_bb0025","article-title":"Technical report: liquid overlay technique allows the generation of homogeneous osteosarcoma, glioblastoma, lung and prostate adenocarcinoma spheroids that can be used for drug cytotoxicity measurements","author":"Jubelin","year":"2023","journal-title":"Front. Bioeng. Biotechnol."},{"issue":"4","key":"10.1016\/j.bioadv.2026.215022_bb0030","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1593\/tlo.08178","article-title":"Ecological therapy for cancer: defining tumors using an ecosystem paradigm suggests new opportunities for novel cancer treatments","volume":"1","author":"Pienta","year":"2008","journal-title":"Transl. Oncol."},{"issue":"1","key":"10.1016\/j.bioadv.2026.215022_bb0035","doi-asserted-by":"crossref","first-page":"19103","DOI":"10.1038\/srep19103","article-title":"3D tumor spheroid models for in vitro therapeutic screening: a systematic approach to enhance the biological relevance of data obtained","volume":"6","author":"Zanoni","year":"2016","journal-title":"Sci. Rep."},{"issue":"4","key":"10.1016\/j.bioadv.2026.215022_bb0040","doi-asserted-by":"crossref","first-page":"874","DOI":"10.3390\/cancers13040874","article-title":"Organoid and spheroid tumor models: techniques and applications","volume":"13","author":"Gunti","year":"2021","journal-title":"Cancers"},{"key":"10.1016\/j.bioadv.2026.215022_bb0045","doi-asserted-by":"crossref","first-page":"1798","DOI":"10.1016\/j.jtho.2021.07.017","article-title":"Mechanism of drug tolerant persister cancer cells: the landscape and clinical implication for therapy","volume":"16","author":"Mikubo","year":"2021","journal-title":"J. Thorac. Oncol."},{"issue":"4","key":"10.1016\/j.bioadv.2026.215022_bb0050","first-page":"266","article-title":"Modeling physiological events in 2D vs. 3D cell culture","volume":"32","author":"Duval","year":"2017","journal-title":"Physiology (Bethesda)"},{"issue":"3","key":"10.1016\/j.bioadv.2026.215022_bb0055","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1016\/j.ccell.2023.02.016","article-title":"The evolving tumor microenvironment: from cancer initiation to metastatic outgrowth","volume":"41","author":"De Visser","year":"2023","journal-title":"Cancer Cell"},{"issue":"13","key":"10.1016\/j.bioadv.2026.215022_bb0060","article-title":"3D cell cultures: evolution of an ancient tool for new applications","author":"Cacciamali","year":"2022","journal-title":"Front. Physiol."},{"issue":"1","key":"10.1016\/j.bioadv.2026.215022_bb0065","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1186\/s12964-020-0530-4","article-title":"Tumor microenvironment complexity and therapeutic implications at a glance","volume":"18","author":"Baghban","year":"2020","journal-title":"Cell Commun. Signal"},{"issue":"1","key":"10.1016\/j.bioadv.2026.215022_bb0070","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1186\/s12951-023-02021-y","article-title":"Heterotypic tumor spheroids: a platform for nanomedicine evaluation","volume":"21","author":"Vakhshiteh","year":"2023","journal-title":"J. Nanobiotechnol."},{"issue":"1","key":"10.1016\/j.bioadv.2026.215022_bb0075","doi-asserted-by":"crossref","first-page":"5120","DOI":"10.1038\/s41467-020-18794-x","article-title":"Concepts of extracellular matrix remodelling in tumour progression and metastasis","volume":"11","author":"Winkler","year":"2020","journal-title":"Nat. Commun."},{"issue":"2","key":"10.1016\/j.bioadv.2026.215022_bb0080","doi-asserted-by":"crossref","first-page":"146","DOI":"10.3390\/biomimetics8020146","article-title":"The extracellular matrix: its composition, function, remodeling, and role in tumorigenesis","volume":"8","author":"Dzobo","year":"2023","journal-title":"Biomimetics"},{"issue":"1","key":"10.1016\/j.bioadv.2026.215022_bb0085","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1002\/bit.26845","article-title":"3D tumor spheroids as in vitro models to mimic in vivo human solid tumors resistance to therapeutic drugs","volume":"116","author":"Nunes","year":"2019","journal-title":"Biotechnol. Bioeng."},{"issue":"12","key":"10.1016\/j.bioadv.2026.215022_bb0090","article-title":"Breaking the mold: 3D cell cultures reshaping the future of cancer research","volume":"26","author":"Cordeiro","year":"2024","journal-title":"Front. Cell Dev. Biol."},{"issue":"8","key":"10.1016\/j.bioadv.2026.215022_bb0095","article-title":"Morphological response in cancer spheroids for screening photodynamic therapy parameters","volume":"18","author":"Aguilar Cosme","year":"2021","journal-title":"Front. Mol. Biosci."},{"issue":"1","key":"10.1016\/j.bioadv.2026.215022_bb0100","doi-asserted-by":"crossref","first-page":"23526","DOI":"10.1038\/s41598-024-73680-6","article-title":"Multicellular ovarian cancer spheroids: novel 3D model to mimic tumour complexity","volume":"14","author":"Fl\u00f6rkemeier","year":"2024","journal-title":"Sci. Rep."},{"issue":"8","key":"10.1016\/j.bioadv.2026.215022_bb0105","doi-asserted-by":"crossref","first-page":"6949","DOI":"10.3390\/ijms24086949","article-title":"Applications and advances of multicellular tumor spheroids: challenges in their development and analysis","volume":"24","author":"Mitrakas","year":"2023","journal-title":"IJMS"},{"issue":"8","key":"10.1016\/j.bioadv.2026.215022_bb0110","doi-asserted-by":"crossref","first-page":"1672","DOI":"10.1002\/bit.25210","article-title":"Optimization of liquid overlay technique to formulate heterogenic 3D co-cultures models","volume":"111","author":"Costa","year":"2014","journal-title":"Biotechnol. Bioeng."},{"issue":"5","key":"10.1016\/j.bioadv.2026.215022_bb0115","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1089\/ten.teb.2013.0537","article-title":"Three-dimensional aggregates of mesenchymal stem cells: cellular mechanisms, biological properties, and applications","volume":"20","author":"Sart","year":"2014","journal-title":"Tissue Eng. Part B Rev."},{"issue":"11","key":"10.1016\/j.bioadv.2026.215022_bb0120","doi-asserted-by":"crossref","first-page":"2506","DOI":"10.3390\/polym12112506","article-title":"Natural and synthetic biomaterials for engineering multicellular tumor spheroids","volume":"12","author":"Kamatar","year":"2020","journal-title":"Polymers"},{"issue":"1","key":"10.1016\/j.bioadv.2026.215022_bb0125","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1186\/1741-7007-10-29","article-title":"Advances in establishment and analysis of three-dimensional tumor spheroid-based functional assays for target validation and drug evaluation","volume":"10","author":"Vinci","year":"2012","journal-title":"BMC Biol."},{"issue":"12","key":"10.1016\/j.bioadv.2026.215022_bb0130","article-title":"Implications of three-dimensional cell culture in cancer therapeutic research","volume":"12","author":"Poornima","year":"2022","journal-title":"Front. Oncol."},{"issue":"1","key":"10.1016\/j.bioadv.2026.215022_bb0135","doi-asserted-by":"crossref","DOI":"10.1002\/biot.201700417","article-title":"Spheroids formation on non-adhesive surfaces by liquid overlay technique: considerations and practical approaches","volume":"13","author":"Costa","year":"2018","journal-title":"Biotechnol. J."},{"key":"10.1016\/j.bioadv.2026.215022_bb0140","doi-asserted-by":"crossref","first-page":"105024","DOI":"10.1016\/j.jmbbm.2021.105024","article-title":"Measuring the density and viscosity of culture media for optimized computational fluid dynamics analysis of in vitro devices","volume":"126","author":"Poon","year":"2022","journal-title":"J. Mech. Behav. Biomed. Mater."},{"issue":"1","key":"10.1016\/j.bioadv.2026.215022_bb0145","doi-asserted-by":"crossref","first-page":"9751","DOI":"10.1038\/s41598-025-92037-1","article-title":"Influence of experimental variables on spheroid attributes","volume":"15","author":"Zhu","year":"2025","journal-title":"Sci. Rep."},{"issue":"10","key":"10.1016\/j.bioadv.2026.215022_bb0150","doi-asserted-by":"crossref","first-page":"1748","DOI":"10.1177\/08853282211037781","article-title":"A new cell-sized support for 3D cell cultures based on recombinant spider silk fibers","volume":"36","author":"Stern-Tal","year":"2022","journal-title":"J. Biomater. Appl."},{"key":"10.1016\/j.bioadv.2026.215022_bb0155","doi-asserted-by":"crossref","DOI":"10.1016\/j.bej.2025.109929","article-title":"Methylcellulose in culture medium regulates size, cell viability, cytokine production, and exosome secretion in adipose-derived stem cell spheroids cultured using SphereRing\u00ae system","volume":"225","author":"Sakamoto","year":"2026","journal-title":"Biochem. Eng. J."},{"issue":"2","key":"10.1016\/j.bioadv.2026.215022_bb0160","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1039\/C4BM00319E","article-title":"Media additives to promote spheroid circularity and compactness in hanging drop platform","volume":"3","author":"Leung","year":"2015","journal-title":"Biomater. Sci."},{"issue":"6","key":"10.1016\/j.bioadv.2026.215022_bb0165","doi-asserted-by":"crossref","DOI":"10.1002\/adhm.201700980","article-title":"Biomaterials-based approaches to tumor spheroid and organoid modeling","volume":"7","author":"Thakuri","year":"2018","journal-title":"Adv Healthcare Materials."},{"key":"10.1016\/j.bioadv.2026.215022_bb0170","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2016\/7461041","article-title":"Non-mulberry and mulberry silk protein sericins as potential media supplement for animal cell culture","volume":"2016","author":"Sahu","year":"2016","journal-title":"Biomed. Res. Int."},{"issue":"22","key":"10.1016\/j.bioadv.2026.215022_bb0175","doi-asserted-by":"crossref","first-page":"4931","DOI":"10.3390\/polym14224931","article-title":"Silk Sericin: a promising sustainable biomaterial for biomedical and pharmaceutical applications","volume":"14","author":"Silva","year":"2022","journal-title":"Polymers (Basel)."},{"issue":"1","key":"10.1016\/j.bioadv.2026.215022_bb0180","doi-asserted-by":"crossref","DOI":"10.1093\/jisesa\/iey137","article-title":"Silk sericin hydrolysate is a potential candidate as a serum-substitute in the culture of Chinese Hamster ovary and Henrietta lacks cells","volume":"19","author":"Zhang","year":"2019","journal-title":"J. Insect Sci."},{"issue":"5","key":"10.1016\/j.bioadv.2026.215022_bb0185","doi-asserted-by":"crossref","first-page":"4951","DOI":"10.3390\/ijms24054951","article-title":"Silk Sericin protein materials: characteristics and applications in food-sector industries","volume":"24","author":"Seo","year":"2023","journal-title":"IJMS"},{"key":"10.1016\/j.bioadv.2026.215022_bb0190","doi-asserted-by":"crossref","DOI":"10.1016\/j.biomaterials.2022.121638","article-title":"Silk sericin-based materials for biomedical applications","volume":"287","author":"Liu","year":"2022","journal-title":"Biomaterials"},{"issue":"17","key":"10.1016\/j.bioadv.2026.215022_bb0195","doi-asserted-by":"crossref","first-page":"7219","DOI":"10.1007\/s00253-015-6576-3","article-title":"Viability and proliferation of L929, tumour and hybridoma cells in the culture media containing sericin protein as a supplement or serum substitute","volume":"99","author":"Cao","year":"2015","journal-title":"Appl. Microbiol. Biotechnol."},{"issue":"1\/3","key":"10.1016\/j.bioadv.2026.215022_bb0200","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1023\/A:1023993400608","article-title":"Sericin, a protein derived from silworms, accelerates the proliferation of several mammalian cell lines including a hybridoma","volume":"40","author":"Terada","year":"2002","journal-title":"Cytotechnology"},{"key":"10.1016\/j.bioadv.2026.215022_bb0205","series-title":"Animal Cell Technology Meets Genomics","first-page":"585","article-title":"Silk protein Sericin accelerates proliferation of various mammalian cells","author":"Terada","year":"2005"},{"issue":"1","key":"10.1016\/j.bioadv.2026.215022_bb0210","doi-asserted-by":"crossref","first-page":"45","DOI":"10.4067\/S0716-97602012000100006","article-title":"Effects of silk sericin on the proliferation and apoptosis of colon cancer cells","volume":"45","author":"Kaewkorn","year":"2012","journal-title":"Biol. Res."},{"issue":"1","key":"10.1016\/j.bioadv.2026.215022_bb0215","doi-asserted-by":"crossref","first-page":"21273","DOI":"10.1038\/s41598-020-78087-7","article-title":"Advanced co-culture 3D breast cancer model for investigation of fibrosis induced by external stimuli: optimization study","volume":"10","author":"Yakavets","year":"2020","journal-title":"Sci. Rep."},{"issue":"12","key":"10.1016\/j.bioadv.2026.215022_bb0220","doi-asserted-by":"crossref","first-page":"277","DOI":"10.3390\/cells7120277","article-title":"A dynamic culture method to produce ovarian cancer spheroids under physiologically-relevant shear stress","volume":"7","author":"Masiello","year":"2018","journal-title":"Cells"},{"issue":"3","key":"10.1016\/j.bioadv.2026.215022_bb0225","doi-asserted-by":"crossref","DOI":"10.1088\/1758-5090\/abe6f2","article-title":"Cell spheroids as a versatile research platform: formation mechanisms, high throughput production, characterization and applications","volume":"13","author":"Decarli","year":"2021","journal-title":"Biofabrication"},{"issue":"1","key":"10.1016\/j.bioadv.2026.215022_bb0230","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0262044","article-title":"Engineering solutions for biological studies of flow-exposed endothelial cells on orbital shakers. Maghsoudlou P, editor","volume":"17","author":"Fernandes","year":"2022","journal-title":"PLoS ONE"},{"issue":"12","key":"10.1016\/j.bioadv.2026.215022_bb0235","article-title":"Orbital shaking conditions augment human nasoseptal cartilage formation in 3D culture","volume":"15","author":"Jovic","year":"2024","journal-title":"Front. Bioeng. Biotechnol."},{"issue":"22","key":"10.1016\/j.bioadv.2026.215022_bb0240","doi-asserted-by":"crossref","first-page":"7432","DOI":"10.1039\/D3BM01011B","article-title":"Fluid flow-induced modulation of viability and osteodifferentiation of periodontal ligament stem cell spheroids-on-chip","volume":"11","author":"Mishra","year":"2023","journal-title":"Biomater. Sci."},{"issue":"1","key":"10.1016\/j.bioadv.2026.215022_bb0245","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.cmpb.2015.02.006","article-title":"AnaSP: a software suite for automatic image analysis of multicellular spheroids","volume":"119","author":"Piccinini","year":"2015","journal-title":"Comput. Methods Programs Biomed."},{"issue":"2","key":"10.1016\/j.bioadv.2026.215022_bb0250","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.cmpb.2014.12.003","article-title":"Cancer multicellular spheroids: volume assessment from a single 2D projection","volume":"118","author":"Piccinini","year":"2015","journal-title":"Comput. Methods Programs Biomed."},{"issue":"4","key":"10.1016\/j.bioadv.2026.215022_bb0255","doi-asserted-by":"crossref","first-page":"564","DOI":"10.3390\/foods13040564","article-title":"Comparative study of spheroids (3D) and monolayer cultures (2D) for the in vitro assessment of cytotoxicity induced by the mycotoxins Sterigmatocystin, Ochratoxin a and Patulin","volume":"13","author":"Zingales","year":"2024","journal-title":"Foods"},{"issue":"25","key":"10.1016\/j.bioadv.2026.215022_bb0260","doi-asserted-by":"crossref","first-page":"38500","DOI":"10.18632\/oncotarget.9522","article-title":"Enhanced anti-tumor activity and cytotoxic effect on cancer stem cell population of metformin-butyrate compared with metformin HCl in breast cancer","volume":"7","author":"Lee","year":"2016","journal-title":"Oncotarget"},{"issue":"1","key":"10.1016\/j.bioadv.2026.215022_bb0265","doi-asserted-by":"crossref","DOI":"10.3892\/ol.2022.13325","article-title":"Metformin: a promising drug for human cancers (review)","volume":"24","author":"Wu","year":"2022","journal-title":"Oncol. Lett."},{"issue":"1","key":"10.1016\/j.bioadv.2026.215022_bb0270","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1186\/s13045-020-00931-0","article-title":"Modeling neoplastic disease with spheroids and organoids","volume":"13","author":"Zanoni","year":"2020","journal-title":"J. Hematol. Oncol."},{"issue":"3","key":"10.1016\/j.bioadv.2026.215022_bb0275","doi-asserted-by":"crossref","DOI":"10.1088\/1758-5090\/abe6f2","article-title":"Cell spheroids as a versatile research platform: formation mechanisms, high throughput production, characterization and applications","volume":"13","author":"Decarli","year":"2021","journal-title":"Biofabrication"},{"issue":"12","key":"10.1016\/j.bioadv.2026.215022_bb0280","doi-asserted-by":"crossref","first-page":"277","DOI":"10.3390\/cells7120277","article-title":"A dynamic culture method to produce ovarian cancer spheroids under physiologically-relevant shear stress","volume":"7","author":"Masiello","year":"2018","journal-title":"Cells"},{"issue":"9\u201310","key":"10.1016\/j.bioadv.2026.215022_bb0285","doi-asserted-by":"crossref","first-page":"1172","DOI":"10.1002\/biot.200700228","article-title":"Recent advances in three-dimensional multicellular spheroid culture for biomedical research","volume":"3","author":"Lin","year":"2008","journal-title":"Biotechnol. J."},{"issue":"2","key":"10.1016\/j.bioadv.2026.215022_bb0290","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1016\/j.tibtech.2012.12.003","article-title":"Spheroid culture as a tool for creating 3D complex tissues","volume":"31","author":"Fennema","year":"2013","journal-title":"Trends Biotechnol."},{"issue":"4","key":"10.1016\/j.bioadv.2026.215022_bb0295","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1089\/adt.2014.573","article-title":"Three-dimensional cell culture systems and their applications in drug discovery and cell-based biosensors","volume":"12","author":"Edmondson","year":"2014","journal-title":"Assay Drug Dev. Technol."},{"key":"10.1016\/j.bioadv.2026.215022_bb0300","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1016\/j.actbio.2022.09.052","article-title":"Engineered biomaterials to guide spheroid formation, function, and fabrication into 3D tissue constructs","volume":"165","author":"Caprio","year":"2023","journal-title":"Acta Biomater."},{"issue":"6","key":"10.1016\/j.bioadv.2026.215022_bb0305","doi-asserted-by":"crossref","DOI":"10.1002\/adhm.201700980","article-title":"Biomaterials-based approaches to tumor spheroid and organoid modeling","volume":"7","author":"Thakuri","year":"2018","journal-title":"Adv Healthcare Materials."},{"issue":"3\u20134","key":"10.1016\/j.bioadv.2026.215022_bb0310","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1007\/s10911-016-9359-2","article-title":"Generation of multicellular breast cancer tumor spheroids: comparison of different protocols","volume":"21","author":"Froehlich","year":"2016","journal-title":"J. Mammary Gland Biol. Neoplasia"},{"key":"10.1016\/j.bioadv.2026.215022_bb0315","article-title":"Live-cell imaging and analysis of 3D spheroids in hypoxia- and radiotherapy-related research","volume":"51","author":"Beckers","year":"2025","journal-title":"Clin. Transl. Radiat. Oncol."},{"issue":"1","key":"10.1016\/j.bioadv.2026.215022_bb0320","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1111\/j.1745-4514.2008.00204.x","article-title":"Antioxidant activities of silk Sericin from silkworm Bombyx Mori","volume":"33","author":"Fan","year":"2009","journal-title":"J. Food Biochem."},{"issue":"216","key":"10.1016\/j.bioadv.2026.215022_bb0325","article-title":"Integrating simulation and experimental validation of nutrient-limited growth in breast cancer spheroids","volume":"1","author":"Nieto","year":"2026","journal-title":"Eur. J. Pharm. Sci."},{"issue":"6","key":"10.1016\/j.bioadv.2026.215022_bb0330","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1007\/s12551-024-01244-z","article-title":"Mechanobiology of 3D cell confinement and extracellular crowding","volume":"16","author":"Da Silva","year":"2024","journal-title":"Biophys. Rev."},{"issue":"9","key":"10.1016\/j.bioadv.2026.215022_bb0335","doi-asserted-by":"crossref","first-page":"206","DOI":"10.3390\/ph13090206","article-title":"Metformin restores the drug sensitivity of MCF-7 cells resistant Derivates via the cooperative modulation of growth and apoptotic-related pathways","volume":"13","author":"Sorokin","year":"2020","journal-title":"Pharmaceuticals"},{"issue":"6","key":"10.1016\/j.bioadv.2026.215022_bb0340","doi-asserted-by":"crossref","first-page":"1695","DOI":"10.1158\/1078-0432.CCR-09-1805","article-title":"Metformin: a therapeutic opportunity in breast cancer","volume":"16","author":"Gonzalez-Angulo","year":"2010","journal-title":"Clin. Cancer Res."},{"issue":"1","key":"10.1016\/j.bioadv.2026.215022_bb0345","doi-asserted-by":"crossref","first-page":"1487","DOI":"10.1186\/s12885-025-14908-0","article-title":"Combined anti-tumor effects of metformin and azacitidine in breast cancer cells","volume":"25","author":"Hosseini","year":"2025","journal-title":"BMC Cancer"},{"key":"10.1016\/j.bioadv.2026.215022_bb0350","article-title":"Combination of simvastatin and metformin reduces triple-negative breast cancer tumor growth through AKT\/AMPK\/ACC signaling axis","author":"Maurya","year":"2025","journal-title":"Mol. Carcinog."},{"issue":"1","key":"10.1016\/j.bioadv.2026.215022_bb0355","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1007\/s11095-024-03811-1","article-title":"Repurposing of metabolic drugs metformin and simvastatin as an emerging class of cancer therapeutics","volume":"42","author":"Maurya","year":"2025","journal-title":"Pharm. Res."}],"container-title":["Biomaterials Advances"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2772950826003201?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2772950826003201?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T21:36:33Z","timestamp":1786052193000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S2772950826003201"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,11]]},"references-count":71,"alternative-id":["S2772950826003201"],"URL":"https:\/\/doi.org\/10.1016\/j.bioadv.2026.215022","relation":{},"ISSN":["2772-9508"],"issn-type":[{"value":"2772-9508","type":"print"}],"subject":[],"published":{"date-parts":[[2026,11]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Impact of silk-derived sericin on the formation and metformin sensitivity of breast cancer-fibroblast heterotypic spheroids","name":"articletitle","label":"Article Title"},{"value":"Biomaterials Advances","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.bioadv.2026.215022","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2026 The Authors. Published by Elsevier B.V.","name":"copyright","label":"Copyright"}],"article-number":"215022"}}