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This highlights the urgent need for robust preclinical models that accurately represent the disease in order to facilitate the discovery of new therapeutics. Compared to traditional 2D cultures and animal models, 3D in vitro models offer a better representation of the tumor's 3D structure and cell\u2010extracellular matrix (ECM) interactions, which play a key role in drug response, while reducing the need for animal testing. In this work, we present a novel 3D bioprinted OS model by incorporating OS spheroids into an OS\u2010tailored bioink, enriched with OS cell\u2010derived decellularized ECM. The bioink exhibits high water content, minimal mass loss, fast UV\u2010induced gelation, and enhanced printability and biocompatibility. Despite having a compressive modulus at the lower end of the range associated with OS, the bioprinted model shows an increased expression of OS prognostic markers, lower sensitivity to doxorubicin, and overexpression of P\u2010glycoprotein. This is likely due to the model's ability to mimic both the 3D structure and composition of the OS\u2010ECM, emphasizing its enhanced reliability and potential for exploring novel alternative OS therapeutic approaches in future research.<\/jats:p>","DOI":"10.1002\/adhm.202503633","type":"journal-article","created":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T05:20:28Z","timestamp":1770096028000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A 3D Bioprinted Spheroid\u2010Laden dECM\u2010Enriched Osteosarcoma Model for Enhanced Drug Testing and Therapeutic Discovery"],"prefix":"10.1002","volume":"15","author":[{"given":"Margarida F.","family":"Domingues","sequence":"first","affiliation":[{"name":"Department of Bioengineering and Institute for Bioengineering and Biosciences Instituto Superior T\u00e9cnico Universidade de Lisboa  Lisbon Portugal"},{"name":"Associate Laboratory i4HB\u2013\u2010Institute for Health and Bioeconomy Instituto Superior T\u00e9cnico Universidade de Lisboa  Lisbon Portugal"}]},{"given":"Maria Catarina","family":"Carreira","sequence":"additional","affiliation":[{"name":"Department of Bioengineering and Institute for Bioengineering and Biosciences Instituto Superior T\u00e9cnico Universidade de Lisboa  Lisbon Portugal"},{"name":"Associate Laboratory i4HB\u2013\u2010Institute for Health and Bioeconomy Instituto Superior T\u00e9cnico Universidade de Lisboa  Lisbon Portugal"}]},{"given":"Mafalda S.","family":"Santos","sequence":"additional","affiliation":[{"name":"Department of Bioengineering and Institute for Bioengineering and Biosciences Instituto Superior T\u00e9cnico Universidade de Lisboa  Lisbon Portugal"},{"name":"Associate Laboratory i4HB\u2013\u2010Institute for Health and Bioeconomy Instituto Superior T\u00e9cnico Universidade de Lisboa  Lisbon Portugal"}]},{"given":"Daniela","family":"Pacheco","sequence":"additional","affiliation":[{"name":"Bac3Gel Lda Taguspark Innov. 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