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To improve the clinical outcome, a better understanding of the tumor and its microenvironment (TME) is crucial. Three \u2010dimensional (3D) bioprinting is emerging as a powerful tool for recreating the TME in vitro. To establish long\u2010term HNSCC bioprinted constructs for personalized drug\u2010testing, this proof\u2010of\u2010principle study aims to compare two different innovative tunicate\u2010derived nanocellulose (NC) hydrogels against the widely used semi\u2010synthetic gelatin methacryloyl (GelMA). Cell lines of different tumor origin sites are printed in TEMPO and Carboxy\u2010NC, and GelMA in alginate (GelMAA). Both NC hydrogels show higher bioprintability than GelMAA. Carboxy\u2010NC supported long\u2010term HNSCC survival, proliferation, and maintenance of epithelial phenotype in 3D bioprinted constructs similar to GelMAA. The hydrogel microstructure revealed differences in pore size. Importantly, the established HNSCC bioprinted model allowed the testing of radiochemotherapy (RCT) both in cell lines and patient\u2010derived cultures. Compared to a spheroid model, the cytotoxic effects are less, better reflecting the response in patients. The proof\u2010of\u2010principle findings indicate that Carboxy\u2010NC is a viable alternative to gelatin\u2010based bioink with improved bioprintability allowing personalized drug\u2010testing. By adding other cell\u2010types of the TME, this model can be advanced to a heterotypic one.<\/jats:p>","DOI":"10.1002\/adhm.202403114","type":"journal-article","created":{"date-parts":[[2025,1,13]],"date-time":"2025-01-13T03:03:59Z","timestamp":1736737439000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["3D Bioprinted Head and Neck Squamous Cell Carcinoma (HNSCC) Model Using Tunicate Derived Nanocellulose (NC) Bioink"],"prefix":"10.1002","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2482-5974","authenticated-orcid":false,"given":"Alexya","family":"Azhakesan","sequence":"first","affiliation":[{"name":"Medical Faculty of Mannheim University of Heidelberg Department of Otorhinolarynlogy Head and Neck Surgery  68167 Mannheim 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