3D Bioprinted Head and Neck Squamous Cell Carcinoma (HNSCC) Model Using Tunicate Derived Nanocellulose (NC) Bioink
Journal article, 2025

Head and neck squamous cell carcinoma (HNSCC) are invasive solid tumors accounting for high mortality. To improve the clinical outcome, a better understanding of the tumor and its microenvironment (TME) is crucial. Three -dimensional (3D) bioprinting is emerging as a powerful tool for recreating the TME in vitro. To establish long-term HNSCC bioprinted constructs for personalized drug-testing, this proof-of-principle study aims to compare two different innovative tunicate-derived nanocellulose (NC) hydrogels against the widely used semi-synthetic gelatin methacryloyl (GelMA). Cell lines of different tumor origin sites are printed in TEMPO and Carboxy-NC, and GelMA in alginate (GelMAA). Both NC hydrogels show higher bioprintability than GelMAA. Carboxy-NC supported long-term 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-derived cultures. Compared to a spheroid model, the cytotoxic effects are less, better reflecting the response in patients. The proof-of-principle findings indicate that Carboxy-NC is a viable alternative to gelatin-based bioink with improved bioprintability allowing personalized drug-testing. By adding other cell-types of the TME, this model can be advanced to a heterotypic one.

head and neck squamous cell carcinoma

bioink

3D Bio-printing

3D tumor model

nanocellulose

Author

Alexya Azhakesan

Medizinische Fakultät Mannheim

Johann Kern

Medizinische Fakultät Mannheim

Ankit Mishra

Heidelberg University

Christine Selhuber-Unkel

Heidelberg University

Annette Affolter

Medizinische Fakultät Mannheim

Paul Gatenholm

Chalmers, Chemistry and Chemical Engineering, Applied Chemistry

Nicole Rotter

Medizinische Fakultät Mannheim

Karen Bieback

Medizinische Fakultät Mannheim

Advanced healthcare materials

2192-2640 (ISSN) 2192-2659 (eISSN)

Vol. In Press

Subject Categories (SSIF 2025)

Cancer and Oncology

DOI

10.1002/adhm.202403114

More information

Latest update

1/20/2025