A 3D-bioprinted head and neck cancer model for drug screening.

The development of effective treatment strategies against head and neck cancer (HNC) poses a significant challenge due to the heterogeneity of HNC and the limitations of traditional two-dimensional (2D)in vitrocell cultures. Consequently, there is an urgent need for more advanced HNC models that allow for reliable drug screening. The recent advances in tissue engineering, including the use of digital light processing-based three-dimensional (3D) bioprinters, have enabled the precise fabrication of complex constructs that mimic native tissue environments, exhibiting potential for use in disease modeling and drug discovery. Here, we fabricated a bioprintedin vitroHNC model using the gelatin methacryloyl bioink encapsulating FaDu cells to analyze the drug screening against HNC. The bioprinted tissues showed gradually increased cell viability as well as stable morphology and phenotype expression. The cytotoxicity analyses suggested increased resistance to anti-cancer drugs for cells in 3D-bioprinted tissues than those cultured in 2D, possibly due to the presence of native cell-cell interactions and diffusion barriers. The engineered exosomes with anti-cancer drugs also revealed significantly increased resistance in cells cultured in 3D than in 2D. This study provides a proof-of-concept bioprinted HNC model mimicking some of the native functional and structural components, having the potential for screening novel anti-HNC treatments and paving the way for personalized therapeutic strategies for HNC patients in the future.