Hydrogels in head and neck cancer: Innovations and translational advances in research and therapy

Head and neck cancer (HNC) presents significant clinical challenges due to its complex tumor biology, heterogeneous microenvironment, and limited therapeutic outcomes. Hydrogels, an innovative biopolymeric material, have gained considerable attention in both basic and translational oncology owing to their biocompatibility, biodegradability, tunable physicochemical properties, and ability to recapitulate the native tissue environment. This review provides a comprehensive overview of HNC epidemiology, molecular and cellular mechanisms, current and emerging therapeutic approaches, and the defining features of the tumor microenvironment. We then highlight diverse hydrogel systems under development, detailing their structural characteristics and biomedical applications. Hydrogel-based platforms have advanced tumor modeling by enabling three-dimensional (3D) culture systems that more accurately reflect in vivo conditions compared to conventional two-dimensional (2D) models. Cutting-edge technologies, including 3D bioprinting and tumor-on-a-chip microfluidic systems, offer new opportunities for precision modeling and drug testing in HNC. In addition, hydrogels are being engineered for therapeutic applications, such as localized and sustained drug delivery, immunomodulation, and tissue regeneration following tumor resection. Finally, we critically examine the challenges and limitations of current hydrogel-based approaches and outline future directions for their integration into HNC research and clinical practice.