A bioengineered tumor matrix-based scaffold for the evaluation of melatonin efficacy on head and neck squamous cancer stem cells López de Andrés, Julia Rodríguez Santana, César Lara-Peña, Laura de Jiménez González, Gema Escames Rosa, Germaine Marchal Corrales, Juan Antonio Head and neck squamous cell carcinoma Cancer stem cells Melatonin Head and neck squamous cell carcinoma (HNSCC) presents a significant challenge worldwide due to its aggressiveness and high recurrence rates post-treatment, often linked to cancer stem cells (CSCs). Melatonin shows promise as a potent tumor suppressor; however, the effects of melatonin on CSCs remain unclear, and the development of models that closely resemble tumor heterogeneity could help to better understand the effects of this molecule. This study developed a tumor scaffold based on patient fibroblast-derived decellularized extracellular matrix that mimics the HNSCC microenvironment. Our study investigates the antitumoral effects of melatonin within this context. We validated its strong antiproliferative effect on HNSCC CSCs and the reduction of tumor invasion and migration markers, even in a strongly chemoprotective environment, as it is required to increase the minimum doses necessary to impact tumor viability compared to the non-scaffolded tumorspheres culture. Moreover, melatonin exhibited no cytotoxic effects on healthy cells co-cultured in the tumor hydrogel. This scaffold-based platform allows an in vitro study closer to HNSCC tumor reality, including CSCs, stromal component, and a biomimetic matrix, providing a new valuable research tool in precision oncology. 2024-10-04T12:32:44Z 2024-10-04T12:32:44Z 2024-09-14 journal article J. López de Andrés et al. Materials Today Bio 29 (2024) 101246 [https://doi.org/10.1016/j.mtbio.2024.101246] https://hdl.handle.net/10481/95551 10.1016/j.mtbio.2024.101246 eng info:eu-repo/grantAgreement/EC/European Union NextGenerationEU/PRTR (PID2022-140151OB-C22) http://creativecommons.org/licenses/by-nc-nd/4.0/ open access Attribution-NonCommercial-NoDerivatives 4.0 Internacional Elsevier