A 3D Bioprinted Spheroid-Laden dECM-Enriched Osteosarcoma Model for Enhanced Drug Testing and Therapeutic Discovery.

Osteosarcoma (OS) is the most common bone cancer, characterized by high mortality rates and limited treatment options, due to its heterogeneity, metastatic potential, and chemoresistance. This highlights the urgent need for robust preclinical models that accurately represent the disease in order to facilitate the discovery of new therapeutics. Compared to traditional 2D cultures and animal models, 3D in vitro models offer a better representation of the tumor's 3D structure and cell-extracellular matrix (ECM) interactions, which play a key role in drug response, while reducing the need for animal testing. In this work, we present a novel 3D bioprinted OS model by incorporating OS spheroids into an OS-tailored bioink, enriched with OS cell-derived decellularized ECM. The bioink exhibits high water content, minimal mass loss, fast UV-induced gelation, and enhanced printability and biocompatibility. Despite having a compressive modulus at the lower end of the range associated with OS, the bioprinted model shows an increased expression of OS prognostic markers, lower sensitivity to doxorubicin, and overexpression of P-glycoprotein. This is likely due to the model's ability to mimic both the 3D structure and composition of the OS-ECM, emphasizing its enhanced reliability and potential for exploring novel alternative OS therapeutic approaches in future research.