Biomimetic hydrogel for the construction of patient-derived bladder cancer organoids with aggressive growth

In cancer, the extracellular matrix (ECM) reorganization, notably collagen, forming dense, thickened, and orderly structures, affects tumor traits. Bladder cancer organoids (BCOs) mimic tumor properties for personalized medicine. However, current organoid scaffolds lack tumor-such as collagen, crucial for cell growth and migration. Previous efforts to incorporate mesoscale collagen fibers extracted directly from tumors into scaffolds were limited by the size of the tumor tissue and the efficiency of extraction. In this study, we used cellulose microfibers (MCFs) to mimic <i>in vivo</i> mesoscale collagen's role, enhancing BCO viability, invasiveness, and migration, aligning with tumor growth patterns. These organoids preserved tumor architecture and mutations, showing drug sensitivities similar to those of parental tissue-derived cells and correlating with patient outcomes. This suggests that such organoids can serve as preclinical models to inform therapeutic strategies.