Engineered, personalized tissues are transforming healthcare by accelerating clinical testing and serving as cell-based therapies. The emergence of induced pluripotent stem cells coupled with innovations in biomanufacturing and cellular engineering have rapidly advanced engineered tissue cellular and structural complexity. However, generating functional, mature tissues remains an enormous challenge. Control over biophysical forces governing development and disease is ultimately required to build functional tissue, and engineered tissues can simultaneously illuminate opportunities to therapeutically modulate mechanical cues. In the first part of my talk, I will explain how I leveraged hydrogel-based models to investigate cell-matrix interactions driving brain tumor cell invasion. While studies have traditionally focused on integrin-driven invasion, this work elucidated how the transmembrane receptor CD44 directly contributes to cell motility in the brain and may represent an important therapeutic target. In the second part of my talk, I will describe the biofabrication of a stem cell-derived kidney collecting duct on-chip. Collecting ducts are a major site for kidney disease and dysfunction, and this on-chip model could serve as a platform to study flow-dependent function in patient-derived cells. Moreover, I demonstrate that scalable organoid culture methods combined with bioprinting offers a promising approach to integrating these collecting ducts with biomanufactured kidney tissues. Moving forward, the combination of stem-cell derived tissues and organoids with the ability to control mechanical cues establish a paradigm for investigating the mechanobiology of the urogenital tract, with potential applications in kidney and reproductive health.