Bioreactors are important tools to generate tissue-engineered 3D constructs in a more physiologically relevant environment through the automated control of multiple operating parameters (e.g. pH, pO2, pressure). We design custom-built bioreactors through integrated experimental-computational approaches applying CFD simulations to guide the design process. In particular, we implemented the Oscillating Perfusion Bioreactor (OPB) with an automated control system and sensors for real-time monitoring of critical culture parameters in up to 18 independent culture chamber. Furthermore, we developed bioreactors for the application of controlled mechanical and/or electrical stimuli to drive cell behavior for bone, cartilage, and cardiac tissue engineering.