Abstract: The present invention provides a bioreactor for large-mammal lung tissue. The bioreactor is capable of hydraulic driven negative-pressure and positive-pressure perfusion and ventilation. Perfusion and ventilation is delivered at physiological rates and is easily controllable. In one embodiment, the bioreactor comprises a support scaffold to support the size of a large-mammal lung tissue. In another embodiment, the bioreactor comprises a pleural sack that provides a small isolated fluid chamber which surrounds an engineered lung, thereby minimizing the amount of culture media needed. The present invention also provides an in vitro model for examining the function of a test agent and compositions and methods for alleviating a lung defect in a large-mammal.