Abstract: A bioreactor capable of producing complex, three-dimensional tissue constructs has improved media transfer and increased controllability with regard to exposure to the external environment. The bioreactor includes an external surface, a first tissue culture side for culturing a first cell source in a first tissue culture support region, a second tissue culture side for culturing a second cell source in a second tissue culture support region, and a plurality of ports. At least one of the ports of the plurality of ports extend from the first tissue culture support region of the first tissue culture side to the external surface. The plurality of ports can include an external port that is configured to be a liquid inlet when the bioreactor is in a first orientation and a gas outlet when the bioreactor is in a second orientation.