Abstract: Described herein are systems and methods relating to three-dimensional (3D) cell manufacturing utilizing a 3D growth media. According to aspects of the present disclosure, pluralities of cells and ECM components can be printed into a bioreactor as a sheet. Sheets can be retrieved, digested, split, and re-printed, thereby expanding the number of cells in an efficient manner that conserves space in a tissue culture incubator, conserves bioreactor consumables, and consumes nutrients required for cell maintenance and growth.