Self-assembling multicellular bodies and methods of producing a three-dimensional biological structure using the same

Abstract

Structures and methods for tissue engineering include a multicellular body including a plurality of living cells. A plurality of multicellular bodies can be arranged in a pattern and allowed to fuse to form an engineered tissue. The arrangement can include filler bodies including a biocompatible material that resists migration and ingrowth of cells from the multicellular bodies and that is resistant to adherence of cells to it. Three-dimensional constructs can be assembled by printing or otherwise stacking the multicellular bodies and filler bodies such that there is direct contact between adjoining multicellular bodies, suitably along a contact area that has a substantial length. The direct contact between the multicellular bodies promotes efficient and reliable fusion. The increased contact area between adjoining multicellular bodies also promotes efficient and reliable fusion. Methods of producing multicellular bodies having characteristics that facilitate assembly of the three-dimensional constructs are also provided.

1 - 174 . (canceled) 
     
     
         175 . A method of producing a multicellular body comprising a plurality of living cells, the method comprising:
 shaping a cell paste comprising a plurality of living cells in a device that holds the cell paste in a three-dimensional shape; and   incubating the shaped cell paste in a controlled environment while it is held in said three-dimensional shape for a sufficient time to produce a body that has sufficient cohesion to support itself on a flat surface.   
     
     
         176 - 194 . (canceled) 
     
     
         195 . A three-dimensional structure comprising a plurality of engineered elongate multicellular bodies, each multicellular body comprising a plurality of living cells cohered to one another, wherein the multicellular bodies are arranged in a pattern in which each multicellular body contacts at least one other multicellular body and the multicellular bodies are not cohered to one another. 
     
     
         196 . A method of producing a three-dimensional biological engineered tissue, the method comprising:
 arranging a plurality of elongate multicellular bodies according to a pattern such that each of the multicellular bodies contacts at least one other multicellular body, wherein each multicellular body comprises a plurality of living cells,   allowing at least one of the multicellular bodies to fuse with at least one other multicellular body.