Self-assembling multicellular bodies and methods of producing a three-dimensional biological structure using the same
First Claim
1. A method of producing a three-dimensional biological engineered tissue, the method comprising:
- arranging a plurality of elongate multicellular bodies on a substrate 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,arranging one or more filler bodies in the pattern with the multicellular bodies so that each filler body contacts at least one multicellular body or another filler body, each filler body comprising a biocompatible material that resists migration and ingrowth of cells from the multicellular bodies into the filler bodies and resists adherence of cells in the multicellular bodies to the filler bodies,allowing at least one of the multicellular bodies to fuse with at least one other multicellular body to produce a three-dimensional biological engineered tissue; and
removing the one or more filler bodies.
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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.
107 Citations
24 Claims
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1. A method of producing a three-dimensional biological engineered tissue, the method comprising:
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arranging a plurality of elongate multicellular bodies on a substrate 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, arranging one or more filler bodies in the pattern with the multicellular bodies so that each filler body contacts at least one multicellular body or another filler body, each filler body comprising a biocompatible material that resists migration and ingrowth of cells from the multicellular bodies into the filler bodies and resists adherence of cells in the multicellular bodies to the filler bodies, allowing at least one of the multicellular bodies to fuse with at least one other multicellular body to produce a three-dimensional biological engineered tissue; and removing the one or more filler bodies. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24)
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Specification