# US 9,752,116 B2 · Self-assembling cell aggregates and methods of making engineered tissue using the same

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- Number: US 9,752,116 B2
- Document ID: US9752116B2
- Status: Granted
- Kind: B2
- Application number: 15/235,422
- Filed: 2016-08-12
- Published: 2016-12-01
- Granted: 2017-09-05
- Earliest claimed: 2004-02-24
- Assignees: The Curators of the University of Missouri; MUSC Foundation for Research Development
- Applicants: The Curators of the University of Missouri; MUSC Foundation for Research Development
- Inventors: Gabor Forgacs; Karoly Jakab; Adrian Neagu; Vladimir Mironov
- Web page: https://patentgrep.com/patent/US9752116B2

## CPC

- C12N 5/0062: {General methods for three-dimensional culture}
- B29C 64/112: using individual droplets, e.g. from jetting heads
- B29C 64/209: Heads; Nozzles
- B29C 64/393: for controlling or regulating additive manufacturing processes
- B33Y 10/00: Processes of additive manufacturing
- B33Y 30/00: Apparatus for additive manufacturing; Details thereof or accessories therefor
- B33Y 50/02: for controlling or regulating additive manufacturing processes
- B33Y 70/00: Materials specially adapted for additive manufacturing
- B33Y 80/00: Products made by additive manufacturing
- C12M 21/08: {for producing artificial tissue or for ex-vivo cultivation of tissue (prostheses A61F2/00, grafts A61L27/00)}
- C12M 33/12: {by pressure}
- C12M 41/48: {Automatic or computerized control (automatic analysis G01N35/00)}
- C12M 47/00: {Means for after-treatment of the produced biomass or of the fermentation or metabolic products, e.g. storage of biomass (filters in general B01D24/00 - B01D41/00)}
- C12M 47/02: {Separating microorganisms from the culture medium; Concentration of biomass (separating microorganisms from their culture media C12N1/02)}
- C12N 5/0697: {Artificial constructs associating cells of different lineages, e.g. tissue equivalents (blood vessels C12N5/0691)}
- B29K 2033/26: {Polymers of acrylamide or methacrylamide}
- B29K 2105/0035: {Medical or pharmaceutical agents}
- B29K 2105/0061: {Gel or sol}
- B29L 2031/7532: {Artificial members, protheses}
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)
- B29C: SHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING (making preforms B29B11/00; making laminated products by combining previously unconnected layers which become one product whose layers will remain together B32B37/00 - B32B41/00)
- B33Y: ADDITIVE MANUFACTURING, i.e. MANUFACTURING OF THREE-DIMENSIONAL [3D] OBJECTS BY ADDITIVE DEPOSITION, ADDITIVE AGGLOMERATION OR ADDITIVE LAYERING, e.g. BY 3D PRINTING, STEREOLITHOGRAPHY OR SELECTIVE LASER SINTERING
- C12M: APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; {APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS}
- B29K: INDEXING SCHEME ASSOCIATED WITH SUBCLASSES B29B, B29C OR B29D, RELATING TO MOULDING MATERIALS OR TO MATERIALS FOR {MOULDS, } REINFORCEMENTS, FILLERS OR PREFORMED PARTS, e.g. INSERTS
- B29L: INDEXING SCHEME ASSOCIATED WITH SUBCLASS B29C, RELATING TO PARTICULAR ARTICLES

## Abstract

A composition comprising a plurality of cell aggregates for use in the production of engineered organotypic tissue by organ printing. A method of making a plurality of cell aggregates comprises centrifuging a cell suspension to form a pellet, extruding the pellet through an orifice, and cutting the extruded pellet into pieces. Apparatus for making cell aggregates comprises an extrusion system and a cutting system. In a method of organ printing, a plurality of cell aggregates are embedded in a polymeric or gel matrix and allowed to fuse to form a desired three-dimensional tissue structure. An intermediate product comprises at least one layer of matrix and a plurality of cell aggregates embedded therein in a predetermined pattern. Modeling methods predict the structural evolution of fusing cell aggregates for combinations of cell type, matrix, and embedding patterns to enable selection of organ printing processes parameters for use in producing an engineered tissue having a desired three-dimensional structure.

## Claims

### Claim 1

A method of producing a tissue construct, comprising depositing cell aggregates from a dispensing device, and allowing the cell aggregates to fuse.

### Claim 2 (depends on 1)

The method of claim 1, wherein the cell aggregates are dispensed in a pattern.

### Claim 3 (depends on 1)

The method of claim 1, wherein the cell aggregates are homocellular.

### Claim 4 (depends on 1)

The method of claim 1, wherein the cell aggregates are heterocellular.

### Claim 5 (depends on 1)

The method of claim 1, wherein the dispensing device is instructed by a control unit.