Self-assembling cell aggregates and methods of making engineered tissue using the same

• US 9,752,116 B2
• Filed: 08/12/2016
• Issued: 09/05/2017
• Est. Priority Date: 02/24/2004
• Status: Active Grant

• Current Assignee: MUSC Foundation For Research Development (State of South Carolina), Curators of the University of Missouri (University of Missouri)
• Original Assignee: MUSC Foundation For Research Development (State of South Carolina), Curators of the University of Missouri (University of Missouri)
• Inventors: Forgacs, Gabor, Jakab, Karoly, Neagu, Adrian, Mironov, Vladimir
• Primary Examiner(s): Ware, Debbie K
• Assistant Examiner(s): Srivastava, Kailash C
• Application Number:
  US15/235,422
• Publication Number:
  US 20160348067A1
• Time in Patent Office: 389 Days
• Field of Search: 435395, 435397, 435174, 435325, 425166
• CPC Class Codes: B29C 64/112 using individual droplets, e.g. from jetting heads
• CPC Class Codes: B29C 64/209 Heads; Nozzles
• CPC Class Codes: B29C 64/393 for controlling or regulating additive manufacturing processes
• CPC Class Codes: B29K 2033/26 Polymers of acrylamide or methacrylamide
• CPC Class Codes: B29K 2105/0035 Medical or pharmaceutical agents
• CPC Class Codes: B29K 2105/0061 Gel or sol
• CPC Class Codes: B29L 2031/7532 Artificial members, protheses
• CPC Class Codes: B33Y 10/00 Processes of additive manufacturing
• CPC Class Codes: B33Y 30/00 Apparatus for additive manufacturing; Details thereof or accessories therefor
• CPC Class Codes: B33Y 50/02 for controlling or regulating additive manufacturing processes
• CPC Class Codes: B33Y 70/00 Materials specially adapted for additive manufacturing
• CPC Class Codes: B33Y 80/00 Products made by additive manufacturing
• CPC Class Codes: C12M 21/08 for producing artificial tissue or for ex-vivo cultivation of tissue prostheses A61F2/00, grafts A61L27/00
• CPC Class Codes: C12M 33/12 by pressure
• CPC Class Codes: C12M 41/48 Automatic or computerized control automatic analysis G01N35/00
• CPC Class Codes: 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
• CPC Class Codes: C12M 47/02 Separating microorganisms from the culture medium; Concentration of biomass separating microorganisms from their culture media C12N1/02
• CPC Class Codes: C12N 5/0062 General methods for three-dimensional culture
• CPC Class Codes: C12N 5/0697 Artificial constructs associating cells of different lineages, e.g. tissue equivalents blood vessels C12N5/0691

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

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

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

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

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

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