TISSUE ENGINEERED DEVICES AND METHODS FOR MAKING SAME

• US 20160243286A1
• Filed: 10/27/2014
• Published: 08/25/2016
• Est. Priority Date: 10/25/2013
• Status: Active Grant

• Current Assignee: TeVido BioDevices, Board of Regents of the University of Texas System (University of Texas System)
• Original Assignee: Board of Regents of the University of Texas System (University of Texas System)
• Inventors: COLLINS, Scott Forrest, BOLAND, Thomas, YANEZ, Maria
• Granted Patent: US 10,159,765 B2
• Time in Patent Office: Days
• US Class Current: 1/1
• CPC Class Codes: A61F 2/12 Mammary prostheses and implants
• CPC Class Codes: A61F 2210/0076 multilayered, e.g. laminated structures
• CPC Class Codes: A61F 2220/005 using adhesives
• CPC Class Codes: A61F 2240/004 Using a positive or negative model, e.g. moulds
• CPC Class Codes: A61F 2310/00371 Collagen
• CPC Class Codes: A61F 2310/00377 Fibrin
• CPC Class Codes: A61F 2310/00383 Gelatin
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 35/28 Bone marrow; Haematopoietic stem cells; Mesenchymal stem cells of any origin, e.g. adipose-derived stem cells
• CPC Class Codes: A61K 35/33 Fibroblasts
• CPC Class Codes: A61K 35/35 Fat tissue; Adipocytes; Stromal cells; Connective tissues adipose-derived stem cells A61K35/28; collagen A61K38/39
• CPC Class Codes: A61K 35/44 Vessels; Vascular smooth muscle cells; Endothelial cells; Endothelial progenitor cells
• CPC Class Codes: A61L 2430/04 for mammary reconstruction
• CPC Class Codes: A61L 27/225 Fibrin; Fibrinogen
• CPC Class Codes: A61L 27/227 Other specific proteins or polypeptides not covered by A61L27/222, A61L27/225 or A61L27/24
• CPC Class Codes: A61L 27/3804 characterised by specific cells or progenitors thereof, e.g. fibroblasts, connective tissue cells, kidney cells
• CPC Class Codes: A61L 27/3808 Endothelial cells
• CPC Class Codes: A61L 27/3834 Cells able to produce different cell types, e.g. hematopoietic stem cells, mesenchymal stem cells, marrow stromal cells, embryonic stem cells
• CPC Class Codes: A61L 27/3839 characterised by the site of application in the body materials for artificial blood vessels A61L27/507; materials for use in artificial skin A61L27/60
• CPC Class Codes: A61L 27/3886 comprising two or more cell types
• CPC Class Codes: A61L 27/52 : Hydrogels or hydrocolloids
• CPC Class Codes: C12N 2502/1352 : Mesenchymal stem cells
• CPC Class Codes: C12N 2502/28 : Vascular endothelial cells
• CPC Class Codes: C12N 2533/56 : Fibrin; Thrombin
• CPC Class Codes: C12N 2533/76 : Agarose, agar-agar
• CPC Class Codes: C12N 2535/10 : Patterned coating
• CPC Class Codes: C12N 5/0653 : Adipocytes; Adipose tissue
• CPC Class Codes: C12N 5/0697 : Artificial constructs associating cells of different lineages, e.g. tissue equivalents blood vessels C12N5/0691

Abstract

Tissue engineered constructs and methods for fabricating the disclosed constructs are provided. Some of the disclosed tissue engineered constructs are designed to fill a void in the body due to surgical resection, for example from mastectomy or lumpectomy, wounds and the like. Some disclosed constructs comprise one or more projections designed to mimic the appearance of a structural feature when implanted into a host.

Claims

1. A volume forming unit (VFU) comprising adipocytes and at least one projection.

2. The VFU of claim 1, wherein the VFU further comprises endothelial channels.

3. The VFU of claim 1, wherein the at least one projection is designed to simulate at least one structural feature of a nipple.

4. The VFU of claim 3, wherein a second projection is designed to simulate the at least one structural feature of an areola and the second projection circumscribes the at least one projection designed to simulate at least one structural feature of a nipple.

5. A method for creating a VFU, comprising:

adding (i) a mixture comprising at least one biocompatible hydrogel material and a multiplicity of cells to (ii) a negative mold;

incubating the mold under conditions suitable for hydrogel formation, thereby creating the VFU.

6. The method of claim 5, wherein the cells comprise at least one of adipocytes, endothelial cells, fibroblasts, or mesenchymal stem cells.

7. The method of claim 5, wherein the mixture comprising at least one biocompatible hydrogel material and a multiplicity of cells comprises at least two solutions that may be added to the mold simultaneously or in any order.

8. The method of claim 5, wherein at least one component of the mixture is added to the mold using bioprinting.

10. The method of claim 5, wherein:

(a) the cells comprise at least one of adipocytes, endothelial cells, fibroblasts, or mesenchymal stem cells; and

(b) at least one component of the mixture is added to the mold using bioprinting.

11. The method in claim 5, wherein the negative mold is formed from a positive mold

12. The method in claim 5, wherein the negative mold comprises at least one indention for creating a projection in the VFU.

22. A VFU manufactured according to the method of claim 5.

23. A VFU manufactured according to the method of claim 8.

9. The method of 5, wherein the at least one biocompatible hydrogel material comprises at least one of fibrinogen, a fibrinogen activator, or thrombin.

13. A method for creating a multilayer tissue engineered construct, comprising:

creating a multiplicity of construct layers, each comprising adipocytes, endothelial cells, or both;

adhering at least one first construct layer in juxtaposition with at least one second construct layer to create a multilayer construct.

14. The method of claim 13, wherein at least three construct layers are adhered in juxtaposition to create a multilayer construct.

15. The method of claim 13, wherein the multilayer construct comprises a VFU.

16. The method of claim 13, wherein the adhering comprises a biocompatible adhesive comprising at least one of fibrin glue, fibrinogen, thrombin, gelatin, albumin, collagen, including biologically active synthetics versions thereof, or polyethylene glycol.

17. The method of claim 13, wherein at least one construct layer is formed by:

adding a first solution comprising adipocytes and either fibrinogen or thrombin, but not both fibrinogen and thrombin, to a substrate;

combining the first solution with a second solution comprising endothelial cells, and either thrombin or fibrinogen, but not both fibrinogen and thrombin; and

incubating the substrate comprising the first and the second solutions to allow a construct layer to form.

18. The method of claim 17, wherein overlaying the first solution with the second solution comprises bioprinting.

19. The method of claim 17, wherein the bioprinting comprises adding the endothelial cells in a defined pattern.

20. The method of claim 13, wherein the first solution, the second solution, or bath further comprises at least one of mesenchymal stem cells or fibroblasts.

21. The method of claim 13, wherein at least one construct layer is formed by:

adding a solution comprising adipocytes, fibrinogen, thrombin, and endothelial cells to a substrate; and

incubating the substrate to allow an endothelial channel to form.

24. A multilayer tissue engineered construct manufactured by the method of claim 13.

25. A multilayer tissue engineered construct according to the method of claim 18.