Injectable hydrogel compositions

• US 6,129,761 A
• Filed: 06/07/1995
• Issued: 10/10/2000
• Est. Priority Date: 06/07/1995
• Status: Expired due to Fees

• Current Assignee: Reprogenesis, Inc. (Curis, Inc.)
• Original Assignee: Reprogenesis, Inc. (Curis, Inc.)
• Inventors: Hubbell, Jeffrey A.
• Primary Examiner(s): Yu, Mickey
• Assistant Examiner(s): Nguyen, Dinh X.
• Application Number:
  US08/478,690
• Time in Patent Office: 1,952 Days
• Field of Search: 623/4, 623/8, 623/11, 623/12, 623/16, 623/66, 623/901, 623/93.7, 424/423, 424/426, 424/485, 424/548, 424/549
• US Class Current: 623/23.72
• CPC Class Codes: A61F 2/00 Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents as cosmetic articles, see the relevant subclasses, e.g. wigs, hair pieces, A41G3/00, A41G5/00; artificial nails A45D31/00; dental prostheses A61C13/00; materials for prostheses A61L27/00; artificial hearts A61M60/00; artificial kidneys A61M1/14
• CPC Class Codes: A61L 27/38 containing added animal cells organs or tissue containing native cells A61L27/36
• 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 27/3839 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 27/52 Hydrogels or hydrocolloids
• CPC Class Codes: C12N 2533/70 Polysaccharides
• CPC Class Codes: C12N 5/0068 General culture methods using substrates for specific animal cell type C12N5/06

Abstract

Slowly polymerizing hydrogels are provided which are useful as a means of delivering large numbers of isolated cells via injection. The gels promote engraftment and provide three dimensional templates for new cell growth. The resulting tissue is similar in composition and histology to naturally occurring tissue. This method can be used for a variety of reconstructive procedures, including custom molding of cell implants to reconstruct three dimensional tissue defects, as well as implantation of tissues generally. The polymers permit construction of muscle and cartilage tissues which are useful to repair defects such as reflux and incontinence.

Claims

1. A method for making and implanting a cell-hydrogel suspension into an animal comprising

mixing dissociated cells with a solution comprising a biocompatible polymer capable of crosslinking to form a hydrogel to form a cell-polymer suspension, wherein the polymer is selected from the group consisting of (a) modified hyaluronic acids, (b) synthetic modified alginates, (c) polymers which are covalently crosslinkable by a radical reaction and (d) polymers which gel by exposure to monovalent ions;

implanting the suspension into the animal; and

permitting the biocompatible polymer to crosslink and form a hydrogel matrix having the dissociated cells dispersed therein.

2. The method of claim 1 wherein the hydrogel matrix containing the dissociated cells forms before the suspension is implanted.

3. The method of claim 1 wherein the suspension of the biocompatible polymer and the dissociated cells is injected into the animal as a cell suspension;

and

wherein the hydrogel matrix containing the cells forms after the mixture is injected.

4. The method of claim 1 wherein the biocompatible polymer is selected from the group consisting of modified alginates and a modified hyaluronic acid.

5. The method of claim 1 wherein the hydrogel is formed by exposure of the polymer to a crosslinking agent selected from the group consisting of ions, radical initiators, and enzymes.

6. The method of claim 1 wherein the biocompatible polymer is a polysaccharide which forms a hydrogel upon exposure to a monovalent cation.

7. The method of claim 6 wherein the polymer is a polysaccharide which forms a hydrogel upon exposure to a monovalent cation.

8. The method of claim 6 wherein the monovalent cation is sodium.

9. The method of claim 5 wherein the biocompatible polymer comprises substituents capable of crosslinking by a radical reaction in the presence of a radical initiator to form a hydrogel, and wherein the biocompatible polymer is contacted with the radical initiator thereby to covalently crosslink the polymer by a radical reaction and form the hydrogel.

10. The method of claim 9 wherein the radical initiator is selected from the group consisting of a dye, ultraviolet light and visible light.

11. The method of claim 1 wherein the dissociated cells are selected from the group consisting of cells that form cartilage, cells that form bone, muscle cells, fibroblasts, and organ cells.

12. The method of claim 2 wherein the hydrogel is molded to form a specific shape prior to implantation.

13. The method of claim 3 wherein the hydrogel is molded to form a specific shape after mixing with the dissociated cells and being implanted into the animal.

14. The method of claim 1 for treating vesicoureteral reflux.

15. The method of claim 1 for treating incontinence.

16. The method of claim 1 for treating a defect in a patient within the thoracic region.

17. The method of claim 1 for treating a patient within the upper gastrointestinal tract.