HYDROGEL PRECURSORS HAVING NANOPARTICLES

• US 20160038643A1
• Filed: 10/20/2015
• Published: 02/11/2016
• Est. Priority Date: 09/25/2013
• Status: Active Grant

• Current Assignee: University of Kansas
• Original Assignee: University of Kansas
• Inventors: Detamore, Michael, Berkland, Cory, Beck, Emily, Gehrke, Stevin
• Granted Patent: US 10,335,515 B2
• Time in Patent Office: Days
• US Class Current: 1/1
• CPC Class Codes: A61L 2430/06 for cartilage reconstruction, e.g. meniscus
• CPC Class Codes: A61L 2430/32 for nerve reconstruction
• CPC Class Codes: A61L 27/20 Polysaccharides
• CPC Class Codes: A61L 27/3817 Cartilage-forming cells, e.g. pre-chondrocytes
• CPC Class Codes: A61L 27/383 Nerve cells, e.g. dendritic cells, Schwann 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 27/48 with macromolecular fillers
• CPC Class Codes: A61L 27/50 Materials characterised by their function or physical properties , e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
• CPC Class Codes: A61L 27/52 Hydrogels or hydrocolloids
• CPC Class Codes: A61L 27/54 Biologically active materials, e.g. therapeutic substances A61L27/227 takes precedence
• CPC Class Codes: C08L 5/08 Chitin; Chondroitin sulfate; Hyaluronic acid; Derivatives thereof

Abstract

An implantable hydrogel precursor composition can include: a cross-linkable polymer matrix that is biocompatible; and a plurality of polymer particles in the cross-linkable polymer matrix. The cross-linkable polymer matrix can include a cross-linkable hyaluronic acid polymer that has cross-linkable functional groups. The hyaluronic acid polymer can be a methacrylated hyaluronic acid polymer. The methacrylated hyaluronic acid polymer can have a molecular weight from about 500 kDa to about 1.8 MDa. The polymer particles can include a cross-linked hyaluronic acid. The cross-linkable polymer matrix having the polymer particles has a yield stress. The cross-linkable polymer matrix having the polymer particles has shape retention at physiological temperatures. The composition can include live cells in the cross-linkable polymer matrix. The composition can include a biologically active agent in the cross-linkable polymer matrix.

Claims

1. An implantable hydrogel precursor composition comprising:

a cross-linkable polymer matrix that is biocompatible; and

a plurality of polymer particles in the cross-linkable polymer matrix.

2. The composition of claim 1, wherein the cross-linkable polymer matrix includes a cross-linkable hyaluronic acid polymer that has cross-linkable functional groups.

3. The composition of claim 2, wherein the hyaluronic acid polymer is a methacrylated hyaluronic acid polymer.

4. The composition of claim 1, wherein the methacrylated hyaluronic acid polymer has a molecular weight from about 500 kDa to about 1.8 MDa.

5. The composition of claim 1, wherein the polymer particles include a cross-linked hyaluronic acid.

6. The composition of claim 1, wherein the polymer particles have a molecular weight of about 10 kDa to about 20 kDa.

7. The composition of claim 1, wherein the polymer particles have a particle size of about 10 nm to about 500 nm.

8. The composition of claim 1, wherein:

the cross-linkable polymer is present from about 2% to about 10%; and

the polymer particles are present from about 5% to about 40%.

9. The composition of claim 1, wherein the ratio of cross-linkable polymer to polymer particles is from 1:

15 to about 2;

1.

10. The composition of claim 1, wherein the cross-linkable polymer matrix having the polymer particles has a yield stress.

11. The composition of claim 1, wherein the cross-linkable polymer matrix having the polymer particles has shape retention at physiological temperatures.

12. The composition of claim 1, further comprising live cells in the cross-linkable polymer matrix.

13. The composition of claim 1, further comprising a biologically active agent in the cross-linkable polymer matrix.

14. A hydrogel composition comprising:

a crosslinked polymeric hydrogel matrix that is biocompatible; and

a plurality of polymer particles in the crosslinked polymer matrix.

15. The composition of claim 14, wherein the crosslinked polymeric hydrogel matrix is cross-linked methacrylated hyaluronic acid polymer and the polymer particle is cross-linked hyaluronic acid, wherein the crosslinked polymer matrix encapsulates the polymer particles.

16. A method of forming an implant, comprising:

providing an implantable hydrogel precursor composition comprising;

a cross-linkable polymer matrix that is biocompatible; and

a plurality of polymer particles in the cross-linkable polymer matrix;

implanting the hydrogel precursor composition into a body; and

crosslinking the cross-linkable polymer matrix to form a hydrogel containing the plurality of polymer particles.

17. The method of claim 16, comprising shaping the hydrogel precursor composition while in the body.

18. The method of claim 16, comprising:

placing the hydrogel precursor in a defect in a tissue in the body; and

crosslinking the cross-linkable polymer in the defect.

19. The method of claim 18, wherein the defect is in a cartilage tissue.

20. The method of claim 18, wherein the defect is in a nerve tissue.