Dendritic macroporous hydrogels prepared by crystal templating

• US 10,442,911 B2
• Filed: 02/07/2018
• Issued: 10/15/2019
• Est. Priority Date: 02/26/2008
• Status: Active Grant

• Current Assignee: 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: Zawko, Scott, Schmidt, Christine
• Primary Examiner(s): Richter, Johann R
• Assistant Examiner(s): Alley, Genevieve S
• Application Number:
  US15/890,719
• Publication Number:
  US 20180163012A1
• Time in Patent Office: 615 Days
• CPC Class Codes: A61L 26/0023 Polysaccharides
• CPC Class Codes: A61L 26/0095 Composite materials, i.e. containing one material dispersed in a matrix of the same or different material
• CPC Class Codes: A61L 27/52 Hydrogels or hydrocolloids
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: B01J 13/0065 containing an organic phase
• CPC Class Codes: C08B 37/0015 Inclusion compounds, i.e. host-guest compounds, e.g. polyrotaxanes
• CPC Class Codes: C08B 37/003 Chitin, i.e. 2-acetamido-2-deoxy-(beta-1,4)-D-glucan or N-acetyl-beta-1,4-D-glucosamine; Chitosan, i.e. deacetylated product of chitin or (beta-1,4)-D-glucosamine; Derivatives thereof
• CPC Class Codes: C08B 37/0045 alpha-D-Galacturonans, e.g. methyl ester of (alpha-1,4)-linked D-galacturonic acid units, i.e. pectin, or hydrolysis product of methyl ester of alpha-1,4-linked D-galacturonic acid units, i.e. pectinic acid; Derivatives thereof
• CPC Class Codes: C08B 37/0072 Hyaluronic acid, i.e. HA or hyaluronan; Derivatives thereof, e.g. crosslinked hyaluronic acid (hylan) or hyaluronates
• CPC Class Codes: C08B 37/0075 Heparin; Heparan sulfate; Derivatives thereof, e.g. heparosan; Purification or extraction methods thereof
• CPC Class Codes: C08B 37/0084 Guluromannuronans, e.g. alginic acid, i.e. D-mannuronic acid and D-guluronic acid units linked with alternating alpha- and beta-1,4-glycosidic bonds; Derivatives thereof, e.g. alginates
• CPC Class Codes: C08H 1/06 derived from horn, hoofs, hair, skin or leather
• CPC Class Codes: C08J 2201/0424 containing halogen, nitrogen, sulphur or phosphorus atoms
• CPC Class Codes: C08J 2205/022 Hydrogel, i.e. a gel containing an aqueous composition
• CPC Class Codes: C08J 2205/04 characterised by the foam pores
• CPC Class Codes: C08J 2207/10 Medical applications, e.g. biocompatible scaffolds
• CPC Class Codes: C08J 2305/00 Characterised by the use of polysaccharides or of their derivatives not provided for in groups C08J2301/00 or C08J2303/00
• CPC Class Codes: C08J 2305/04 Alginic acid; Derivatives thereof
• CPC Class Codes: C08J 2305/08 Chitin; Chondroitin sulfate; Hyaluronic acid; Derivatives thereof
• CPC Class Codes: C08J 3/075 Macromolecular gels
• CPC Class Codes: C08J 3/24 : Crosslinking, e.g. vulcanising, of macromolecules mechanical aspects B29C35/00; crosslinking agents C08K
• CPC Class Codes: C08J 3/242 : Applying crosslinking or accelerating agent onto compounding ingredients such as fillers, reinforcements
• CPC Class Codes: C08J 3/26 : of latex
• CPC Class Codes: C08J 3/28 : Treatment by wave energy or particle radiation
• CPC Class Codes: C08J 5/10 : characterised by the additives used in the polymer mixture
• CPC Class Codes: C08J 5/18 : Manufacture of films or sheets
• CPC Class Codes: C08J 9/26 : by elimination of a solid phase from a macromolecular composition or article, e.g. leaching out
• CPC Class Codes: C08K 5/0025 : Crosslinking or vulcanising agents; including accelerators
• CPC Class Codes: C08K 5/0083 : Nucleating agents promoting the crystallisation of the polymer matrix
• CPC Class Codes: C08K 5/21 : Urea; Derivatives thereof, e.g. biuret
• CPC Class Codes: C08L 5/00 : Compositions of polysaccharides or of their derivatives not provided for in groups C08L1/00 or C08L3/00
• CPC Class Codes: C08L 5/04 : Alginic acid; Derivatives thereof
• CPC Class Codes: C08L 5/06 : Pectin; Derivatives thereof
• CPC Class Codes: C08L 5/08 : Chitin; Chondroitin sulfate; Hyaluronic acid; Derivatives thereof
• CPC Class Codes: C08L 5/10 : Heparin; Derivatives thereof
• CPC Class Codes: C08L 5/16 : Cyclodextrin; Derivatives thereof
• CPC Class Codes: C08L 89/06 : derived from leather or skin , e.g. gelatin

Abstract

The present invention includes a hydrogel and a method of making a porous hydrogel by preparing an aqueous mixture of an uncrosslinked polymer and a crystallizable molecule; casting the mixture into a vessel; allowing the cast mixture to dry to form an amorphous hydrogel film; seeding the cast mixture with a seed crystal of the crystallizable molecule; growing the crystallizable molecule into a crystal structure within the uncrosslinked polymer; crosslinking the polymer around the crystal structure under conditions in which the crystal structure within the crosslinked polymer is maintained; and dissolving the crystals within the crosslinked polymer to form the porous hydrogel.

Claims

1. An apparatus comprising:

a hydrogel film having first and second opposing ends;

wherein the hydrogel film includes (a)(i) uncrosslinked hyaluronic acid, (a)(ii) crosslinked alginate, and (a)(iii) at least one of a protein or a biomineral;

wherein (b)(i) the alginate is crosslinked with calcium, and (b)(ii) the alginate is crosslinked around the uncrosslinked hyaluronic acid.

2. The apparatus of claim 1 wherein the hydrogel film includes the biomineral.

3. The apparatus of claim 1 wherein the hydrogel film includes the protein.

4. The apparatus of claim 3 wherein the protein includes a cell adhesive protein.

5. The apparatus of claim 3 wherein the hydrogel film includes a drug.

6. The apparatus of claim 3 included in a kit, the kit comprising a calcium chelator.

7. The apparatus of claim 3, wherein the hydrogel film consists essentially of the uncrosslinked hyaluronic acid and the crosslinked alginate.

8. The apparatus of claim 3 wherein the hydrogel film includes chitosan.

9. The apparatus of claim 3 wherein the hydrogel film includes urea.

10. The apparatus of claim 3 wherein the hydrogel film includes at least one crystal.

11. The apparatus of claim 10 wherein the at least one crystal is (a) dendritically branched, and (b) at least 1 micron in diameter.

12. The apparatus of claim 10 wherein the at least one crystal comprises cyclodextrin.

13. An apparatus comprising:

a hydrogel film having first and second opposing ends;

wherein the hydrogel film includes (a)(i) uncrosslinked hyaluronic acid, (a)(ii) crosslinked alginate, and (a)(iii) a protein;

wherein (b)(i) the alginate is crosslinked with an ion, and (b)(ii) the alginate is crosslinked around the uncrosslinked hyaluronic acid.

14. The apparatus of claim 13 included in a kit, wherein:

the kit comprises a sequestering agent; and

the sequestering agent is configured to sequester the ion.

15. The apparatus of claim 14 wherein the ion includes calcium and the sequestering agent includes a calcium chelator.

16. The apparatus of claim 14, wherein the hydrogel film consists essentially of the uncrosslinked hyaluronic acid and the crosslinked alginate.

17. An apparatus comprising:

a hydrogel film having first and second opposing ends;

wherein the hydrogel film includes (a)(i) uncrosslinked hyaluronic acid, (a)(ii) crosslinked alginate, and (a)(iii) an amide;

wherein (b)(i) the alginate is crosslinked with an ion, and (b)(ii) the alginate is crosslinked around the uncrosslinked hyaluronic acid.

18. The apparatus of claim 17 included in a kit, wherein:

the kit includes a sequestering agent; and

the sequestering agent is configured to sequester the ion.

19. The apparatus of claim 18 wherein:

the ion includes calcium;

the sequestering agent includes a calcium chelator; and

the amide is included within a protein.

20. The apparatus of claim 19 wherein the hydrogel film consists essentially of the uncrosslinked hyaluronic acid and the crosslinked alginate.