One-step processing of hydrogels for mechanically robust and chemically desired features

• US 8,946,194 B2
• Filed: 10/07/2011
• Issued: 02/03/2015
• Est. Priority Date: 10/08/2010
• 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: Mayes, Sarah, Schmidt, Christine E.
• Primary Examiner(s): Fetterolf, Brandon
• Assistant Examiner(s): White, Everett
• Application Number:
  US13/269,366
• Publication Number:
  US 20120088735A1
• Time in Patent Office: 1,215 Days
• Field of Search: 514/62, 514/53, 514/54, 536/3
• US Class Current: 514/62
• CPC Class Codes: A61K 31/738 Cross-linked polysaccharides
• CPC Class Codes: A61K 47/36 Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin

Abstract

The application of a highly controlled, micron-sized, branched, porous architecture to enhance the handling properties and degradation rate of hydrogels is described in the instant invention. A previously described pattern created through one-step nucleated crystallization in a hydrogel film creates tunable mechanical properties and/or chemical stability for use in tissue engineering applications. The bulk mechanical properties and the degradation rate of the material can be tuned easily by the addition or subtraction of crystalline structure or by the addition and subtraction of backfill material, making this useful for a variety of applications. Relevant mechanical properties that can be tuned through the application of this unique porosity are moduli, elasticity, tensile strength, and compression strength. The method of the present invention can be applied to biopolymers and natural materials as well as synthetic materials.

Claims

1. An apparatus comprising:

uncrosslinked hyaluronic acid included in a hydrogel film; and

crosslinked alginate included in the hydrogel;

wherein (a) the alginate is crosslinked with calcium, (b) the alginate is crosslinked around the uncrosslinked hyaluronic acid, (c) the hyaluronic acid and the alginate are formed around a network of pores that are backfilled with a backfill material; and

(d) the apparatus is included in a kit comprising a chemical component that dissolves the backfill material.

2. The apparatus of claim 1, wherein the network is branched.

3. The apparatus of claim 1, wherein the backfill material includes at least one of hyaluronic acid and alginate.

4. The apparatus of claim 1, wherein the backfill material is bound to at least one of the hyaluronic acid and the alginate.

5. The apparatus of claim 1, wherein degradation rate of the hydrogel is based on the backfill material.

6. The apparatus of claim 5, wherein mechanical properties of the hydrogel are based on the backfill material, the mechanical properties selected from the group consisting of moduli, elasticity, tensile strength, and compression strength.

7. The apparatus of claim 1, wherein the hydrogel encapsulates at least one of a drug, growth factor, hormone, protein, and combinations thereof.

8. The apparatus of claim 1, wherein the hydrogel includes at least one of a drug, growth factor, hormone, protein, and combinations thereof.

9. The apparatus of claim 1, wherein the network is a crystal templated network.

10. The apparatus of claim 9, wherein the network includes a crystal.

11. The apparatus of claim 1, wherein the backfill material is bound to at least itself.

12. The apparatus of claim 1, wherein the kit comprises a calcium chelator.

13. The apparatus of claim 1, wherein water has been at least partially removed from the hydrogel film.

14. An apparatus comprising:

a hydrogel film having first and second opposing ends;

uncrosslinked hyaluronic acid included in the hydrogel;

crosslinked alginate included in the hydrogel;

extending within the hydrogel;

wherein (a) the alginate is crosslinked with calcium, (b) the alginate is crosslinked around the uncrosslinked hyaluronic acid, (c) the pores are backfilled with a backfill material, and (d) the backfill material is bound to at least one of the hyaluronic acid and the alginate.

15. The apparatus of claim 14, wherein the backfill material includes at least one of hyaluronic acid and alginate.

16. The apparatus of claim 14, wherein the backfill material is bound to at least itself.

17. The apparatus of claim 14, wherein the degradation rate of the hydrogel is based on the backfill material.

18. The apparatus of claim 14, wherein the mechanical properties of the hydrogel are based on the backfill material, the mechanical properties selected from the group consisting of moduli, elasticity, tensile strength, and compressive strength and the backfill material bound to at least one of the hyaluronic acid and the alginate includes the backfill material being at least one of (i) cross-linked to at least one of the hyaluronic acid and the alginate, and (ii) covalently bound to at least one of the hyaluronic acid and the alginate.

19. The apparatus of claim 14, wherein the backfill material includes at least one of a drug, growth factor, hormone, peptide, protein, and combinations thereof.

20. The apparatus of claim 14 included in a kit comprising a calcium chelator.

21. The apparatus of claim 14 included in a kit comprising a chemical component that dissolves the backfill material.

22. The apparatus of claim 14, wherein water has been at least partially removed from the hydrogel film.

23. An apparatus comprising:

uncrosslinked hyaluronic acid included in a hydrogel film; and

crosslinked alginate included in the hydrogel;

wherein (a) the alginate is crosslinked with calcium, (b) the alginate is crosslinked around the uncrosslinked hyaluronic acid, (c) the hyaluronic acid and the alginate are formed around a network of pores that are backfilled with a backfill material; and

(d) the backfill material includes at least one of hyaluronic acid and alginate.

24. The apparatus of claim 23, wherein the backfill material is bound to at least one of the hyaluronic acid and the alginate.

25. The apparatus of claim 23, wherein degradation rate of the hydrogel is based on the backfill material.

26. The apparatus of claim 25, wherein mechanical properties of the hydrogel are based on the backfill material, the mechanical properties selected from the group consisting of moduli, elasticity, tensile strength, and compression strength.

27. The apparatus of claim 23, wherein the hydrogel encapsulates at least one of a drug, growth factor, hormone, protein, and combinations thereof.

28. The apparatus of claim 23, wherein the hydrogel includes at least one of a drug, growth factor, hormone, protein, and combinations thereof.

29. The apparatus of claim 23, wherein the network is a crystal templated network.

30. The apparatus of claim 29, wherein the network includes a crystal.

31. The apparatus of claim 23, wherein the backfill material is bound to at least itself.

32. The apparatus of claim 23 included in a kit comprising a calcium chelator.

33. The apparatus of claim 23 included in a kit comprising a chemical component that dissolves the backfill material.

34. The apparatus of claim 23, wherein water has been at least partially removed from the hydrogel film.

35. The apparatus of claim 23, wherein the backfill material includes at least one of a drug, growth factor, hormone, peptide, protein, and combinations thereof.