Anisotropic hydrogels

• US 8,465,771 B2
• Filed: 03/30/2006
• Issued: 06/18/2013
• Est. Priority Date: 03/30/2005
• Status: Active Grant

• Current Assignee: University of Western Ontario
• Original Assignee: University of Western Ontario
• Inventors: Wan, Wankei, Millon, Leonardo E., Mohammadi, Hadi
• Primary Examiner(s): DAVIS, RUTH A
• Application Number:
  US11/909,880
• Publication Number:
  US 20090214623A1
• Time in Patent Office: 2,637 Days
• Field of Search: 424/447
• US Class Current: 424/477
• CPC Class Codes: A61B 17/2251 characterised by coupling elements between the apparatus, e.g. shock wave apparatus or locating means, and the patient, e.g. details of bags, pressure control of bag on patient
• CPC Class Codes: A61F 2007/0098 ways of manufacturing heating or cooling devices for therapy
• CPC Class Codes: A61F 7/10 Cooling bags, e.g. ice-bags
• CPC Class Codes: A61L 15/24 Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds; Derivatives thereof A61L15/225 takes precedence
• CPC Class Codes: A61L 15/44 Medicaments
• CPC Class Codes: A61L 15/60 Liquid-swellable gel-forming materials, e.g. super-absorbents
• CPC Class Codes: A61L 15/62 Compostable, hydrosoluble or hydrodegradable materials
• CPC Class Codes: A61L 2300/00 Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
• CPC Class Codes: A61L 27/16 obtained by reactions only involving carbon-to-carbon unsaturated bonds
• 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: A61L 29/041 obtained by reactions only involving carbon-to-carbon unsaturated bonds
• CPC Class Codes: A61L 29/145 Hydrogels or hydrocolloids
• CPC Class Codes: A61L 29/16 Biologically active materials, e.g. therapeutic substances A61L29/048 takes precedence
• CPC Class Codes: A61L 31/048 obtained by reactions only involving carbon-to-carbon unsaturated bonds A61L31/041 takes precedence
• CPC Class Codes: A61L 31/145 Hydrogels or hydrocolloids
• CPC Class Codes: A61L 31/16 Biologically active materials, e.g. therapeutic substances A61L31/047 takes precedence
• CPC Class Codes: C08F 16/06 Polyvinyl alcohol ; Vinyl alcohol
• CPC Class Codes: C08F 8/00 Chemical modification by after-treatment graft polymers, block polymers, crosslinking with unsaturated monomers or with polymers C08F251/00 - C08F299/00; of conjugated diene rubbers C08C
• CPC Class Codes: C08J 2329/04 Polyvinyl alcohol; Partially hydrolysed homopolymers or copolymers of esters of unsaturated alcohols with saturated carboxylic acids
• CPC Class Codes: C08J 3/075 : Macromolecular gels
• CPC Class Codes: C08L 29/04 : Polyvinyl alcohol; Partially hydrolysed homopolymers or copolymers of esters of unsaturated alcohols with saturated carboxylic acids
• CPC Class Codes: F16L 9/00 : Rigid pipes

Abstract

The invention relates to an anisotropic hydrogel and a method of producing the anisotropic hydrogel. The hydrogel exhibiting anisotropic properties is poly(vinyl alcohol) produced by preparing a solution of poly(vinyl alcohol) with a pre-selected concentration, thermally cycling the solution by freezing and thawing, stretching the hydrogel and thermally cycling the hydrogel at least one more time The anisotropic hydrogel is used for tissue replacement and reconstruction, bioagent entrapment and delivery, in preparing ultrasound or radiofrequency thermal therapy transmission pads and substitutes for ice bags, as denture base, in soft contact lens material, for wound covering bandages and phantoms for medical-related use.

Claims

1. A method of producing an anisotropic hydrogel, comprising:

a) preparing a solution of poly(vinyl alcohol) with a pre-selected concentration;

b) thermally cycling the solution by freezing and thawing to obtain a PVA hydrogel;

c) stretching the hydrogel; and

d) thermally cycling the hydrogel at least one more time while stretching the hydrogel.

2. The method according to claim 1 wherein, the solvent for the PVA solution in a) is water, distilled water, isotonic saline or an isotonic buffered saline.

3. The method according to claim 2, wherein the solvent is distilled water.

4. The method according to claim 1, wherein the concentration of the PVA solution in a) is about 5% to about 25%.

5. The method according to claim 4, wherein the concentration of the PVA solution in a) is about 7% to about 15%.

6. The method according to claim 5 wherein the concentration of the PVA solution in a) is about 10%.

7. The method according to claim 1, wherein the PVA solution is prepared by heating at a temperature of about 80°

C. to about 100°

C. for about 2 to about 4 hours.

8. The method according to claim 1, wherein thermal cycling of the PVA solution involves cooling the solution from a temperature of about 30°

C. to about 15°

C. to about −

15°

C. about −

30°

C., holding the solution at −

30°

C. for about 0.5 hour to about 2 hour, and heating the solution back to about 30°

C.

9. The method according to claim 1, wherein thermal cycling of the PVA solution involves cooling the PVA solution from a starting temperature of about 10°

C. to about 30°

C. to finishing temperature of about −

10°

C. to about −

30°

C. at a rate of about 0.5°

C./min to about 0.05°

C./min, holding the solution at the finishing temperature for about 0.5 hour to about 2 hour and heating the solution to the starting temperature at a rate of about 0.5°

C./min to about 0.05°

C./min.

10. The method according to claim 1, wherein thermal cycling of the PVA solution involves cooling the PVA solution from a starting temperature of about 15°

C. to about 25°

C. to finishing temperature of about −

15°

C. to about −

25°

C. at a rate of about 0.5°

C./min to about 0.05°

C./min, holding the solution at the finishing temperature for about 0.5 hour to about 2 hour and heating the solution back to the starting temperature at a rate of about 0.5°

C./min to about 0.05°

C./min.

11. The method according to claim 1, wherein thermal cycling of the PVA solution involves cooling the PVA solution from a starting temperature of about 20°

C. to finishing temperature of about −

20°

C. at a rate of about 0.1°

C./min, holding the solution at the finishing temperature for about 1 hour and heating the solution back to the starting temperature at a rate of about 0.1°

C./min.

12. The method according to claim 1, wherein the PVA hydrogel is stretched to a strain of about 25% to about 100%.

13. The method according to claim 12, wherein the PVA hydrogel is stretched to a strain of about 50% to about 90%.

14. The method according to claim 13, wherein the PVA hydrogel is stretched to a strain of about 70% to about 80%.

15. The method according to claim 14, wherein the PVA hydrogel is stretched to a strain of about 75%.

16. The method according to claim 1, wherein the PVA hydrogel is thermally cycled 1-6 times while stretching the hydrogel.

17. The method according to claim 16, wherein the PVA hydrogel is thermally cycled 2-5 times while stretching the hydrogel.

18. The method according to claim 17, wherein the PVA hydrogel is thermally cycled 3 times while stretching the hydrogel.

19. The method according to claim 1, further comprising adding one or more bioactive agents to the PVA solution in a).

20. The method according to claim 1, further comprising incorporating one or more bioagents into the hydrogel after d).

21. The method according to claim 19, wherein one or more bioactive agents are added to the hydrogel and wherein the one or more bioactive agents are selected from cells, antibodies, cytokines, thrombins, thrombin inhibitors, proteases, anticoagulants, heparin, growth factors, collagen crosslinking inhibitors, matrix inhibitors, glycosaminoglycans and antimicrobial agents.

22. The method according to claim 21, wherein the bioactive agent is heparin.

23. The method according to claim 21, wherein the cells are eukaryotic cells.

24. The method according to claim 23, wherein the eukaryotic cells are vascular cells or connective tissue cells.

25. The method according to claim 24, wherein the vascular cells are selected from the group consisting of endothelial cells, smooth muscle cells, and fibroblasts.

26. The method according to claim 1 wherein the PVA solution is transferred into molds of the shape of a final material, device or apparatus following a).

27. The method according to 26 wherein the final material, device or apparatus is selected from replacement soft tissue, an ultrasound or radio frequency thermal therapy transmission pad, a substitute for an ice bag, a denture base, soft contact lens material, wound covering bandage and phantoms for medical-related use.

28. The method according to claim 27, wherein the soft tissue is selected from vascular vessels, coronary arteries, heart valve leaflets, heart valve stent, cartilage, ligaments and skin.

29. The method according to claim 28, wherein the vascular vessels are selected from aorta and coronary arteries.

30. The method according to claim 27, wherein the medical related use is selected from training and education, ultrasound and magnetic resonance imaging and robotic surgery.

31. A method of producing an anisotropic hydrogel, comprising:

a) preparing a solution of poly(vinyl alcohol) with a pre-selected concentration while heating and mixing for 3 hours at a temperature around 90°

C.;

b) thermally cycling the solution by freezing from about 20°

C. to about −

20°

C. at a rate of about 0.1°

C./min, holding it at about −

20°

C. for about one hour, and then thawing it back to 20°

C. at a warming rate of about 0.1°

/min thereby obtaining a hydrogel;

c) stretching the hydrogel; and

d) thermally cycling the hydrogel at least one more time while stretching the hydrogel.