Preparing porous hydrogel products

• US 6,511,650 B1
• Filed: 04/18/2002
• Issued: 01/28/2003
• Est. Priority Date: 04/09/1999
• Status: Expired due to Fees

• Current Assignee: Board of Regents of the University of Michigan (University of Michigan)
• Original Assignee: Board of Regents of the University of Michigan (University of Michigan)
• Inventors: Eiselt, Petra, Halberstadt, Craig, Yeh, Julia, Latvala, Rachel, Mooney, David, Rowley, Jon A.
• Primary Examiner(s): Foelak, Morton
• Application Number:
  US09/958,376
• Time in Patent Office: 285 Days
• Field of Search: 424/44, 424/45, 424/485, 424/488, 424/489, 424/499, 424/500, 521/182, 521/185, 521/84.1
• US Class Current: 424/44
• CPC Class Codes: A61L 27/20 Polysaccharides
• CPC Class Codes: A61L 27/52 Hydrogels or hydrocolloids
• CPC Class Codes: A61L 27/56 Porous materials, e.g. foams or sponges
• CPC Class Codes: A61L 31/042 Polysaccharides
• CPC Class Codes: A61L 31/145 Hydrogels or hydrocolloids
• CPC Class Codes: A61L 31/146 Porous materials, e.g. foams or sponges
• CPC Class Codes: C08J 2205/022 Hydrogel, i.e. a gel containing an aqueous composition
• CPC Class Codes: C08J 2305/04 Alginic acid; Derivatives thereof
• CPC Class Codes: C08J 9/08 developing carbon dioxide
• CPC Class Codes: C08J 9/30 by mixing gases into liquid compositions or plastisols, e.g. frothing with air
• CPC Class Codes: C08L 5/04 Alginic acid; Derivatives thereof
• CPC Class Codes: C12N 2533/74 Alginate
• CPC Class Codes: C12N 5/0068 General culture methods using substrates for specific animal cell type C12N5/06

Abstract

This invention is directed to a new approach to form porous hydrogel materials by first creating gas pockets in the gel and then removing this gas. The removal of the gas creates a porous material, and the initial incorporation of sufficient gas allows one to create a material with an open, interconnected pore structure. Advantageous features of the resulting materials, in addition to their interconnected pore structure, may include that the pore structure is maintained over extended time periods and that the gels maintain a high mechanical integrity that allows seeding with cells and implantation without destruction or compression of the material.

Claims

1. A method for preparing a hydrogel material having macroporous open pore porosity, which comprises:

a) providing a solution of a hydrogel-forming material, a surfactant and, optionally, a gas-generating component, which solution is capable of being mixed in the presence of a gas to incorporate the gas in the solution and form a stable foam;

b) forming a stable foam by mixing the solution in the presence of a gas and/or, if the gas-generating component is present, by subjecting the solution to conditions or agents which result in generation of gas from the gas-generating component;

c) exposing the stable foam to conditions and/or agents which result in gelling of the hydrogel-forming material to form a hydrogel containing gas bubbles therein;

d) releasing the gas bubbles from the hydrogel to form a hydrogel material having macroporous open pore porosity.

2. The method of claim 1, wherein the hydrogel is an alginate hydrogel.

3. The method of claim 1, wherein the hydrogel-forming material is an alginate solution, the surfactant is BSA, a gas-generating component which is sodium bicarbonate is used and a solution of calcium chloride and acetic acid in water is used as the gelling agent and agent for generation of gas from the gas-generating component, respectively.

4. The method of claim 3, wherein the alginate solution is a solution of 3 to 5% w:

w sodium alginate, the BSA is provided as a 1.0 to 10 weight percent solution in water and the sodium bicarbonate is provided as a 1.0M to 2.0M solution, wherein the BSA solution and sodium bicarbonate solution are combined with the alginate in a weight ratio of the BSA solution to the sodium bicarbonate solution from 2;

1 to 1;

1, and wherein the solution of calcium chloride and acetic acid in water has a calcium chloride concentration from 0.1 to 1.0M and an amount of acetic acid of about 10 volume %.

5. The method of claim 2, wherein the alginate is an alginate having a reduced molecular weight of 1600 to 80,000 daltons.

6. The method of claim 1, wherein the surfactant is BSA, a pluronic surfactant or a propylene glycol alginate surfactant.

7. The method of claim 1, wherein the solution contains a gas-generating component.

8. The method of claim 1, wherein the stable foam is exposed to the conditions and/or agents which result in gelling of the hydrogel-forming material by dropwise addition through a syringe opening into a gelling solution to form microbeads.

9. The method of claim 3, wherein the stable foam is exposed to the conditions and/or agents which result in gelling of the hydrogel-forming material by dropwise addition through a syringe opening into a gelling solution to form microbeads.

10. The method of claim 8, wherein the dropwise addition is conducted with a syringe pump.

11. The method of claim 3, wherein the solution to be mixed to form a stable foam contains 3-10% weight of alginate, 0.05-1.0% weight BSA and 0.5 to 5.0% weight of sodium bicarbonate.

12. The method of claim 2, wherein the alginate is an alginate having a reduced molecular weight of 8,000 to 50,000 daltons.

13. The method of claim 1, wherein the surfactant is a pluronic surfactant.

14. The method of claim 12, wherein the surfactant is a pluronic surfactant.

15. The method of claim 1, wherein the releasing of the gas bubbles, step (d), is conducted by exposing the hydrogel to a vacuum.

16. The method of claim 7, wherein the gas-generating component is sodium bicarbonate.

17. The method of claim 1, wherein steps b) and c) are conducted substantially simultaneously.