Biodegradable porous polymer scaffolds for tissue engineering prepared from an effervescent mixture and its preparation

• US 6,562,374 B1
• Filed: 10/27/2000
• Issued: 05/13/2003
• Est. Priority Date: 06/23/2000
• Status: Expired due to Fees

• Current Assignee: Biomedlab Corporation, Korea Advanced Institute of Science and Technology
• Original Assignee: Korea Advanced Institute of Science and Technology
• Inventors: Kim, Jong-Man, Han, Dong Keun, Ahn, Kwang-Duk, Ju, Young Min
• Primary Examiner(s): Krass, Frederick
• Assistant Examiner(s): OSTRUP, CLINTON T
• Application Number:
  US09/699,213
• Time in Patent Office: 928 Days
• Field of Search: 424/484, 424/426, 424/422, 424/444, 435/399, 514/802, 514/945, 514/955, 521/98, 521/84.1, 521/113, 521/51
• US Class Current: 424/484
• CPC Class Codes: A61L 27/18 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
• CPC Class Codes: A61L 27/56 Porous materials, e.g. foams or sponges
• CPC Class Codes: A61L 27/58 Materials at least partially resorbable by the body
• CPC Class Codes: C08J 2201/048 Elimination of a frozen liquid phase
• CPC Class Codes: C08J 2367/04 Polyesters derived from hydroxy carboxylic acids, e.g. lactones C08J2367/06 takes precedence
• CPC Class Codes: C08J 9/08 developing carbon dioxide
• CPC Class Codes: C08J 9/28 by elimination of a liquid phase from a macromolecular composition or article, e.g. drying of coagulum
• CPC Class Codes: C08L 67/04 Polyesters derived from hydroxycarboxylic acids, e.g. lactones C08L67/06 takes precedence

Abstract

The present invention provides a method for preparing biodegradable porous polymer scaffolds for tissue engineering, comprising:

a) fabricating a polymer sample from a polymer solution containing at least one biodegradable polymer and an effervescent mixture;

b) effervescing the polymer sample in the presence of an effervescent medium such as an aqueous alcohol solution; and

c) drying.

The method for preparing biodegradable polymer scaffolds of the present invention has the advantages that the process is simple, that pore size can be easily controlled, that the problem caused by the secretion and existence of the toxic substance can be avoid by using a material harmless to human body, and that high efficiency can be achieved. In addition, biodegradable porous polymer scaffolds prepared by above method have the advantages that high porosity can be achieved and an open cell structure in which pores are interconnected is obtained.

Claims

1. A method for preparing a biodegradable porous polymer scaffold comprising:

a) fabricating a polymer sample from a polymer solution containing at least one biodegradable polymer and an effervescent mixture comprising a carbonate and an organic acid;

b) effervescing the polymer sample in contact with an effervescent medium comprising an aqueous alcohol solution; and

c) drying.

2. The method according to claim 1, wherein the biodegradable porous polymer scaffold has a porosity of 93-98%.

3. The method according to claim 1, wherein the biodegradable porous polymer scaffold has an open cell structure in which pores are interconnected with each other.

4. The method according to claim 1, wherein the biodegradable polymer is at least one selected from the group consisting of polyglycolic acid (PGA), polylactic acid (PLA), lactic acid-glycolic acid copolymer (PGLA), poly-ε

-caprolactone (PCL), polyamino acid, polyanhydride, polyorthoester, and copolymers thereof.

5. The method according to claim 1, wherein the molecular weight of the biodegradable polymer is in the range of 5,000 to 2,000,000.

6. The method according to claim 1, wherein the concentration of the biodegradable polymer in the polymer solution is 5-15% by weight.

7. The method according to claim 1, wherein a solvent used in the polymer solution is selected from the group consisting of chloroform, dichloromethane, acetone, dioxane, tetrahydrofuran, and mixtures thereof.

8. The method according to claim 1, wherein the carbonate in the effervescent mixture is a substance harmless to the human body, which can be used in a medicine and can be easily dissolved in water, having a size of 10-500 μ

m.

9. The method according to claim 1, wherein the carbonate in the effervescent mixture is at least one selected from the group consisting of sodium bicarbonate, sodium carbonate, ammonium bicarbonate, ammonium carbonate, potassium bicarbonate, potassium carbonate, calcium carbonate, and mixtures thereof.

10. The method according to claim 1, wherein the organic acid in the effervescent mixture is at least one selected from the group consisting of citric acid, tartaric acid, succinic acid, maleic acid, fumaric acid, malonic acid, malic acid, gluconic acid, mucic acid, amino acids and mixtures thereof.

11. The method according to claim 1, wherein the weight ratio of the effervescent mixture to the polymer is 5/1-20/1.

12. The method according to claim 1, wherein the molar ratio of the organic acid to the carbonate in the effervescent mixture is in the range from 1:

1 to 1;

3.

13. The method according to claim 1, wherein the alcohol used in the effervescent medium is selected from the group consisting of ethanol, methanol, isopropyl alcohol, and mixtures thereof.

14. The method according to claim 1, wherein the content of alcohol in the aqueous alcoholic solution is 1-95% by volume.

15. The method according to claim 1, wherein the effervescing (foaming) is accompanied by the use of a physical method selected from the group consisting of ultrasonification, microwaving, and agitation.

16. The method according to claim 1, wherein the drying is performed by freeze-drying or vacuum-drying at room temperature, or vacuum-drying below the glass transition temperature of the biodegradable polymers used.