Polysaccharide sponges for cell culture and transplantation

• US 6,793,675 B2
• Filed: 10/23/2001
• Issued: 09/21/2004
• Est. Priority Date: 05/22/1996
• Status: Expired due to Term

• Current Assignee: Ben Gurion University of The Negev
• Original Assignee: Ben Gurion University of The Negev
• Inventors: Cohen, Smadar, Glicklis, Rachel, Shapiro, Lilia
• Primary Examiner(s): Isabella, David J
• Application Number:
  US10/004,467
• Publication Number:
  US 20030078672A1
• Time in Patent Office: 1,064 Days
• Field of Search: 424/423-426, 623/11.11, 623/23.64, 623/23.65, 623/23.72, 623/23.71, 514/773-777, 428/305.5, 428/315.7, 428/318.4, 428/317.9, 428/321.7
• US Class Current: 623/11.11
• CPC Class Codes: A61F 2/105 Skin implants, e.g. artificial skin
• CPC Class Codes: A61F 2210/0004 bioabsorbable
• CPC Class Codes: A61F 2250/0067 Means for introducing or releasing pharmaceutical products into the body
• CPC Class Codes: A61K 9/0024 Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue compositions for intravenous administration, normal injectable solutions or dispersions for, e.g. subcutaneous administration A61K9/0019; brain implants A61K9/0085; (coated) prostheses, catheters or stents A61L
• CPC Class Codes: A61K 9/122 Foams; Dry foams edible foams A61K9/0056
• CPC Class Codes: A61L 27/20 Polysaccharides
• CPC Class Codes: A61L 27/3804 characterised by specific cells or progenitors thereof, e.g. fibroblasts, connective tissue cells, kidney cells
• CPC Class Codes: A61L 27/56 Porous materials, e.g. foams or sponges
• CPC Class Codes: A61L 27/60 Materials for use in artificial skin
• CPC Class Codes: C08J 2305/02 Dextran; Derivatives thereof
• 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: C08L 5/02 Dextran; Derivatives thereof

Abstract

A polysaccharide sponge characterized by having: (i) an average pore size in the range between about 10 μm to about 300 μm; (ii) an average distance between the pores being the wall thickness of the pores in the range between about 5 μm to about 270 μm; and (iii) an E-modulus of elasticity being a measure of the rigidity of the sponge in the range of about 50 kPa to about 500 kPa.

Claims

1. A polysaccharide sponge characterized by having:

(i) an average pore size in the range between about 10 μ

m to 300 μ

m;

(ii) an average distance between the pores in the range between about 5 μ

m to about 270 μ

m; and

(iii) an E-modulus of elasticity being a measure of the rigidity of the sponge in the range of about 50 kPa to about 500 kPa.

2. A polysaccharide sponge according to claim 1, wherein said sponge comprises a polyanionic polysaccharide selected from the group consisting of:

alginates, gellan, gellan gum, xanthan, agar, and carrageenan.

3. A polysaccharide sponge according to claim 1, wherein said sponge comprises a cross-linked polysaccharide.

4. A polysaccharide sponge according to claim 3, wherein said cross-linking agent is used in the form of a cross-linking agent solution having a concentration of cross-linking agent sufficient to provide a cross-linking agent concentration between about 0.1% to about 0.3% w/v in the final solution from which the sponge is obtained.

5. A polysaccharide sponge according to claim 1 for use as a matrix, substrate or scaffold for growing mammalian cells in vitro.

6. An artificial organ comprising a polysaccharide sponge according to claim 1, wherein the artificial organ is seeded with active cells of the corresponding natural organ, wherein said cells in vitro exhibit activity similar to their native activity in vivo, said artificial organ being suitable for transplantation or implantation into a patient in need thereof following organ damage, removal or dysfunction.

7. An artificial organ according to claim 6, wherein the artificial organ is an artificial liver wherein said cells are hepatocytes in vivo, and said artificial liver is suitable for transplantation or implantation into a patient suffering from liver dysfunction, damage or at least partial removal.

8. A polysaccharide sponge according to claim 1, wherein said sponge comprises a polycationic polysaccharide:

chitosan.

9. A polysaccharide sponge according to claim 3, wherein said polysaccharide is cross-linked by a cross-linking agent selected from the group consisting of salts of calcium, copper, aluminum, magnesium, strontium, barium, tin, zinc, chromium, organic cations, poly(amino acids), poly(ethyleneimine), poly(vinylamine), poly(allylamine), and polysaccharides.

10. A polysaccharide sponge according to claim 3, wherein said sponge further comprises a cross-linking agent selected from the group consisting of calcium chloride (CaCl₂), strontium chloride (SrCl₂), and calcium gluconate (Ca-Gl).