Porous polysaccharide scaffold comprising nano-hydroxyapatite and use for bone formation

Patent metadata

Field	Value
Publication number	US-10143774-B2
Application number	US-201715657868-A
Country	US
Kind code	B2
Filing date	Jul 24, 2017
Priority date	Aug 31, 2010
Publication date	Dec 4, 2018
Grant date	Dec 4, 2018

Abstract

The present invention relate to three dimensional porous polysaccharide matrices able to induce mineralization of a tissue in osseous site, as well as in non-osseous site, in the absence of stem cells or growth factors.

First claim

The invention claimed is:

1. A porous polysaccharide scaffold obtained by:
i) preparing an alkaline aqueous solution comprising at least one polysaccharide, a cross-linking agent and a porogen agent,
ii) transforming the solution into a hydrogel by placing said solution at a temperature from 4° C. to 80° C. for a sufficient time to allow cross-linking of said at least one polysaccharide,
iii) submerging said hydrogel into a solvent, and
iv) washing the porous polysaccharide scaffold obtained at step iii),

wherein the alkaline aqueous solution of step i) further comprises hydroxyapatite and wherein the porous polysaccharide scaffold lacks exogenously added cells and growth factors.

2. The porous polysaccharide scaffold according to claim 1 , wherein the porogen agent is selected from the group consisting of sodium chloride, calcium chloride, ammonium carbonate, ammonium bicarbonate, calcium carbonate, sodium carbonate, sodium bicarbonate and mixtures thereof.

3. The porous polysaccharide scaffold according to claim 1 , wherein a weight ratio of the at least one polysaccharide to the porogen agent is in a range from 1:50 to 50:1.

4. The porous polysaccharide scaffold according to claim 1 , wherein said at least one polysaccharide is selected from the group consisting of dextran, pullulan, agar, alginic acid, starch, hyaluronic acid, inulin, heparin, fucoidan, chitosan and mixtures thereof.

5. The porous polysaccharide scaffold according to claim 1 , wherein said at least one polysaccharide is a mixture of pullulan/dextran in a ratio in a range from 95:5 to 5:95.

6. The porous polysaccharide scaffold according to claim 1 , wherein said at least one polysaccharide is a mixture of pullulan/dextran/fucoidan in a ratio in a range from 70:20:10 to 50:20:30.

7. The porous polysaccharide scaffold according to claim 1 , wherein said cross-linking agent is selected from the group consisting of trisodium trimetaphosphate (STMP), phosphorus oxychloride (POCl 3 ), epichlorohydrin, formaldehydes, carbodiimides, glutaraldehydes, and mixtures thereof.

8. The porous polysaccharide scaffold according to claim 1 , wherein said hydroxyapatite is nano-hydroxyapatite.

9. The porous polysaccharide scaffold according to claim 8 wherein said nano-hydroxyapatite is obtained from a solution of phosphoric acid at a concentration between 0.3 to 1M, with a solution of calcium hydroxide at a concentration between 0.5 to 1.5M, through chemical precipitation at room temperature.

10. The porous polysaccharide scaffold according to claim 9 , wherein said phosphoric acid concentration is 0.6M and said calcium hydroxide concentration is 1M.

11. The porous polysaccharide scaffold of claim 10 , wherein said nano-hydroxide concentration is between 0.1 and 0.5% (w/v) or between 0.1 and 0.3% (w/v).

12. The porous polysaccharide scaffold according to claim 8 wherein a concentration of nano-hydroxyapatite in the alkaline aqueous solution is between 0.01 and 10% (w/v).

13. The porous polysaccharide scaffold according to claim 1 , wherein said porous polysaccharide scaffold contains pores from 1 μm to 500 μm in size and the porosity is from 4% to 75%.

14. The porous polysaccharide scaffold of claim 13 , wherein the pores are from 10 to 200 μm in size and the porosity is from 4% to 50%.

15. The porous polysaccharide scaffold according to claim 1 wherein said solvent is an aqueous solution.

16. The porous polysaccharide scaffold according to claim 1 , wherein a weight ratio of the at least one polysaccharide to said porogen agent is in a range from 1:30 to 30:1 (w/w).

17. The porous polysaccharide scaffold according to claim 16 , wherein said weight ratio is 75:25 (w/w).

18. The porous polysaccharide scaffold according to claim 16 , wherein said ratio is selected from the group consisting of 70:20:10 (w/w), 50:30:20 (w/w), and 73:22:5 (w/w).

Assignees

• Amedee Joelle
• Letourneur Didier
• Le Visage Catherine
• Derkaoui Sidi Mohammed
• Fricain Jean Christophe
• Catros Sylvain
• Inst Nat Sante Rech Med
• Univ De Bordeaux Ii Victor Segalen
• Univ Paris Diderot—Paris 7

Inventors

• Amedee Joelle
• Letourneur Didier
• Le Visage Catherine
• Derkaoui Sidi Mohammed
• Fricain Jean-Christophe
• Catros Sylvain

Classifications

• A61L2400/08

  Methods for forming porous structures using a negative form which is filled and then removed by pyrolysis or dissolution · CPC title

• C08J2201/0444

  Salts · CPC title

• A61L27/20 Primary

  Polysaccharides · CPC title

• A61L27/46

  with phosphorus-containing inorganic fillers · CPC title

• C08J9/26

  by elimination of a solid phase from a macromolecular composition or article, e.g. leaching out · CPC title