COMPLEX SUPPORT BODY FOR REGENERATING BONE-CARTILAGE, METHOD FOR MANUFACTURING THEREOF, AND COMPOSITION FOR TREATING BONE AND CARTILAGE RELATED DISEASES COMPRISING SAME AS ACTIVE INGREDIENT

• US 20140012393A1
• Filed: 02/20/2012
• Published: 01/09/2014
• Est. Priority Date: 03/31/2011
• Status: Active Grant

• Current Assignee: Industry-Academia Cooperation Group (Inje University)
• Original Assignee: Industry-Academia Cooperation Group (Inje University)
• Inventors: Shin, Jung Woog, Shin, Ji Won, Park, So Hee
• Granted Patent: US 9,681,953 B2
• Time in Patent Office: Days
• US Class Current: 623/23.51
• CPC Class Codes: A61F 2/28 Bones joints A61F2/30
• CPC Class Codes: A61F 2/30756 Cartilage endoprostheses A61F2/3603 takes precedence
• CPC Class Codes: A61F 2/3094 Designing or manufacturing processes
• CPC Class Codes: A61F 2002/30766 Scaffolds for cartilage ingrowth and regeneration
• CPC Class Codes: A61L 2430/02 for reconstruction of bones; weight-bearing implants
• CPC Class Codes: A61L 2430/06 for cartilage reconstruction, e.g. meniscus
• CPC Class Codes: A61L 27/12 Phosphorus-containing materials, e.g. apatite
• CPC Class Codes: A61L 27/3817 Cartilage-forming cells, e.g. pre-chondrocytes
• CPC Class Codes: A61L 27/54 Biologically active materials, e.g. therapeutic substances A61L27/227 takes precedence
• 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

Abstract

The present invention relates to a complex support body for regenerating bone-cartilage, a method for manufacturing thereof, and a composition for treating bone and cartilage related diseases comprising the same as an active ingredient, and more particularly, to a complex support body for regenerating bone-cartilage, which comprises a bone regeneration layer consisting of a biodegradable polymer and a biocompatible ceramic, and a cartilage regeneration layer, which is coupled to the bone regeneration layer and in which cells that can be differentiated into cartilages cells are fixed; a method for manufacturing thereof; and a composition for treating bone and cartilage related diseases comprising the same as an active ingredient. The complex support body of the present invention for regenerating bone-cartilage is manufactured as a three-dimensional support body, which is similar to a living tissue, according to a bioplotting method, and exerts the effect of regeneration into a bone tissue and a cartilage tissue, respectively, depending on materials encountered in the environment where the complex support body for regenerating bone-cartilage is used.

Claims

1. A complex support body for regenerating bone-cartilage comprising:

(a) a bone regeneration layer; and

(b) a cartilage regeneration layer, which is coupled to the bone regeneration layer and in which cells that can be differentiated into cartilage cells are fixed.

2. The complex support body for regenerating bone-cartilage according to claim 1, wherein the bone regeneration layer comprises a biodegradable polymer and a biocompatible ceramic.

3. The complex support body for regenerating bone-cartilage according to claim 2, wherein the bone regeneration layer comprises the biodegradable polymer in an amount of 85 to 95 wt % and the biocompatible ceramic in an amount of 5 to 15 wt %.

4. The complex support body for regenerating bone-cartilage according to claim 1, wherein the cartilage regeneration layer is a cell-fixed biodegradable polymer support body.

5. The complex support body for regenerating bone-cartilage according to claim 2, wherein the biodegradable polymer is at least one biodegradable polymer selected from the group consisting of alginate, hyaluronic acid, collagen, gelatin, cellulose methyl cellulose, chitosan, poly(lactic acid), poly(glycolic acid) (PGA), poly(lactic-co-glycolic acid) (PLGA), poly-caprolactone, poly(anhydrides), polyorthoesters, polyvinylalcohol, poly (ethyleneglycol), polyurethane, polyacrylic acid, poly (N-isopropyl acrylamide), poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) copolymer and a copolymer of two or more of them.

6. The complex support body for regenerating bone-cartilage according to claim 2, wherein the biodegradable polymer is a poly-caprolactone.

7. The complex support body for regenerating bone-cartilage according to claim 4, wherein the biodegradable polymer is alginate.

8. The complex support body for regenerating bone-cartilage according to claim 2, wherein the biocompatible ceramic is at least one selected from the group consisting of hydroxyapatite (HA), ceramic-containing inorganic substances, fluorinated apatite, monocalcium calcium phosphate Ca(H₂PO₄)₂, dibasic calcium phosphate (CaHPO₄), tribasic calcium phosphate (Ca₃(PO₄)₂), Octacalcium phosphate (Ca₈H₂ (PO₄)₆.5H₂O)

9. The complex support body for regenerating bone-cartilage according to claim 1, wherein the cells that can be differentiated into cartilage cells is at least one cells selected from the group consisting of:

mesenchymal stem cells and interstitial cells, which are isolated from any one of bone marrow, muscle, fat, umbilical cord, amnion and amniotic fluid; and

precursor cells, which are derived from the cells and can be differentiated into cartilage cells.

10. The complex support body for regenerating bone-cartilage according to claim 1, wherein the bone regeneration layer comprises pores in the size of 100 to 700 μ

m, and the cartilage regeneration layer comprises pores in the size of 50 to 700 μ

m.

11. A composition for treating bone-cartilage related diseases comprising the complex support body for regenerating bone-cartilage of claim 1 as an active ingredient.

12. The composition for treating bone-cartilage related diseases according to claim 11, which further comprises a bone morphogenic inducing factor.

13. A method for manufacturing a complex support body for regenerating bone-cartilage comprising:

i) a step of manufacturing a cartilage regeneration layer;

ii) a step of manufacturing a bone regeneration layer; and

iii) a step of linking the cartilage regeneration layer and the bone regeneration layer.

14. The method for manufacturing a complex support body for regenerating bone-cartilage according to claim 13, wherein the step of manufacturing a cartilage regeneration layer comprises:

i-1) a step of mixing alginate to a solution containing a cell culture medium, 0.3 wt % CaCl₂ and 0.15 M NaCl up to 4 wt % to prepare cross-linked alginate;

i-2) a step of mixing cells that can be differentiated into cartilages cells to the cross-linked alginate; and

i-3) a step of manufacturing a cartilage regeneration layer by using the mixture of the cross-linked alginate and the cells that can be differentiated into cartilages cells according to a rapid prototype method.

15. The method for manufacturing a complex support body for regenerating bone-cartilage according to claim 13, wherein the step of manufacturing a bone regeneration layer comprises:

ii-1) a step of dissolving a biodegradable polymer by heating;

ii-2) a step of mixing the biodegradable polymer of 85 to 95 wt % and a biocompatible ceramic of 5 to 15 wt % followed by stirring and cooling thereof for solidification;

ii-3) a step of manufacturing a bone regeneration layer by using the solidified material according to a rapid prototype method; and

ii-4) a step of seeding cells that can be differentiated into bone cells to the manufactured bone regeneration layer.

16. The method for manufacturing a complex support body for regenerating bone-cartilage according to claim 13, wherein the cells that can be differentiated into bone cells are at least one cells selected from the group consisting of:

mesenchymal stem cells and interstitial cells, which are isolated from any one of bone marrow, muscle, fat, umbilical cord, amnion and amniotic fluid; and

precursor cells, winch are derived from the cells and can be differentiated into bone cells.

17. The method for manufacturing a complex support body for regenerating bone-cartilage according to claim 14, wherein the rapid prototype method is using a bioplotting system.

18. The method for manufacturing a complex support body for regenerating bone-cartilage according to claim 13, wherein, in the step of linking the cartilage regeneration layer and the bone regeneration layer, the manufactured cartilage regeneration layer and bone regeneration layer are linked by at least one glue selected from the group consisting of fibrin glue, gelatin glue, polyurethane-containing glue and cyanoacrylate-containing glue.