Nanofiber construct and method of preparing thereof

• US 20060154063A1
• Filed: 12/15/2005
• Published: 07/13/2006
• Est. Priority Date: 12/15/2004
• Status: Abandoned Application

• Current Assignee: National University of Singapore
• Original Assignee: National University of Singapore
• Inventors: Chan, Kwan-Ho C., Kotaki, Masaya, Ramakrishna, Seeram, Fujihara, Kazutoshi
• Application Number:
  US11/300,379
• Publication Number:
  US 20060154063A1
• Time in Patent Office: Days
• US Class Current: 428/373
• CPC Class Codes: A61L 2400/12 Nanosized materials, e.g. nanofibres, nanoparticles, nanowires, nanotubes; Nanostructured surfaces
• CPC Class Codes: A61L 2400/18 Modification of implant surfaces in order to improve biocompatibility, cell growth, fixation of biomolecules, e.g. plasma treatment
• CPC Class Codes: A61L 27/18 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
• CPC Class Codes: A61L 27/46 with phosphorus-containing inorganic fillers
• CPC Class Codes: C08L 67/04 Polyesters derived from hydroxycarboxylic acids, e.g. lactones C08L67/06 takes precedence
• CPC Class Codes: D01D 5/0007 Electro-spinning non-woven fabrics produced by electro-spinning D04H1/728
• CPC Class Codes: D01F 1/10 Other agents for modifying properties
• CPC Class Codes: D01F 6/625 derived from hydroxy-carboxylic acids, e.g. lactones
• CPC Class Codes: Y10T 428/2929 Bicomponent, conjugate, composite or collateral fibers or filaments [i.e., coextruded sheath-core or side-by-side type]

Abstract

The present invention provides a composite nanofiber construct comprising: at least a first nanofiber comprising at least a polymer and at least a calcium salt nanoparticle, wherein the ratio of polymer to calcium salt nanoparticle is between the range of 99:1 and 10:90 weight percent; and at least a second nanofiber comprising at least a polymer and at least a calcium salt nanoparticle, wherein the ratio of polymer to calcium salt nanoparticle is between the range of 100:0 and 70:30 weight percent. The present invention also provides a method of preparing the composite nanofiber construct.

Claims

1. A composite nanofiber construct comprising:

at least a first nanofiber comprising at least a polymer and at least a calcium salt nanoparticle, wherein the ratio of polymer to calcium salt nanoparticle is between the range of 99;

1 and 10;

90 weight percent; and

at least a second nanofiber comprising at least a polymer and at least a calcium salt nanoparticle, wherein the ratio of polymer to calcium salt nanoparticle is between the range of 100;

0 and 70;

30 weight percent.

2. The construct according to claim 1, wherein the at least first nanofiber and the at least second nanofiber have the same or a different polymer to calcium salt nanoparticle ratio.

3. The construct according to claim 1, wherein the ratio of polymer to calcium salt nanoparticle of the first nanofiber is 75:

25 weight percent.

4. The construct according to claim 1, wherein the ratio of polymer to calcium salt nanoparticle of the second nanofiber is 95:

5 weight percent.

5. The construct according to claim 1, wherein the ratio of polymer to calcium salt nanoparticle of the second nanofiber is 100:

0 weight percent.

6. The construct according to claim 1, wherein the average diameter of the at least first nanofiber is smaller than the average diameter of the at least second nanofiber.

7. The construct according to claim 1, wherein the at least first nanofiber and the at least second nanofiber form one structure.

8. The construct according to claim 1, wherein the at least first nanofiber forms a first structure and the at least second nanofiber forms a second structure, and wherein the first and second structures are in contact with each other.

9. The construct according to claim 1, wherein the first nanofiber and second nanofiber are intertwined.

10. The construct according to claim 7, wherein the structure is a layer.

11. The construct according to claim 8, wherein the first and second structures are layers.

12. The construct according to claim 1, wherein the polymer is a bioabsorbable polymer.

13. The construct according to claim 1, wherein the polymer is selected from the group consisting of:

polycaprolactone, polyethylene oxide, poly-L-lactic acid, polygyycolide, poly(DL-lactide), poly(L-lactide), polydioxanone, chitin, collagen in its native or cross-linked form, poly(glutamic-co-leucine), poly-lactic-glycolide acid, poly(L-lactic acid-caprolactone) copolymer and blends, copolymers and terpolymers thereof.

14. The construct according to claim 1, wherein the polymer is ε

-polycaprolactone.

15. The construct according to claim 1, wherein the calcium salt nanoparticle is selected from the group consisting of:

calcium carbonate, calcium sulphate, calcium phosphate or hydroxyapatite.

16. The construct according to claim 15, wherein the calcium salt is calcium carbonate.

17. The construct according to claim 1, wherein the construct further comprises seeded cells.

18. The construct according to claim 17, wherein the cells are selected from the group consisting of osteoblasts, endothelial cells, smooth muscle cells, mesenchymal stem cells, embryonic stem cells, chondroblasts, fibrocytes, fibroblasts and chondrocytes.

19. The construct according to claim 1, wherein the construct is an implant.

20. The construct according to claim 1, wherein the construct is surface functionalized.

21. The construct according to claim 20, wherein the construct is surface functionalized by plasma treatment.

34. A method of repairing fractured bone segments in a subject, comprising the step of surgically implanting the construct of claim 1.

22. A method of preparing a composite nanofiber construct, the method comprising the steps of:

preparing at least a first nanofiber comprising at least a polymer and at least a calcium salt nanoparticle, wherein the ratio of polymer to calcium salt nanoparticles is between the range of 99;

1 and 10;

90 weight percent;

preparing at least a second nanofiber comprising at least a polymer and at least a calcium salt nanoparticle, wherein the ratio of polymer to calcium salt nanoparticle is between the range of 100;

0 and 70;

30 weight percent; and

preparing a composite nanofiber construct by contacting the first nanofiber with the second nanofiber.

23. The method according to claim 22, wherein the at least first nanofiber and the at least second nanofiber have the same or a different polymer to calcium salt nanoparticle ratio.

24. The method according to claim 22, wherein the first nanofiber is prepared by adding calcium salt to a solvent and mixing the resulting mixture with the first polymer obtaining a first solvent mixture;

and the second nanofiber is prepared by adding calcium salt to a solvent and mixing the resulted mixture with the second polymer obtaining a second solvent mixture.

25. The method according to claim 22, wherein the first nanofiber is prepared by adding calcium salt to a solvent and mixing the resulting mixture with the first polymer obtaining a first solvent mixture;

and the second nanofiber is prepared by adding the second polymer to a solvent obtaining a second solvent mixture.

26. The method according to claim 24, wherein the first and second solvent mixtures comprise methanol and/or chloroform.

27. The method according to claim 25, wherein the first and second solvent mixtures comprise methanol and/or chloroform.

28. The method according to claim 22, wherein the ratio of polymer to calcium salt nanoparticle of the second nanofiber is 100:

0 weight percent.

29. The method according to claim 22, wherein the average diameter of the at least first nanofiber is smaller than the average diameter of the at least second nanofiber.

30. The method according to claim 24, wherein the first solvent mixture and second solvent mixture are provided simultaneously, and wherein the at least first nanofiber and the at least second nanofiber are intertwined.

31. The method according to claim 25, wherein the first solvent mixture and the second solvent mixture are provided consecutively, and wherein the at least first nanofiber and the at least second nanofiber are separate from each other.

32. The method according to claim 22, wherein the method further comprises the step of surface functionalizing the construct.

33. A kit comprising a composite nanofiber construct comprising:

at least a first nanofiber comprising at least a polymer and at least a calcium salt nanoparticle, wherein the ratio of polymer to calcium salt nanoparticle is between the range of 99;

1 and 10;

90 weight percent; and

at least a second nanofiber comprising at least a polymer and at least a calcium salt nanoparticle, wherein the ratio of polymer to calcium salt nanoparticle is between the range of 100;

0 and 70;

30 weight percent.