Curable bone substitute

• US 20070087031A1
• Filed: 10/19/2006
• Published: 04/19/2007
• Est. Priority Date: 10/19/2005
• Status: Abandoned Application

• Current Assignee: A Enterprises, Inc.
• Original Assignee: A Enterprises, Inc.
• Inventors: Ashman, Arthur, Shipp, Devon
• Application Number:
  US11/584,735
• Publication Number:
  US 20070087031A1
• Time in Patent Office: Days
• US Class Current: 424/423
• CPC Class Codes: A61F 2/28 Bones joints A61F2/30
• CPC Class Codes: A61F 2002/2817 Bone stimulation by chemical reactions or by osteogenic or biological products for enhancing ossification, e.g. by bone morphogenetic or morphogenic proteins [BMP] or by transforming growth factors [TGF]
• CPC Class Codes: A61F 2002/30677 Means for introducing or releasing pharmaceutical products, e.g. antibiotics, into the body
• CPC Class Codes: A61F 2310/00293 containing a phosphorus-containing compound, e.g. apatite
• CPC Class Codes: A61F 2310/00353 Bone cement, e.g. polymethylmethacrylate or PMMA
• CPC Class Codes: A61L 2300/222 Steroids, e.g. corticosteroids
• CPC Class Codes: A61L 2300/252 Polypeptides, proteins, e.g. glycoproteins, lipoproteins, cytokines
• CPC Class Codes: A61L 2300/406 Antibiotics
• CPC Class Codes: A61L 2300/414 Growth factors
• CPC Class Codes: A61L 2300/602 Type of release, e.g. controlled, sustained, slow
• CPC Class Codes: A61L 2430/02 for reconstruction of bones; weight-bearing implants
• CPC Class Codes: A61L 27/46 with phosphorus-containing inorganic fillers
• CPC Class Codes: A61L 27/50 Materials characterised by their function or physical properties , e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
• 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

Abstract

A novel composition, kit, and method of using the composition as a bone substitute for dental, orthopedic and drug delivery purposes. Specifically, the bone substitute comprises a plurality of polymeric beads having a crosslinkable shell where the shell is cured by light and/or chemical curing.

Claims

1. A crosslinkable bone substitute material comprising micron sized particles, each particle having

a core comprising one or more first biologically-compatible material(s), and

a shell generally surrounding the core, the shell comprising one or more second biologically-compatible polymer or polymerizable material(s) having at least one crosslinkable reactive group;

wherein the bone substitute material has interstices between the particles forming pores into which bone tissue can grow; and

wherein the shell forms a crosslinked polymer upon curing by light and/or redox chemistry.

2. The bone substitute of claim 1, wherein the core comprises a polymeric alloplast.

3. The bone substitute of claim 1, wherein the core comprises polymethylmethacrylate and polymeric hydroxyethylmethacrylate.

4. The bone substitute of claim 3, wherein the core comprises calcium hydroxide distributed on the outer surfaces of the core particles.

5. The bone substitute of claim 3, wherein the core comprises intra-particle pores and extra-particle pores into which bone tissue can grow.

6. The bone substitute of claim 1, wherein the core comprises a ceramic or ceramic/polymer hybrid.

7. The bone substitute of claim 6, wherein the core comprises a hydroxyapatite, tricalcium phosphate, or mixture thereof.

8. The bone substitute of claim 1, wherein the shell comprises a hydrophilic polymer.

9. The bone substitute of claim 1, wherein the shell comprises a polymer or prepolymer comprising a vinyl group.

10. The bone substitute of claim 9, wherein the shell comprises hydroxyethylmethacrylate, poly(ethylene glycol) diacrylate, poly hydroxyethylmethacrylate, or a combination thereof.

11. The bone substitute of claim 10, wherein the shell comprises hydroxyethylmethacrylate.

12. The bone substitute of claim 10, wherein the shell comprises poly(ethylene glycol) diacrylate.

13. The bone substitute of claim 1, wherein the shell is crosslinked using a photoinitiator blue dental light or a UV light.

14. The bone substitute of claim 1, further comprising a bone or soft tissue growth factor or a therapeutic agent.

15. The bone substitute of claim 14, wherein the growth factor or therapeutic agent is protected by gelatin-based wet granulation.

16. The bone substitute of claim 14, wherein the growth factor is a steroid or an antibiotic.

17. The bone substitute of claim 14, wherein the therapeutic agent is a bone morphogenic protein.

18. The bone substitute of claim 14, wherein the growth factor or therapeutic agent is released slowly from the bone substitute.

19. A crosslinked bone substitute comprising a matrix of micron sized particles, each particle having

a core comprising one or more first biologically-compatible material(s) and a shell generally surrounding the core, the shell comprising one or more second biologically-compatible polymeric material(s);

wherein each particle shell has at least one crosslinked moiety electrostatically or chemically bound to a crosslinked moiety of a different particle shell;

wherein the bone substitute has interstices between the particles forming pores into which bone tissue can grow.

20. The bone substitute of claim 19, wherein the core comprises a polymeric alloplast.

21. The bone substitute of claim 19, wherein the core comprises polymethylmethacrylate and polymeric hydroxyethylmethacrylate.

22. The bone substitute of claim 21, wherein the core comprises calcium hydroxide distributed on the outer surfaces of the core particles.

23. The bone substitute of claim 19, wherein the core comprises a ceramic or ceramic/polymer hybrid.

24. The bone substitute of claim 19, wherein the shell comprises a hydrophilic polymer.

25. The bone substitute of claim 19, wherein the shell comprises hydroxyethylmethacrylate, polyhydroxyethylmethacrylate, poly(ethylene glycol) methacrylate, poly(ethylene glycol) diacrylate, or a combination thereof.

26. The bone substitute of claim 19, wherein the shell is crosslinked using a photoinitiator blue dental light or a UV light.

27. The bone substitute of claim 19, further comprising a bone or soft tissue growth factor or a therapeutic agent.

28. A method of promoting bone generation comprising the steps:

(i) mixing a core comprising one or more first biologically-compatible material(s), a shell material comprising one or more second biologically-compatible hydrophilic polymer or polymerizable material(s) having at least one crosslinkable reactive group, and an initiator to form a crosslinkable bone substitute;

(ii) applying the crosslinkable bone substitute to an area in need of bone generation; and

(iii) crosslinking the bone substitute,

wherein the bone substitute promotes and/or induces bone generation.

29. The method of claim 28, wherein the initiator comprises a photoinitiator and crosslinking comprises applying light.

30. The method of claim 28, wherein the initiator comprises a redox couple.

31. The method of claim 28, wherein the initiator comprises component A which comprises a photochemical initiator and a radical generator;

and component B which comprises a photochemical accelerator and a reducing agent.

32. A delivery system comprising:

(i) micron sized core particles comprising one or more first biologically-compatible material(s) and

(ii) a shell material comprising one or more second biologically-compatible hydrophilic polymer or polymerizable material(s) having at least one crosslinkable reactive group;

(iii) initiator component A comprising a photochemical initiator; and

(iv) initiator component B comprising a photochemical accelerator.

33. The delivery system of claim 32, wherein the shell material generally surrounds the core particles.

34. The delivery system of claim 32, wherein initiator component A further comprises an oxidizing agent and component B further comprises a reducing agent.

35. The delivery system of claim 32, wherein the core particles, shell material, and initiator component B are combined in one container and initiator component A is in a second container.

36. The delivery system of claim 32, wherein the photochemical initiator of component A is camphorquinone.

37. The delivery system of claim 32, wherein the oxidizing agent of component A is a peroxide or azo compound.

38. The delivery system of claim 32, wherein initiator component A comprises camphorquinone and benzoyl peroxide and initiator component B comprises 4-ethyl-dimethyl amino benzoate and N,N-dimethyl-p-toluidine.