Functionalized artificial bone and joint compositions and methods of use and manufacture

Abstract

The present invention provides a functionalized ceramic body for in vitro and in vivo use comprising a calcium aluminate containing phase that is functionalized with a linker group comprising at least one of an organic acid molecule, a phosphonic acid, an amine, and N,N-dicyclohexylcarbodiimide for providing a reactive location for the attachment of at least one of another chemical moiety or a biologically active moiety to the ceramic body. Functionalized compositions are provided comprising a calcium aluminate containing phase that is functionalized with the linker group. Methods of manufacturing a functionalized artificial prosthesis that may be used as artificial bones, joints, in-vitro support structures, and in-vivo support structures for cells, tissues, organs, and nerve growth and regeneration are disclosed.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1. MG-63 cells attach and proliferate on compositions comprising a calcium aluminate containing phase of the present inventions under static (A) and dynamic (B) culture conditions as assessed by CyQuant assay.

FIG. 2. MG-63 cells maintain high viability when seeded and cultured on compositions comprising a calcium aluminate containing phase of the present invention.

FIG. 3. MG-63 cells attach on compositions comprising a calcium aluminate containing phase of the present invention as assessed by scanning electron microscopy.

FIG. 4. Human adult mesenchymal stem cells attach and show high viability but variable proliferation on compositions comprising a calcium aluminate containing phase of the present invention under static (A) and dynamic (B) culture conditions.

FIG. 5. Human adult mesenchymal stem cells attach on compositions comprising a calcium aluminate containing phase of the present invention as assessed by scanning electron microscopy.

FIG. 6. hAMSC on CA express alkaline phosphatase in response to an osteogenic supplement.

FIG. 7. Compositions comprising a calcium aluminate containing phase of the present invention is non-toxic as assessed by chick CAM assays.

FIGS. 8-17 Show spectra of various embodiments of the functionalized compositions comprising a calcium aluminate containing phase of the present invention.

FIGS. 18 Shows bone implants used to help repair or replace damaged bone.

FIG. 19 Shows a preferable form of the compositions comprising a calcium aluminate containing phase of the present invention and the functionalized “interface” between the “surface” of the compositions and the biologic “tissue”.

FIG. 20 shows that by varying the functionality of the head and tail groups of acids used as linkers that the calcium aluminate containing compositions may be modified in many ways to provide reactive locations for attachment of other chemical moieties and/or biologic moieties.

FIG. 21 shows phosphonic acid as the linker to functionalize the calcium aluminate containing phase of the compositions of this invention.

FIG. 22 shows an example of carboxylic acid binding onto the surface of a calcium aluminate containing composition of this invention. The spectra shown is that of stearic acid absorbed on the surface of a calcium aluminate containing composition.

FIG. 23 shows the functionalization of a calcium aluminate containing composition of this invention with organic acid tail group variations.

FIG. 24 shows the functionalization (coupling) for bonding an antibiotic, namely ampicillin, to a calcium aluminate containing composition of this invention.

FIG. 25 shows the spectra of an antibiotic, namely ampicillin, linked to a dicarboxylic-functionalized calcium aluminate containing composition of this invention.

FIG. 26 shows RGDC peptide coupling to an amino-functionalized calcium aluminate containing composition of this invention.

Claims

1. A functionalized ceramic body for in vitro and in vivo use comprising: a calcium aluminate containing phase that is functionalized with a linker group comprising at least one of an organic acid molecule, a phosphonic acid, an amine, and N,N-dicyclohexylcarbodiimide for providing a reactive location for the attachment of at least one of another chemical moiety or a biologically active moiety to the ceramic body.

2. The functionalized ceramic body of claim 1 wherein the calcium aluminate containing phase comprising one or more phases, analogs and derivatives of calcium aluminate that result from the interaction of CnAy, CnAy-hydrates, CaO, Al2O3, AlnOy-hydrates with or without PnOyx to form CX and/or AX and/or CAX, wherein n is an integer from about 1 to about 12, y is an integer from about 1 to about 24, x is an integer from about 1 to about 12, X is a phosphate moiety, C is CaO, and A is Al2O3.

3. The functionalized ceramic body of claim 1 wherein said organic acid has a formula of (CO2H)aCnH2n+(−2+2)Xd, wherein X is selected from the group of CH3, COOH, OH, NH2, and Br and wherein a is a number from about 1 to about 3, wherein n is a number from about 1 to about 1000, and wherein d is a number from about 1 to about 3.

4. The functionalized ceramic body of claim 1 wherein an antibiotic is the moiety attached to the calcium aluminate containing phase.

5. The functionalized ceramic body of claim 1 further comprising at least one of a retarder, water, an accelerator, a surfactant, a foaming agent, a fiber, a source of phosphate, an orthophosphate, and a reactive alumina, and combinations thereof.

6. The functionalized ceramic body of claim 1 functionalized with an organic acid and subsequently reacted with 3-maleimidopropionic acid N-hydroxysuccinimide ester for binding one or more peptides to an amino-functionalized calcium aluminate containing phase.

7. The functionalized ceramic body of claim 1 that is an artificial prosthesis wherein said artificial prosthesis is selected from the group consisting of an artificial bone, artificial joint, in-vitro support structure, an in-vivo support structure, and a scaffolding matrix for support of cell, tissue, organ, and nerve growth.

8. A functionalized composition comprising: a calcium aluminate containing phase that is functionalized with a linker group comprising at least one of an organic acid molecule, a phosphonic acid, an amine, and N,N-dicyclohexylcarbodiimide for providing a reactive location for the attachment of at least one of another chemical moiety or a biologically active moiety to said calcium aluminate containing phase.

9. The functionalized composition of claim 8 wherein said calcium aluminate containing phase comprising one or more phases, analogs and derivatives of calcium aluminate that result from the interaction of CnAy, CnAy-hydrates, CaO, Al2O3, AlnOy-hydrates with or without PnOyx to form CX and/or AX and/or CAX, wherein n is an integer from about 1 to about 12, y is an integer from about 1 to about 24, x in an integer from about 1 to about 12, X is a phosphate moiety, C is CaO, and A is Al2O3.

10. The functionalized composition of claim 8 wherein said organic acid has a formula of (CO2H)aCnH2n+(−2+2)Xd, wherein X is selected from the group of CH3, COOH, OH, NH2, and Br and wherein a is a number from about 1 to about 3, wherein n is a number from about 1 to about 1000, and wherein d is a number from about 1 to about 3.

11. The functionalized composition of claim 8 wherein an antibiotic is the moiety attached to the calcium aluminate containing phase.

12. The functionalized composition of claim 8 further comprising at least one of a retarder, water, an accelerator, a surfactant, a foaming agent, a fiber, a source of phosphate, an orthophosphate, and a reactive alumina, and combinations thereof.

13. The functionalized composition of claim 8 wherein said calcium aluminate containing phase is functionalized with and organic acid and subsequently reacted with 3-maleimidopropionic acid N-hydroxysuccinimide ester for binding one or more peptides to an amino-functionalized calcium aluminate containing phase.

14. A method of making an artificial prosthesis comprising: mapping of a patient's identified bone or tissue structure;creating a three dimensional pattern of said identified bone or tissue structure from said mapped bone or tissue structure;creating a mold or negative of said identified bone or tissue structure from said pattern;casting a functionalized composition comprising a calcium aluminate containing phase that is functionalized with a linker group comprising at least one of an organic acid molecule, a phosphonic acid, an amine, and N,N-dicyclohexylcarbodiimide for providing a reactive location for the attachment of at least one of another chemical moiety or a biologically active moiety to said calcium aluminate containing phase, into said mold thereby forming said artificial prosthesis.

15. The method of claim 14 including wherein said calcium aluminate containing phase comprising one or more phases, analogs and derivatives of calcium aluminate that result from the interaction of CnAy, CnAy-hydrates, CaO, Al2O3, AlnOy-hydrates with or without PnOyx to form CX and/or AX and/or CAX, wherein n is an integer from about 1 to about 12, y is an integer from about 1 to about 24, x in an integer from about 1 to about 12, X is a phosphate moiety, C is CaO, and A is Al2O3.

16. The method of claim 14 including wherein said linker group is an organic acid having a formula of (CO2H)aCnH2n+(−2+2)Xd, wherein X is selected from the group of CH3, COOH, OH, NH2, and Br and wherein a is a number from about 1 to about 3, wherein n is a number from about 1 to about 1000, and wherein d is a number from about 1 to about 3.

17. The method of claim 14 including wherein an antibiotic is the moiety attached to said calcium aluminate containing phase.

18. The method of claim 14 including wherein said functionalized composition further comprises at least one of a retarder, water, an accelerator, a surfactant, a foaming agent, a fiber, a source of phosphate, an orthophosphate, and a reactive alumina, and combinations thereof.

19. The method of claim 14 including wherein said calcium aluminate containing phase is functionalized with an organic acid and subsequently reacted with 3-maleimidopropionic acid N-hydroxysuccinimide ester for binding one or more peptides to an amino-functionalized calcium aluminate.