Porous ceramic composite bone grafts

• US 20060198939A1
• Filed: 09/24/2002
• Published: 09/07/2006
• Est. Priority Date: 09/24/2001
• Status: Active Grant

• Current Assignee: Warsaw Orthopedic Incorporated (Medtronic Plc)
• Original Assignee: Warsaw Orthopedic Incorporated (Medtronic Plc)
• Inventors: Jason, Hendry, Reginald, Smith, Smith, Timothy J.N., Sydney, M Pugh
• Granted Patent: US 7,875,342 B2
• Time in Patent Office: Days
• US Class Current: 427/2.1
• 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 27/425 of phosphorus containing material, e.g. apatite
• CPC Class Codes: A61L 27/46 with phosphorus-containing inorganic fillers
• CPC Class Codes: A61L 27/56 Porous materials, e.g. foams or sponges
• CPC Class Codes: A61P 19/00 Drugs for skeletal disorders
• CPC Class Codes: B33Y 80/00 Products made by additive manufacturing
• CPC Class Codes: Y10T 428/249967 Inorganic matrix in void-containing component
• CPC Class Codes: Y10T 428/249978 Voids specified as micro
• CPC Class Codes: Y10T 428/249979 Specified thickness of void-containing component [absolute or relative] or numerical cell dimension
• CPC Class Codes: Y10T 428/249981 Plural void-containing components
• CPC Class Codes: Y10T 428/249987 With nonvoid component of specified composition

Abstract

The invention relates to porous ceramic composites incorporating biodegradable polymers for use as a bone substitute in the fields of orthopaedics and dentistry or as a scaffold for tissue engineering applications. The porous ceramic composite implant for connective tissue replacement comprises a porous ceramic matrix having a biodegradable polymer provided on internal and external surfaces of the ceramic matrix. The biodegradable polymer allows for the passage and/or delivery of a variety of agents throughout the porous ceramic matrix and improves mechanical properties of the implant in vivo.

Claims

1. A porous ceramic composite implant, said implant comprising;

a porous ceramic matrix having a biodegradable polymer provided on internal and external surfaces of said ceramic matrix, wherein said biodegradable polymer allows for the passage and/or delivery of a variety of agents throughout said porous ceramic matrix and improves mechanical properties of said implant.

2. The implant of claim 1, wherein said biodegradable polymer is provided as a continuous coating.

3. The implant of claim 1, wherein said biodegradable polymer is provided as a discontinuous coating.

4. The implant of any one of claims 1 to 3, wherein said biodegradable polymer is porous.

5. The implant of claim 2, 3 or 4, wherein said biodegradable polymer is provided as a polymer composite further comprising particles of ceramic matrix.

6. The implant of claims 4 or 5, wherein said biodegradable polymer is selected from the group consisting of photosensitive polymers, polycaprolactone, polyanhydrides, poly(ortho esters), poly(amino acids), pseudo-poly(amino acids), polyethylene glycol, polyesters and mixtures thereof.

7. The implant of claim 6, wherein said photosensitive polymers are selected from polyhydroxybutyrate, polyhydroxyvalerate and copolymers thereof.

8. The implant of claim 6, wherein said polyester is selected from poly(lactic acid) and poly(glycolic acid).

9. The implant of claim 4 or 5, wherein said coating has a thickness of up to about 250 microns.

10. The implant of claim 9, wherein said biodegradable polymer has a pharmaceutical agent incorporated therein.

11. The implant of claim 10, wherein said pharmaceutical agent is an agent selected from the group consisting of epidermal growth factor, fibroblast growth factor, platelet derived growth factor, transforming growth factor, antimicrobials, antibiotics, parathyroid hormone, leukemia inhibitory factor, insulin-like growth factor, bone morphogenetic proteins, osteogenin, sodium fluoride, estrogens, calcitonin, biphosphonates, calcium carbonate, prostaglandins, vitamin K and mixtures thereof.

12. The implant of claim 9 or 10, wherein said porous ceramic matrix is loaded with a population of cells selected from the group consisting of cartilage cells, tendon cells, bone cells, ligament cells, organ cells, musculotendinous cells and mixtures thereof.

13. The implant of claim 1 or 9, wherein said porous ceramic matrix is a compound comprising calcium, oxygen and phosphorous, wherein a portion of at least one of said elements is substituted with an element having an ionic radius of approximately 0.1 to 0.6 Å

.

14. The implant of claim 13, wherein said compound has the formula:

(Ca)_i{(P_1-x-y-zB_xC_yD_z)O_j}₂

wherein B, C and D are selected from those elements having an ionic radius of approximately 0.1 to0.4 Å

;

x is greater than or equal to zero but less than 1;

y is greater than or equal to zero but less than 1;

z is greater than or equal to zero but less than 1;

x+y+z is greater than zero but less than 1;

i is greater than or equal to 2 but less than or equal to 4; and

j is equal 4−

δ

, where δ

is greater than or equal to zero but less than or equal to 1.

15. The implant of claim 4, wherein said biodegradable polymer has a porosity of about 50 to about 200 microns.

16. The implant of claim 1 or 4, wherein said biodegradable polymer has a substantially high degree of porosity.

17. The implant of claim 16, wherein said porous ceramic matrix has a porosity of about 200 to about 600 microns.

18. The implant of claim 5, wherein said ceramic particles are up to about 50 microns.

19. The implant of claim 17, wherein said porous ceramic matrix has a gradient porosity.

20. A method of making a porous ceramic implant for connective tissue replacement, said method comprising;

(i) impregnating an organic reticulated foam structure with a slurry of calcium-phosphate compound;

(ii) drying the impregnated foam structure to form a slurry coated foam structure; and

(iii) pyrolyzing the slurry coated foam structure formed in (ii) and sintering to provide a fused ceramic porous implant having a plurality of interconnected voids.

21. The method of claim 20, wherein said slurry is formed by mixing a calcium phosphate compound with water and a dispersing agent.

22. The method of claim 21, wherein said dispersing agent is selected from the group consisting of sodium polyacrylate, ammonium polyacrylate, sodium citrate, sodium tartrate, sodium carbonate, sodium silicate, tetrasodium pyrophosphate and mixtures thereof.

23. The method of claim 22, wherein said slurry comprises about 1 to about 3.5% by volume dispersing agent.

24. The method of claim 21, wherein said slurry is milled to contain solid particle sizes of up to about 50 microns prior to impregnation of said foam structure.

25. The method of claim 24, wherein one or more additives is added to said slurry.

26. The method of claim 25, wherein said additive is selected from the group consisting of binder, wetting agent, anti-foaming agent and mixtures thereof.

27. The method of claim 26, wherein said slurry comprises about less than 10% by volume binder.

28. The method of claim 26, wherein said slurry comprises less than about 2% by volume wetting agent.

29. The method of claim 26, wherein said slurry comprises less than about 2% by volume anti-foaming agent.

30. The method of claim 20, wherein step (ii) is repeated until a desired thickness of coating of up to about 100 microns is achieved.

31. The method of claim 24, wherein said slurry has a solid content of milled particles of up to about 30% by volume.

32. The method of claim 20, wherein after step (i) any excess slurry is removed by vacuum.

33. The method of claim 20, wherein step (ii) is conducted at a temperature of up to about 90°

C.

34. The method of claim 33, wherein step (iii) heating is conducted at a temperature of up to about 200°

C. and sintering is conducted at a temperature of up to about 1300°

C.

35. The method of claim 20, wherein after step (iii) a thermally decomposable material is provided within interstices of the porous ceramic composite and a slip casting process is used to coat selected surfaces of said porous ceramic composite followed by thermal processing to provide a solid ceramic coating on said ceramic porous implant.

36. The method of claim 20 or 35, wherein said calcium phosphate compound comprises calcium, oxygen and phosphorous, wherein a portion of at least one of said elements is substituted with an element having an ionic radius of approximately 0.1 to 0.6 Å

.

37. The method of claim 36, wherein said compound has the formula:

(Ca)_i{(P_1-x-y-zB_xC_yD_z)O_j}₂

wherein B, C and D are selected from those elements having an ionic radius of approximately 0.1 to 0.4 Å

;

x is greater than or equal to zero but less than 1;

y is greater than or equal to zero but less than 1;

z is greater than or equal to zero but less than 1;

x+y+z is greater than zero but less than 1;

i is greater than or equal to 2 but less than or equal to 4; and

j is equal 4−

δ

, where δ

is greater than or equal to zero but less than or equal to 1.

38. The method of claim 20, wherein step (i) is conducted using centripetal force to provide gradient porosity.

39. The method of claim 20 or 35, wherein a biodegradable polymer is applied to exterior and interior surfaces of said porous ceramic implant.

40. The method of claim 39, wherein said biodegradable polymer is provided as a continuous coating.

41. The method of claim 40, wherein said biodegradable polymer is provided as a discontinuous coating.

42. The method of claim 40 or 41, wherein said biodegradable polymer is porous.

43. The method of claim 40, 41 or 42, wherein said biodegradable polymer is provided as a polymer composite containing particles of porous ceramic matrix.

44. The method of claim 41, 42 or 43, wherein said biodegradable polymer is selected from the group consisting of photosensitive polymers, polycaprolactone, polyanhydrides, poly(ortho esters), poly(amino acids), pseudo-poly(amino acids), polyethylene glycol, polyesters and mixtures thereof.

45. The method of claim 44, wherein said photosensitive polymers are selected from polyhydroxybutyrate, polyhydroxyvalerate and copolymers thereof.

46. The method of claim 44, wherein said polyester is selected from poly(lactic acid) and poly(glycolic acid).