Porous ceramic composite bone grafts

• US 7,875,342 B2
• Filed: 09/24/2002
• Issued: 01/25/2011
• 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, Smith, Timothy J. N., Reginald, Smith, Sydney, M. Pugh
• Primary Examiner(s): Vo; Hai
• Application Number:
  US10/490,492
• Publication Number:
  US 20060198939A1
• Time in Patent Office: 3,045 Days
• Field of Search: 428/319.3, 428/319.7, 428/316.6, 428/317.9, 428/312.2, 428/315.5, 428/315.7, 623 2356- 2359
• US Class Current: 428/312.2
• 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 orthopedics 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. An implant comprising:

a sintered matrix body of a calcium phosphate-based compound, the sintered matrix body possessing an open interconnected porous structure with internal and external surfaces; and

a biodegradable polymer coating provided throughout the sintered matrix body on the external and internal surfaces of the open interconnected porous structure, wherein the biodegradable polymer coating still allows for the passage and/or delivery of agents and/or cells throughout the open interconnected porous structure and improves the mechanical properties of the sintered matrix body, the biodegradable polymer coating forming a discontinuous coating throughout the internal and external surfaces of the open interconnected porous structure;

wherein the biodegradable polymer coating includes a polymer 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.

2. The implant of claim 1, wherein the interconnected porous structure has pores of about 200 microns to about 600 microns

3. The implant of claim 1, wherein the biodegradable polymer coating has pores of about 50 to about 200 microns.

4. The implant of claim 1, wherein the biodegradable polymer coating is a composite material comprising a biodegradable polymer and ceramic particles.

5. The implant of claim 4, wherein the ceramic particles have the same composition as the sintered matrix body.

6. The implant of claim 4, wherein the ceramic particles have a particle size of not greater than about 50 microns.

7. The implant of claim 1, wherein the photosensitive polymers are selected from the group consisting of polyhydroxybutyrate, polyhydroxyvalerate and copolymers thereof.

8. The implant of claim 1, wherein the polyester is selected from poly(lactic acid) and poly(glycolic acid).

9. The implant of claim 1, wherein the biodegradable polymer coating includes polycaprolactone.

10. The implant of claim 1, wherein the biodegradable polymer coating has a thickness not greater than about 250 microns.

11. The implant of claim 1, wherein the biodegradable polymer coating includes a pharmaceutical agent incorporated therein.

12. The implant of claim 11, wherein the 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.

13. The implant of claim 1, wherein the sintered matrix body 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.

14. The implant of claim 1, wherein the calcium phosphate-based compound 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

.

15. The implant of claim 14, wherein the 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.

16. The implant of claim 1, wherein the sintered matrix body has a gradient density.

17. The implant of claim 16, wherein an outermost region of the sintered matrix body is partially surrounded by a solid layer of a composition the same as the ceramic phosphate-based compound.

18. The implant of claim 1, wherein sintered matrix body has hollow ligaments.

19. The implant of claim 18, wherein the hollow ligaments are filled with the biodegradable polymer.

20. An implant comprising:

a sintered matrix body possessing an open interconnected porous structure with internal and external surfaces, the open interconnected porous structure including pores of about 200 microns to about 600 microns, the sintered matrix body 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

; and

a biodegradable polymer coating provided throughout the sintered matrix body on the external and internal surfaces of the open interconnected porous structure, wherein the biodegradable polymer coating still allows for the passage and/or delivery of agents and/or cells throughout the open interconnected porous structure and improves the mechanical properties of the sintered matrix body, the biodegradable polymer coating forming a discontinuous coating throughout the internal and external surfaces of the open interconnected porous structure and having pores of about 50 to about 200 microns;

wherein the biodegradable polymer coating includes a polymer 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.

21. The implant of claim 20, wherein the biodegradable polymer coating includes a biodegradable polymer and ceramic particles.