Shaped load-bearing osteoimplant and methods of making same

• US 20030039676A1
• Filed: 08/27/2002
• Published: 02/27/2003
• Est. Priority Date: 02/23/1999
• Status: Active Grant

• Current Assignee: Warsaw Orthopedic Incorporated (Medtronic Plc)
• Original Assignee: Osteotech Incorporated (Medtronic Plc)
• Inventors: Boyce, Todd M., Manrique, Albert, Winterbottom, John M., Shimp, Lawrence
• Granted Patent: US 6,696,073 B2
• Time in Patent Office: Days
• US Class Current: 424/423
• CPC Class Codes: A61B 17/0401 Suture anchors, buttons or pledgets, i.e. means for attaching sutures to bone, cartilage or soft tissue; Instruments for applying or removing suture anchors A61B17/0642 takes precedence; fixation devices for tendons or ligaments A61F2/0811
• CPC Class Codes: A61B 17/72 Intramedullary pins, nails or other devices A61B17/744 takes precedence
• CPC Class Codes: A61B 17/7291 for small bones, e.g. in the foot, ankle, hand or wrist
• CPC Class Codes: A61B 17/742 having one or more longitudinal elements oriented along or parallel to the axis of the neck
• CPC Class Codes: A61B 17/80 Cortical plates , i.e. bone plates; Instruments for holding or positioning cortical plates, or for compressing bones attached to cortical plates
• CPC Class Codes: A61B 17/86 Pins or screws or threaded wires; nuts therefor A61B17/72 take precedence
• CPC Class Codes: A61B 2017/0409 Instruments for applying suture anchors for applying suture clamps, clips or locks A61B2017/0488
• CPC Class Codes: A61B 2017/0414 having a suture-receiving opening, e.g. lateral opening lateral eyelet for attaching suture to needle A61B2017/06019
• CPC Class Codes: A61B 2017/044 with a threaded shaft, e.g. screws
• CPC Class Codes: A61C 8/0012 characterised by the material or composition, e.g. ceramics, surface layer, metal alloy use of specific materials A61K6/00
• CPC Class Codes: A61C 8/0036 Tooth replica
• CPC Class Codes: A61F 2/28 Bones joints A61F2/30
• CPC Class Codes: A61F 2/2803 for mandibular reconstruction temporo-mandibular joints A61F2/3099; bone plates for the jaw A61B17/8071
• CPC Class Codes: A61F 2/2875 Skull or cranium A61F2/2803 and A61F2/3099 take precedence
• CPC Class Codes: A61F 2/30965 Reinforcing the prosthesis by embedding particles or fibres during moulding or dipping
• CPC Class Codes: A61F 2/32 for the hip
• CPC Class Codes: A61F 2/34 Acetabular cups
• CPC Class Codes: A61F 2/36 Femoral heads ; Femoral endoprostheses
• CPC Class Codes: A61F 2/442 Intervertebral or spinal discs, e.g. resilient non-disc-shaped intervertebral inflatable pockets A61F2/441; non-disc-shaped intervertebral fusion implants A61F2/4455
• CPC Class Codes: A61F 2/446 having a circular or elliptical cross-section substantially parallel to the axis of the spine, e.g. cylinders or frustocones
• CPC Class Codes: A61F 2/4611 : of spinal prostheses
• CPC Class Codes: A61F 2/4644 : Preparation of bone graft, bone plugs or bone dowels, e.g. grinding or milling bone material bone material A61F2/28; disintegrating or milling devices B02C
• 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 2002/2825 : Femur
• CPC Class Codes: A61F 2002/2835 : Bone graft implants for filling a bony defect or an endoprosthesis cavity, e.g. by synthetic material or biological material
• CPC Class Codes: A61F 2002/2871 : Radius
• CPC Class Codes: A61F 2002/2892 : Tibia
• CPC Class Codes: A61F 2002/30004 : the prosthesis being made from materials having different values of a given property at different locations within the same prosthesis
• CPC Class Codes: A61F 2002/30059 : differing in bone mineralization, e.g. made from both mineralized and demineralized adjacent parts
• CPC Class Codes: A61F 2002/30062 : (bio)absorbable, biodegradable, bioerodable, (bio)resorbable, resorptive
• CPC Class Codes: A61F 2002/30113 : circular
• CPC Class Codes: A61F 2002/30125 : elliptical or oval
• CPC Class Codes: A61F 2002/30143 : hexagonal
• CPC Class Codes: A61F 2002/30146 : octagonal
• CPC Class Codes: A61F 2002/30148 : lozenge- or diamond-shaped
• CPC Class Codes: A61F 2002/30153 : rectangular
• CPC Class Codes: A61F 2002/30154 : square
• CPC Class Codes: A61F 2002/30158 : trapezoidal
• CPC Class Codes: A61F 2002/30225 : Flat cylinders, i.e. discs
• CPC Class Codes: A61F 2002/30237 : partial tubes
• CPC Class Codes: A61F 2002/30261 : parallelepipedal
• CPC Class Codes: A61F 2002/30266 : wedge-shaped parallelepipeds
• CPC Class Codes: A61F 2002/30433 : using additional screws, bolts, dowels, rivets or washers e.g. connecting screws
• CPC Class Codes: A61F 2002/30535 : Special structural features of bone or joint prostheses not otherwise provided for
• CPC Class Codes: A61F 2002/30561 : breakable or frangible
• CPC Class Codes: A61F 2002/30622 : Implant for fusing a joint or bone material
• CPC Class Codes: A61F 2002/30677 : Means for introducing or releasing pharmaceutical products, e.g. antibiotics, into the body
• CPC Class Codes: A61F 2002/30785 : parallel
• CPC Class Codes: A61F 2002/3085 : with a threaded, e.g. self-tapping, bone-engaging surface, e.g. external surface
• CPC Class Codes: A61F 2002/3092 : having an open-celled or open-pored structure
• CPC Class Codes: A61F 2002/30948 : using computerized tomography, i.e. CT scans
• CPC Class Codes: A61F 2002/30952 : using CAD-CAM techniques or NC-techniques
• CPC Class Codes: A61F 2002/30957 : using a positive or a negative model, e.g. moulds
• CPC Class Codes: A61F 2002/30962 : using stereolithography
• CPC Class Codes: A61F 2002/30968 : Sintering
• CPC Class Codes: A61F 2002/3611 : Heads or epiphyseal parts of femur
• CPC Class Codes: A61F 2002/365 : Connections of heads to necks
• CPC Class Codes: A61F 2002/3686 : bent
• CPC Class Codes: A61F 2210/0004 : bioabsorbable
• CPC Class Codes: A61F 2220/0041 : using additional screws, bolts, dowels or rivets, e.g. connecting screws
• CPC Class Codes: A61F 2230/0006 : circular
• CPC Class Codes: A61F 2230/0008 : elliptical or oval
• CPC Class Codes: A61F 2230/0017 : Angular shapes
• CPC Class Codes: A61F 2230/0019 : rectangular
• CPC Class Codes: A61F 2230/0021 : square
• CPC Class Codes: A61F 2230/0026 : trapezoidal
• CPC Class Codes: A61F 2230/0069 : cylindrical
• CPC Class Codes: A61F 2230/0082 : parallelepipedal
• CPC Class Codes: A61F 2250/0014 : having different values of a given property or geometrical feature, e.g. mechanical property or material property, at different locations within the same prosthesis
• CPC Class Codes: A61F 2250/0058 : Additional features; Implant or prostheses properties not otherwise provided for
• CPC Class Codes: A61F 2250/0071 : breakable or frangible
• CPC Class Codes: A61F 2310/00011 : Metals or alloys
• CPC Class Codes: A61F 2310/00161 : Carbon; Graphite
• CPC Class Codes: A61F 2310/00173 : Graphite
• CPC Class Codes: A61F 2310/00293 : containing a phosphorus-containing compound, e.g. apatite
• CPC Class Codes: A61F 2310/00347 : Nacre or mother-of-pearl
• CPC Class Codes: A61F 2310/00365 : Proteins; Polypeptides; Degradation products thereof
• CPC Class Codes: A61L 2430/02 : for reconstruction of bones; weight-bearing implants
• CPC Class Codes: A61L 27/3608 : Bone, e.g. demineralised bone matrix [DBM], bone powder
• CPC Class Codes: A61L 27/3641 : characterised by the site of application in the body materials for artificial blood vessels A61L27/507; materials for use in artificial skin A61L27/60
• CPC Class Codes: A61L 27/3645 : Connective tissue
• CPC Class Codes: A61L 27/3683 : subjected to a specific treatment prior to implantation, e.g. decellularising, demineralising, grinding, cellular disruption/non-collagenous protein removal, anti-calcification, crosslinking, supercritical fluid extraction, enzyme treatment
• CPC Class Codes: A61L 27/3691 : characterised by physical conditions of the treatment, e.g. applying a compressive force to the composition, pressure cycles, ultrasonic/sonication or microwave treatment, lyophilisation
• CPC Class Codes: A61L 27/3839 : characterised by the site of application in the body materials for artificial blood vessels A61L27/507; materials for use in artificial skin A61L27/60
• CPC Class Codes: A61L 27/3847 : Bones
• CPC Class Codes: A61L 31/005 : Ingredients of undetermined constitution or reaction products thereof
• CPC Class Codes: B33Y 80/00 : Products made by additive manufacturing

Abstract

A load-bearing osteoimplant, methods of making the osteoimplant and method for repairing hard tissue such as bone and teeth employing the osteoimplant are provided. The osteoimplant comprises a shaped, coherent mass of bone particles which may exhibit osteogenic properties. In addition, the osteoimplant may possess one or more optional components which modify its mechanical and/or bioactive properties, e.g., binders, fillers, reinforcing components, etc.

Claims

1. A load-bearing osteoimplant comprising a shaped, coherent mass of bone particles.

2. The osteoimplant of claim 1 possessing a bulk density of greater than about 0.7 g/cm³.

3. The osteoimplant of claim 1 possessing a wet compressive strength of at least about 3 MPa.

4. The osteoimplant of claim 1 wherein the bone particles are those of nondemineralized bone, substantially fully demineralized bone, partially demineralized bone, superficially demineralized bone or combinations thereof.

5. The osteoimplant of claim 1 wherein the bone particles are in the form of powders, chips, elongate particles or combinations thereof.

6. The osteoimplant of claim 1 wherein at least part of the bone particles possess surface exposed collagen, the bone particles being bonded by crosslinking of their mutually contacting exposed collagen surfaces.

7. The osteoimplant of claim 1 containing at least one additional component selected from the group consisting of binder, filler, coupling agent, plasticizer, wetting agent, surface active agent, biostatic/biocidal agent, bioactive substance, reinforcing material, reinforcing structure or combinations thereof.

8. The osteoimplant of claim 7 wherein the binder component is a natural, synthetic or semisynthetic bioresorbable or nonbioresorbable polymer.

9. The osteoimplant of claim 7 wherein the binder component is selected from the group consisting of fibrin glue, fibrinogen, thrombin, mussel adhesive protein, silk, elastin, collagen, casein, gelatin, albumin, keratin, chitin or chitosan;

natural or modified polysaccharide, oxidized cellulose, genetically-engineered protein polymer;

cyanoacrylate;

epoxy-based compound;

dental resin sealant;

bioactive glass ceramic, dental resin cement;

glass ionomer cement;

gelatin-resorcinol-formaldehyde glue;

collagen-based glue;

polylactic acid;

polyglycolic acid;

polylactic-co-glycolic acid;

polylactide, polyglycolide, poly(lactide-co-glycolide);

polydioxanone;

polycaprolactone;

polycarbonate;

polyorthoesters;

polyamino acid;

polyanhydride;

polyhydroxybutyrate;

polyhyroxyvalyrate;

poly (propylene glycol-co-fumaric acid);

tyrosine-based polycarbonate;

pharmaceutical tablet binder;

polyvinylpyrrolidone;

cellulose;

ethyl cellulose;

micro-crystalline cellulose;

starch;

starch ethylenevinyl alcohol;

polycyanoacrylate;

polyphosphazene;

polyacrylate;

polymethyl methacrylate;

polytetrafluoroethylene;

polyurethane; and

, polyamide.

10. The osteo implant of claim 7 wherein the binder component is selected from the group consisting of amino acid-derived polycarbonate;

amino acid-derived polyarylate;

polyarylate derived from dicarboxylic acid and amino acid-derived diphenol;

anionic polymer derived from L-tyrosine;

polyarylate random block copolymer;

polycarbonate;

poly(-hydroycarboxylic acids);

poly(caprolactone);

poly(hydroxybutyrates);

polyanhydrides;

poly(ortho esters);

polyester;

bisphenol-A based poly(phosphoesters); and

, copolymer of polyalkylene glycol and polyester.

11. The osteoimplant of claim 7 wherein the filler is selected from the group consisting of graphite, pyrolytic carbon, bioceramic, dentin tooth enamel, aragonite, calcite, inorganic nacre, calcium-containing compound and glass.

12. The osteoimplant of claim 11 wherein the inorganic calcium containing compound is hydroxyapatite, amorphous calcium phosphate, tricalcium phosphate or combinations thereof.

13. The osteoimplant of claim 7 wherein the biostatic/biocidal component is selected from the group consisting of vericide, antibiotic, povidone, sugar and mucopolysaccharide.

14. The osteoimplant of claim 13 wherein the antibiotic is selected from the group consisting of erythromycrin, bacitracin, neomycin, penicillin, polymycin B, tetracycline, biomycin, chloromycetin, and streptomycin, cefazolin, ampicillin, azactam, tobramycin, clindamycin, gentamicin and combinations thereof.

15. The osteoimplant of claim 7 wherein the bioactive substance is selected from the group consisting of collagen, insoluble collagen derivative;

amino acid;

peptide;

vitamin;

inorganic element;

co-factor for protein synthesis;

hormone;

endocrine tissue or tissue fragment;

synthesizer;

enzyme;

polymer cell scaffold with parenchymal cells;

angiogenic agent;

collagen lattice;

antigenic agent;

cytoskeletal agent;

cartilage fragment;

chondrocytes;

bone marrow cells;

mesenchymal stem cells;

natural extract;

modified living cells;

DNA or DNA fragment;

tissue transplant;

autogenous tissue;

bone morphogenic protein;

osteoinductive factor;

fibronectin;

osteonectin;

endothelial cell growth factor;

cementum attachment extract;

ketanserin, human growth hormone;

animal growth hormone;

epidermal growth factor;

interleukin-1;

human alpha thrombin;

transforming growth factor;

insulin-like growth factor;

platelet derived growth factor;

fibroblast growth factor;

periodontal ligament chemotactic factor;

somatotropin;

bone digestor;

antitumor agent;

immuno-suppressant;

permeation enhancer;

nucleic acid; and

, combinations thereof.

16. The osteoimplant of claim 7 wherein the reinforcing component is one or a combination of fiber, fibrous web, woven textile, nonwoven textile, mesh, nonflexible structural member or semiflexible structure member made from a natural, synthetic or semisynthetic nonbioresorbable or bioresorbable material.

17. The osteoimplant of claim 16 wherein the reinforcing component is oriented along the axis of the mechanical forces that can be expected to be exerted against the osteoimplant following its installation at a hard tissue repair site.

18. The osteoimplant of claim 17 configured as a sheet, plate, dish, cone, pin, screw, tube, tooth, tooth root, bone, bone portion, wedge, wedge portion, cylinder, dowel, intervertebral implant or suture anchor.

19. The osteoimplant of claim 17 configured as an anterior or posterior ramp or non-ramp intervertebral implant with substantially flat or lordotic surfaces, the implant being substantially solid or possessing at least one internal void structure or void network communicating with the surface of the implant, the void structure or void network being partially or completely filled with at least one bioactive substance.

20. The osteoimplant of claim 19 wherein the bioactive substance is a bone growth-promoting substance.

21. The osteoimplant of claim 19 wherein the bone growth-promoting substance contains demineralized bone powder.

22. The osteoimplant of claim 7 configured as a sheet, plate, dish, cone, pin, screw, tube, tooth, tooth root, bone, bone portion, wedge, wedge portion, cylinder, dowel, intervertebral implant or suture anchor.

23. The osteoimplant of claim 7 configured as an anterior or posterior ramp or non-ramp intervertebral implant with substantially flat or lordotic surfaces, the implant being substantially solid or possessing at least one internal void structure or void network communicating with the surface of the implant, the void structure or void network being partially or completely filled with at least one bioactive substance.

24. The osteoimplant of claim 23 wherein the bioactive substance is a bone growth-promoting substance.

25. The osteoimplant of claim 23 wherein the bone growth-promoting substance contains demineralized bone powder.

26. A method for making a load-bearing osteoimplant which comprises:

a) providing an aggregate containing bone particles and, optionally, one or more optional components selected from the group consisting of binder, filler, plasticizer, wetting agent, surface active agent, biostatic/biocidal agent, bioactive substance, reinforcing material and reinforcing structure; and

,

b) shaping the aggregate into a coherent mass in at least one shaping operation to provide a shaped composite having an initial configuration for subsequent shaping into a desired osteoimplant or a final configuration corresponding to that of the osteoimplant.

27. The method of claim 26 wherein shaping step (b) further comprises an initial shaping of the aggregate into an osteoimplant blank and a subsequent shaping of the osteoimplant blank into a fully shaped osteoimplant.

28. The method of claim 26 wherein the shaping of the aggregate is accomplished by compressing the aggregate within a mold, optionally at elevated temperature.

29. The method of claim 26 wherein the aggregate is shaped at least in part by molding.

30. The method of claim 26 wherein the molding is injection molding.

31. The method of claim 30 wherein the molding is blow molding.

32. The method of claim 30 wherein the molding is rotational molding.

33. The method of claim 30 wherein the molding is leach molding.

34. The method of claim 30 wherein the molding is leavening molding.

35. The method of claim 26 wherein the aggregate is shaped at least in part by casting.

36. The method of claim 35 wherein the casting is solvent casting.

37. The method of claim 35 wherein the casting is gel casting.

38. The method of claim 26 wherein the aggregate is shaped at least in part by a CAD/CAM operation.

39. The method of claim 26 wherein the aggregate is shaped at least in part by rolling.

40. The method of claim 26 wherein the aggregate is shaped at least in part by vacuum-forming.

41. The method of claim 26 wherein the aggregate is shaped at least in part by sintering.

42. The method of claim 26 wherein the aggregate is shaped at least in part by melt-forming.

43. The method of claim 26 wherein the aggregate is shaped at least in part by thermoforming.

44. The method of claim 26 wherein the aggregate is shaped at least in part by foam molding.

45. The method of claim 26 wherein the aggregate is shaped at least in part by forging.

46. The method of claim 26 wherein the aggregate is shaped at least in part by laser fusion of polymer binder therein.

47. The method of claim 27 wherein subsequent shaping of the blank into the fully shaped osteoimplant includes a machining operation.

48. The method of claim 38 which further comprises:

a. imaging a patient'"'"'s implantation site to provide digital information for a three dimensional model of an osteoimplant to be implanted at the site;

b. converting the three dimensional model of the osteoimplant into a CAD file stored in the memory of a computer;

c. machining a blank which is a coherent mass of an aggregate containing bone particles and, optionally, one or more optional components selected from the group consisting of binder, filler, plasticizer, wetting agent, surface active agent, biostatic/biocidal agent, bioactive substance, reinforcing material and reinforcing structure to provide the osteoimplant, the machining being carried out by a machine executing a defined tool path numerically controlled by the computer in which the CAD file is stored.

49. The method of claim 48 wherein imaging step (a) is carried out by CAT scan, MRI or MUI.

50. The method of claim 38 which further comprises;

a) imaging a patient'"'"'s implantation site to provide digital information for a three dimensional model of an osteoimplant to be implanted at the site;

b) converting the three dimensional model of the osteoimplant into a CAD file stored in memory of a computer;

c) forming a mold whose shaping surface conforms to the osteoimplant using the CAD file; and

d) forming the osteoimplant in the mold.

51. The method of claim 50 wherein imaging step (a) is carried out by CAT scan, MRI or MUI.

52. An integral implant insertion instrument and implant comprising an implant insertion instrument portion integrally attached to an implant portion by a weakened, break-away connection such that on insertion of the implant portion at the implantation site, the implant insertion instrument portion is separated from the implant portion by a breaking-away force applied thereto, the implant portion being a load-bearing osteoimplant comprising a shaped, coherent mass of bone particles.

53. The integral implant insertion instrument and implant of claim 52 in which the load-bearing osteoimplant portion contains at least one additional component selected from the group consisting of binder, filler, plasticizer, wetting agent, surface active agent, biostatic/biocidal agent, bioactive substance, reinforcing material, reinforcing structure or combinations thereof.

54. The integral implant insertion instrument and implant of claim 53 in which the binder present in the load-bearing osteoimplant is a natural, synthetic or semisynthetic bioresorbable or nonbioresorbable polymer.