Claims
- 1. A biomaterial compound comprising calcium, oxygen and phosphorous, wherein at least one of said elements is substituted with an element having an ionic radius of approximately 0.1 to 1.1 Å.
- 2. The biomaterial compound as claimed in claim 1, wherein a portion of the phosphorous is substituted by at least one element having an ionic radius of approximately 0.1 to 0.4 Å.
- 3. The biomaterial compound as claimed in claim 1, wherein said element of substitution is selected from the group consisting of silicon and boron.
- 4. The biomaterial compound as claimed in claim 2, wherein said compound additionally comprises at least one element selected from elements having an ionic radius from approximately 0.4 to 1.1 Å, wherein said additional elements substitute at sites other than phosphorous.
- 5. The biomaterial compound as claimed in claim 4, wherein said element has an effective charge to compensate any imbalance of charge resulting from the partial substitution of phosphorous.
- 6. The biomaterial compound as claimed in claim 3 wherein said compound is defined by those peaks in the x-ray diffraction spectrum of FIG. 16.
- 7. A biomaterial compound having the formula:
- 8. The biomaterial compound as claimed in claim 7, wherein w and 6 are determined by charge compensation of the elements present in the compound.
- 9. The biomaterial compound as claimed in claim 8, wherein B is selected from the group consisting of silicon and boron.
- 10. The biomaterial compound as claimed in claim 7, wherein A is selected from the group of elements consisting of Ce, La, Sc, Y and Zr.
- 11. The biomaterial compound as claimed in claims 1 in combination with at least one calcium phosphate material selected from the group consisting of calcium hydroxyapatite, α-TCP, β-TCP, octacalcium phosphate, tetracalcium phosphate, dicalcium phosphate and calcium oxide.
- 12. The biomaterial compound as claimed in claim 11, wherein said compound is mixed with calcium hydroxyapatite in a ratio of approximately 20:80 to 80:20.
- 13. The biomaterial compound as claimed in claim 11 wherein said compound additionally comprises an additive to increase the mechanical toughness and strength of said compound.
- 14. The biomaterial compound as claimed in claim 1, wherein said compound is selected from the group consisting of Ca3(P0.750Si0.25O3 875)2 and Ca3(P0.9375Si0.0625O3.96875)2.
- 15. The biomaterial compound as claimed in claim 11 wherein said combination exists as a physical mixture or a solid solution.
- 16. The biomaterial compound as claimed in claim 1, wherein said compound has a microporous structure.
- 17. The biomaterial compound as claimed in claim 16 wherein said compound is formed as a macroporous structure comprising an open cell construction with interconnected voids having a pore size of approximately 50 to 1000 microns.
- 18. The biomaterial compound as claimed in claim 17 wherein said macroporous structure is formed by coating said compound onto a reticulated polymer and subsequently removing said polymer through pyrolysis.
- 19. The biomaterial compound as claimed in claim 16, wherein said compound has a nanoporous structure.
- 20. The biomaterial compound as claimed in claim 1, wherein said compound exhibits monoclinic pseudo-rhombic symmetry and is in the monoclinic space group P21/a.
- 21. The biomaterial compound as claimed in claim 1, wherein said compound is resorbed by the cellular activity of osteoclasts and promotes the generation of new mineralized bone matrix by the activity of osteoblasts.
- 22. The biomaterial compound as claimed in claim 21, wherein said compound is progressively replaced with natural bone in vivo.
- 23. The biomaterial compound as claimed in claim 21, wherein said compound is essentially insoluble in biological media at human physiological pH of 6.4-7.3.
- 24. The biomaterial compound as claimed in claim 23 in combination with collagen.
- 25. The use of the biomaterial compound as claimed in claim 1, in orthopedic, maxillo-facial and dental applications wherein said compound exists as a fine or coarse powder, pellets, three-dimensional shaped pieces, macroporous structures, thin films and coatings.
- 26. The use of the biomaterial compound as claimed in claim 25 as a thin film or a coating of thickness 0.1 to 10 microns.
- 27. The use of the biomaterial compound as claimed in claim 25 in tissue engineering.
- 28. The use of the biomaterial compound as claimed in 25 as a carrier for pharmaceutical agents.
- 29. A method for substituting natural bone at sites of skeletal surgery in human and animal hosts with a biomaterial compound comprising calcium, oxygen and phosphorous wherein at least one of said elements is substituted with an element having an ionic radius of approximately 0.1 to 1.1 Å;
said method comprising the steps of: implanting said biomaterial compound at the site of skeletal surgery wherein such implantation promotes the formation of new bone tissue at the interfaces between said biomaterial compound and said host, the progressive removal of said biomaterial compound primarily through osteoclast activity, and the replacement of that portion of said biomaterial compound removed by further formation of new bone tissue by osteoblast activity, such progressive removal and replacement being inherent in the natural bone remodeling process.
- 30. A method for repairing large segmental skeletal gaps and non-union fractures arising from trauma or surgery in human and animal hosts using a biomaterial compound comprising calcium, oxygen and phosphorous wherein at least one of said elements is substituted with an element having an ionic radius of approximately 0.1 to 1.1 Å;
said method comprising the steps of: implanting said biomaterial compound at the site of the segmental skeletal gap or non-union fracture wherein such implantation promotes the formation of new bone tissue at the interfaces between said biomaterial compound and said host, the progressive removal of said biomaterial compound primarily through osteoclast activity, and the replacement of that portion of said biomaterial compound removed by further formation of new bone tissue by osteoblast activity, such progressive removal and replacement being inherent in the natural bone remodeling process.
- 31. A method for aiding the attachment of implantable prostheses to skeletal sites and for maintaining the long term stability of said prostheses in human and animal hosts using a biomaterial compound comprising calcium, oxygen and phosphorous wherein at least one of said elements is substituted with an element having an ionic radius of approximately 0.1 to 1.1 Å;
said method comprising the steps of: coating selected regions of an implantable prosthesis with said biomaterial compound, implanting said coated prosthesis into a skeletal site wherein such implantation promotes the formation of new bone tissue at the interfaces between said biomaterial compound and said host, the generation of a secure interfacial bond between said host bone and said coating, the subsequent progressive removal of said coating primarily through osteoclast activity such that the coating is diminished, and the replacement of that portion of said biomaterial compound removed by further formation of new bone tissue to generate a secure interfacial bond directly between said host bone and said prosthesis.
- 32. A method for providing tissue-engineering scaffolds for bone replacement in human or animal hosts using a biomaterial compound comprising calcium, oxygen and phosphorous wherein at least one of said elements is substituted with an element having an ionic radius of approximately 0.1 to 1.1 Å;
said method comprising the steps of: forming said biomaterial compound as a macroporous structure comprising an open cell construction with interconnected voids, combining mature and/or precursor bone cells with said macroporous structure, and allowing the cells to infiltrate said structure in order to develop new mineralized matrix throughout said structure.
- 33. A method for delivering pharmaceutical agents to the site of skeletal surgery in human or animal hosts using a biomaterial compound comprising calcium, oxygen and phosphorous wherein at least one of said elements is substituted with an element having an ionic radius of approximately 0.1 to 1.1 Å;
said method comprising the steps of: combining a pharmaceutical agent with said biomaterial compound and applying the pharmaceutical agent combined with said biomaterial compound to a site of skeletal surgery, wherein such application results in controlled local release of said pharmaceutical agent.
- 34. The method of claims 29 wherein said biomaterial compound has the formula;
- 35. The method of any one of claim 29 wherein said biomaterial compound is combined with at least one calcium phosphate material selected from the group consisting of calcium hydroxyapatite, α-TCP, β-TCP, octacalcium phosphate, tetracalcium phosphate, dicalcium phosphate and calcium oxide.
- 36. The method of claim 35, wherein said biomaterial compound additionally comprises an additive to increase the mechanical toughness and strength of said compound.
- 37. A bioactive synthetic sintered composition for providing a morphology capable of consistently supporting bone cell activity thereon, said composition comprising stabilized calcium phosphate compound developed by the conversion of a hydroxyapatite substance in the presence of stabilizing entities at sintering temperatures wherein said stabilizing entities stabilize and insolubilize the calcium phosphate compound.
- 38. A composition as claimed in claim 37, wherein said hydroxyapatite substance before sintering is provided on a substrate and said stabilizing entities are released from said substrate during sintering.
- 39. A composition as claimed in claim 37, wherein said stabilizing entities are added to the hydroxyapatite substance before sintering.
- 40. A composition as claimed in claim 37, wherein the composition exists as a fine or coarse powder, pellets, 3-dimensional shaped pieces, macroporous structures, thin films and coatings.
- 41. A process for preparing a synthetic sintered composition comprising a stabilized calcium phosphate compound having a morphology suitable for supporting bone cell activity thereon, said process comprising converting a hydroxyapatite substance in the presence of stabilizing entities at sintering temperatures wherein said stabilizing entities stabilize and insolubilize the calcium phosphate compound.
- 42. A process as claimed in claim 41, wherein said stabilizing entities are added in the form of tetrapropyl orthosilicate.
- 43. A process as claimed in claim 41, wherein sintering of the hydroxyapatite substance is done at temperatures of about 900° C. to 1100° C.
- 44. A synthetic sintered microporous polycrystalline structure for supporting bone cell activity, said structure comprising a stabilized calcium phosphate compound having a globular morphology of interconnected rounded particles with an interconnected microporosity in said structure.
- 45. A polycrystalline structure of claim 44, wherein said structure has said globular morphology of FIG. 14a.
- 46. An implant comprising:
a) a scaffold for supporting said implant; and b) a layer of a stabilized calcium phosphate compound developed by the conversion of a hydroxyapatite substance in the presence of stabilizing entities at sintering temperatures wherein said stabilizing entities insolubilize and stabilize the calcium phosphate compound.
- 47. An implant comprising:
a) a scaffold for supporting said implant; b) a layer of a stabilized calcium phosphate compound developed by the conversion of a hydroxyapatite substance in the presence of stabilizing entities at sintering temperatures wherein said stabilizing entities insolubilize and stabilize the calcium phosphate compound; c) a boundary layer deposited by osteoblasts cultured on said layer of the stabilized calcium phosphate compound; and d) a mineralized collagenous matrix secreted by such cultured osteoblasts.
- 48. The implant as claimed in claim 46, wherein said scaffold is selected from a natural or a synthetic polymer.
- 49. A method for the culturing of functional bone cells, said method comprising:
applying a suspension of bone cells in physiological media to a synthetic sintered film comprising a stabilized calcium phosphate compound on a substrate; and incubating said bone cells for a period of time to allow expression of bone cell biological activity.
- 50. A kit for monitoring and quantifying the activity of bone cells, said kit comprising;
a substrate having a sintered film of a stabilized calcium phosphate compound; and a multiwell bone cell culture device adhered to said substrate.
- 51. A composition as claimed in claim 37, wherein said composition is resorbed by the cellular activity of osteoclasts and promotes the generation of new mineralized bone matrix by the activity of osteoblasts.
RELATED APPLICATIONS
[0001] This application is a Continuation-in-part U.S. national phase entry of PCT/CA96/00585 filed Aug. 30, 1996 which is a Continuation-in-part of U.S. Ser. No. 08/576,238 filed Dec. 21, 1995.
Provisional Applications (1)
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Number |
Date |
Country |
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60003157 |
Sep 1995 |
US |
Divisions (1)
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Number |
Date |
Country |
Parent |
09044749 |
Mar 1998 |
US |
Child |
09971148 |
Oct 2001 |
US |
Continuation in Parts (2)
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Number |
Date |
Country |
Parent |
PCT/CA96/00585 |
Aug 1996 |
US |
Child |
09044749 |
Mar 1998 |
US |
Parent |
08576238 |
Dec 1995 |
US |
Child |
PCT/CA96/00585 |
Aug 1996 |
US |