Cell permeable structural implant
(19)AUSTRALIANPATENT OFFICE (54) Title Cell permeablestructural implant (51)6 International Patent Classification(s) A61F 2/28 (2006.01) 20060101AFI20060408 A61F 2/28 BHAU PCT/US2005/015426 (21) Application No: (22) Application Date: 2005 .05.04 (87) WIPO No: WO05/107651 (30) Priority Data (31) Number 11/047,992 60/568,472 (32) Date 2005 .01.31 2004 .05 .04 (33) Country US US (43) Publication Date : 2005.11.17 (71) Applicant(s) Osteotech, Inc. (72) Inventor(s) Knaack, David; Winterbottom, John M.; Boyce, Todd M.; Kaes, David; Lee, Samuel; Belaney, Ryan; Shimp, Lawrence A. (74) Agent/Attorney Davies Collison Cave, 1 Nicholson Street, MELBOURNE, VIC, 3000 (-1-1) Application NoAU2005240145 A1(19)AUSTRALIANPATENT OFFICE (54) Title Cell permeablestructural implant (51)6 International Patent Classification(s) A61F 2/28 (2006.01) 20060101AFI20060408 A61F 2/28 BHAU PCT/US2005/015426 (21) Application No: (22) Application Date: 2005 .05.04 (87) WIPO No: WO05/107651 (30) Priority Data (31) Number 11/047,992 60/568,472 (32) Date 2005 .01.31 2004 .05 .04 (33) Country US US (43) Publication Date : 2005.11.17 (71) Applicant(s) Osteotech, Inc. (72) Inventor(s) Knaack, David; Winterbottom, John M.; Boyce, Todd M.; Kaes, David; Lee, Samuel; Belaney, Ryan; Shimp, Lawrence A. (74) Agent/Attorney Davies Collison Cave, 1 Nicholson Street, MELBOURNE, VIC, 3000 -1- An implant including a cell conducting phase and a binder phase. At least a portion of the surface of the implant includes the cell conducting phase, and the cell conducting phase defines a path from the surface of the implant to an interior of the implant. 1. An implant comprising a cell conducting phase and a binder phase, wherein: at least a portion of the surface of the implant comprises the cell conducting phase, and the cell conducting phase defines a path from the surface of the implant to an interior of the implant. 2. The implant of claim 1, wherein at least a portion of the cell conducting phase, at least a portion of the binder phase, or both, swells upon exposure to a physiological environment. 3. The implant of claim 1 or claim 2, wherein the cell conducting phase comprises particles having a distribution of aspect ratios, and wherein the volume fraction of the cell conducting phase is at least as great as the percolation threshold of the implant for particles having an aspect ratio equal to the largest aspect ratio in the distribution. 4. The implant of any one of the preceding claims, wherein the implant provides an environment that, in vivo, allows cells to penetrate at least 1 mm into the implant from the surface; or in vivo, allows tissue ingrowth to extend into the implant at least 1 mm from the surface. 5. The implant of any one of the preceding claims, wherein the cell conducting phase comprises allograft bone. 6. The implant of any one of the preceding claims, wherein the cell conducting phase exceeds about 50 weight percent of the implant; or exceeds about 60 weight percent of the implant or exceeds about 70 weight percent of the implant; or exceeds about 27 percent by volume of the implant; or exceeds about 35 percent by volume of the implant; or exceeds about 40 percent by volume of the implant; or exceeds about percent by volume of the implant. 7. The implant of any one of the preceding claims, wherein at least a portion of the surface of the implant comprises a cell conducting material. 8. The implant of any one of the preceding claims, wherein the cell conducting phase includes a connected cluster of cell conducting material that occupies at least 10% of the area of a cross section of the implant; or at least 20% of the area of a cross section of the implant; or at least 30% of the area of a cross section of the implant; or at least 40% of the area of a cross section of the implant; or at least 50% of the area of a cross section of the implant; or at least 60% of the area of a cross section of the implant; or at least 70% of the area of a cross section of the implant; or at least 80% of the area of a cross section of the implant; or at least 90% of the area of a cross section of the implant. 9. The implant of any one of the preceding claims, wherein the cell conducting phase comprises a tissue-derived material having a plurality of pores with a size between 10 and 500m. 10. The implant of any one of the preceding claims, wherein the implant lacks porosity sufficiently large to permit the migration of cells.
il. The implant of any one of the preceding claims, wherein the ratio of the cell conducting phase to the binder phase exhibits a gradient proceeding from a portion of the surface of the implant to a predetermined portion of an interior of the implant. 12. The implant of claim 11, wherein the gradient is in the direction of decreasing cell conductor phase to binder phase ratio. 13. The implant of any one of the preceding claims, wherein the cell conducting phase defines at least one blind path from a surface of the implant to a location in the interior of the implant. 14. The implant of any one of the preceding claims, wherein the cell conducting phase, the binder phase, or both, include a member of a bioactive agent, biomolecule, or small molecule. 15. The implant of claim 14, wherein a concentration of the member exhibits a gradient between two predetermined locations in the implant. 16. The implant of claim 15, wherein a concentration of the member exhibits a gradient exhibiting radial symmetry. 17. The implant of any one of the preceding claims, wherein the cell conducting phase comprises one or more of a tissue-derived material, an extracellular matrix component, a synthetic extracellular matrix analog, a polymer, and a ceramic material. 18. The implant of claim 17, wherein the cell conducting phase comprises a tyrosine-based polycarbonate, a polylactide, a polyurethane, or any combination of the above or wherein the cell conducting phase comprises a synthetic material. 19. The implant of any one of the preceding claims, wherein the binder phase includes a cell conducting material; or wherein the binder phase comprises one or more of a polymer and an inorganic material. 20. The implant of any one of the preceding claims, wherein the implant exhibits a gradient in its transformation rate. 21. The implant of any one of the preceding claims, wherein a predetermined portion of the implant is free of cell conducting material. 22. An implant comprising a cell conducting phase and a binder phase, wherein at least one cross-section of the implant exhibits a connected cluster of the cell conducting phase that defines a path from the surface of the implant to a location in the interior of the implant. 23. The implant of claim 22, wherein the implant provides an environment that, in vivo, allows cells to penetrate at least:
1 mm into the implant from the surface; or 2mm into the implant from the surface; or 3 mm into the implant from the surface; or 4 mm into the implant from the surface; or 5 mm into the implant from the surface; or wherein the implant provides an environment that, in vivo, allows tissue ingrowth to extend into the implant at least:
1 mm from the surface; or 2 mm from the surface; or 3 mm from the surface; or 4 mm from the surface; or mm from the surface; or wherein the implant provides an environment that, in vivo, allows cells tissue, or both to penetrate at least 10% of a radius of the implant into the implant from the surface; or at least:
20% of a radius of the implant into the implant from the surface; or 30% of a radius fo the implant into the implant from the surface; or 40% of a radius of the implant into the implant from the surface; or wherein at least one cross section of the implant exhibits a connected cluster of the cell conducting phase that occupies at least 10% of the area of the cross section. 24. The implant of claim 22 or 23, wherein at least a portion of the surface of the implant comprises a cell conducting material. 25. The implant of any one of claims 22 to 24, wherein the cell conducting phase, the binder phase, or both, include a member of a bioactive agent, biomolecule, or small molecule. 26. The implant of claim 25, wherein a concentration of the member exhibits a gradient between two predetermined points in the implant; or a concentration of the member exhibits a gradient exhibiting radial symmetry. 27. The implant of any one of claims 22 to 26, wherein the cell conducting phase comprises one or more of a tissue-derived material, an extracellular matrix component, a synthetic extracellular matrix analog, a polymer, and a ceramic material. 28. The implant of claim 27, wherein the cell conducting phase comprises a tyrosine-based polycarbonate, a polyactide, a polyurethane, or any combination of the above; or wherein the cell conducting phase comprises a synthetic material. 29. The implant of any one of claims 22 to 28, wherein the binder phase includes a cell conducting material. 30. The implant of any one of claims 22 to29, wherein the binder phase comprises one or more of a polymer and an inorganic material. 31. The implant of any one of claims 22 to 30, wherein the implant exhibits a gradient in its transformation rate.
32 The implant of any one of claims 22 to 31, wherein, a predetermined portion of the implant is free of a cell conducting material. 33. A composite material, comprising: a cell conducting phase comprising bone fibers, wherein the long axis of the bone fibers corresponds to a long axis of a bone from which the bone fibers were derived; and a binder phase combined with the cell conducting phase. 34. An implant disposed in an in vivo tissue site and comprising a composite, the composite comprising a cell conducting phase and a binder phase, wherein: the cell conducting phase comprises a cell-free bone-derived material, and at least one living cell derived from a host in which the implant is disposed is disposed within the implant. 35. The implant of claim 34, wherein at least one cell is disposed at least 1 mm from the surface of the implant. 36. An implant disposed in an in vivo tissue site and comprising a composite, the composite comprising a cell conducting phase and a binder phase, wherein: the cell conducting phase comprises a cell-free bone-derived material, and living tissue provides mechanical communication between an interior of the implant and tissue exterior to the implant.