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Last Updated: October 16, 2019

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Claims for Patent: 6,541,022

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Summary for Patent: 6,541,022
Title: Mineral and cellular patterning on biomaterial surfaces
Abstract:Disclosed are advantageous methods for patterning and/or mineralizing biomaterial surfaces. The techniques described are particularly useful for generating three-dimensional or contoured bioimplant materials with patterned surfaces or patterned, mineralized surfaces. Also provided are various methods of using the mineralized and/or patterned biomaterials in tissue engineering, such as bone tissue engineering, providing more control over ongoing biological processes, such as mineralization, growth factor release, cellular attachment and tissue growth.
Inventor(s): Murphy; William L. (Ann Arbor, MI), Mooney; David J. (Ann Arbor, MI), Kohn; David H. (Ann Arbor, MI), Spalding; Gabriel C. (Bloomington, IL), Dearing; Matthew T. (Ithaca, NY)
Assignee: The Regents of the University of Michigan (Ann Arbor, MI)
Application Number:09/527,638
Patent Claims:1. A method for generating a patterned surface on a biocompatible material, comprising irradiating at least a first photosensitive surface of a biocompatible material with pre-patterned electromagnetic radiation in the form of constructively and destructively interfering electromagnetic radiation, thereby generating a pattern on said at least a first surface of said biocompatible material.

2. The method of claim 1, wherein said biocompatible material is fabricated in an implantable device.

3. The method of claim 1, wherein said pre-patterned radiation is constructively and destructively interfering radiation generated by impinging monochromatic radiation on a diffractive optical element that converts said monochromatic radiation into constructively and destructively interfering radiation.

4. The method of claim 3, wherein said monochromatic radiation is generated from a laser.

5. The method of claim 3, wherein said monochromatic radiation is generated from a mercury bulb.

6. The method of claim 3, wherein said monochromatic radiation is generated from an electromagnetic radiation source in combination with a filter.

7. The method of claim 3, wherein said diffractive optical element is a diffractive lens, a deflector/array generator, a hemispherical lenslet, a kinoform, a diffraction grating, a fresnel microlens or a phase-only hologram.

8. The method of claim 3, wherein said diffractive optical element is fabricated from a transparent polymer or glass.

9. The method of claim 8, wherein said diffractive optical element is fabricated from a transparent polymer selected from the group consisting of a poly(propylene), poly(methyl methacrylate), poly(styrene), and a high density poly(ethylene).

10. The method of claim 3, wherein said diffractive optical element is a diffraction grating fabricated from metal on glass, metal on polymer or metal with transmission apertures.

11. The method of claim 3, wherein said diffractive optical element is fabricated from fused silica or sapphire.

12. The method of claim 1, wherein said photosensitive surface is prepared by applying a photosensitive composition to at least a first surface of said biocompatible material.

13. The method of claim 12, wherein said photosensitive composition comprises a combined effective amount of at least a first photoinitiator and at least a first polymerizable component.

14. The method of claim 13, wherein said photosensitive composition comprises a polymerization-initiating amount of at least a first UV-excitable photoinitiator.

15. The method of claim 14, wherein said photosensitive composition comprises a polymerization-initiating amount of at least a first UV-excitable photoinitiator selected from the group consisting of a benzoin derivative, benzil ketal, hydroxyalkylphenone, alpha-amino ketone, acylphosphine oxide, benzophenone derivative and a thioxanthone derivative.

16. The method of claim 13, wherein said photosensitive composition comprises a polymerization-initiating amount of at least a first visible light-excitable photoinitiator.

17. The method of claim 16, wherein said photosensitive composition comprises a polymerization-initiating amount of at least a first visible light-excitable photoinitiator selected from the group consisting of eosin, methylene blue, rose bengal, dialkylphenacylsulfonium butyltriphenylborate, a fluorinated diaryltitanocene, a cyanine, a cyanine borate, a ketocoumarin and a fluorone dye.

18. The method of claim 16, wherein said photosensitive composition further comprises a co-initiating amount of at least a first accelerator.

19. The method of claim 18, wherein said photosensitive composition further comprises a co-initiating amount of at least a first accelerator selected from the group consisting of a tertiary amine, peroxide, organotin compound, borate salt and an imidazole.

20. The method of claim 13, wherein said photosensitive composition comprises a photopolymerizable amount of at least a first monomeric, oligomeric or polymeric polymerizable component.

21. The method of claim 20, wherein said photosensitive composition comprises a photopolymerizable amount of at least a first polymerizable monomer selected from the group consisting of an unsaturated fumaric polyester, maleic polyester, styrene, a multifunctional acrylate monomer, an epoxide or a vinyl ether.

22. The method of claim 13, wherein said photosensitive composition comprises a combined effective amount of an eosin photoinitiator, a poly(ethylene glycol) diacrylate polymerizable component and a triethanolamine accelerator.

23. The method of claim 1, wherein said pre-patterned radiation is applied to at least a first substantially level surface of said biocompatible material.

24. The method of claim 1, wherein said pre-patterned radiation is applied to at least a first contoured surface of said biocompatible material.

25. The method of claim 1, wherein the pattern generated comprises a pattern with a resolution of between about 1 .mu.M and about 500 .mu.M.

26. The method of claim 25, wherein the pattern generated comprises a pattern with a resolution of between about 1 .mu.M and about 100 .mu.M.

27. The method of claim 26, wherein the pattern generated comprises a pattern with a resolution of between about 10 .mu.M and about 100 .mu.M.

28. The method of claim 26, wherein the pattern generated comprises a pattern with a resolution of between about 1 .mu.M and about 10 .mu.M.

29. The method of claim 26, wherein the pattern generated comprises a pattern with a resolution of between about 10 .mu.M and about 20 .mu.M.

30. The method of claim 1, wherein said method is executed at a temperature compatible to mammalian biological systems.

31. The method of claim 1, wherein said biocompatible material is maintained on a temperature-controlled support during said irradiation.

32. The method of claim 1, wherein the pattern generated comprises a pattern of polar oxygen groups on at least a first surface of said biocompatible material.

33. The method of claim 1, wherein said biocompatible material is operatively associated with a biologically effective amount of at least a first mineral, bioactive substance or biological cell.

34. The method of claim 33, wherein said biocompatible material is operatively associated with a biologically effective amount of at least two minerals, bioactive substances or biological cells.

35. The method of claim 34, wherein said biocompatible material is operatively associated with a biologically effective amount of a plurality of minerals, bioactive substances or biological cells.

36. The method of claim 33, wherein said biocompatible material is operatively associated with a biologically effective amount of at least a first mineral.

37. The method of claim 36, wherein said biocompatible material is operatively associated with a biologically effective amount of calcium.

38. The method of claim 33, wherein said biocompatible material is operatively associated with a biologically effective amount of at least a first bioactive substance or bioactive drug.

39. The method of claim 38, wherein said biocompatible material is operatively associated with a biologically effective amount of at least a first marker protein, transcription or elongation factor, cell cycle control protein, kinase, phosphatase, DNA repair protein, oncogene, tumor suppressor, angiogenic protein, anti-angiogenic protein, cell surface receptor, accessory signaling molecule, transport protein, enzyme, anti-bacterial agent, anti-viral agent, antigen, immunogen, apoptosis-inducing agent, anti-apoptosis agent, cytotoxin, hormone, neurotransmitter, growth factor, hormone, neurotransmitter or growth factor receptor, interferon, interleukin, chemokine, cytokine, colony stimulating factor, chemotactic factor, extracellular matrix component or an adhesion molecule, ligand or peptide.

40. The method of claim 39, wherein said biocompatible material is operatively associated with a biologically effective amount of growth hormone, parathyroid hormone (PTH), bone morphogenetic protein (BMP), transforming growth factor-.alpha. (TGF-.alpha.), TGF-.beta.1, TGF-.beta.2, fibroblast growth factor (FGF), granulocyte/macrophage colony stimulating factor (GMCSF), epidermal growth factor (EGF), platelet derived growth factor (PDGF), insulin-like growth factor (IGF), scatter factor/hepatocyte growth factor (HGF), fibrin, collagen, fibronectin, vitronectin, hyaluronic acid, an RGD-containing peptide or polypeptide, an angiopoietin or vascular endothelial cell growth factor (VEGF).

41. The method of claim 38, wherein said biocompatible material is operatively associated with a biologically effective amount of at least a first bioactive DNA molecule, RNA molecule, antisense nucleic acid, ribozyme, plasmid, expression vector, viral vector or recombinant virus.

42. The method of claim 33, wherein said biocompatible material is operatively associated with a biologically effective amount of at least a first biological cell.

43. The method of claim 42, wherein said biocompatible material is operatively associated with a biologically effective amount of at least a first bone progenitor cell, fibroblast or endothelial cell.

44. The method of claim 43, wherein said biocompatible material is operatively associated with a biologically effective amount of at least a first bone progenitor cell selected from the group consisting of a stem cell, macrophage, fibroblast, vascular cell, osteoblast, chondroblast and osteoclast.

45. The method of claim 42, wherein said biocompatible material is operatively associated with a biologically effective amount of at least a first recombinant cell that expresses at least a first exogenous nucleic acid segment that produces a transcriptional or translated product in said cell.

46. The method of claim 33, wherein said biocompatible material is operatively associated with a combined biologically effective amount of at least a first bioactive substance and at least a first biological cell.

47. The method of claim 41, wherein said biocompatible material is operatively associated with a combined biologically effective amount of at least a first osteotropic growth factor or osteotropic growth factor nucleic acid and a cell population comprising bone progenitor cells.

48. The method of claim 46, wherein said biocompatible material is operatively associated with a combined biologically effective amount of VEGF or a VEGF nucleic acid and a cell population comprising endothelial cells.

49. The method of claim 33, wherein said at least a first mineral, bioactive substance or biological cell is incorporated into said biocompatible material prior to the generation of said patterned surface.

50. The method of claim 33, wherein said at least a first mineral, bioactive substance or biological cell is incorporated into said biocompatible material during or subsequent to the generation of said patterned surface to form a pattern of minerals, bioactive substances or biological cells on least a first surface of said biocompatible material.

51. The method of claim 50, wherein said at least a first mineral, bioactive substance or biological cell is incorporated into said biocompatible material during the generation of said patterned surface.

52. The method of claim 50, wherein said at least a first mineral, bioactive substance or biological cell is incorporated into said biocompatible material subsequent to the generation of said patterned surface.

53. The method of claim 50, wherein at least a first mineral is incorporated into said biocompatible material during or subsequent to the generation of said patterned surface to form a mineralized biocompatible material comprising a pattern of minerals on least a first surface.

54. The method of claim 53, wherein at least a first mineral is incorporated into said biocompatible material subsequent to the generation of said patterned surface by exposure of said patterned surface to a mineral-containing solution in vitro.

55. The method of claim 53, wherein at least a first mineral is incorporated into said biocompatible material subsequent to the generation of said patterned surface by exposure of said patterned surface to a mineral-containing body fluid in vivo.

56. The method of claim 55, wherein at least a first mineral-adherent biological cell is subsequently bound to said mineralized biocompatible material to form a pattern of biological cells on least a first surface of said biocompatible material.

57. The method of claim 56, wherein said at least a first mineral-adherent biological cell is bound to said mineralized biocompatible material by exposure of said mineralized biocompatible material to a population of mineral-adherent cells in vitro.

58. The method of claim 56, wherein said at least a first mineral-adherent biological cell is bound to said mineralized biocompatible material by exposure of said mineralized biocompatible material to a population of mineral-adherent cells in vivo.

59. The method of claim 1, wherein said biocompatible material comprises at least a first portion that is a biodegradable material.

60. The method of claim 1, wherein said biocompatible material comprises at least a first portion that is a non-biodegradable material.

61. The method of claim 1, wherein said biocompatible material comprises at least a first portion that is a substantially 2-dimensional biomaterial film.

62. The method of claim 1, wherein said biocompatible material comprises at least a first portion that is a 3-dimensional biomaterial scaffold.

63. The method of claim 1, wherein said biocompatible material comprises at least a first portion that has an interconnected or open pore structure.

64. The method of claim 1, wherein said biocompatible material comprises at least a first portion that is fabricated from a metal, bioglass, aluminate, biomineral or bioceramic material.

65. The method of claim 64, wherein said biocompatible material comprises at least a first portion that is fabricated from titanium or titanium coated with a biomineral.

66. The method of claim 64, wherein said biocompatible material comprises at least a first portion that is fabricated from a biomineral selected from the group consisting of hydroxyapatite, carbonated hydroxyapatite and calcium carbonate.

67. The method of claim 1, wherein said biocompatible material comprises at least a first portion that is fabricated from a synthetic polymer or a naturally-occurring polymer.

68. The method of claim 67, wherein said biocompatible material comprises at least a first portion that is fabricated from a synthetic polymer selected from the group consisting of a poly(vinyl alcohol), poly(ethylene glycol), pluronic, poly(vinylpyrollidone), hydroxyethyl cellulose, hydroxypropyl cellulose, carboxymethyl cellulose, poly(ethylene terephthalate), poly(anhydride) and poly(propylene fumarate).

69. The method of claim 68, wherein said biocompatible material comprises at least a first portion that is fabricated from a polylactic acid (PLA) polymer, polyglycolic acid (PGA) polymer or polylactic-co-glycolic acid (PLG) copolymer.

70. The method of claim 67, wherein said biocompatible material comprises at least a first portion that is fabricated from a naturally-occurring polymer selected from the group consisting of collagen, fibrin, matrigel, alginate, modified alginate, elastin, chitosan and gelatin.

71. The method of claim 1, wherein said pre-patterned radiation is constructively and destructively interfering radiation in the visible spectrum.

72. A method for forming a mineral pattern on a biocompatible material, comprising preparing a patterned biocompatible material by the process of claim 1 and contacting said patterned biocompatible material with an effective amount of a mineral-containing solution.

73. The method of claim 1, wherein said pre-patterned radiation is constructively and destructively interfering radiation in the infrared spectrum.

74. A 3-dimensional patterned biocompatible material prepared by the process of claim 1.

75. The 3-dimensional patterned biocompatible material of claim 74, further comprising a biologically effective amount of at least a first mineral, bioactive substance or biological cell.

76. The 3-dimensional patterned bicompatible material of claim 75, wherein said at least a first mineral, bioactive substance or biological cell forms a pattern on least a first surface of said biocompatible material.

77. The 3-dimensional patterned biocompatible material of claim 76, comprising a biologically effective amount of at least a first mineral bound in a mineralized pattern to at least a first surface of said biocompatible material and a biologically effective amount of at least a first biological cell bound to said mineralized pattern.

78. A biocompatible device comprising at least a first patterned 3-dimensional portion prepared by the process of claim 1.

79. The method of claim 1, wherein said pre-patterned radiation is constructively and destructively interfering radiation in the ultraviolet (UV) spectrum.

Details for Patent 6,541,022

Applicant Tradename Biologic Ingredient Dosage Form BLA Number Approval Date Patent No. Assignee Estimated Patent Expiration Status Orphan Source
Nps Pharms Inc NATPARA parathyroid hormone INJECTABLE;INJECTION 125511 001 2015-01-23   Start Trial The Regents of the University of Michigan (Ann Arbor, MI) 2019-03-19 RX Orphan search
Nps Pharms Inc NATPARA parathyroid hormone INJECTABLE;INJECTION 125511 002 2015-01-23   Start Trial The Regents of the University of Michigan (Ann Arbor, MI) 2019-03-19 RX Orphan search
Nps Pharms Inc NATPARA parathyroid hormone INJECTABLE;INJECTION 125511 003 2015-01-23   Start Trial The Regents of the University of Michigan (Ann Arbor, MI) 2019-03-19 RX Orphan search
Nps Pharms Inc NATPARA parathyroid hormone INJECTABLE;INJECTION 125511 004 2015-01-23   Start Trial The Regents of the University of Michigan (Ann Arbor, MI) 2019-03-19 RX Orphan search
>Applicant >Tradename >Biologic Ingredient >Dosage Form >BLA >Number >Approval Date >Patent No. >Assignee >Estimated Patent Expiration >Status >Orphan >Source

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