CA2370063A1 - Mineralization and cellular patterning on biomaterial surfaces - Google Patents

Mineralization and cellular patterning on biomaterial surfaces Download PDF

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Publication number
CA2370063A1
CA2370063A1 CA002370063A CA2370063A CA2370063A1 CA 2370063 A1 CA2370063 A1 CA 2370063A1 CA 002370063 A CA002370063 A CA 002370063A CA 2370063 A CA2370063 A CA 2370063A CA 2370063 A1 CA2370063 A1 CA 2370063A1
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biocompatible material
mineral
cell
effective amount
modified
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CA002370063A
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French (fr)
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CA2370063C (en
Inventor
William L. Murphy
Martin C. Peters
David J. Mooney
David H. Kohn
Gabriel C. Spalding
Matthew T. Dearing
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University of Michigan
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2400/00—Materials characterised by their function or physical properties
    • A61L2400/18—Modification of implant surfaces in order to improve biocompatibility, cell growth, fixation of biomolecules, e.g. plasma treatment

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.

Claims (118)

1. A method for surface-modification of a biocompatible material, comprising:
(a) generating a patterned surface on a biocompatible material by a method comprising irradiating at least a first photosensitive surface of a biocompatible material with pre-patterned electromagnetic radiation, thereby generating a pattern on at least a first surface of said biocompatible material; or (b) generating an extended mineralized surface on a biocompatible material by a method comprising functionalizing at least a first surface of a biocompatible material and contacting the functionalized surface with an amount of a mineral-containing solution, thereby generating extended mineralization on at least a first surface of said biocompatible material.
2. The method of claim 1, comprising generating a patterned surface on a biocompatible material by a method comprising functionalizing at least a first photosensitive surface of a biocompatible material by irradiating said photosensitive surface with an amount of pre-patterned electromagnetic radiation effective to generate a pattern on said at least a first surface of said biocompatible material.
3. The method of claim 2, wherein said pre-patterned radiation is constructively and destructively interfering electromagnetic radiation.
4. The method of claim 3, wherein said pre-patterned radiation is constructively and destructively interfering radiation in the visible spectrum.
5. The method of claim 3, wherein said pre-patterned radiation is constructively and destructively interfering radiation in the UV spectrum.
6. The method of claim 3, wherein said pre-patterned radiation is constructively and destructively interfering radiation in the infrared spectrum.
7. The method of any one of claims 3 through 6, 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.
8. The method of claim 7, wherein said monochromatic radiation is generated from a laser.
9. The method of claim 7, wherein said monochromatic radiation is generated from a mercury bulb.
10. The method of claim 7, wherein said monochromatic radiation is generated from an electromagnetic radiation source in combination with a filter.
11. The method of claim 7, 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.
12. The method of claim 7, wherein said diffractive optical element is fabricated from a transparent polymer or glass.
13. The method of claim 12, wherein said diffractive optical element is fabricated from a transparent polymer selected from the group consisting of a poly(methyl methacrylate), poly(styrene), and a high density poly(ethylene).
14. The method of claim 7, wherein said diffractive optical element is a diffraction grating fabricated from metal on glass, metal on polymer or metal with transmission apertures.
15. The method of claim 7, wherein said diffractive optical element is fabricated from fused silica or sapphire.
16. The method of any one of claims 2 through 15, wherein said photosensitive surface is prepared by applying a photosensitive composition to at least a first surface of said biocompatible material.
17. The method of claim 16, wherein said photosensitive composition is applied to at least a first surface of said biocompatible material by contacting said biocompatible material with a formulation of said photosensitive composition in a volatile solvent and evaporating said solvent to coat said photosensitive composition onto said at least a first surface.
18. The method of claim 16, wherein said photosensitive composition is applied to at least a first surface of said biocompatible material by contacting said biocompatible material with a formulation of said photosensitive composition in an aqueous or colloidal solution to adsorb said photosensitive composition onto said at least a first surface.
19. The method of any one of claims 16 through 18, wherein said photosensitive composition comprises a combined effective amount of at least a first photoinitiator and at least a first polymerizable component.
20. The method of claim 19, wherein said photosensitive composition comprises a polymerization-initiating amount of at least a first UV-excitable photoinitiator.
21. The method of claim 20, 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.
22. The method of claim 19, wherein said photosensitive composition comprises a polymerization-initiating amount of at least a first visible light-excitable photoinitiator.
23. The method of claim 22, 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.
24. The method of claim 22, wherein said photosensitive composition further comprises a co-initiating amount of at least a first accelerator.
25. The method of claim 24, 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.
26. The method of any one of claims 19 through 25, wherein said photosensitive composition comprises a photopolymerizable amount of at least a first monomeric, oligomeric or polymeric polymerizable component.
27. The method of claim 26, 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 and a vinyl ether.
28. The method of claim 19, wherein said photosensitive composition comprises a combined effective amount of an eosin photoinitiator, a polyethylene glycol) diacrylate polymerizable component and a triethanolamine accelerator.
29. The method of any one of claims 2 through 28, wherein the pattern generated comprises a pattern with a resolution of between about 1 µM and about 500 µM.
30. The method of claim 29, wherein the pattern generated comprises a pattern with a resolution of between about 1 µM and about 100 µM.
31. The method of claim 30, wherein the pattern generated comprises a pattern with a resolution of between about 10 µM and about 100 µM.
32. The method of claim 30, wherein the pattern generated comprises a pattern with a resolution of between about 1 µM and about 10 µM.
33. The method of claim 30, wherein the pattern generated comprises a pattern with a resolution of between about 10 µM and about 20 µM.
34. The method of any one of claims 2 through 33, wherein said biocompatible material is maintained on a temperature-controlled support during said irradiation.
35. The method of any one of claims 2 through 34, wherein the pattern generated comprises a pattern of polar oxygen groups on at least a first surface of said biocompatible material.
36. The method of any one of claims 2 through 35, wherein said biocompatible material is contacted with an amount of a mineral-containing solution effective to generate extended mineralization on at least a first surface of said biocompatible material.
37. The method of claim 36, wherein said biocompatible material is contacted with said mineral-containing solution prior to the generation of said parterned surface on said biocompatible material.
38. The method of claim 36, wherein said biocompatible material is contacted with said mineral-containing solution during or subsequent to the generation of said patterned surface, thereby forming a mineralized biocompatible material comprising a pattern of minerals on least a first surface.
39. The method of claim 38, 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.
40. The method of claim 39, 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.
41. The method of claim 39, 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.
42. The method of claim 1, comprising generating an extended mineralized surface on a biocompatible material by a method comprising functionalizing at least a first surface of a biocompatible material to create a plurality of polar oxygen groups at a functionalized surface and contacting said functionalized surface with an amount of a mineral-containing solution effective to generate extended mineralization on said at least a first surface of said biocompatible material.
43. The method of claim 42, wherein said functionalized surface is generated by exposing at least a first surface of said biocompatible material to a functionalizing pre-treatment prior to contact with said mineral-containing solution.
44. The method of claim 43, wherein said functionalizing pre-treatment comprises exposure to an effective amount of electromagnetic radiation.
45. The method of claim 44, wherein said functionalizing pre-treatment comprises exposure to an effective amount of UV radiation.
46. The method of claim 43, wherein said functionalizing pre-treatment comprises exposure to an effective amount of electron beam (e-beam) irradiation.
47. The method of claim 43, wherein said functionalizing pre-treatment comprises exposure to an effective amount of a NaOH solution.
48. The method of claim 42, wherein said functionalized surface is generated during said contact with said mineral-containing solution.
49. The method of any one of claims 36 through 48, wherein said mineral-containing solution comprises calcium and wherein said extended mineralization comprises an extended calcium coating.
50. The method of any one of claims 36 through 49, wherein said mineral-containing solution comprises at least a first and second mineral and wherein said extended mineralization comprises a mixture of said first and second minerals.
51. The method of any one of claims 36 through 49, wherein said mineral-containing solution comprises a plurality of distinct minerals and wherein said extended mineralization comprises a heterogeneous polymineralized coating.
52. The method of any one of claims 36 through 51, wherein said extended mineralization comprises a substantially homogeneous mineral coating.
53. The method of any one of claims 36 through 51, wherein said extended mineralization comprises at least a first hypermineralized portion.
54. The method of any one of claims 36 through 51, wherein said at least a first surface of said biocompatible material is an inner pore surface of a porous biocompatible material and wherein an extended mineral coating is generated on said inner pore surface.
55. The method of any one of claims 36 through 51, wherein said extended mineralization comprises a plurality of discrete mineral islands.
56. The method of any one of claims 36 through 55, wherein said mineral-containing solution is a body fluid.
57. The method of any one of claims 36 through 55, wherein said mineral-containing solution is a synthetic medium that mimics a body fluid.
58. The method of any one of claims 36 through 57, wherein said biocompatible material is contacted with said mineral-containing solution by exposure to a mineral-containing solution in vitro.
59. The method of any one of claims 36 through 57, wherein said biocompatible material is contacted with said mineral-containing solution by exposure to a mineral-containing body fluid in vivo.
60. The method of any preceding claim, wherein said biocompatible material comprises at least a first biodegradable portion.
61 61. The method of any preceding claim, wherein said biocompatible material comprises at least a first non-biodegradable portion.
62. The method of any preceding claim, wherein said biocompatible material comprises at least a first 3-dimensional scaffold portion.
63. The method of any preceding claim, wherein said biocompatible material comprises at least a first portion having an interconnected or open pore structure.
64. The method of any preceding claim, wherein said biocompatible material comprises at least a first substantially 2-dimensional biomaterial film portion.
65. The method of any preceding claim, wherein said biocompatible material comprises at least a first metal, bioglass, aluminate, biomineral, bioceramic, titanium or biomineral-coated titanium portion.
66. The method of any preceding claim, wherein said biocompatible material comprises at least a first portion comprising a biomineral selected from the group consisting of hydroxyapatite, carbonated hydroxyapatite and calcium carbonate.
67. The method of any preceding claim, wherein said biocompatible material comprises at least a first naturally-occurring or synthetic polymer portion.
68. The method of any preceding claim, wherein said biocompatible material comprises at least a first portion comprising a naturally-occurring polymer selected from the group consisting of collagen, alginate, fibrin, matrigel, modified alginate, elastin, chitosan and gelatin.
69. The method of any preceding claim, wherein said biocompatible material comprises at least a first portion comprising a synthetic polymer selected from the group consisting of a polyvinyl alcohol), polyethylene glycol), pluronic, poly(vinylpyrollidone), hydroxyethyl cellulose, hydroxypropyl cellulose, carboxymethyl cellulose, polyethylene terephthalate), poly(anhydride) and polypropylene fumarate).
70. The method of any preceding claim, wherein said biocompatible material comprises at least a first surface portion that is enriched in carboxylic acid groups.
71. The method of any preceding claim, wherein said biocompatible material comprises at least a first portion comprising a polylactic acid (PLA) polymer, polyglycolic acid (PGA) polymer or polylactic-co-glycolic acid (PLG) copolymer.
72. The method of any preceding claim, wherein said biocompatible material comprises at least a first portion comprising a PLG copolymer biomaterial having a ratio of about 85 percent lactide to about 15 percent glycolide.
73. The method of any preceding claim, wherein said biocompatible material comprises at least a first portion prepared by a process comprising gas foaming and particulate leaching.
74. The method of claim 73, wherein at least a first bioactive substance is operatively associated with said biocompatible material during the gas foaming and particulate leaching process.
75. The method of claim 73, wherein said biocompatible material is prepared by a gas foaming and particulate leaching process comprising the steps of:
(a) preparing an admixture at least comprising a teachable particulate material and particles capable of forming a porous, degradable polymer biomaterial;
(b) subjecting said admixture to a gas foaming process to create a porous, degradable polymer biomaterial that comprises said teachable particulate material; and (c) subjecting said porous, degradable polymer biomaterial to a leaching process that removes said teachable particulate material from said porous, degradable polymer biomaterial, thereby creating additional porosity.
76. The method of claim 75, wherein said leaching process comprises contacting said porous, degradable polymer biomaterial with a mineral-containing leaching material.
77. The method of any preceding claim, wherein said at least a first surface of said biocompatible material is a substantially level surface.
78. The method of any one of claims 1 through 76, wherein said at least a first surface of said biocompatible material is a contoured surface.
79. The method of any preceding claim, wherein said method is executed at a temperature compatible to mammalian biological systems.
80. The method of any preceding claim, wherein said biocompatible material is fabricated as at least a portion of an implantable device.
81. The method of any preceding claim, wherein said biocompatible material further comprises a biologically effective amount of at least a first bioactive substance, bioactive drug or biological cell.
82. The method of any preceding claim, wherein said biocompatible material further comprises a biologically effective amount of at least two bioactive substances, drugs or biological cells.
83. The method of any preceding claim, wherein said biocompatible material further comprises a biologically effective amount of a plurality of bioactive substances, drugs or biological cells.
84. The method of any preceding claim, wherein said biocompatible material further comprises a biologically effective amount of at least first DNA molecule, RNA
molecule, antisense nucleic acid, ribozyme, plasmid, expression vector, viral vector or recombinant virus.
85. The method of any preceding claim, wherein said biocompatible material further comprises 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 or cytotoxin.
86. The method of any preceding claim, wherein said biocompatible material further comprises a biologically effective amount of at least a first 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.
87. The method of any preceding claim, wherein said biocompatible material further comprises 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).
88. The method of any preceding claim, wherein said biocompatible material further comprises a biologically effective amount of at least a first bone progenitor cell, fibroblast or endothelial cell.
89. The method of any preceding claim, wherein said biocompatible material further comprises a biologically effective amount of at least a first stem cell, macrophage, fibroblast, vascular cell, osteoblast, chondroblast or osteoclast.
90. The method of any preceding claim, wherein said biocompatible material further comprises 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.
91. The method of any preceding claim, wherein said biocompatible material further comprises a combined biologically effective amount of at least a first bioactive substance and at least a first biological cell.
92. The method of any preceding claim, wherein said biocompatible material further comprises 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.
93. The method of any preceding claim, wherein said biocompatible material further comprises a combined biologically effective amount of VEGF or a VEGF nucleic acid and a cell population comprising endothelial cells.
94. The method of any preceding claim, wherein at least a first bioactive substance, drug or biological cell is incorporated into said biocompatible material prior to the surface-modification process.
95. The method of any preceding claim, wherein at least a first bioactive substance, drug or biological cell is incorporated into said biocompatible material during the surface-modification process.
96. The method of any preceding claim, wherein at least a first bioactive substance, drug or biological cell is incorporated into said biocompatible material subsequent to the surface-modification process.
97. The method of any preceding claim, wherein said biocompatible material comprises at least a first patterned surface and wherein at least a first bioactive substance, drug or biological cell is bound in a pattern at said patterned surface.
98. The method of any preceding claim, wherein said biocompatible material comprises at least a first mineralized surface and wherein at least a first mineral-adherent bioactive substance, drug or biological cell is bound to said mineralized surface.
99. The method of claim 98, wherein generation of said at least a first mineralized surface controls the release of said bioactive substance, drug or biological cell from said biocompatible material.
100. A surface-modified biocompatible material comprising at least a first modified surface prepared by a method in accordance with any preceding claim.
101. A surface-modified biocompatible material in accordance with claim 100 for use in cell culture.
102. A surface-modified biocompatible material in accordance with claim 100 for use in cell transplantation.
103. A surface-modified biocompatible material in accordance with claim 100 for use in tissue engineering.
104. A surface-modified biocompatible material in accordance with claim 100 for use in guided tissue regeneration.
105. Use of a surface-modified biocompatible material in accordance with claim 100 in the preparation of a medicament for treating a medical condition in need of cell transplantation.
106. Use of a surface-modified biocompatible material in accordance with claim 100 in the preparation of a medicament for treating a medical condition in need of tissue engineering.
107. Use of a surface-modified biocompatible material in accordance with claim 100 in the preparation of a medicament for treating a medical condition in need of guided tissue regeneration.
108. A cell culture device comprising a surface-modified biocompatible material in accordance with claim 100.
109. An implantable biomedical device comprising a surface-modified biocompatible material in accordance with claim 100.
110. A method for culturing cells, comprising growing a cell population in contact with a surface-modified biocompatible material in accordance with claim 100.
111. The method of claim 110, wherein said cell population is maintained in contact with said surface-modified biocompatible material under conditions and for a period of time effective to generate a two or three dimensional tissue-like structure.
112. The method of claim 110, wherein said cell population is maintained in contact with said surface-modified biocompatible material under conditions and for a period of time effective to generate bone-like tissue.
113. The method of claim 110, wherein said cell population is maintained in contact with said surface-modified biocompatible material under conditions and for a period of time effective to generate neovascularized or vascularized tissue.
114. The method of claim 110, wherein said cell population is contacted with said surface-modified biocompatible material in vitro.
115. The method of claim 114, wherein the cultured cells are separated from said surface-modified biocompatible material and provided to an animal.
116. The method of claim 114, wherein the cultured cells are maintained in contact with said surface-modified biocompatible material and wherein the cultured cell-surface-modified biocompatible material composition is provided to an animal.
117. A method for transplanting cells into an animal, comprising applying to a tissue site of an animal a biologically effective amount of a cell-biocompatible material composition that comprises a cell population in operative association with a surface-modified biocompatible material in accordance with claim 100.
118. A method for tissue engineering in an animal, comprising applying to a tissue progenitor site of an animal a biologically effective amount of a biocompatible material composition that provides a scaffold for tissue growth and that comprises a surface-modified biocompatible material in accordance with claim 100.
CA2370063A 1999-03-19 2000-03-17 Mineralization and cellular patterning on biomaterial surfaces Expired - Lifetime CA2370063C (en)

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Application Number Priority Date Filing Date Title
US12511899P 1999-03-19 1999-03-19
US60/125,118 1999-03-19
US16728999P 1999-11-24 1999-11-24
US60/167,289 1999-11-24
PCT/US2000/007207 WO2000056375A2 (en) 1999-03-19 2000-03-17 Mineralization and cellular patterning on biomaterial surfaces

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CA2370063C CA2370063C (en) 2012-10-02

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AT (1) ATE241397T1 (en)
AU (1) AU4173000A (en)
CA (1) CA2370063C (en)
DE (1) DE60003006T2 (en)
DK (1) DK1163018T3 (en)
ES (1) ES2199815T3 (en)
WO (1) WO2000056375A2 (en)

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