WO2000048642B1 - Biocompatible material with a novel functionality - Google Patents

Biocompatible material with a novel functionality

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Publication number
WO2000048642B1
WO2000048642B1 PCT/DK2000/000065 DK0000065W WO0048642B1 WO 2000048642 B1 WO2000048642 B1 WO 2000048642B1 DK 0000065 W DK0000065 W DK 0000065W WO 0048642 B1 WO0048642 B1 WO 0048642B1
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Prior art keywords
material according
substratum
macromolecule
contact angle
cell
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PCT/DK2000/000065
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French (fr)
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WO2000048642A3 (en
WO2000048642A2 (en
Inventor
Volkmar Thom
Gunnar Jonsson
Mathias Ulbricht
Katja Jankova
George Altankov
Original Assignee
Surfarc Aps
Volkmar Thom
Gunnar Jonsson
Mathias Ulbricht
Katja Jankova
George Altankov
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Application filed by Surfarc Aps, Volkmar Thom, Gunnar Jonsson, Mathias Ulbricht, Katja Jankova, George Altankov filed Critical Surfarc Aps
Priority to EP00903567A priority Critical patent/EP1152774A2/en
Priority to JP2000599431A priority patent/JP2002537025A/en
Priority to AU25366/00A priority patent/AU2536600A/en
Publication of WO2000048642A2 publication Critical patent/WO2000048642A2/en
Publication of WO2000048642A3 publication Critical patent/WO2000048642A3/en
Publication of WO2000048642B1 publication Critical patent/WO2000048642B1/en

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
    • A61K9/0024—Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue
    • 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
    • A61L27/28—Materials for coating prostheses
    • A61L27/34—Macromolecular 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
    • A61L29/00—Materials for catheters, medical tubing, cannulae, or endoscopes or for coating catheters
    • A61L29/08—Materials for coatings
    • A61L29/085—Macromolecular 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
    • A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
    • A61L31/08—Materials for coatings
    • A61L31/10—Macromolecular materials
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B82—NANOTECHNOLOGY
    • B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
    • B82Y30/00—Nanotechnology for materials or surface science, e.g. nanocomposites
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B82—NANOTECHNOLOGY
    • B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
    • B82Y5/00—Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
    • C12N5/0068—General culture methods using substrates
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2533/00—Supports or coatings for cell culture, characterised by material
    • C12N2533/30—Synthetic polymers

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  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Epidemiology (AREA)
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  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Nanotechnology (AREA)
  • Medicinal Chemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Biotechnology (AREA)
  • Biomedical Technology (AREA)
  • General Engineering & Computer Science (AREA)
  • Dermatology (AREA)
  • Crystallography & Structural Chemistry (AREA)
  • Wood Science & Technology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Genetics & Genomics (AREA)
  • Organic Chemistry (AREA)
  • Zoology (AREA)
  • Cell Biology (AREA)
  • Microbiology (AREA)
  • Neurosurgery (AREA)
  • Transplantation (AREA)
  • Biochemistry (AREA)
  • Oral & Maxillofacial Surgery (AREA)
  • Vascular Medicine (AREA)
  • Physics & Mathematics (AREA)
  • Composite Materials (AREA)
  • Condensed Matter Physics & Semiconductors (AREA)
  • General Physics & Mathematics (AREA)
  • Materials Engineering (AREA)
  • Surgery (AREA)
  • Heart & Thoracic Surgery (AREA)
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  • Molecular Biology (AREA)
  • Materials For Medical Uses (AREA)

Abstract

The present invention is in the area of biomaterials, i.e. materials that are used in contact with living tissue and biological fluids for prosthetical, therapeutical, storage and the like. In particular, the invention relates to a novel approach of creating biocompatible surfaces, said surfaces being capable of functionally interacting with biological material. Said biocompatible surfaces comprise at least two components, such as a hydrophobic substratum and a macromolecule of hydrophilic nature, that cooperatively form a novel biocompatible surface. The novel approach is based on contacting said hydrophobic substratum with a laterally patterned monomolecular layer of hydrophilic and flexible macromolecules that exhibit a pronounced excluded volume. The surface is, in respect to polarity and morphology, a molecularly heterogeneous surface. Structural features of said macromolecular monolayer (as e.g. the layer thickness or its lateral density) are determined by, i) the structural features of the layer forming macromolecules (as e.g. their MW or their molecular architecture) and, ii) the method of creating said monomolecular layer (as e.g. by physi- or chemisorbing, or by chemically binding said macromolecules). The structural features of the layer forming macromolecule(s) is in turn determined by synthesis.

Claims

97AMENDED CLAIMS[received by the International Bureau on 26 October 2000 (26.10.00); original claims 1-146 amended (17 pages)]
1. Material comprising a substratum, said substratum being contactable with a macromolecule, said material further comprising at least one macromolecule,
said material having a first contact angle a,
said substratum having a second contact angle b0when not contacted by a macromolecule, and another second contact angle bsat, when said substratum is saturated by said macromolecules as defined herein,
wherein the relation between said contact angles is as defined by the ratio R,
R = (bo - a) / (bo - bMt)
and wherein the numerical value of R is in the interval from and including 0 to less than 0.6.
2. Material according to claim 1 , said material comprising a substratum, said substratum being contactable with a macromolecule, said material further compris- ing at least one macromolecule,
said material having a first contact angle a,
said substratum having a second contact angle b0when not contacted by a macromolecule,
said contact angle a being substantially identical to said contact angle b0.
3. Material having a first contact angle and comprising a substratum having a second contact angle, said substratum being contacted by a macromolecule, wherein the relation between said first and second contact angle as defined by the ratio between 98 i) the difference between said second contact angle, when no macromolecule is present, and said first contact angle, and ii) the difference between said second contact angle, when no macromolecule is present, and the contact angle of said substratum, when said substratum is saturated by said macromolecules as defined herein, is more than -0.6 and less than 0.6.
4. Material having a first contact angle and comprising a substratum having a second contact angle, said substratum being contacted by a plurality of soluble substances capable of forming a self-assembled monolayer comprising a macromolecule and having a third contact angle, wherein the relation between said contact angles as defined by the ratio between i) the difference between the third contact angle of said monolayer, when no macromolecule is present, and said first contact angle, and ii) the difference between the third contact angle of said monolayer, when no macromolecule is present, and the contact angle of said self- assembled monolayer, when said monolayer is saturated by said macromolecules as defined herein, is more than -0.6 and less than 0.6.
5. Material according to claim 4, wherein said soluble substance is selected from the group consisting of molecules capable of forming a self-assembled mono- layer.
6. Material according to any of claims 1 to 5, wherein said substratum is pre- treated or modified.
7. Material according to claim 6 wherein said pretreated or modified substratum is the result of said substratum being contacted by and/or operably linked to a charged group or a hydrophilic compound.
8. Material according to any of the preceding claims, wherein said first contact angle is the advancing contact angle. 99
9. Material according to claim 8, wherein said first contact angle is in the range of from 50 degrees to 140 degrees.
10. Material according to claim 8, wherein said first contact angle is in the range of from 60 degrees to 125 degrees.
1 1. Material according to claim 8, wherein said first contact angle is in the range of from 70 degrees to 120 degrees.
12. Material according to claim 8, wherein said first contact angle is in the range of from 75 degrees to 110 degrees.
13. Material according to claim 8, wherein said first contact angle is in the range of from 80 degrees to 100 degrees.
14. Material according to claim 8, wherein said ratio is less than 0.50.
15. Material according to claim 8, wherein said ratio is less than 0.40.
16. Material according to claim 8, wherein said ratio is less than 0.30.
17. Material according to claim 8, wherein said ratio is less than 0.25.
18. Material according to claim 8, wherein said ratio is less than 0.20.
19. Material according to claim 8, wherein said ratio is less than 0.15.
20. Material according to claim 8, wherein said ratio is less than 0.10.
21. Material according to claim 8, wherein said ratio is less than 0.05.
22. Material according to any of claims 1 to 7, wherein said first contact angle is the receding contact angle and wherein said ratio is less than 0.40. 100
23. Material according to claim 22, wherein said first contact angle is in the range of from 30 degrees to 120 degrees.
24. Material according to claim 22, wherein said first contact angle is in the range of from 40 degrees to 110 degrees.
25. Material according to claim 22, wherein said first contact angle is in the range of from 50 degrees to 100 degrees.
26. Material according to claim 22, wherein said first contact angle is in the range of from 60 degrees to 90 degrees.
27. Material according to claim 22, wherein said first contact angle is in the range of from 70 degrees to 80 degrees.
28. Material according to claim 22, wherein said ratio is less than 0.35.
29. Material according to claim 22, wherein said ratio is less than 0.30.
30. Material according to claim 22, wherein said ratio is less than 0.25.
31. Material according to claim 22, wherein said ratio is less than 0.20.
32. Material according to claim 22, wherein said ratio is less than 0.15.
33. Material according to claim 22, wherein said ratio is less than 0.10.
34. Material according to claim 22, wherein said ratio is less than 0.05.
35. Material according to any of the preceding claims, wherein said material, when contacted by a first determinant comprising a compound selected from the group consisting of a polypeptide, or part thereof, a nucleic acid moiety, a carbohydrate moiety, and a lipid moiety, including any combination thereof, is capable of maintaining said compound in a biologically active form. 101
36. Material according to claim 35 wherein said compound is a polypeptide or part thereof.
37. Material according to claim 35 or 36 further comprising said first determinant comprising said compound, wherein said first determinant is maintained in a biologically active form when contacted by said substratum and/or said macromolecule.
38. Material according to claim 37 wherein said biologically active form is essen- tially a biologically active conformation.
39. Material according to any of claims 35 to 38 wherein said biologically active form or conformation is maintained and/or improved and/or stabilized by means of the cooperativity of said substratum and said macromolecule.
40. Material according to claim 35 to 39 wherein said biologically active form or confirmation is maintained and/or improved and/or stabilized when contacted by said substratum and said macromolecule.
41. Material according to any of the preceding claims, wherein said material is biocompatible.
42. Material according to any of the preceding claims, wherein the weight increase per area unit arising from the part of the macromolecule essentially consisting of PEG or poly(ethylene oxide) (PEO) is less than 2.0 x 10"22 grams (g) per square nanometer (nm2).
43. Material according to claim 42, wherein said difference is less than 1.0 x 10"22 grams (g) per square nanometer (nm2).
44. Material according to claim 42, wherein said difference is less than 0.8 x 10"22 grams (g) per square nanometer (nm2).
45. Material according to claim 42, wherein said difference is less than 0.5 x 10"22 grams (g) per square nanometer (nm2). 102
46. Material according to claim 42, wherein said difference is less than 0.3 x 10"22 grams (g) per square nanometer (nm2).
47. Material according to any of the preceding claims, wherein said substratum is contacted by a plurality of soluble compounds capable of forming a layer of self-assembled macromolecules.
48. Material according to claim 47, wherein said soluble compounds are n-alkane chains preferably containing from 8 to 24 carbons.
49. Material according to any of the preceding claims wherein each macromolecule is associated with an excluded volume.
50. Material according to any of the preceding claims, wherein said substratum comprises a hydrophobic polymer.
51. Material according to claim 50, wherein said substratum is at least substantially flexible.
52. Material according to claim 50, wherein said substratum is a film.
53. Material according to claim 50, wherein said substratum is essentially rigid or at least substantially non-flexible.
54. Material according to claim 53, wherein said substratum comprises a crystalline structure capable of supporting a self-assembled monolayer such as gold, silicon oxide, and similar crystalline structures and/or structures that are smooth on a nanometer scale.
55. Material according to any of the preceding claims, wherein said macromolecule comprises a hydrophilic polymer.
56. Material according to claim 55, wherein said macromolecule comprises an amphiphilic polymer. 103
57. Material according to any of the preceding claims, wherein said macromolecule has a MW of more than 400 Da.
58. Material according to claim 57, wherein said macromolecule has a MW of more than 1.000 Da.
59. Material according to claim 57, wherein said macromolecule has a MW of more than 5.000 Da.
60. Material according to claim 57, wherein said macromolecule has a MW of more than 10.000 Da.
61. Material according to claim 57, wherein said macromolecule has a MW of more than 50.000 Da.
62. Material according to claim 57, wherein said macromolecule has a MW of more than 100.000 Da.
63. Material according to any of the preceding claims, wherein said macromolecule is a conjugate comprising a head group, a guiding group, a linker group, a polymer chain or a main body, and a functional end group.
64. Material according to claim 63, wherein said head group is capable of forming a chemical bond.
65. Material according to claim 63, wherein said head group may adsorb to the substratum.
66. Material according to claim 63, wherein said head group is capable of forming an ionic bond.
67. Material according to claim 63, wherein said head group may be entangled into or with the substratum.
68. Material according to claim 63, wherein said head group is capable of forming a self-assembled monolayer.
69. Material according to claim 63, wherein said guiding group is a bifunctional group comprising an aliphatic, linear or weakly branched group.
70. Material according to claim 63, wherein said linker group is capable of being enzymatically or chemically hydrolyzed.
71. Material according to claim 63, wherein said linker group is hydrolytically unstable.
72. Material according to claim 63, wherein said linker group is essentially stable against cleavage under practical circumstances.
73. Material according to claim 63, wherein said polymer chain or main body is preferably hydrophilic, uncoiling in an aqueous environment and exhibiting an excluded volume.
74. Material according to claim 63, wherein said functional end group is capable of linking permanently or reversibly other biological or synthetic molecules or materials.
75. Material according to any of claims 35 to 74, wherein said first determinant comprises a biologically active compound comprising a polypeptide, or a part thereof, a nucleic acid moiety, a carbohydrate moiety, and a lipid moiety, including any combination thereof.
76. Material according to claim 75, wherein said biologically active compound comprises a polypeptide.
77. Material according to claim 75, wherein said biologically active compound is selected from the group consisting of membrane associated and/or extracellular matrix polypeptides natively produced by a microbial cell, a plant cell or a mammalian cell. 105
78. Material according to claim 75 wherein said biologically active compound is selected from the group consisting of a polypeptide, an antibody, a polyclonal antibody, a monoclonal antibody, an immunogenic determinant, an antigenic determinant, a receptor, a receptor binding protein, an interleukine, a cytokine, a cellular differentiation factor, a cellular growth factor, and an antagonist to a receptor.
79. Material according to claim 75, wherein said biologically active compound is a synthetic polypeptide, or part thereof, capable of contacting said substratum and/or said macromolecule.
80. Material according to claim 75, wherein said biologically active compound is a synthetic polypeptide, or part thereof, capable of contacting said substratum and said macromolecule.
81. Material according to claim 75, wherein said biologically active compound is an adhesion polypeptide, preferably fibronectin or vitronectin.
82. Material according to any of claims 35 to 81 , wherein said biologically active compound results in an improved contact between said material and a biological entity, such as a biological cell or a virus, or part thereof, including a polypeptide, or a part thereof, a nucleic acid moiety, a carbohydrate moiety, and a lipid moiety, including any combination thereof.
83. Material according to any of the preceding claims, said material further comprising a second determinant.
84. Material according to claim 83, wherein said second determinant comprises a biological entity, such as a biological cell or a virus, or part thereof, including a polypeptide, or a part thereof, a nucleic acid moiety, a carbohydrate moiety, and a lipid moiety, including any combination thereof.
85. Material according to claim 83, wherein said biological entity is selected from the group consisting of a polypeptide, an antibody, a polyclonal antibody, a 106
monoclonal antibody, an immunogenic determinant, an antigenic determinant, a receptor, a receptor binding protein, an interleukine, a cytokine, a differentiation factor, a growth factor, and an antagonist to the receptor.
86. Material according to claim 84, wherein said biological cell, or part thereof, is selected from the group consisting of a mammalian cell, including a human cell and an animal cell, a plant cell, a microbial cell, including a eukaryotic microbial cell, including a yeast and a fungus, and a prokaryotic microbial cell including a bacteria.
87. Material according to claim 86 wherein said biological cell is a mammalian cell.
88. Material according to claim 84, wherein said virus, or part thereof, is selected from a mammalian virus, including a human virus and an animal virus, a plant virus, a microbial virus, including a eukaryotic microbial virus, including a yeast virus and a fungal virus, and a prokaryotic microbial virus including a bacterio- phage.
89. Material according to claim 88 wherein said virus is a mammalian virus.
90. Material according to any of the preceding claims, wherein said substratum is porous and preferably a membrane.
91. Material according to claim 90, wherein the flux of water through said material is substantially unchanged as compared to the flux of water through said porous substratum.
92. Material according to any of claims 1 to 91 , wherein said substratum is non- porous and/or substantially non-penetrable to water.
93. Material according to any of the preceding claims for use in a method of controlling cellular growth and/or cellular proliferation and/or cellular differentiation ex vivo. 107
94. Material according to any of the preceding claims for use in a method of separating and/or isolating biological material ex vivo.
95. Material according to any of the preceding claims for use in a method of pro- ducing a biohybrid organ ex vivo.
96. Material according to any of claims 1 to 95 for use in a diagnostic method carried out on the human or animal body.
97. Material according to any of claims 1 to 96 for use in a method of therapy carried out on the human or animal body.
98. Material according to any of claims 1 to 97 for use in a method of surgery carried out on the human or animal body.
99. Material according to any of claims 1 to 98 for use in a method of producing a biohybrid organ in vivo.
100. Material according to any of claims 1 to 99 for use as a carrier for in vivo de- livery of a medicament to a human or animal body in need of said medicament.
101. Material according to any of claims 1 to 100 for use in a method of controlling cellular growth and/or cellular proliferation and/or cellular differentiation in vivo.
102. Material according to any of claims 1 to 101 for use in a method of separating and/or isolating biological material in vivo.
103. Composition comprising the material according to any of the preceding claims and a physiologically acceptable carrier.
104. Pharmaceutical composition comprising the material according to any of claims 1 to 102 or the composition of claim 103 and a pharmaceutically active ingredient and optionally a pharmaceutically active carrier. 108
105. Use of the material according to any of claims 1 to 102 or the composition according to claim 103 or the pharmaceutical composition according to claim 104 in a method of therapy carried out on the human or animal body.
106. Use of the material according to any of claims 1 to 102 or the composition according to claim 103 or the pharmaceutical composition according to claim 104 in a method of surgery carried out on the human or animal body.
107. Use of the material according to any of claims 1 to 102 or the composition ac- cording to claim 103 or the pharmaceutical composition according to claim 104 in a diagnostic method carried out on the human or animal body.
108. Use of the material according to any of claims 1 to 102 or the composition according to claim 103 or the pharmaceutical composition according to claim 104 in a method of producing a biohybrid organ in vivo.
109. Use of the material according to any of claims 1 to 102 or the composition according to claim 103 or the pharmaceutical composition according to claim 104 as a carrier for in vivo delivery of a medicament to a human or animal body in need of said medicament.
110. Use of the material according to any of claims 1 to 102 or the composition according to claim 103 or the pharmaceutical composition according to claim 104 in a method of controlling cellular growth and/or cellular proliferation and/or cellular differentiation in vivo.
11 1. Use of the material according to any of claims 1 to 102 or the composition according to claim 103 or the pharmaceutical composition according to claim 104 in a method of separating and/or isolating biological material in vivo.
112. Use of the material according to any of claims 1 to 102 or the composition according to claim 103 or the pharmaceutical composition according to claim 104 in a method of controlling cellular growth and/or cellular proliferation and/or cellular differentiation ex vivo. 109
1 13. Use of the material according to any of claims 1 to 102 or the composition according to claim 103 or the pharmaceutical composition according to claim 104 in a method of separating and/or isolating biological material ex vivo.
1 14. Use of the material according to any of claims 1 to 102 or the composition according to claim 103 or the pharmaceutical composition according to claim 104 in a method of producing a biohybrid organ ex vivo.
115. Use of the material according to any of claims 1 to 102 or the composition ac- cording to claim 103 or the pharmaceutical composition according to claim 104 in the manufacture of an implantable organ or part thereof.
116. Use of the material according to any of claims 1 to 102 as a carrier for a pharmaceutically active ingredient or a pharmaceutical composition.
117. Method of controlling cellular growth and/or cellular proliferation and/or cellular differentiation ex vivo, said method comprising the steps of contacting a ceil with the material according to any of claims 1 to 102 or the composition according to claim 103 or the pharmaceutical composition according to claim 104 and incubating said cell and said material under conditions allowing said cell to grow and/or proliferate and/or differentiate.
118. Method of separating and/or isolating biological material ex vivo, said method comprising the steps of contacting said biological material to be separated and/or isolated with the material according to any of claims 1 to 102 or the composition according to claim 103 or the pharmaceutical composition according to claim 104 and incubating said biological material and said material under conditions that allow separation and/or isolation.
119. Method of producing a biohybrid organ ex vivo, said method comprising the steps of contacting biohybrid organ cells with the material according to any of claims 1 to 102 or the composition according to claim 103 or the pharmaceutical composition according to claim 104 and incubating said biohybrid organ cells under conditions allowing the production of said biohybrid organ. 1 10
120. Method of therapy carried out on the human or animal body, said method comprising the step of contacting said body with the material according to any of claims 1 to 102 or the composition according to claim 103 or the pharmaceutical composition according to claim 104.
121. Method of surgery carried out on the human or animal body, said method comprising the step of contacting said body with the material according to any of claims 1 to 102 or the composition according to claim 103 or the pharmaceutical composition according to claim 104.
122. Method of diagnosis carried out on the human or animal body, said method comprising the steps of contacting said body with the material according to any of claims 1 to 102 or the composition according to claim 103 or the pharmaceutical composition according to claim 104 and detecting a signal gener- ated directly or indirectly by said material.
123. Method of controlling cellular growth and/or cellular proliferation and/or cellular differentiation in vivo, said method comprising the steps of contacting a cell with the material according to any of claims 1 to 102 or the composition ac- cording to claim 103 or the pharmaceutical composition according to claim 104 and incubating said cell and said material under conditions allowing said cell to grow and/or proliferate and/or differentiate.
124. Method of separating and/or isolating biological material in vivo, said method comprising the steps of contacting said biological material to be separated and/or isolated with the material according to any of claims 1 to 102 or the composition according to claim 103 or the pharmaceutical composition according to claim 104 and incubating said biological material and said material under conditions that allow separation and/or isolation.
125. Method of producing a biohybrid organ in vivo, said method comprising the steps of contacting biohybrid organ cells with the material according to any of claims 1 to 102 or the composition according to claim 103 or the pharmaceutical composition according to claim 104 and incubating said biohybrid organ cells under conditions allowing the production of said biohybrid organ. 1 1 1
126. Method of in vivo delivery of a medicament to a human or animal body in need of said medicament, said method comprising the steps of contacting said body with the pharmaceutical composition according to claim 104 and incubating said body contacted by said pharmaceutical composition under conditions allowing delivery of said medicament.
127. Method for producing the material according to any of claims 1 to 102, said method comprising the steps of i) providing a substratum having a second contact angle, and ii) contacting said substratum with a composition comprising a plurality of macromolecules.
128. Method according to claim 127, wherein said substratum comprises a hydro- phobic polymer.
129. Method according to claim 127, wherein said substratum is pretreated prior to being contacted by said macromolecule.
130. Method according to claim 129, wherein said pretreatment is effective in in- creasing the wettability of said substratum.
131. Method according to claim 127, wherein said macromolecule comprises a hydrophilic polymer.
132. Method according to claim 127, wherein said macromolecule comprises a latently reactive polymer.
133. Method according to claim 127, wherein macromolecule has a MW of more than 400 Da.
134. Method according to claim 127, wherein said macromolecule comprises a conjugate comprising a cross likable head group, a linker group, a polymer chain, and a functional end group. 112
135. Method according to claim 134, wherein said cross likable head group is a photo-reactive aryl azide head group.
136. Method according to claim 134, wherein said macromolecule further com- prises a modifying agent.
137. Method according to claim 136 wherein said modifying agent is capable of contacting said substratum and forming a self assembled monolayer.
138. Method according to any of claims 127 to 137 for producing the material according to any of claims 1 to 102, said method comprising the further step of contacting said material with a first determinant comprising a biologically active compound.
139. Method according to claim 138, wherein said biologically active compound is selected from the group consisting of a polypeptide, an antibody, a polyclonal antibody, a monoclonal antibody, an immunogenic determinant, an antigenic determinant, a receptor, a receptor binding protein, an interleukine, a cytokine, a cellular differentiation factor, a cellular growth factor, and an antagonist to a receptor.
140. Method according to claim 138, wherein said biologically active compound is a membrane associated and/or extracellular matrix polypeptide natively produced by a microbial cell, a plant cell or a mammalian cell.
141. Method according to any of claims 138 to 140 for producing the material according to any of claims 1 to 102, said method comprising the further step of contacting said material with a second determinant comprising a biological entity.
142. Method according to claim 141 , wherein said biological entity comprises a cell or a virus, or a part thereof.
143. Method according to claim 142, wherein said cell, or part thereof, is selected from the group consisting of a mammalian cell, including a human cell and an 1 13
animal cell, a plant cell, a microbial cell, including a eukaryotic microbial cell, including a yeast and a fungus, and a prokaryotic microbial cell including a bacteria.
144. Method according to claim 142, wherein said virus, or part thereof, is selected from a mammalian virus, including a human virus and an animal virus, a plant virus, a microbial virus, including a eukaryotic microbial virus, including a yeast virus and a fungal virus, and a prokaryotic microbial virus including a bacterio- phage.
145. Method according to claim 141 , wherein said biological entity comprises a polypeptide, or a part thereof, a nucleic acid moiety, a carbohydrate moiety, and a lipid moiety, including any combination thereof.
146. Method according to claim 141 , wherein said biological entity is selected from the group consisting of a polypeptide, an antibody, a polyclonal antibody, a monoclonal antibody, an immunogenic determinant, an antigenic determinant, a receptor, a receptor binding protein, an interleukine, a cytokine, a differentiation factor, a growth factor, and an antagonist to the receptor.
114
STATEMENT UNDER ARTICLE 19
The claims have been amended only with respect to mutual dependency and no amendments have thus been made going beyond the disclosure in the international application as filed.
PCT/DK2000/000065 1999-02-17 2000-02-17 Biocompatible material with a novel functionality WO2000048642A2 (en)

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AU25366/00A AU2536600A (en) 1999-02-17 2000-02-17 Biocompatible material with a novel functionality

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EP1326655A2 (en) * 2000-08-23 2003-07-16 Surfarc APS Biocompatible materials
GB0115204D0 (en) * 2001-06-21 2001-08-15 Zellwerk Gmbh Ceramic materials, method for their production and use thereof
WO2004015376A2 (en) * 2002-08-07 2004-02-19 National Institutes Of Health Measurement systems and methods
EP2080603A1 (en) 2008-01-18 2009-07-22 Nederlandse Organisatie voor toegepast-natuurwetenschappelijk Onderzoek TNO Manufacturing film or sheet material having openings
JP6901252B2 (en) * 2015-10-21 2021-07-14 株式会社日本触媒 Adhesive cell culture substrate, cell culture container and cell culture method using this
WO2017220108A1 (en) 2016-06-20 2017-12-28 Csf-Dynamics A/S A shunt device and a method for shunting cerebrospinal fluid
FR3061524B1 (en) * 2017-01-03 2019-05-24 Vianney Rabhi SYNCHRONIZED ROLLER WITH FREE WHEELS

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US5128170A (en) * 1989-05-11 1992-07-07 Kanegafunchi Kagaku Kogyo Kabushiki Kaisha Method for manufacturing medical device having a highly biocompatible surface
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US5330911A (en) * 1989-09-28 1994-07-19 Board Of Regents, The University Of Texas System Surfaces having desirable cell adhesive effects
US5512474A (en) * 1992-05-29 1996-04-30 Bsi Corporation Cell culture support containing a cell adhesion factor and a positively-charged molecule
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WO2000048642A2 (en) 2000-08-24

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