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Interfacial biomaterials

Assignee: Duke University
•
Filing: 2002-11-20
•
Granted: —
•
Expires: 2022-11-20
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Abstract

Abstract An interfacial biomaterial prepared using a plurality of binding agents, each binding agent including a first ligand that specifically binds a non-biological substrate and a second ligand that specifically binds a biological substrate. Also provided is an interfacial biomaterial prepared using a plurality of binding agents, each binding agent including a ligand that specifically binds a non-biological substrate and a non-binding domain that shows substantially no binding to a biological substrate. Also provided are methods for preparing a binding agent, methods for preparing an interfacial biomaterial, and methods for using interfacial biomaterials.

Inventors

  • 👤 Mark Grinstaff
  • 👤 Daniel Kenan
  • 👤 Elisabeth Walsh
  • 👤 Crystan Middleton

Bibliographic Details

Application Number —
Jurisdiction US
Data Source google_patents
Last Synchronized 2026-10-23 04:51
CPC Classifications
G; G01; G01N; G01N33/00; G01N33/48; G01N33/50; G01N33/53; G01N33/543; A; A61; A61L; A61L27/00; A61L27/14; A61L27/22; A61L27/227; A61L27/28; A61L27/34

Claims Analysis

Total Claims: 254
Claim 1
Independent Claim 57 words
1 . An interfacial biomaterial comprising a plurality of binding agents, wherein each binding agent comprises a first ligand that specifically binds a target non-biological substrate and a second ligand that specifically binds a target biological substrate, and wherein the plurality of binding agents define an interface between the target non-biological substrate and the target biological substrate.
Claim 2
Dependent Claim 57 words
1 . An interfacial biomaterial comprising a plurality of binding agents, wherein each binding agent comprises a first ligand that specifically binds a target non-biological substrate and a second ligand that specifically binds a target biological substrate, and wherein the plurality of binding agents define an interface between the target non-biological substrate and the target biological substrate.
Claim 3
Dependent Claim 22 words
2 . The interfacial biomaterial of claim 1 , wherein the plurality of binding agents comprises a plurality of identical binding agents.
Claim 4
Dependent Claim 22 words
3 . The interfacial biomaterial of claim 1 , wherein the plurality of binding agents comprises a plurality of non-identical binding agents.
Claim 5
Dependent Claim 30 words
4 . The interfacial biomaterial of claim 3 , wherein each of the plurality of non-identical binding agents comprises an identical first ligand that specifically binds a target non-biological substrate.
Claim 6
Dependent Claim 20 words
5 . The interfacial biomaterial of claim 1 , wherein the plurality of binding agents further comprise a spatial pattern.
Claim 7
Dependent Claim 24 words
6 . The interfacial biomaterial of claim 1 , further comprising a linker, wherein the linker links the first ligand and the second ligand.
Claim 8
Dependent Claim 21 words
7 . The interfacial biomaterial of claim 1 , wherein the first ligand comprises a peptide or a single chain antibody.
Claim 9
Dependent Claim 57 words
8 . The interfacial biomaterial of claim 1 , wherein the first ligand specifically binds a target non-biological substrate, the target non-biological substrate being selected from the group consisting of a synthetic polymer, a plastic, a metal, a metal oxide, a non-metal oxide, a silicone material, a ceramic material, a drug, a drug carrier, and combinations thereof.
Claim 10
Dependent Claim 16 words
9 . The interfacial biomaterial of claim 8 , wherein the synthetic polymer comprises polyglycolic acid.
Claim 11
Dependent Claim 28 words
10 . The interfacial biomaterial of claim 9 , wherein the first ligand comprises a peptide comprising an amino acid sequence of any one of SEQ ID NOs:37-50.
Claim 12
Dependent Claim 15 words
11 . The interfacial biomaterial of claim 8 , wherein the synthetic polymer comprises nylon.
Claim 13
Dependent Claim 16 words
12 . The interfacial biomaterial of claim 11 , wherein the nylon forms a nylon suture.
Claim 14
Dependent Claim 29 words
13 . The interfacial biomaterial of claim 8 , wherein the first ligand specifically binds a plastic selected from the group consisting of polystyrene, polycarbonate, polyurethane, and combinations thereof.
Claim 15
Dependent Claim 19 words
14 . The interfacial biomaterial of claim 13 , wherein the first ligand specifically binds a plastic comprising polystyrene.
Claim 16
Dependent Claim 29 words
15 . The interfacial biomaterial of claim 14 , wherein the first ligand comprises a peptide comprising an amino acid sequence of any one of SEQ ID NOs:X-X. (polystyrene)
Claim 17
Dependent Claim 19 words
16 . The interfacial biomaterial of claim 13 , wherein the first ligand specifically binds a plastic comprising polyurethane.
Claim 18
Dependent Claim 26 words
17 . The interfacial biomaterial of claim 16 , wherein the first ligand comprises a peptide comprising an amino acid sequence of SEQ ID NO:X-X. (polyurethane)
Claim 19
Dependent Claim 19 words
18 . The interfacial biomaterial of claim 13 , wherein the first ligand specifically binds a plastic comprising polycarbonate.
Claim 20
Dependent Claim 29 words
19 . The interfacial biomaterial of claim 18 , wherein the first ligand comprises a peptide comprising an amino acid sequence of any one of SEQ ID NOs:X-X. (polycarbonate)
Claim 21
Dependent Claim 19 words
20 . The interfacial biomaterial of claim 8 , wherein the first ligand specifically binds a metal comprising titanium.
Claim 22
Dependent Claim 29 words
21 . The interfacial biomaterial of claim 20 , wherein the first ligand comprises a peptide comprising an amino acid sequence of any one of SEQ ID NOs:X-X. (titanium)
Claim 23
Dependent Claim 20 words
22 . The interfacial biomaterial of claim 8 , wherein the first ligand specifically binds a metal comprising stainless steel.
Claim 24
Dependent Claim 30 words
23 . The interfacial biomaterial of claim 22 , wherein the first ligand comprises a peptide comprising an amino acid sequence of any one of SEQ ID NOs:X-X. (stainless steel)
Claim 25
Dependent Claim 21 words
24 . The interfacial biomaterial of claim 1 , wherein the second ligand comprises a peptide or a single chain antibody.
Claim 26
Dependent Claim 39 words
25 . The interfacial biomaterial of claim 1 , wherein the second ligand specifically binds a target biological substrate, the target biological substrate being selected from the group consisting of a tissue, a cell, a macromolecule, and combinations thereof.
Claim 27
Dependent Claim 24 words
26 . The interfacial biomaterial of either of claims 24 or 25 , wherein the target biological substrate comprises collagen or a Tie2 receptor.
Claim 28
Dependent Claim 36 words
27 . The interfacial biomaterial of claim 1 comprising a plurality of binding agents, wherein one or more of the plurality of binding agents comprises an amino acid sequence of SEQ ID NO:27 or 28. (linkers)
Claim 29
Dependent Claim 38 words
28 . An interfacial biomaterial comprising a plurality of binding agents, wherein each binding agent comprises a ligand that specifically binds a target non-biological substrate and a non-binding domain that substantially lacks binding to a target biological substrate.
Claim 30
Dependent Claim 38 words
28 . An interfacial biomaterial comprising a plurality of binding agents, wherein each binding agent comprises a ligand that specifically binds a target non-biological substrate and a non-binding domain that substantially lacks binding to a target biological substrate.
Claim 31
Dependent Claim 22 words
29 . The interfacial biomaterial of claim 28 , wherein the plurality of binding agents comprises a plurality of identical binding agents.
Claim 32
Dependent Claim 22 words
30 . The interfacial biomaterial of claim 28 , wherein the plurality of binding agents comprises a plurality of non-identical binding agents.
Claim 33
Dependent Claim 28 words
31 . The interfacial biomaterial of claim 30 , wherein each of the plurality of non-identical binding agents comprises an identical ligand that specifically binds a non-biological substrate.
Claim 34
Dependent Claim 20 words
32 . The interfacial biomaterial of claim 28 , wherein the plurality of binding agents further comprise a spatial pattern.
Claim 35
Dependent Claim 30 words
33 . The interfacial biomaterial of claim 28 , wherein one or more of the plurality of binding agents comprises a linker that links the ligand and the non-binding domain.
Claim 36
Dependent Claim 20 words
34 . The interfacial biomaterial of claim 29 , wherein the ligand comprises a peptide or a single chain antibody.
Claim 37
Dependent Claim 56 words
35 . The interfacial biomaterial of claim 29 , wherein the ligand specifically binds a target non-biological substrate, the target non-biological substrate being selected from the group consisting of a synthetic polymer, a plastic, a metal, a metal oxide, a non-metal oxide, a silicone material, a ceramic material, a drug, a drug carrier, and combinations thereof.
Claim 38
Dependent Claim 16 words
36 . The interfacial biomaterial of claim 35 , wherein the synthetic polymer comprises polyglycolic acid.
Claim 39
Dependent Claim 15 words
37 . The interfacial biomaterial of claim 35 , wherein the synthetic polymer comprises nylon.
Claim 40
Dependent Claim 16 words
38 . The interfacial biomaterial of claim 37 , wherein the nylon forms a nylon suture.
Claim 41
Dependent Claim 28 words
39 . The interfacial biomaterial of claim 35 , wherein the ligand specifically binds a plastic selected from the group consisting of polystyrene, polycarbonate, polyurethane, and combinations thereof.
Claim 42
Dependent Claim 18 words
40 . The interfacial biomaterial of claim 39 , wherein the ligand specifically binds a plastic comprising polystyrene.
Claim 43
Dependent Claim 27 words
41 . The interfacial biomaterial of claim 40 , wherein the ligand comprises a peptide comprising an amino acid sequence of any one of SEQ ID NOs:1-22.
Claim 44
Dependent Claim 18 words
42 . The interfacial biomaterial of claim 39 , wherein the ligand specifically binds a plastic comprising polyurethane.
Claim 45
Dependent Claim 24 words
43 . The interfacial biomaterial of claim 42 , wherein the ligand comprises a peptide comprising an amino acid sequence of SEQ ID NO:23.
Claim 46
Dependent Claim 18 words
44 . The interfacial biomaterial of claim 35 , wherein the ligand specifically binds a metal comprising titanium.
Claim 47
Dependent Claim 27 words
45 . The interfacial biomaterial of claim 44 , wherein the ligand comprises a peptide comprising an amino acid sequence of any one of SEQ ID NOs:24-36.
Claim 48
Dependent Claim 19 words
46 . The interfacial biomaterial of claim 35 , wherein the ligand specifically binds a metal comprising stainless steel.
Claim 49
Dependent Claim 27 words
47 . The interfacial biomaterial of claim 46 , wherein the ligand comprises a peptide comprising an amino acid sequence of any one of SEQ ID NOs:51-65.
Claim 50
Dependent Claim 20 words
48 . The interfacial biomaterial of claim 28 , wherein the domain comprises a peptide or a single chain antibody.
Claim 51
Dependent Claim 41 words
49 . The interfacial biomaterial of claim 28 , wherein the non-binding domain shows substantially no binding to a target biological substrate, the target biological substrate selected from the group consisting of a tissue, a cell, a macromolecule, and combinations thereof.
Claim 52
Dependent Claim 17 words
50 . The interfacial biomaterial of claim 49 , wherein the non-binding domain comprises a cytophobic agent.
Claim 53
Dependent Claim 16 words
51 . The interfacial biomaterial of claim 50 , wherein the cytophobic agent is polyethylene glycol.
Claim 54
Dependent Claim 20 words
52 . The interfacial biomaterial of claim 28 , wherein the interfacial biomaterial inhibits fouling of the target non-biological substrate.
Claim 55
Dependent Claim 19 words
53 . A synthetic peptide that specifically binds polystyrene comprising a peptide having less than 20 amino acid residues.
Claim 56
Dependent Claim 19 words
53 . A synthetic peptide that specifically binds polystyrene comprising a peptide having less than 20 amino acid residues.
Claim 57
Dependent Claim 20 words
54 . The synthetic peptide of claim 53 comprising an amino acid sequence of any one of SEQ ID NOs:1-22
Claim 58
Dependent Claim 19 words
55 . A synthetic peptide that specifically binds polyurethane comprising a peptide having less than 20 amino acid residues.
Claim 59
Dependent Claim 19 words
55 . A synthetic peptide that specifically binds polyurethane comprising a peptide having less than 20 amino acid residues.
Claim 60
Dependent Claim 17 words
56 . The synthetic peptide of claim 55 comprising an amino acid sequence of SEQ ID NO:23.
Claim 61
Dependent Claim 19 words
57 . A synthetic peptide that specifically binds polycarbonate comprising a peptide having less than 20 amino acid residues.
Claim 62
Dependent Claim 19 words
57 . A synthetic peptide that specifically binds polycarbonate comprising a peptide having less than 20 amino acid residues.
Claim 63
Dependent Claim 20 words
58 . The synthetic peptide of claim 57 comprising an amino acid sequence of any one of SEQ ID NOs:66-71.
Claim 64
Dependent Claim 20 words
59 . A synthetic peptide that specifically binds polyglycolic acid comprising a peptide having less than 20 amino acid residues.
Claim 65
Dependent Claim 20 words
59 . A synthetic peptide that specifically binds polyglycolic acid comprising a peptide having less than 20 amino acid residues.
Claim 66
Dependent Claim 20 words
60 . The synthetic peptide of claim 59 comprising an amino acid sequence of any one of SEQ ID NOs:37-50.
Claim 67
Dependent Claim 19 words
61 . A synthetic peptide that specifically binds nylon comprising a peptide having less than 20 amino acid residues.
Claim 68
Dependent Claim 19 words
61 . A synthetic peptide that specifically binds nylon comprising a peptide having less than 20 amino acid residues.
Claim 69
Dependent Claim 19 words
62 . A synthetic peptide that specifically binds titanium comprising a peptide having less than 20 amino acid residues.
Claim 70
Dependent Claim 19 words
62 . A synthetic peptide that specifically binds titanium comprising a peptide having less than 20 amino acid residues.
Claim 71
Dependent Claim 20 words
63 . The synthetic peptide of claim 62 comprising an amino acid sequence of any one of SEQ ID NOs:24-36.
Claim 72
Dependent Claim 20 words
64 . A synthetic peptide that specifically binds stainless steel comprising a peptide having less than 20 amino acid residues.
Claim 73
Dependent Claim 20 words
64 . A synthetic peptide that specifically binds stainless steel comprising a peptide having less than 20 amino acid residues.
Claim 74
Dependent Claim 20 words
65 . The synthetic peptide of claim 64 comprising an amino acid sequence of any one of SEQ ID NOs:51-65.
Claim 75
Dependent Claim 19 words
66 . A synthetic peptide that specifically binds collagen comprising a peptide having less than 20 amino acid residues.
Claim 76
Dependent Claim 19 words
66 . A synthetic peptide that specifically binds collagen comprising a peptide having less than 20 amino acid residues.
Claim 77
Dependent Claim 21 words
67 . A synthetic peptide that specifically binds a Tie2 receptor comprising a peptide having less than 20 amino acid residues.
Claim 78
Dependent Claim 21 words
67 . A synthetic peptide that specifically binds a Tie2 receptor comprising a peptide having less than 20 amino acid residues.
Claim 79
Dependent Claim 63 words
68 . A method for preparing a binding agent, the method comprising: (a) panning a library of diverse molecules over a target non-biological substrate, whereby a first ligand that specifically binds a target non-biological substrate is identified; and (b) linking the first ligand to a second ligand, wherein the second ligand specifically binds a target biological substrate, whereby a binding agent is prepared.
Claim 80
Dependent Claim 63 words
68 . A method for preparing a binding agent, the method comprising: (a) panning a library of diverse molecules over a target non-biological substrate, whereby a first ligand that specifically binds a target non-biological substrate is identified; and (b) linking the first ligand to a second ligand, wherein the second ligand specifically binds a target biological substrate, whereby a binding agent is prepared.
Claim 81
Dependent Claim 20 words
69 . The method of claim 68 , wherein the first ligand comprises a peptide or a single chain antibody.
Claim 82
Dependent Claim 56 words
70 . The method of claim 68 , wherein the first ligand specifically binds a target non-biological substrate, the target non-biological substrate being selected from the group consisting of a synthetic polymer, a plastic, a metal, a metal oxide, a non-metal oxide, a silicone material, a ceramic material, a drug, a drug carrier, and combinations thereof.
Claim 83
Dependent Claim 15 words
71 . The method of claim 70 , wherein the synthetic polymer comprises polyglycolic acid.
Claim 84
Dependent Claim 14 words
72 . The method of claim 70 , wherein the synthetic polymer comprises nylon.
Claim 85
Dependent Claim 15 words
73 . The method of claim 72 , wherein the nylon forms a nylon suture.
Claim 86
Dependent Claim 28 words
74 . The method of claim 70 , wherein the first ligand specifically binds a plastic selected from the group consisting of polystyrene, polycarbonate, polyurethane, and combinations thereof.
Claim 87
Dependent Claim 18 words
75 . The method of claim 74 , wherein the first ligand specifically binds a plastic comprising polystyrene.
Claim 88
Dependent Claim 27 words
76 . The method of claim 75 , wherein the first ligand comprises a peptide comprising an amino acid sequence of any one of SEQ ID NOs:1-22.
Claim 89
Dependent Claim 18 words
77 . The method of claim 74 , wherein the first ligand specifically binds a plastic comprising polyurethane.
Claim 90
Dependent Claim 24 words
78 . The method of claim 77 , wherein the first ligand comprises a peptide comprising an amino acid sequence of SEQ ID NOs:23.
Claim 91
Dependent Claim 18 words
79 . The method of claim 74 , wherein the first ligand specifically binds a plastic comprising polycarbonate.
Claim 92
Dependent Claim 24 words
80 . The method of claim 79 , wherein the first ligand comprises a peptide comprising an amino acid sequence of SEQ ID NOs:66-71.
Claim 93
Dependent Claim 18 words
81 . The method of claim 70 , wherein the first ligand specifically binds a metal comprising titanium.
Claim 94
Dependent Claim 27 words
82 . The method of claim 81 , wherein the first ligand comprises a peptide comprising an amino acid sequence of any one of SEQ ID NOs:24-36.
Claim 95
Dependent Claim 19 words
83 . The method of claim 70 , wherein the first ligand specifically binds a metal comprising stainless steel.
Claim 96
Dependent Claim 24 words
84 . The method of claim 83 , wherein the first ligand comprises a peptide comprising an amino acid sequence of SEQ ID NOs:51-65.
Claim 97
Dependent Claim 20 words
85 . The method of claim 68 , wherein the second ligand comprises a peptide or a single chain antibody.
Claim 98
Dependent Claim 33 words
86 . The method of claim 68 , wherein the second ligand specifically binds a target biological substrate selected from the group consisting of a tissue, a cell, a macromolecule, and combinations thereof.
Claim 99
Dependent Claim 24 words
87 . The method of any one of claims 85 or 86 , wherein the target biological substrate comprises collagen or a Tie2 receptor.
Claim 100
Dependent Claim 30 words
88 . The method of claim 68 , further comprising panning a ligand over a target biological substrate, whereby a ligand that specifically binds a target biological substrate is identified.
Claim 101
Dependent Claim 13 words
89 . A binding agent produced by the method of claim 68 .
Claim 102
Dependent Claim 26 words
90 . The binding agent of claim 89 , wherein the binding agent comprises an amino acid sequence of either of SEQ ID NO:72 or 73.
Claim 103
Dependent Claim 64 words
91 . A method for preparing a binding agent, the method comprising: (a) panning a library of diverse molecules over a target non-biological substrate, whereby a ligand that specifically binds a target non-biological substrate is identified; and (b) linking the ligand to a non-binding domain, wherein the non-binding domain shows substantially no binding to a target biological substrate, whereby a binding agent is prepared.
Claim 104
Dependent Claim 64 words
91 . A method for preparing a binding agent, the method comprising: (a) panning a library of diverse molecules over a target non-biological substrate, whereby a ligand that specifically binds a target non-biological substrate is identified; and (b) linking the ligand to a non-binding domain, wherein the non-binding domain shows substantially no binding to a target biological substrate, whereby a binding agent is prepared.
Claim 105
Dependent Claim 19 words
92 . The method of claim 91 , wherein the ligand comprises a peptide or a single chain antibody.
Claim 106
Dependent Claim 46 words
93 . The method of claim 91 , wherein the ligand specifically binds a target non-biological substrate selected from the group consisting of a synthetic polymer, plastic, metal, a metal oxide, a non-metal oxide, silicone, a ceramic material, a drug, a drug carrier, and combinations thereof.
Claim 107
Dependent Claim 15 words
94 . The method of claim 93 , wherein the synthetic polymer comprises polyglycolic acid.
Claim 108
Dependent Claim 26 words
95 . The method of claim 94 , wherein the ligand comprises a peptide comprising an amino acid sequence of any one of SEQ ID NOs:37-50.
Claim 109
Dependent Claim 14 words
96 . The method of claim 93 , wherein the synthetic polymer comprises nylon.
Claim 110
Dependent Claim 15 words
97 . The method of claim 96 , wherein the nylon forms a nylon suture.
Claim 111
Dependent Claim 27 words
98 . The method of claim 93 , wherein the ligand specifically binds a plastic selected from the group consisting of polystyrene, polycarbonate, polyurethane, and combinations thereof.
Claim 112
Dependent Claim 17 words
99 . The method of claim 98 , wherein the ligand specifically binds a plastic comprising polystyrene.
Claim 113
Dependent Claim 26 words
100 . The method of claim 99 , wherein the ligand comprises a peptide comprising an amino acid sequence of any one of SEQ ID NOs:1-22.
Claim 114
Dependent Claim 17 words
101 . The method of claim 98 , wherein the ligand specifically binds a plastic comprising polyurethane.
Claim 115
Dependent Claim 23 words
102 . The method of claim 101 , wherein the ligand comprises a peptide comprising an amino acid sequence of SEQ ID NOs:23.
Claim 116
Dependent Claim 17 words
103 . The method of claim 98 , wherein the ligand specifically binds a plastic comprising polycarbonate.
Claim 117
Dependent Claim 23 words
104 . The method of claim 103 , wherein the ligand comprises a peptide comprising an amino acid sequence of SEQ ID NOs:66-71.
Claim 118
Dependent Claim 17 words
105 . The method of claim 93 , wherein the ligand specifically binds a metal comprising titanium.
Claim 119
Dependent Claim 26 words
106 . The method of claim 105 , wherein the ligand comprises a peptide comprising an amino acid sequence of any one of SEQ ID NOs:24-36.
Claim 120
Dependent Claim 18 words
107 . The method of claim 93 , wherein the ligand specifically binds a metal comprising stainless steel.
Claim 121
Dependent Claim 26 words
108 . The method of claim 107 , wherein the ligand comprises a peptide comprising an amino acid sequence of any one of SEQ ID NOs:51-65.
Claim 122
Dependent Claim 20 words
109 . The method of claim 91 , wherein the non-binding domain comprises a peptide or a single chain antibody.
Claim 123
Dependent Claim 36 words
110 . The method of claim 91 , wherein the non-binding domain shows substantially no binding to a target biological substrate selected from the group consisting of a tissue, a cell, a macromolecule, and combinations thereof.
Claim 124
Dependent Claim 16 words
111 . The method of claim 91 , wherein the non-binding domain comprises a cytophobic agent.
Claim 125
Dependent Claim 15 words
112 . The method of claim 111 , wherein the cytophobic agent is polyethylene glycol.
Claim 126
Dependent Claim 34 words
113 . The method of claim 91 , further comprising panning a ligand over a target biological substrate, whereby a non-binding domain that shows substantially no binding to a target biological substrate is identified.
Claim 127
Dependent Claim 13 words
114 . A binding agent produced by the method of claim 91 .
Claim 128
Dependent Claim 111 words
115 . A method for preparing an interfacial biomaterial, the method comprising: (a) applying to a non-biological substrate a plurality of binding agents, wherein each of the plurality of binding agents comprises a first ligand that specifically binds to the non-biological substrate and a second ligand that specifically binds a target biological substrate, and wherein the applying is free of coupling; (b) contacting the non-biological substrate, wherein the plurality of binding agents are bound to the non-biological substrate, with a sample comprising the target biological substrate; and (c) allowing a time sufficient for binding of the target biological substrate to the plurality of binding agents, wherein an interfacial biomaterial is prepared.
Claim 129
Dependent Claim 111 words
115 . A method for preparing an interfacial biomaterial, the method comprising: (a) applying to a non-biological substrate a plurality of binding agents, wherein each of the plurality of binding agents comprises a first ligand that specifically binds to the non-biological substrate and a second ligand that specifically binds a target biological substrate, and wherein the applying is free of coupling; (b) contacting the non-biological substrate, wherein the plurality of binding agents are bound to the non-biological substrate, with a sample comprising the target biological substrate; and (c) allowing a time sufficient for binding of the target biological substrate to the plurality of binding agents, wherein an interfacial biomaterial is prepared.
Claim 130
Dependent Claim 23 words
116 . The method of claim 115 , wherein the applying comprises applying the plurality of binding agents in a spatially restricted manner.
Claim 131
Dependent Claim 46 words
117 . The method of claim 115 , wherein the non-biological substrate is selected from the group consisting of a synthetic polymer, a plastic, a metal, a metal oxide, a non-metal oxide, a silicone material, a ceramic material, a drug, a drug carrier, and combinations thereof.
Claim 132
Dependent Claim 15 words
118 . The method of claim 117 , wherein the synthetic polymer comprises polyglycolic acid.
Claim 133
Dependent Claim 14 words
119 . The method of claim 117 , wherein the synthetic polymer comprises nylon.
Claim 134
Dependent Claim 15 words
120 . The method of claim 119 , wherein the nylon forms a nylon suture.
Claim 135
Dependent Claim 24 words
121 . The method of claim 120 , wherein the plastic is selected from the group consisting of polystyrene, polycarbonate, polyurethane, and combinations thereof.
Claim 136
Dependent Claim 13 words
122 . The method of claim 121 , wherein the plastic comprises polystyrene.
Claim 137
Dependent Claim 13 words
123 . The method of claim 121 , wherein the plastic comprises polyurethane.
Claim 138
Dependent Claim 13 words
124 . The method of claim 121 , wherein the plastic comprises polycarbonate.
Claim 139
Dependent Claim 13 words
125 . The method of claim 117 , wherein the metal comprises titanium.
Claim 140
Dependent Claim 14 words
126 . The method of claim 117 , wherein the metal comprises stainless steel.
Claim 141
Dependent Claim 21 words
127 . The method of claim 115 , wherein the plurality of binding agents comprises a plurality of identical binding agents.
Claim 142
Dependent Claim 21 words
128 . The method of claim 115 , wherein the plurality of binding agents comprises a plurality of non-identical binding agents.
Claim 143
Dependent Claim 27 words
129 . The method of claim 128 , wherein each of the plurality of non-identical binding agents comprises an identical ligand that specifically binds the non-biological substrate.
Claim 144
Dependent Claim 29 words
130 . The method of claim 115 , wherein one or more of the plurality of binding agents comprises an amino acid sequence of SEQ ID NO:72 or 73.
Claim 145
Dependent Claim 28 words
131 . The method of claim 115 , wherein one or more of the binding agents comprises a linker that links the first ligand and the second ligand.
Claim 146
Dependent Claim 20 words
132 . The method of claim 115 , wherein the first ligand comprises a peptide or a single chain antibody.
Claim 147
Dependent Claim 27 words
133 . The method of claim 132 , wherein the first ligand comprises a peptide comprising an amino acid sequence of any one of SEQ ID NOs:37-50.
Claim 148
Dependent Claim 27 words
134 . The method of claim 132 , wherein the first ligand comprises a peptide comprising an amino acid sequence of any one of SEQ ID NOs:1-22.
Claim 149
Dependent Claim 24 words
135 . The method of claim 132 , wherein the first ligand comprises a peptide comprising an amino acid sequence of SEQ ID NO:23.
Claim 150
Dependent Claim 27 words
136 . The method of claim 132 , wherein the first ligand comprises a peptide comprising an amino acid sequence of any one of SEQ ID NOs:66-71.
Claim 151
Dependent Claim 27 words
137 . The method of claim 132 , wherein the first ligand comprises a peptide comprising an amino acid sequence of any one of SEQ ID NOs:24-36.
Claim 152
Dependent Claim 27 words
138 . The method of claim 132 , wherein the first ligand comprises a peptide comprising an amino acid sequence of any one of SEQ ID NOs:51-65.
Claim 153
Dependent Claim 20 words
139 . The method of claim 115 , wherein the second ligand comprises a peptide or a single chain antibody.
Claim 154
Dependent Claim 33 words
140 . The method of claim 115 , wherein the second ligand specifically binds a target biological substrate selected from the group consisting of a tissue, a cell, a macromolecule, and combinations thereof.
Claim 155
Dependent Claim 23 words
141 . The method of either of claims 139 or 140 , wherein the target biological substrate comprises collagen or a Tie2 receptor.
Claim 156
Dependent Claim 20 words
142 . The method of claim 115 , wherein the contacting comprises contacting in vitro, ex vivo, or in vivo.
Claim 157
Dependent Claim 14 words
143 . An interfacial biomaterial prepared according to the method of claim 115 .
Claim 158
Dependent Claim 112 words
144 . A method for preparing a biological array, the method comprising: (a) providing a non-biological substrate having a plurality of positions; (b) applying to each of the plurality of positions a binding agent comprising a first ligand that specifically binds the non-biological substrate and a second ligand that specifically binds a target biological substrate, wherein the applying is free of coupling; (c) contacting the non-biological substrate, wherein a plurality of binding agents are bound to the non-biological substrate, with a sample comprising the target biological substrate; and (d) allowing a time sufficient for binding of the target biological substrate to the plurality of binding agents, whereby a biological array is prepared.
Claim 159
Dependent Claim 112 words
144 . A method for preparing a biological array, the method comprising: (a) providing a non-biological substrate having a plurality of positions; (b) applying to each of the plurality of positions a binding agent comprising a first ligand that specifically binds the non-biological substrate and a second ligand that specifically binds a target biological substrate, wherein the applying is free of coupling; (c) contacting the non-biological substrate, wherein a plurality of binding agents are bound to the non-biological substrate, with a sample comprising the target biological substrate; and (d) allowing a time sufficient for binding of the target biological substrate to the plurality of binding agents, whereby a biological array is prepared.
Claim 160
Dependent Claim 46 words
145 . The method of claim 144 , wherein the non-biological substrate is selected from the group consisting of a synthetic polymer, a plastic, a metal, a metal oxide, a non-metal oxide, a silicone material, a ceramic material, a drug, a drug carrier, and combinations thereof.
Claim 161
Dependent Claim 15 words
146 . The method of claim 145 , wherein the synthetic polymer comprises polyglycolic acid.
Claim 162
Dependent Claim 14 words
147 . The method of claim 145 , wherein the synthetic polymer comprises nylon.
Claim 163
Dependent Claim 15 words
148 . The method of claim 147 , wherein the nylon forms a nylon suture.
Claim 164
Dependent Claim 24 words
149 . The method of claim 145 , wherein the plastic is selected from the group consisting of polystyrene, polycarbonate, polyurethane, and combinations thereof.
Claim 165
Dependent Claim 13 words
150 . The method of claim 149 , wherein the plastic comprises polystyrene.
Claim 166
Dependent Claim 13 words
151 . The method of claim 149 , wherein the plastic comprises polyurethane.
Claim 167
Dependent Claim 13 words
152 . The method of claim 149 , wherein the plastic comprises polycarbonate.
Claim 168
Dependent Claim 13 words
153 . The method of claim 145 , wherein the metal comprises titanium.
Claim 169
Dependent Claim 14 words
154 . The method of claim 145 , wherein the metal comprises stainless steel.
Claim 170
Dependent Claim 14 words
155 . The method of claim 144 , wherein the applying comprises dip-pen printing.
Claim 171
Dependent Claim 21 words
156 . The method of claim 144 , wherein the plurality of binding agents comprises a plurality of identical binding agents.
Claim 172
Dependent Claim 21 words
157 . The method of claim 144 , wherein the plurality of binding agents comprises a plurality of non-identical binding agents.
Claim 173
Dependent Claim 27 words
158 . The method of claim 157 , wherein each of the plurality of non-identical binding agents comprises an identical ligand that specifically binds the non-biological substrate.
Claim 174
Dependent Claim 29 words
159 . The method of claim 144 , wherein one or more of the plurality of binding agents comprises an amino acid sequence of SEQ ID NO:72 or 73.
Claim 175
Dependent Claim 30 words
160 . The method of claim 144 , wherein one or more of the plurality of binding agents comprises a linker that links the first ligand and the second ligand.
Claim 176
Dependent Claim 20 words
161 . The method of claim 144 , wherein the first ligand comprises a peptide or a single chain antibody.
Claim 177
Dependent Claim 27 words
162 . The method of claim 161 , wherein the first ligand comprises a peptide comprising an amino acid sequence of any one of SEQ ID NOs:37-50.
Claim 178
Dependent Claim 27 words
163 . The method of claim 161 , wherein the first ligand comprises a peptide comprising an amino acid sequence of any one of SEQ ID NOs:1-22.
Claim 179
Dependent Claim 24 words
164 . The method of claim 161 , wherein the first ligand comprises a peptide comprising an amino acid sequence of SEQ ID NO:23.
Claim 180
Dependent Claim 27 words
165 . The method of claim 161 , wherein the first ligand comprises a peptide comprising an amino acid sequence of any one of SEQ ID NOs:66-71.
Claim 181
Dependent Claim 27 words
166 . The method of claim 161 , wherein the first ligand comprises a peptide comprising an amino acid sequence of any one of SEQ ID NOs:24-36.
Claim 182
Dependent Claim 27 words
167 . The method of claim 161 , wherein the first ligand comprises a peptide comprising an amino acid sequence of any one of SEQ ID NOs:51-65.
Claim 183
Dependent Claim 20 words
168 . The method of claim 144 , wherein the second ligand comprises a peptide or a single chain antibody.
Claim 184
Dependent Claim 33 words
169 . The method of claim 144 , wherein the second ligand specifically binds a target biological substrate selected from the group consisting of a tissue, a cell, a macromolecule, and combinations thereof.
Claim 185
Dependent Claim 24 words
170 . The method of claim one of claims 168 or 169 , wherein the target biological substrate comprises collagen or a Tie2 receptor.
Claim 186
Dependent Claim 14 words
171 . A biological array prepared according to the method of claim 144 .
Claim 187
Dependent Claim 95 words
172 . A method for preparing an interfacial biomaterial, the method comprising: (a) applying to a non-biological substrate a plurality of binding agents, wherein each of the plurality of binding agents comprises a ligand that specifically binds to the non-biological substrate and a non-binding domain that shows substantially no binding to a target biological substrate, and wherein the applying is free of coupling; and (b) contacting the non-biological substrate, wherein the plurality of binding agents are bound to the non-biological substrate, with a sample comprising the target biological substrate, whereby an interfacial biomaterial is prepared.
Claim 188
Dependent Claim 95 words
172 . A method for preparing an interfacial biomaterial, the method comprising: (a) applying to a non-biological substrate a plurality of binding agents, wherein each of the plurality of binding agents comprises a ligand that specifically binds to the non-biological substrate and a non-binding domain that shows substantially no binding to a target biological substrate, and wherein the applying is free of coupling; and (b) contacting the non-biological substrate, wherein the plurality of binding agents are bound to the non-biological substrate, with a sample comprising the target biological substrate, whereby an interfacial biomaterial is prepared.
Claim 189
Dependent Claim 23 words
173 . The method of claim 172 , wherein the applying comprises applying the plurality of binding agents in a spatially restricted manner.
Claim 190
Dependent Claim 46 words
174 . The method of claim 172 , wherein the non-biological substrate is selected from the group consisting of a synthetic polymer, a plastic, a metal, a metal oxide, a non-metal oxide, a silicone material, a ceramic material, a drug, a drug carrier, and combinations thereof.
Claim 191
Dependent Claim 15 words
175 . The method of claim 174 , wherein the synthetic polymer comprises polyglycolic acid.
Claim 192
Dependent Claim 14 words
176 . The method of claim 174 , wherein the synthetic polymer comprises nylon.
Claim 193
Dependent Claim 15 words
177 . The method of claim 176 , wherein the nylon forms a nylon suture.
Claim 194
Dependent Claim 24 words
178 . The method of claim 174 , wherein the plastic is selected from the group consisting of polystyrene, polycarbonate, polyurethane, and combinations thereof.
Claim 195
Dependent Claim 13 words
179 . The method of claim 178 , wherein the plastic comprises polystyrene.
Claim 196
Dependent Claim 13 words
180 . The method of claim 178 , wherein the plastic comprises polyurethane.
Claim 197
Dependent Claim 13 words
181 . The method of claim 178 , wherein the plastic comprises polycarbonate.
Claim 198
Dependent Claim 13 words
182 . The method of claim 174 , wherein the metal comprises titanium.
Claim 199
Dependent Claim 14 words
183 . The method of claim 174 , wherein the metal comprises stainless steel.
Claim 200
Dependent Claim 21 words
184 . The method of claim 172 , wherein the plurality of binding agents comprises a plurality of identical binding agents.
Claim 201
Dependent Claim 21 words
185 . The method of claim 172 , wherein the plurality of binding agents comprises a plurality of non-identical binding agents.
Claim 202
Dependent Claim 27 words
186 . The method of claim 185 , wherein each of the plurality of non-identical binding agents comprises an identical ligand that specifically binds the non-biological substrate.
Claim 203
Dependent Claim 27 words
187 . The method of claim 172 , wherein one or more of the binding agents comprises a linker that links the ligand and the non-binding domain.
Claim 204
Dependent Claim 19 words
188 . The method of claim 172 , wherein the ligand comprises a peptide or a single chain antibody.
Claim 205
Dependent Claim 26 words
189 . The method of claim 188 , wherein the ligand comprises a peptide comprising an amino acid sequence of any one of SEQ ID NOs:37-50.
Claim 206
Dependent Claim 26 words
190 . The method of claim 188 , wherein the ligand comprises a peptide comprising an amino acid sequence of any one of SEQ ID NOs:1-22.
Claim 207
Dependent Claim 23 words
191 . The method of claim 188 , wherein the ligand comprises a peptide comprising an amino acid sequence of SEQ ID NO:23.
Claim 208
Dependent Claim 26 words
192 . The method of claim 188 , wherein the ligand comprises a peptide comprising an amino acid sequence of any one of SEQ ID NOs:66-71.
Claim 209
Dependent Claim 26 words
193 . The method of claim 188 , wherein the ligand comprises a peptide comprising an amino acid sequence of any one of SEQ ID NOs:24-36.
Claim 210
Dependent Claim 26 words
194 . The method of claim 188 , wherein the ligand comprises a peptide comprising an amino acid sequence of any one of SEQ ID NOs:51-65.
Claim 211
Dependent Claim 20 words
195 . The method of claim 172 , wherein the non-binding domain comprises a peptide or a single chain antibody.
Claim 212
Dependent Claim 35 words
196 . The method of claim 172 , wherein the non-binding domain shows substantially no binding to a biological substrate selected from the group consisting of a tissue, a cell, a macromolecule, and combinations thereof.
Claim 213
Dependent Claim 16 words
197 . The method of claim 196 , wherein the non-binding domain comprises a cytophobic agent.
Claim 214
Dependent Claim 15 words
198 . The method of claim 197 , wherein the cytophobic agent is polyethylene glycol.
Claim 215
Dependent Claim 20 words
199 . The method of claim 172 , wherein the contacting comprises contacting in vitro, ex vivo, or in vivo.
Claim 216
Dependent Claim 14 words
200 . An interfacial biomaterial prepared according to the method of claim 179 .
Claim 217
Dependent Claim 94 words
201 . A method for cell culture, the method comprising: (a) applying to a non-biological substrate a plurality of binding agents, wherein each of the plurality of binding agents comprises a first ligand that specifically binds the non-biological substrate and a second ligand that specifically binds cells, wherein the applying is free of coupling; (b) contacting the non-biological substrate, wherein the plurality of binding agents are bound to the non-biological substrate, with cells; (c) allowing a time sufficient for binding of the cells to the plurality of binding agents; and (d) culturing the cells.
Claim 218
Dependent Claim 94 words
201 . A method for cell culture, the method comprising: (a) applying to a non-biological substrate a plurality of binding agents, wherein each of the plurality of binding agents comprises a first ligand that specifically binds the non-biological substrate and a second ligand that specifically binds cells, wherein the applying is free of coupling; (b) contacting the non-biological substrate, wherein the plurality of binding agents are bound to the non-biological substrate, with cells; (c) allowing a time sufficient for binding of the cells to the plurality of binding agents; and (d) culturing the cells.
Claim 219
Dependent Claim 72 words
202 . A method for implanting a device in a subject, the method comprising: (a) applying to an implant a plurality of binding agents, wherein each of the plurality of binding agents comprises a first ligand that specifically binds the implant and a second ligand that specifically binds cells at an implant site, wherein the applying is free of coupling; and (b) placing the implant in a subject at the implant site.
Claim 220
Dependent Claim 72 words
202 . A method for implanting a device in a subject, the method comprising: (a) applying to an implant a plurality of binding agents, wherein each of the plurality of binding agents comprises a first ligand that specifically binds the implant and a second ligand that specifically binds cells at an implant site, wherein the applying is free of coupling; and (b) placing the implant in a subject at the implant site.
Claim 221
Dependent Claim 113 words
203 . A method for modulating an activity of a biological substrate, the method comprising: (a) coating a non-biological substrate with a plurality of binding agents, wherein each of the plurality of binding agents comprises a first ligand that specifically binds the biodegradable, non-biological substrate and a second ligand that specifically binds the biological substrate, wherein the coating is free of coupling; (b) placing the coated biodegradable, non-biological substrate at a target site, wherein the biological substrate is present at the target site; and (c) allowing a time sufficient for binding of the biological substrate at the target site to the binding agents, wherein the binding modulates the activity of the biological substrate.
Claim 222
Dependent Claim 113 words
203 . A method for modulating an activity of a biological substrate, the method comprising: (a) coating a non-biological substrate with a plurality of binding agents, wherein each of the plurality of binding agents comprises a first ligand that specifically binds the biodegradable, non-biological substrate and a second ligand that specifically binds the biological substrate, wherein the coating is free of coupling; (b) placing the coated biodegradable, non-biological substrate at a target site, wherein the biological substrate is present at the target site; and (c) allowing a time sufficient for binding of the biological substrate at the target site to the binding agents, wherein the binding modulates the activity of the biological substrate.
Claim 223
Dependent Claim 28 words
204 . The method of claim 203 , wherein the biological substrate is selected from the group consisting of a tissue, a cell, a macromolecule, and combinations thereof.
Claim 224
Dependent Claim 16 words
205 . The method of claim 204 , wherein the cell is a vascular endothelial cell.
Claim 225
Dependent Claim 19 words
206 . The method of claim 205 , wherein the vascular endothelial cell is a tumor vascular endothelial cell.
Claim 226
Dependent Claim 15 words
207 . The method of claim 204 , wherein the macromolecule is a Tie2 receptor.
Claim 227
Dependent Claim 22 words
208 . The method of claim 203 , wherein the target site is a wound site and the modulating enhances wound healing.
Claim 228
Dependent Claim 21 words
209 . The method of claim 203 , wherein the target site is an angiogenic site and the modulating inhibits angiogenesis.
Claim 229
Dependent Claim 14 words
210 . The method of claim 209 , wherein the angiogenesis is tumor angiogenesis.
Claim 230
Dependent Claim 17 words
211 . The method of claim 203 , wherein the second ligand specifically binds a Tie2 receptor.
Claim 231
Dependent Claim 61 words
212 . A method for creating a lubricant interface comprising applying to a first substrate a plurality of binding agents, wherein the applying is free of coupling, and wherein each of the plurality of binding agents comprises: (a) a ligand that specifically binds to the first substrate; and (b) a non-binding domain that shows substantially no binding to a second substrate.
Claim 232
Dependent Claim 61 words
212 . A method for creating a lubricant interface comprising applying to a first substrate a plurality of binding agents, wherein the applying is free of coupling, and wherein each of the plurality of binding agents comprises: (a) a ligand that specifically binds to the first substrate; and (b) a non-binding domain that shows substantially no binding to a second substrate.
Claim 233
Dependent Claim 16 words
213 . The method of claim 212 , wherein the first substrate comprises a non-biological substrate.
Claim 234
Dependent Claim 75 words
214 . The method of claim 212 further comprising: (a) applying to an implant a plurality of binding agents, wherein each of the plurality of binding agents comprises a ligand that specifically binds the implant and a non-binding domain that shows substantially no binding to cells at an implant site, wherein the applying is free of coupling; and (b) placing the implant in a subject at the implant site, whereby a lubricant interface is created.
Claim 235
Dependent Claim 16 words
215 . The method of claim 212 , wherein the first substrate comprises a biological substrate.
Claim 236
Dependent Claim 76 words
216 . The method of claim 212 further comprising: (a) administering to a subject a plurality of binding agents, wherein each of the plurality of binding agents comprises a ligand that specifically binds a first biological substrate and a non-binding domain that shows substantially no binding to a second biological substrate; and (b) allowing a time sufficient for binding of the plurality of binding agents to the first biological substrate, whereby a lubricant interface is created.
Claim 237
Dependent Claim 56 words
217 . A method for preparing a non-biological substrate with a non-fouling agent comprising coating a non-biological substrate with a plurality of binding agents, wherein each of the plurality of binding agents comprises: (a) a ligand that specifically binds the non-biological substrate; and (b) a non-binding domain that shows substantially no binding to a fouling agent.
Claim 238
Dependent Claim 56 words
217 . A method for preparing a non-biological substrate with a non-fouling agent comprising coating a non-biological substrate with a plurality of binding agents, wherein each of the plurality of binding agents comprises: (a) a ligand that specifically binds the non-biological substrate; and (b) a non-binding domain that shows substantially no binding to a fouling agent.
Claim 239
Dependent Claim 88 words
218 . A method for drug administration to a subject, the method comprising: (a) applying to a non-biological drug, or to a non-biological carrier of the drug, a plurality of binding agents, wherein each of the plurality of binding agents comprises a first ligand that specifically binds the drug or the drug carrier and a second ligand that specifically binds a target cell; (b) administering the drug to a subject; and (c) allowing a sufficient time for binding of the plurality of binding agents to the target cell.
Claim 240
Dependent Claim 88 words
218 . A method for drug administration to a subject, the method comprising: (a) applying to a non-biological drug, or to a non-biological carrier of the drug, a plurality of binding agents, wherein each of the plurality of binding agents comprises a first ligand that specifically binds the drug or the drug carrier and a second ligand that specifically binds a target cell; (b) administering the drug to a subject; and (c) allowing a sufficient time for binding of the plurality of binding agents to the target cell.
Claim 241
Dependent Claim 19 words
219 . The method of claim 218 , wherein the target cell has on its surface a Tie2 receptor.
Claim 242
Dependent Claim 22 words
220 . The method of claim 218 , wherein the second ligand binds the Tie2 receptor on the surface of the cell.
Claim 243
Dependent Claim 98 words
221 . A method for screening a candidate substance for interaction with a biological substrate, the method comprising: (a) preparing a biological array comprising a plurality of biological substrates, wherein each of the plurality of biological substrates is specifically bound to one of a plurality of positions on a non-biological substrate; (b) contacting the biological array with a candidate substance; (c) allowing a time sufficient for binding of the candidate substance to the biological array; and (d) assaying an interaction between one or more of the biological substrates and the candidate substance, whereby an interacting molecule is identified.
Claim 244
Dependent Claim 98 words
221 . A method for screening a candidate substance for interaction with a biological substrate, the method comprising: (a) preparing a biological array comprising a plurality of biological substrates, wherein each of the plurality of biological substrates is specifically bound to one of a plurality of positions on a non-biological substrate; (b) contacting the biological array with a candidate substance; (c) allowing a time sufficient for binding of the candidate substance to the biological array; and (d) assaying an interaction between one or more of the biological substrates and the candidate substance, whereby an interacting molecule is identified.
Claim 245
Dependent Claim 41 words
222 . The method of claim 221 , wherein the interacting molecule is identified by a technique selected from the group consisting of spectroscopic, enzymatic, and electrochemical via a detectable label on one of the biological substrate or the non-biological substrate.
Claim 246
Dependent Claim 16 words
223 . A kit comprising a first container containing an interfacial biomaterial of claim 1 .
Claim 247
Dependent Claim 16 words
224 . A kit containing a first container containing an interfacial biomaterial of claim 29 .
Claim 248
Dependent Claim 41 words
225 . A kit for preparing an interfacial biomaterial, the kit comprising: (a) a first binding agent comprising a ligand that specifically binds a non-biological substrate; and (b) a second binding agent comprising a ligand that specifically binds a biological substrate.
Claim 249
Dependent Claim 41 words
225 . A kit for preparing an interfacial biomaterial, the kit comprising: (a) a first binding agent comprising a ligand that specifically binds a non-biological substrate; and (b) a second binding agent comprising a ligand that specifically binds a biological substrate.
Claim 250
Dependent Claim 43 words
226 . A kit for preparing an interfacial biomaterial, the kit comprising: (a) a binding agent comprising a ligand that specifically binds a non-biological substrate; and (b) a non-binding domain, wherein the non-binding domain shows substantially no binding to a target biological substrate.
Claim 251
Dependent Claim 43 words
226 . A kit for preparing an interfacial biomaterial, the kit comprising: (a) a binding agent comprising a ligand that specifically binds a non-biological substrate; and (b) a non-binding domain, wherein the non-binding domain shows substantially no binding to a target biological substrate.
Claim 252
Dependent Claim 26 words
227 . The kit of any one of claims 225 and 226 , further comprising a reagent for linking the binding agent and the non-binding domain.
Claim 253
Dependent Claim 18 words
228 . The kit of any one of claims 223 - 226 , further comprising a non-biological substrate.
Claim 254
Dependent Claim 16 words
229 . The method of claim 203 , wherein the non-biological substrate is biodegradable or non-biodegradable.

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