METHOD FOR THE MODIFICATION OF A DEVICE SURFACE BY GRAFTING A CD31-DERIVED PEPTIDE ONTO THE SURFACE OF SAID DEVICE
Disclosed is a method for the modification of the surface of a metallic implantable device for interventional neuroradiology by grafting a CD31-derived peptide onto the surface of the device, wherein the CD31-derived peptide consists of a sequence selected from: SEQ ID NO: 2 to 8, SEQ ID NO: 12 to 79, and SEQ ID NO: 81, the method includes: a) coating a polydopamine layer onto the surface of the device in order to obtain a polydopamine coated surface; b) modifying the polydopamine coated surface by adding a linker including at least one reactive moiety chosen from alkyne functions, to obtain a modified polydopamine coated surface; and c) adding a CD31-derived peptide including an azide terminal group and its reaction with the alkyne function of the linker of step b), to obtain a polydopamine coated surface grafted by a CD31-derived peptide.
1 . A method for the modification of a surface of a metallic implantable device for interventional neuroradiology by grafting a CD31-derived peptide onto the surface of said device, wherein the CD31-derived peptide consists of a sequence selected from the group consisting of: SEQ ID NO: 2 to 8, SEQ ID NO: 12 to 79, and SEQ ID NO: 81, said method comprising the following steps:
a) coating a polydopamine layer onto the surface of a metallic implantable device for interventional neuroradiology in order to obtain a polydopamine coated surface;
b) modifying the polydopamine coated surface by the addition of a linker, comprising at least one reactive moiety chosen from alkyne functions, in order to obtain a modified polydopamine coated surface; and
c) adding a CD31-derived peptide comprising an azide terminal group and reacting the CD31-derived peptide comprising an azide terminal group with the alkyne function of the linker of step b), in order to obtain a polydopamine coated surface grafted by a CD31-derived peptide, wherein the CD31-derived peptide comprising an azide terminal group is a CD31-derived peptide as defined above which is chemically modified with an azide terminal group.
2 . The method of claim 1 , wherein step a) comprises contacting the surface of the device with a solution of dopamine and incubating said device and said solution.
3 . The method of claim 1 , wherein step a) is followed by a rinsing step of the polydopamine coated surface.
4 . The method of claim 1 , wherein the polydopamine layer has a thickness comprised between 20 nm and 100 nm.
5 . The method of claim 1 , wherein the linker of step b) has the following formula (I-1):
wherein R is a radical of formula —X 1 -A 1 -NH 2 ,
X 1 being chosen from the group consisting of: —CONH—, —CO—, —CS— and —CSNH, and
A 1 being an alkylene radical comprising from 2 to 40 carbon atoms, possibly interrupted by at least one oxygen atom.
6 . The method of claim 1 , wherein the linker of step b) has the following formula (I):
wherein n is an integer comprised between 2 and 14.
7 . The method of claim 1 , wherein the linker of step b) has the following formula:
8 . The method of claim 1 , wherein step b) comprises contacting the polydopamine coated surface of the device with a solution of the linker and incubating said device and said solution, under stirring.
9 . The method of claim 8 , wherein step b) is followed by a rinsing step of the modified polydopamine coated surface.
10 . The method of claim 1 , wherein the layer made of the linker has a thickness comprised between 0.03 nm and 3 nm.
11 . The method of claim 1 , wherein the CD31-derived peptide comprising an azide terminal group has the formula:
N − ═N + ═N—(CD31-derived peptide)-OH
wherein the CD31-derived peptide consists of a sequence selected from the group consisting of: SEQ ID NO: 2 to 8, SEQ ID NO: 12 to 79, and SEQ ID NO: 81.
12 . The method of claim 1 , wherein the CD31-derived peptide comprising an azide terminal group comprises a peptide having the sequence KWPALFVR (SEQ ID NO: 6) and consisting of D-enantiomer amino acids.
13 . The method of claim 1 , wherein the CD31-derived peptide comprising an azide terminal group comprises a peptide having the sequence KGGGKWPALFVR (SEQ ID NO: 81) and consisting of D-enantiomer amino acids.
14 . The method of claim 1 , wherein the CD31-derived peptide comprising an azide terminal group has the following formula:
15 . The method of claim 1 , wherein step c) comprises a step of copper-free click chemistry reaction.
16 . The method of claim 1 , wherein the thickness of the layers made of the linker and of the CD31-derived peptide is comprised between 0.5 nm and 15 nm.
17 . The method of claim 1 , wherein the thickness of the polydopamine layer and of the layers made of the linker and of the CD31-derived peptide is comprised between 20 nm and 200 nm.
18 . The method of claim 1 , wherein the surface of the device is made of metals or metal alloys.
19 . The method of claim 1 , wherein the device for interventional neuroradiology is chosen from the group consisting of: intracranial stents, flow-diverter stents, and metallic embolization devices.
20 . A modified surface device for interventional neuroradiology, wherein the surface of said device is grafted by a CD31-derived peptide, said device and CD31-derived peptide being as defined in claim 1 , said modified surface device being obtainable by the method of claim 1 .
21 . The modified surface device of claim 20 , wherein said modified surface comprises a coating made of a layer of polydopamine and a layer made of the linker and the CD31-derived peptide.