Modified hyaluronic acid as dopant for PEDOT and/or PProDOT polymers
A polymer of hyaluronic acid modified by the grafting thereto of at least one of the functions —SO 3 − and aromatic rings may be used as dopant for a polymer formed from one or monomers chosen from EDOT, ProDOT, and derivatives thereof. An aqueous suspension, or ink, and materials, in particular hydrogels, based on at least one PEDOT and/or PProDOT polymer may be doped by at least one such modified hyaluronic acid polymer. Such modified hyaluronic acid polymers may be used in bioelectronic or biosensor devices.
1 . A method of doping a first polymer, the method comprising:
doping the first polymer with a modified hyaluronic acid polymer, which is modified by grafting onto a hyaluronic acid polymer at least —SO 3 − functions and aromatic rings,
wherein the first polymer comprises, in reacted form, 3,4-ethylenedioxythiophene (EDOT),
wherein the modified hyaluronic acid polymer has
an average number of SO 3 − functions per repeat unit of hyaluronic acid of 4, and
an average number of aromatic rings per repeat unit of the hyaluronic acid of 0.3, and
wherein the aromatic ring results from the grafting of aminophenylboronic acid with a carboxylic acid function of the hyaluronic acid.
2 . The method of claim 1 , wherein the hyaluronic acid has a weight-average molecular weight, Mw, in a range of from 20,000 to 1,000,000 g/mol.
3 . The method of claim 1 , wherein the modified hyaluronic acid polymer further comprises a crosslinkable function.
4 . The method of claim 3 , wherein the modified hyaluronic acid polymer has an average number of crosslinkable functions grafted per repeat unit of hyaluronic acid in a range of from 0.05 to 0.50.
5 . The method of claim 3 , wherein the crosslinkable functions of the modified hyaluronic acid polymer are carried by
at least some groups bearing at least one aromatic ring, grafted to the modified hyaluronic acid polymer,
and/or
separate grafts of group(s) bearing —SO 3 − function(s) and/or aromatic ring(s).
6 . A material, comprising:
the first polymer made by the method of claim 1 .
7 . The material of claim 6 , which is a hydrogel formed from the first polymer,
wherein the modified hyaluronic acid polymer comprises a crosslinkable function and/or a free carboxylic acid function.
8 . A bioelectronic device or biosensor, configured to be brought into contact with biological material, comprising:
a material comprising the first polymer formed by the method of claim 1 .
9 . A method for preparing a hydrogel, the method comprising:
(a-i) submitting an aqueous suspension, optionally as an ink, to conditions that are favorable for the crosslinking of chains of modified hyaluronic acid to form a hydrogel swollen in an aqueous medium; and, optionally,
(a-ii) submitting the hydrogel swollen in an aqueous medium to a drying, to obtain a dry hydrogel,
or
(b-i) polymerizing 3,4-ethylenedioxythiophene (EDOT), 3,4-propylenedioxythiophene (ProDOT), and/or a derivative thereof, in a hydrogel swollen in an aqueous medium; and, optionally
(b-ii) submitting the hydrogel obtained after the polymerizing (b-i) to a drying, to obtain a dry hydrogel,
or
(c-i) subjecting an aqueous suspension to conditions that are favorable for polymerizing the EDOT, ProDOT, and/or derivative and for crosslinking of chains of modified hyaluronic acid to form the hydrogel swollen in an aqueous medium; and optionally
(c-ii) submitting the hydrogel obtained after the subjecting (c-i) to a drying to obtain a dry hydrogel,
wherein the aqueous suspension comprises a first polymer comprising, in polymerized form, EDOT, ProDOT, and/or a derivative thereof, and, as a dopant, a modified hyaluronic acid polymer comprising crosslinkable function and/or a free carboxylic acid function,
wherein the modified hyaluronic acid polymer is modified by grafting onto a hyaluronic acid polymer at least SO 3 − functions and aromatic rings, and
wherein the hydrogel is formed from the first polymer.
10 . The method of the claim 9 , comprising:
(b-i) the polymerizing of the EDOT, ProDOT, and/or derivative in the hydrogel swollen in the aqueous medium; and, optionally
(b-ii) submitting the hydrogel obtained after the polymerizing (b-i) to the drying, to obtain the dry hydrogel,
wherein the hydrogel in (b-i) is swollen in an aqueous medium, comprises the modified hyaluronic acid polymer comprising the crosslinkable function and/or free carboxylic acid function.
11 . The method of claim 10 , wherein the polymerizing (b-i) comprises soaking the hydrogel swollen in an aqueous medium based on modified hyaluronic acid of EDOT and/or ProDOT monomers, and then subjecting the hydrogel impregnated with the EDOT and/or ProDOT monomers to conditions that are favorable for the polymerization of the EDOT and/or ProDOT monomers.
12 . The method of claim 9 , wherein the modified hyaluronic acid bears reactive functions X,
wherein crosslinking of the chains of the modified hyaluronic acid is carried out in the presence of at least one crosslinking agent bearing at least two reactive functions Y, the functions X and Y being identical or different, each of the functions Y being able to react with a reactive function X of the modified hyaluronic acid polymer, to form a physical or chemical bond.
13 . The method of claim 9 , comprising:
(c-i) the subjecting of the aqueous suspension to conditions favorable for the polymerizing of the EDOT, ProDOT, and/or derivative and for crosslinking of chains of modified hyaluronic acid to form the hydrogel swollen in the aqueous medium; and optionally
(c-ii) submitting the hydrogel obtained after the subjecting (c-i) to the drying to obtain the dry hydrogel,
wherein the aqueous suspension comprises
EDOT and/or ProDOT,
the modified hyaluronic acid polymer comprising free carboxylic acid functions,
a catalyst suitable for polymerizing EDOT and/or ProDOT monomers, and
a crosslinking agent.
14 . The method of claim 13 , wherein the crosslinking agent comprises at least two primary amine or hydrazide functions,
wherein the subjecting (c-i) to crosslinking of the chains of the modified hyaluronic acid is initiated by adding, to the aqueous suspension, an activating agent for the carboxylic acid functions.
15 . The method of claim 9 , wherein the hydrogel is in film form, and
wherein the aqueous suspension, optionally as the solution, is applied to a surface of a substrate, before crosslinking of the chains of the modified hyaluronic acid.
16 . The method of claim 15 , wherein the hydrogel film is bonded covalently to the surface of the substrate.
17 . The method of claim 9 , comprising:
(a-i) the submitting of the aqueous suspension, optionally as the ink, to the conditions favorable for the crosslinking of the chains of the modified hyaluronic acid to form the hydrogel swollen in the aqueous medium; and, optionally,
(a-ii) the submitting of the hydrogel swollen in the aqueous medium to the drying, to obtain the dry hydrogel.
18 . A method of doping a first polymer, the method comprising:
doping the first polymer with a modified hyaluronic acid polymer, which is modified by grafting onto a hyaluronic acid polymer at least —SO 3 − functions and aromatic rings,
wherein the first polymer comprises, in reacted form, 3,4-ethylenedioxythiophene (EDOT), 3,4-propylenedioxythiophene (ProDOT) and/or a derivative thereof, and
wherein the modified hyaluronic acid polymer further comprises a crosslinkable function.
19 . The method of claim 18 , wherein the modified hyaluronic acid polymer has an average number of crosslinkable functions grafted per repeat unit of hyaluronic acid in a range of from 0.05 to 0.50.
20 . The method of claim 18 , wherein the crosslinkable functions of the modified hyaluronic acid polymer are carried by
at least some groups bearing at least one aromatic ring, grafted to the modified hyaluronic acid polymer,
and/or
separate grafts of group(s) bearing —SO 3 − function(s) and/or aromatic ring(s).
21 . An aqueous suspension, called ink, comprising:
a polymer comprising, in polymerized form, 3,4-ethylenedioxythiophene (EDOT),
wherein the polymer is doped with at least one modified hyaluronic acid polymer, which is modified by grafting onto a hyaluronic acid polymer at least —SO 3 − functions and aromatic rings,
wherein the modified hyaluronic acid polymer has
an average number of SO 3 − functions per repeat unit of hyaluronic acid of 4, and
an average number of aromatic rings per repeat unit of the hyaluronic acid of 0.3, and
wherein the aromatic ring results from the grafting of aminophenylboronic acid with a carboxylic acid function of the hyaluronic acid.
22 . A method for preparing the aqueous suspension, or ink, of claim 21 , the method comprising:
polymerizing a monomer comprising the EDOT, in a solution comprising the modified hyaluronic acid polymer in an aqueous medium, to obtain the polymer.
23 . The method of claim 22 , wherein the EDOT and the modified hyaluronic acid polymer are used in a molar ratio of the EDOT to units of the modified hyaluronic acid in a range of from 0.5 to 5.
24 . A method of doping a first polymer, the method comprising:
doping the first polymer with a modified hyaluronic acid polymer, which is modified by grafting onto a hyaluronic acid polymer at least —SO 3 − functions and aromatic rings,
wherein the first polymer comprises, in reacted form, 3,4-ethylenedioxythiophene (EDOT), 3,4-propylenedioxythiophene (ProDOT) and/or a derivative thereof,
wherein the modified hyaluronic acid polymer has formula (I):
wherein
n is degree of polymerization of the hyaluronic acid polymer,
R is independently H or a group —SO 3 − C + , C + being a counterion of the —SO 3 − ; anion,
R optionally differing from one repeat unit to another, provided that at least some of the groups R are —SO 3 − C + ,
R′, independently from one repeat unit to another, are:
O − C + , C + being a counterion of the O − anion,
a group bearing an aromatic ring and optionally at least one crosslinkable function, and
a group bearing at least one crosslinkable function,
provided that at least some of the R′ are groups bearing an aromatic ring.