Method for the production of hydrogel comprising chitosan and negatively charged polyelectrolytes, and cellular, porous material resulting from said hydrogel
The present invention concerns a method for producing a hydrogel comprising the following steps in succession: a first step (i) of providing at least one powder of an anionic polymer (A) and at least one chitosan powder (B) comprising amine functions (—NH 2 ); a second step (ii) consisting in dry mixing at least the powders (A) and (B) from the first step in order to form a mixture of powders; a third step (iii) of suspending the mixture of powders obtained from the second step in an aqueous medium having a pH that can enable the anionic polymer (A) to be dissolved without dissolving the chitosan (B); a fourth step (iv) of adding an acid to the suspension obtained from the third step in order to form the hydrogel; or the third (iii) and fourth (iv) steps are replaced by a mixing fifth step (v), comprising mixing an acidified aqueous medium including at least one compound (C) comprising at least one unit of a hexose or a unit derived from a hexose, and/or at least one phosphate of said compound (C), with said mixture comprising at least the powders (A) and (B) obtained from the second step (ii).
1. A method of producing a hydrogel, comprising the following steps in succession:
a first step (i) of providing at least one powder of an anionic polymer (A) and at least one chitosan powder (B) comprising amine functions (—NH 2 );
a second step (ii) of dry mixing at least the powders (A) and (B) from the first step in order to form a mixture of powders, wherein the powders (A) and (B) are intimately mixed;
a third step (iii) of suspending the mixture of powders obtained from the second step in an aqueous medium having a pH that can enable the anionic polymer (A) to be dissolved without dissolving the chitosan (B); and
a fourth step (iv) of adding an acid to the suspension obtained from the third step in order to form the hydrogel;
wherein the hydrogel is a moldable material and configured to be a self-sustaining shape,
wherein the degree of deacetylation of the chitosan (B) is higher than or equal to 60% and lower than or equal to 85%,
wherein the ratio of the weight of the at least one chitosan powder (B) relative to the total weight of the hydrogel is higher than or equal to 1%,
wherein the ratio of the weight of the at least one anionic polymer powder (A) relative to the total weight of the hydrogel is higher than or equal to 1%, and
wherein the ratio of the weight of the chitosan powder (B) to the weight of the anionic polymer powder (A) (w/w) is from 0.6 to 1.4.
2. The method according to claim 1 , wherein the powder (A) and/or the powder (B) in the first step and/or the mixture of powders comprising at least the powders (A) and (B) in the second step is/are sieved over a sieve with a mesh less than or equal to 500 μm.
3. The method according to claim 1 , wherein the anionic polymer comprises functions selected from among the following functions: acid sulfate functions (—O—S(═O) 2 —OH or —SO 4 H), salts of said acid sulfate functions, sulfonic acid functions (—S(═O) 2 —OH or —SO 3 H) salts of said sulfonic acid functions, phosphoric acid functions (—O—P(═O) 2 —OH or —PO 4 H) salts of said phosphoric acid functions, carboxylic acid functions (—COOH) salts of said carboxylic acid functions, and combinations thereof.
4. The method according to claim 1 , wherein the anionic polymer (A) is a cyclodextrin polymer obtained by a reaction for polymerization of a mixture comprising at least one cyclodextrin and/or at least one cyclodextrin derivative and/or at least one inclusion complex of cyclodextrin and/or at least one inclusion complex of a cyclodextrin derivative, with at least one (poly)carboxylic acid and/or its corresponding (poly)carboxylic acid anhydride (A1).
5. The method according to claim 1 , wherein the aqueous medium in step (iii) comprises at least 1% by weight, of at least one compound (C) comprising at least one unit of a hexose or a unit derived from a hexose, and/or of at least one phosphate of said compound (C), relative to the total volume of said aqueous medium.
6. The method according to claim 1 , comprising adding at least one mineral filler in the form of a powder to the mixture of powders produced during the second step, wherein the ratio of the weight (g) of mineral filler(s) relative to the total weight of the mixture of powders is higher than or equal to 30%.
7. The method according to claim 6 , wherein said mineral filler is a bioceramic selected among: calcium betatriphosphate, calcium carbonate; alumina (Al 2 O 3 ), zirconia (ZrO 2 ), glasses, glass ionomer, and titanium dioxide.
8. A method of producing a cellular material, comprising:
the method of producing the hydrogel according to claim 1 ; and
freeze drying the hydrogel to form the cellular material.
9. The method of producing the cellular material according to claim 8 , further comprising adding a pore-forming agent in the form of a powder to the mixture of powders during the second step (ii) of the method of producing the hydrogel.
10. The method of producing the cellular material according to claim 8 , further comprising heat treating the cellular material at a temperature greater than or equal to 100° C., for at least 5 minutes.
11. The method of producing the cellular material according to claim 8 , further comprising impregnating the cellular material in a solution comprising at least one functional agent and/or at least one living cell, wherein said functional agent is selected from a first list (I) comprising anticoagulants, anti-thrombogenics, antimitotics, anti-proliferation agents, anti-adhesion agents, anti-migration agents, cellular adhesion promoters, growth factors, antiparasitic molecules, anti-inflammatory agents, vitamins, hormones, proteins, antifungals, antimicrobial molecules, antiseptics, antibiotics, nicotine, one or more essential oils, or a mixture thereof; and wherein said at least one living cell is selected from a second list (II) comprising human cells, animal cells, or plant cells.
12. A method device for absorbing and draining and/or for releasing a functional agent and/or for supporting living cells, the method comprising:
the method of producing the hydrogel according to claim 1 ; and
preparing a device comprising the hydrogel, wherein the device is selected from: a syringe comprising at least one reservoir receiving a predetermined volume of hydrogel; a dressing which is capable of delivering at least one functional agent and/or capable of draining a wound; a patch that is capable of delivering at least one functional agent.
13. The method according to claim 1 , wherein the anionic polymer (A) is a cyclodextrin polymer obtained by a reaction for polymerization of a mixture comprising at least one cyclodextrin and/or at least one cyclodextrin derivative and/or at least one inclusion complex of cyclodextrin and/or at least one inclusion complex of a cyclodextrin derivative, with at least one (poly)carboxylic acid and/or its corresponding (poly)carboxylic acid anhydride (A1); or at least one pyrophosphate (A2).
14. The method according to claim 1 , wherein the anionic polymer (A) is a cyclodextrin polymer obtained by a reaction for polymerization of a mixture comprising at least one cyclodextrin and/or at least one cyclodextrin derivative and/or at least one inclusion complex of cyclodextrin and/or at least one inclusion complex of a cyclodextrin derivative, with at least epichlorhydrin, the polymer obtained undergoing a step for carboxyalkylation in a manner such as to graft carboxylic acid functions (A3).
15. A method for absorbing and/or draining and/or releasing a functional agent and/or for supporting at least one living cell, the method comprising:
the method of producing the cellular material according to claim 8 ; and
preparing a device comprising the cellular material, wherein said device is selected from: a syringe comprising at least one reservoir receiving a predetermined volume of hydrogel to be injected; a dressing that is capable of delivering at least one functional agent and/or of draining the wound, and a patch that is capable of delivering at least one functional agent.
16. A method of producing a hydrogel, comprising:
providing at least one powder of an anionic polymer (A) and at least one chitosan powder (B) comprising amine functions (—NH 2 );
dry mixing at least the powders (A) and (B) in order to form a mixture of powders;
receiving, in a first syringe, the mixture comprising at least the powders (A) and (B) obtained from the dry mixing;
receiving, in a second syringe, a predetermined volume of an aqueous medium, fluidly communicating the first syringe and the second syringe with one another with a device for suspending the mixture of powders (A) and (B) in the aqueous medium having a pH that can enable the anionic polymer (A) to be dissolved without dissolving the at least one chitosan powder (B);
mixing the aqueous medium with the mixture comprising at least the powders (A) and (B) obtained from the dry mixing; and
adding an acid to the suspension, after fluidly communicating the first syringe and the second syringe with one another, to form the hydrogel.
17. The method according to claim 16 , wherein the aqueous medium in the mixing comprises at least 4% by weight of at least one compound (C) comprising at least one unit of a hexose or a unit derived from a hexose, and/or of at least one phosphate of the compound (C), relative to the total volume of the aqueous medium.