Method for mineralising a biopolymer membrane and membranes thereby obtained

1 . A biopolymer membrane mineralised on its two faces with nanocrystals of mineral compounds organised in the form of platelets and spherical nanoporous crystals having an alveolar structure,

wherein said nanocrystals are constituted of:

a) hydroxyapatite and/or deficient hydroxyapatite doped with fluoride, silver, or zinc ions and/or poly-substituted apatite or deficient hydroxy-, fluoro- or carboxy-apatite,

b) brushite, and

c) calcium phosphate compounds with labile hydrogen-phosphate groups; and

wherein said mineralised biopolymer membrane resorbs in 5 to 60 days after implantation in a living organism.

2 . The biopolymer membrane according to claim 1 , wherein the biopolymer is collagen.

3 . A biopolymer membrane mineralised on its two faces according to claim 1 , obtained by a method comprising the following steps:

a) introduction of an assembly ( 3 ) constituted of a biopolymer membrane ( 4 ) comprised between two cellulose sheets (A) and (B), in a vessel comprising:

a first compartment ( 1 ) and a second compartment ( 2 ), each comprising an electrode, a first electrode being an anode placed in the first compartment ( 1 ) and a second electrode being a cathode placed in the second compartment ( 2 ),

the walls of the first compartment ( 1 ) and the second compartment ( 2 ) brought into contact with one another each having an opening placing in communication the first and the second compartments,

the assembly ( 3 ) being arranged in said opening between the first and the second compartments in such a way as to close it, the cellulose sheet (A) being on the side of the first compartment ( 1 ) and the cellulose sheet (B) on the side of the second compartment ( 2 ),

b) filling the first compartment ( 1 ) with an aqueous solution containing at least one cation chosen from: calcium ions, silver ions, zinc ions, copper ions, sodium ions, magnesium ions and aluminium ions, and the second compartment ( 2 ) with an aqueous solution containing at least one anion chosen from fluoride ions, sulphate ions, carbonate ions, silicate ions and phosphate ions;

c) application of an electrical voltage between the electrodes;

d) turning over the assembly ( 3 ) in such a way that the cellulose sheet (A) is on the side of the second compartment and the cellulose sheet (B) on the side of the first compartment, or exchange of the solutions and electrodes of the first and the second compartments;

c′) application of an electrical voltage between the electrodes, said voltage being equal to that applied at step (c) and being applied for a duration identical to that of step (c);

e) removal and rinsing of the assembly ( 3 );

f) recovery and drying of the mineralised biopolymer membrane.

4 . The biopolymer membrane according to claim 3 , wherein it is a collagen membrane, an alginate membrane or a chitosan membrane.

5 . The biopolymer membrane according to claim 3 , wherein the aqueous solution placed in the first compartment ( 1 ) contains at least calcium ions, and the aqueous solution placed in the second compartment ( 2 ) contains at least phosphate ions.

6 . The biopolymer membrane according to claim 3 , wherein during steps (c) and (c′), the electrical voltage applied is comprised between 2 to 13 Volts.

7 . The biopolymer membrane according to claim 3 , wherein step (c) of application of an electrical voltage lasts from 8 to 16 hours.

8 . The biopolymer membrane according to claim 3 , wherein during steps (c) and (c′), the aqueous solution containing at least one cation is stirred continuously.

9 . The biopolymer membrane according to claim 3 , wherein during steps (c) and (c′), the aqueous solution containing at least one cation is saturated with cations by a continuous addition of a hydroxide of said cation.

10 . The biopolymer membrane according to claim 3 , wherein the pH of the aqueous solution containing at least one anion is comprised between 7 and 11.

11 . The biopolymer membrane according to claim 3 , wherein step (f) of drying the mineralised biopolymer membrane is carried out at a temperature below 35° C.

12 . A method for producing a biopolymer membrane mineralised on its faces according to claim 1 , comprising the following steps:

a) introduction of an assembly ( 3 ) constituted of a biopolymer membrane ( 4 ) comprised between two cellulose sheets (A) and (B), in a vessel comprising:

a first compartment ( 1 ) and a second compartment ( 2 ), each comprising an electrode, a first electrode being an anode placed in the first compartment ( 1 ) and a second electrode being a cathode placed in the second compartment ( 2 ),

the walls of the first compartment ( 1 ) and the second compartment ( 2 ) brought into contact with one another each having an opening placing in communication the first and the second compartments,

the assembly ( 3 ) being arranged in said opening between the first and the second compartments in such a way as to close it, the cellulose sheet (A) being on the side of the first compartment ( 1 ) and the cellulose sheet (B) on the side of the second compartment ( 2 ),

b) filling the first compartment ( 1 ) with an aqueous solution containing at least one cation chosen from: calcium ions, silver ions, zinc ions, copper ions, sodium ions, magnesium ions and aluminium ions, and the second compartment ( 2 ) with an aqueous solution containing at least one anion chosen from fluoride ions, sulphate ions, carbonate ions, silicate ions and phosphate ions;

c) application of an electrical voltage between the electrodes;

d) turning over the assembly ( 3 ) in such a way that the cellulose sheet (A) is on the side of the second compartment and the cellulose sheet (B) on the side of the first compartment, or exchange of the solutions and electrodes of the first and the second compartments;

c′) application of an electrical voltage between the electrodes, said voltage being equal to that applied at step (c) and being applied for a duration identical to that of step (c);

e) removal and rinsing of the assembly ( 3 );

f) recovery and drying of the mineralised biopolymer membrane.

13 . The method according to claim 12 , wherein the biopolymer membrane is a collagen membrane, an alginate membrane or a chitosan membrane.

14 . The method according to claim 12 , wherein the aqueous solution placed in the first compartment ( 1 ) contains at least calcium ions, and the aqueous solution placed in the second compartment ( 2 ) contains at least phosphate ions.

15 . The method according to claim 12 , wherein during steps (c) and (c′), the electrical voltage applied is comprised between 2 to 13 Volts.

16 . The method according to claim 12 , wherein step (c) of application of an electrical voltage lasts from 8 to 16 hours.

17 . The method according to claim 12 , wherein during steps (c) and (c′), the aqueous solution containing at least one cation is stirred continuously.

18 . The method according to claim 12 , wherein during steps (c) and (c′), the aqueous solution containing at least one cation is saturated with cations by a continuous addition of a hydroxide of said cation.

19 . The method according to claim 12 , wherein the pH of the aqueous solution containing at least one anion is comprised between 7 and 11.

20 . The method according to claim 12 , wherein step (f) of drying the mineralised biopolymer membrane is carried out at a temperature below 35° C.