Hydrogel and biomedical applications thereof

1. A method for preparing an injectable crosslinked sterile homogenous hydrogel, wherein it comprises the following successive steps:

(a) preparing an aqueous solution comprising a water-soluble polymer derived from cellulose and at least one second water-soluble polymer, wherein the total polymer concentration by weight is between 1% and 4% of the total weight;

(b) adding bone substitute comprising solid particles;

(c) pouring the resulting liquid mixture containing the solid particles, in a container, and closing said container by means of a system impervious to water and to gas; and

(d) exposing the container containing the liquid and the optional solid particles to a dose of β or γ radiations comprised between 5 and 50 kGy, thus producing an injectable crosslinked sterile homogenous hydrogel;

wherein the cellulose-derived polymersecond water-soluble polymer weight ratio is between 65/35 and 85/15.

2. The method according to claim 1 , wherein the water-soluble polymer derived from cellulose is hydroxypropylmethyl cellulose or methyl cellulose.

3. The method according to claim 1 , wherein the second water-soluble polymer is chosen from a carboxymethylcellulose, a glycosaminoglycan, a polyvinylpyrrolidone, a polyethylene glycol, a polyvinyl alcohol, and a sodium alginate.

4. The method according to claim 3 , wherein the glycosaminoglycan is chosen from sodium hyaluronate, hyaluronic acid, dermatan sulfate, keratin sulfate, heparin sulfate, chondroitin sulfate, and chitosan.

5. The method according to claim 1 , wherein:

the water-soluble polymer derived from cellulose is hydroxypropylmethylcellulose at a weight concentration comprised between 0.5% and 2.5% of the total weight; and

the second water-soluble polymer is carboxymethylcellulose at a weight concentration between 0.1% and 1% of the total weight, or sodium hyaluronate at a weight concentration between 0.1% and 1% of the total weight.

6. The method according to claim 1 , wherein the aqueous solution of polymers further comprises at least one biocompatible polymer.

7. The method according to claim 6 , wherein the biocompatible polymer is chosen from a polylactic acid, copolymers of polylactic acid and of polyglycolic acid, a poly(ε-caprolactone), a polyhydroxybutyrate, a polyhydroxyvalerate, copolymers of polyhydroxybutyrates and polyhydroxyvalerates, a polyurethane, a cellulose, a polyethylene, a polycarbonate, a polymethylmethacrylate, a silicone, a polyamide, and a polyglycolic acid.

8. The method according to claim 1 , wherein the solid particles are chosen from biphasic calcium phosphate, β tricalcium phosphate, hydroxyapatite, calcium sulfate, alumina zirconite, alumina, nasicon, a bioglass, a vitroceramic, a nanoparticle, and a radio-opaque compound, or any mixture of the previous compounds.

9. The method according to claim 1 , wherein the amount of solid particles is by weight between 15% and 75% of the total weight.

10. The method according to claim 1 , wherein the aqueous mixture comprises by weight:

45% of an aqueous mixture of hydroxypropylmethyl-cellulose and carboxymethylcellulose;

44% of biphasic calcium phosphate granules with a diameter comprised between 80 and 200 μm wherein the hydroxyapatite/β tricalcium phosphate ratio is 60/40; and

11% of biphasic calcium phosphate granules with a diameter comprised between 0.5 and 1.0 mm wherein the hydroxyapatite/β tricalcium phosphate ratio is 60/40.

11. The method according to claim 1 , wherein an active substance is added after irradiation.

12. The method according to claim 11 , wherein the active substance is chosen from an antibiotic, a growth factor, a hormone, a peptide, an anti-osteoporosis agent, and an anti-tumoral agent.

13. The method according to claim 1 , wherein the container is an injection syringe or a cannula.

14. The method according to claim 1 , wherein the cellulose-derived polymersecond water-soluble polymer weight ratio is between 70/30 and 80/20, or about 75/25.

15. The method according to claim 1 , further comprising (e) dehydrating the hydrogel obtained in (d).

16. The method according to claim 1 wherein in (a), the total polymer concentration is by weight between 1.5% and 3% of the total weight.

17. The method according to claim 1 wherein in (d), the dose of β or γ radiations is between 20 and 30 kGy.

18. The method according to claim 2 wherein the water-soluble polymer derived from cellulose is hydroxypropylmethylcellulose.

19. The method according to claim 5 wherein the water-soluble polymer derived from cellulose is hydroxypropylmethylcellulose at a weight concentration between 1% and 2% of the total weight.

20. The method according to claim 5 wherein the second water-soluble polymer is carboxymethylcellulose at a weight concentration between 0.25% and 0.7% of the total weight, or sodium hyaluronate at a weight concentration between 0.25% and 0.7% of the total weight.

21. The method according to claim 8 wherein the solid particles are biphasic calcium phosphate.

22. The method according to claim 8 wherein the solid particles are comprised of hydroxyapatite and β tricalcium phosphate, wherein the hydroxyapatite/β tricalcium phosphate ratio is between 10/90 and 90/10.

23. The method according to claim 8 wherein the solid particles are comprised of hydroxyapatite and β tricalcium phosphate, wherein the hydroxyapatite/β tricalcium phosphate ratio is between 20/80 and 80/20.

24. The method according to claim 9 wherein the amount of solid particles is by weight between 30% and 60% of the total weight.

25. The method according to claim 3 wherein the glycosaminoglycan is sodium hyaluronate.

26. The method according to claim 14 wherein the cellulose-derived Polymer/second water-soluble polymer weight ratio is between 70/30 and 80/20.