GEL MATERIAL FOR REGENERATIVE MEDICINE

Abstract

An object of the present invention is to provide a novel use in which a polymer gel material having a µm-scale porous structure can be suitably used.

Description

Claims

1. A gel material for regenerative medicine comprising a polymer gel in which hydrophilic polymer units are crosslinked with each other, wherein the polymer gel contains water as a solvent and has a three-dimensional network structure having two regions: a first region in which the polymer units are densely present and a second region in which the polymer units are sparsely present, and a mesh size composed of the first region is the range of 1 to 500 µm.

2. The gel material for regenerative medicine according to claim 1, wherein the gel material has a lower transmittance than a transmittance of the polymer units before gelation.

3. The gel material for regenerative medicine according to claim 1 or 2, wherein the gel material has an osmotic pressure of ⅕ to ½ of an osmotic pressure of the polymer units before gelation.

4. The gel material for regenerative medicine according to any one of claims 1 to 3, wherein an osmotic pressure (Πos) and an elastic pressure (Πel) after a lapse of a certain period of time from gelation have a relationship of Πel > Πos.

5. The gel material for regenerative medicine according to any one of claims 1 to 4, wherein a polymer concentration in the first region is from 10 to 99 wt%, and a polymer concentration in the second region is from 0 to 1 wt%.

6. The gel material for regenerative medicine according to any one of claims 1 to 5, wherein the polymer gel has a polymer content of 5 wt% or less.

7. The gel material for regenerative medicine according to any one of claims 1 to 6, wherein the polymer units are polymers having a polyethylene glycol backbone or a polyvinyl backbone.

8. The gel material for regenerative medicine according to any one of claims 1 to 7, wherein the polymer units comprise a first polymer unit having one or more nucleophilic functional groups in a side chain or at an end and a second polymer unit having one or more electrophilic functional groups in a side chain or at an end.

9. The gel material for regenerative medicine according to claim 8, wherein the nucleophilic functional groups are selected from the group consisting of a thiol group and an amino group, and the electrophilic functional groups are selected from the group consisting of a maleimidyl group, an N-hydroxy-succinimidyl (NHS) group, a sulfosuccinimidyl group, a phthalimidyl group, an imidazolyl group, an acryloyl group, a nitrophenyl group, and —CO2PhNO2.

10. The gel material for regenerative medicine according to any one of claims 1 to 9, which is used for regeneration of a tissue.

11. The gel material for regenerative medicine according to claim 10, wherein the tissue is bone, cartilage, skin, or nerve.

12. A treatment process using the gel material for regenerative medicine according to any one of claims 1 to 11.

13. A kit for producing a gel material for regenerative medicine, the kit comprising the following two types of solutions (A) and (B) stored without being mixed with each other: (A) an aqueous solution containing a hydrophilic first raw polymer having a concentration of less than an overlapping concentration and equal to or more than a critical gelation concentration; and(B) an aqueous solution containing a hydrophilic second raw polymer having a concentration of less than an overlapping concentration and equal to or more than a critical gelation concentration;wherein the solution (A) and/or the solution (B)further contains a non-reactive polymer having no functional group capable of crosslinking with the raw polymer in the molecule,a polymer gel obtained by mixing the solutions (A) and (B) is a polymer gel in which the first raw polymer and the second raw polymer are crosslinked with each other, andthe polymer gel has a structure including two regions: a first region in which polymer units derived from the raw polymers are densely present and a second region in which polymer units derived from the raw polymers are sparsely present.

14. A kit for producing a gel material for regenerative medicine, the kit comprising the following two types of solutions (A′) and (B′) stored without being mixed with each other: (A′) an aqueous solution containing a first gel precursor, wherein the first gel precursor is obtained by crosslinking hydrophilic raw polymers under conditions of less than an overlapping concentration and less than a critical gelation concentration, and the first gel precursor has a relationship of G′ < G″ between a storage modulus G′ and a loss modulus G″; and(B′) an aqueous solution containing a second gel precursor, wherein the second gel precursor is obtained by crosslinking hydrophilic raw polymers under conditions of less than an overlapping concentration and less than a critical gelation concentration, and the second gel precursor has a relationship of G′ < G″ between a storage modulus G′ and a loss modulus G″;wherein the solution (A′) and/or the solution (B′)further contains a crosslinking agent,a polymer gel obtained by mixing the solutions (A′) and (B′) is a polymer gel in which the first raw polymer and the second raw polymer are crosslinked with each other, andthe polymer gel has a structure including two regions: a first region in which polymer units derived from the raw polymers are densely present and a second region in which polymer units derived from the raw polymers are sparsely present.

15. The kit according to claim 13 or 14, wherein the raw polymers are polymers having a polyethylene glycol backbone or a polyvinyl backbone.

16. The kit according to any one of claims 13 to 15, wherein the raw polymers comprise a first polymer having one or more nucleophilic functional groups in a side chain or at an end and a second polymer having one or more electrophilic functional groups in a side chain or at an end.

17. The kit according to claim 16, wherein the nucleophilic functional groups are selected from the group consisting of a thiol group and an amino group, and the electrophilic functional groups are selected from the group consisting of a maleimidyl group, an N-hydroxy-succinimidyl (NHS) group, a sulfosuccinimidyl group, a phthalimidyl group, an imidazolyl group, an acryloyl group, a nitrophenyl group, and —CO2PhNO2.

18. The kit according to claim 13, wherein the non-reactive polymer is polyethylene glycol or cellulose, which has no crosslinking reactive group.

19. The kit according to claim 14, wherein the first gel precursor and the second gel precursor both have a first polymer having one or more nucleophilic functional groups in a side chain or at an end and a second polymer having one or more electrophilic functional groups in a side chain or at an end, the first gel precursor has a higher first polymer content than a second polymer content, and the second gel precursor has a higher second polymer content than a first polymer content.

20. The kit according to claim 14, wherein the gel precursors have a diameter of 10 to 1000 nm.

21. A process for producing a gel material for regenerative medicine in vivo using the kit according to any one of claims 13 to 20.

22. Use of the kit according to any one of claims 13 to 20 in tissue regeneration treatment.