Hydrogel compositions
Fragmented polysaccharide based hydrogel compositions and methods of making and using the same are provided. The subject polysaccharide based hydrogel compositions are prepared by combining a polysaccharide component with a hydrophilic polymer and a cross-linking agent. Also provided are kits and systems for use in preparing the subject compositions.
1. A hydrogel composition, comprising
a polysaccharide or derivative thereof having a molecular weight of 1000 Dalton to 80,300 Dalton, a degree of deacetylation of 70% to 99%, and at least two nucleophilic groups, wherein the polysaccharide or derivative thereof is soluble in an aqueous solution;
a multifunctional, multi-armed polyethylene glycol polymer of a molecular weight of 5,000 Dalton to 30,000 Dalton, and comprising at least two nucleophilic groups; and
a multifunctional, multi-armed crosslinker of polyethylene glycol having a molecular weight of 5,000 Dalton to 30,000 Dalton, and comprising at least two electrophilic groups,
wherein the hydrogel composition comprises:
a covalent bond between the polysaccharide or derivative thereof and polyethylene glycol polymer;
a covalent bond between the polysaccharide or derivative thereof and the multi-armed crosslinker; and
a covalent bond between the polyethylene glycol polymer and the multi-armed crosslinker,
wherein the polysaccharide or derivative thereof does not act as a cross-linking agent in the hydrogel.
2. The composition of claim 1 , wherein the aqueous solution is alkaline and the polysaccharide is soluble in the aqueous solution up to a concentration of 30 mM.
3. A hydrogel composition, comprising
a chitosan or derivative thereof having a molecular weight of less than or equal to 5,000 Dalton, a degree of deacetylation of 70% to 99%, and at least two nucleophilic groups, wherein the chitosan or derivative thereof is soluble in an aqueous solution;
a multifunctional, multi-armed polyethylene glycol polymer of a molecular weight of 5,000 Dalton to 30,000 Dalton, and comprising at least two nucleophilic groups; and
a multifunctional, multi-armed crosslinker of polyethylene glycol having a molecular weight of 5,000 Dalton to 30,000 Dalton, and comprising at least two electrophilic groups;
wherein the polyethylene glycol polymer comprises ester groups to provide for degradation via hydrolysis and wherein the hydrogel composition comprises:
a covalent bond between the chitosan or derivative thereof and polyethylene glycol polymer;
a covalent bond between the chitosan or derivative thereof and the multi-armed crosslinker; and
a covalent bond between the polyethylene glycol polymer and the multi-armed crosslinker,
wherein the polysaccharide or derivative thereof does not act as a cross-linking agent in the hydrogel.
4. The composition of claim 3 , wherein the aqueous solution is alkaline and the chitosan is soluble in the aqueous solution up to a concentration of 30 mM.
5. The composition of claim 1 , wherein the polysaccharide substrate is chitosan, carboxymethylcellulose, carboxymethylchitosan or a derivative thereof.
6. The composition of claim 1 , wherein the multifunctional, multi-armed crosslinker comprises an aldehyde.
7. The composition of claim 1 , wherein the multifunctional, multi-armed crosslinker comprises a glutaraldehyde.
8. The composition of claim 1 , wherein the multifunctional, multi-armed crosslinker comprises a heat treated glutaraldehyde.
9. The composition of claim 1 , further comprising one or more of a thickening agent, foaming agent, biologically active agent, pharmaceutically active agent, visualization agent and radiopaque agent.
10. The composition of claim 1 , wherein the ratio of multifunctional, multi-armed polyethylene glycol polymer to polysaccharide derivative is from 5:1 to 10:1 by mass.
11. The composition of claim 1 , wherein the multifunctional, multi-armed polyethylene glycol polymer comprises ester groups to provide for degradation via hydrolysis.
12. The composition of claim 3 , wherein the chitosan derivative is carboxymethylchitosan.
13. The composition of claim 3 , wherein the multifunctional, multi-armed crosslinker comprises an aldehyde.
14. The composition of claim 3 , wherein the multifunctional, multi-armed crosslinker comprises a glutaraldehyde.
15. The composition of claim 3 , wherein the multifunctional, multi-armed crosslinker comprises a heat treated glutaraldehyde.
16. The composition of claim 3 , further comprising one or more of a thickening agent, foaming agent, biologically active agent, pharmaceutically active agent, visualization agent and radiopaque agent.
17. The composition of claim 3 , wherein the ratio of multifunctional, multi-armed polyethylene glycol polymer to polysaccharide derivative is from 5:1 to 10:1 by mass.
18. The composition of claim 3 , wherein the multifunctional, multi-armed polyethylene glycol polymer comprises ester groups to provide for degradation via hydrolysis.