Hydrogel implants with varying degrees of crosslinking
View Patent ↗The present disclosure relates to a hydrogel composition and methods of using the same. The hydrogel composition may include precursors that react with each other upon contact as well as precursors that react upon contact with an initiator. In embodiments, the resulting hydrogels may have varying levels of crosslinking with both denser and less dense regions.
1. A hydrogel composition comprising:
a first reactive precursor comprising a multi-arm polyether possessing electrophilic groups;
a second reactive precursor comprising nucleophilic groups; and
at least one initiated precursor selected from the group consisting of phosphorylcholine containing monomers, furanone functional vinyl monomers, N-vinyl pyrrolidone, siloxane functional vinyl compounds, polyethylene glycol-silicone co-monomers having vinyl groups, pyrrole, liquid crystalline vinyl monomers, liquid crystalline vinyl polymers, and combinations thereof,
wherein the first reactive precursor is reactive with the second reactive precursor to form a first hydrogel, and the initiated precursor forms a second hydrogel upon exposure with an initiator.
2. The hydrogel composition of claim 1 , wherein the first reactive precursor comprises a core selected from the group consisting of polyethylene glycol, polyethylene oxide, polyethylene oxide-co-polypropylene oxide, co-polyethylene oxide block copolymers, co-polyethylene oxide random copolymers, and combinations thereof, and wherein the second reactive precursor comprises a core comprising a component selected from the group consisting of polyethylene glycol, polyethylene oxide, polyethylene oxide-co-polypropylene oxide, co-polyethylene oxide block copolymers, co-polyethylene oxide random copolymers, polyvinyl alcohol, poly(vinyl pyrrolidinone), poly(amino acids), dextran, chitosan, alginates, carboxymethylcellulose, oxidized cellulose, hydroxyethylcellulose, hydroxymethylcellulose, hyaluronic acid, albumin, collagen, casein, gelatin, and combinations thereof.
3. The hydrogel composition of claim 1 , wherein the first reactive precursor possesses N-hydroxysuccinimide groups and the second reactive precursor possesses amine groups.
4. The hydrogel composition of claim 1 , wherein the initiator is selected from the group consisting of redox initiators, free radical initiators, and combinations thereof.
5. The hydrogel composition of claim 1 , further comprising a bioactive agent.
6. The hydrogel composition of claim 1 , wherein the initiated precursor comprises from about 5% to about 30% by weight of the hydrogel composition.
7. The hydrogel composition of claim 6 , wherein the first hydrogel has a modulus of from about 5 kPa to about 90 kPa, and the second hydrogel has a modulus of from about 50 kPa to about 5,000 kPa.
8. The hydrogel composition of claim 6 , wherein the first hydrogel degrades over a period of from about 1 week to about 12 weeks, and the second hydrogel degrades over a period of at least about 2 weeks.
9. A method comprising:
contacting a first reactive precursor with a second reactive precursor and an initiated precursor comprising at least one vinyl group;
crosslinking the first reactive precursor and the second reactive precursor to form a first hydrogel; and
exposing the initiated precursor to an initiator to initiate crosslinking of the initiated precursor.
10. The method of claim 9 , wherein the first reactive precursor, the second reactive precursor, or both, comprise a core comprising a component selected from the group consisting of polyethylene glycol, polyethylene oxide, polyethylene oxide-co-polypropylene oxide, co-polyethylene oxide block copolymers, co-polyethylene oxide random copolymers, polyvinyl alcohol, poly(vinyl pyrrolidinone), poly(amino acids), dextran, chitosan, alginates, carboxymethylcellulose, oxidized cellulose, hydroxyethylcellulose, hydroxymethylcellulose, hyaluronic acid, albumin, collagen, casein, gelatin, and combinations thereof.
11. The method of claim 9 , wherein the first reactive precursor possesses N-hydroxysuccinimide groups and the second reactive precursor possesses amine groups.
12. The method of claim 9 , further comprising an initiator selected from the group consisting of redox initiators, free radical initiators, radiation, and combinations thereof.
13. The method of claim 12 , wherein the radiation is selected from the group consisting of heat, visible light, ultraviolet light, gamma ray, and electron beam.
14. The method of claim 9 , wherein the hydrogel further comprises a bioactive agent.
15. The method of claim 14 , wherein crosslinking the initiated precursor forms a barrier layer on an external surface of the first hydrogel, thereby directing delivery of the bioactive agent from the first hydrogel in a direction opposite the barrier layer.
16. The method of claim 9 , wherein the first reactive precursor and second reactive precursor are applied to a defect in tissue, and wherein crosslinking the initiated precursor forms a barrier layer on a surface of the first hydrogel covering the defect in tissue.
17. The method of claim 16 , wherein the first hydrogel has a modulus of from about 5 kPa to about 90 kPa, and the barrier layer has a modulus of from about 50 kPa to about 5,000 kPa.
18. The method of claim 16 , wherein the first hydrogel degrades over a period of from about 1 week to about 12 weeks, and the barrier layer degrades over a period of at least about 2 weeks.
19. The method of claim 9 , wherein the first reactive precursor, the second reactive precursor, and the initiated precursor are contacted with each other and form the first hydrogel in situ.
20. The method of claim 9 , wherein the first hydrogel is utilized as a component selected from the group consisting of adhesives, hemostats, sealants, implants, protective barriers, drug delivery devices, and combinations thereof.
21. The method of claim 9 , wherein the first reactive precursor, the second reactive precursor, and the initiated precursor are contacted with each other and form the first hydrogel ex vivo.
22. The method of claim 20 , wherein the precursors are applied to a template prior to formation of the first hydrogel.
23. The method of claim 9 , wherein crosslinking the initiated precursor forms a second hydrogel having a differing modulus than the first hydrogel.
24. The method of claim 23 , wherein the first hydrogel and the second hydrogel form an interpenetrating network.
25. The method of claim 24 , wherein the first hydrogel degrades more quickly than the second hydrogel, thereby forming spaces permitting healing comprising tissue in-growth, vascularization, and combinations thereof.