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. An implant comprising:
a first hydrogel including the reaction product of a first reactive precursor including a multi-arm polyether possessing electrophilic groups with a second reactive precursor possessing nucleophilic groups; and
a second hydrogel including the reaction product of at least one initiated precursor possessing at least one vinyl group with an initiator,
wherein the second hydrogel forms a barrier layer encompassing the first hydrogel.
2. The implant of claim 1 , wherein the first reactive precursor includes 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.
3. The implant of claim 1 , wherein the second reactive precursor possesses a core including 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.
4. The implant of claim 1 , wherein the first reactive precursor possesses N-hydroxysuccinimide groups and the second reactive precursor possesses amine groups.
5. The implant of claim 1 , wherein the initiated precursor is selected from the group consisting of acrylic acid, methacrylic acid, phosphorylcholine containing monomers, furanone functional vinyl monomers, potassium sulfopropyl acrylate, potassium sulfopropyl methacrylate, n-vinyl pyrrolidone, hydroxyethyl methacrylate, vinyl monomers having a high refractive index, siloxane functional vinyl compounds, polyethylene glycol-silicone co-monomers having vinyl groups, tris acrylate, pyrrole, liquid crystalline vinyl monomers, liquid crystalline vinyl polymers, and combinations thereof.
6. The implant of claim 1 , wherein the initiator is selected from the group consisting of redox initiators, free radical initiators, radiation, and combinations thereof.
7. The implant of claim 6 , wherein the radiation is selected from the group consisting of heat, visible light, ultraviolet light, gamma ray, and electron beam.
8. The implant of claim 1 , further comprising a bioactive agent.
9. The implant of claim 1 , wherein the first hydrogel has a modulus of from about 10 kPa to about 50 kPa, and the second hydrogel has a modulus of from about 100 kPa to about 1,000 kPa.
10. The implant of claim 1 , wherein the implant is formed ex vivo.
11. A vertebral disc implant comprising:
a first hydrogel including the reaction product of a first reactive precursor including a multi-arm polyether possessing electrophilic groups with a second reactive precursor possessing nucleophilic groups; and
a second hydrogel including the reaction product of at least one initiated precursor possessing at least one vinyl group with an initiator,
wherein the second hydrogel forms a barrier layer encompassing the first hydrogel.
12. The vertebral disc implant of claim 11 , wherein the first reactive precursor includes 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.
13. The vertebral disc implant of claim 11 , wherein the second reactive precursor possesses a core including 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.
14. The vertebral disc implant of claim 11 , wherein the first reactive precursor possesses N-hydroxysuccinimide groups and the second reactive precursor possesses amine groups.
15. The vertebral disc implant of claim 11 , wherein the initiated precursor is selected from the group consisting of acrylic acid, methacrylic acid, phosphorylcholine containing monomers, furanone functional vinyl monomers, potassium sulfopropyl acrylate, potassium sulfopropyl methacrylate, n-vinyl pyrrolidone, hydroxyethyl methacrylate, vinyl monomers having a high refractive index, siloxane functional vinyl compounds, polyethylene glycol-silicone co-monomers having vinyl groups, tris acrylate, pyrrole, liquid crystalline vinyl monomers, liquid crystalline vinyl polymers, and combinations thereof.
16. The vertebral disc implant of claim 11 , wherein the initiator is selected from the group consisting of redox initiators, free radical initiators, radiation, and combinations thereof.
17. The vertebral disc implant of claim 16 , wherein the radiation is selected from the group consisting of heat, visible light, ultraviolet light, gamma ray, and electron beam.
18. The vertebral disc implant of claim 11 , further comprising a bioactive agent.
19. The vertebral disc implant of claim 11 , wherein the first hydrogel has a modulus of from about 10 kPa to about 50 kPa, and the second hydrogel has a modulus of from about 100 kPa to about 1,000 kPa.
20. The vertebral disc implant of claim 11 , wherein the vertebral disc implant is formed ex vivo.