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 method of attaching mesh to tissue comprising:
contacting a mesh possessing an initiated precursor having at least one vinyl group with a first reactive precursor comprising a multi-arm polyether possessing electrophilic groups, and a second reactive precursor comprising nucleophilic groups;
contacting the mesh to tissue;
allowing the first reactive precursor and the second reactive precursor to contact each other and react to form a first hydrogel, the first hydrogel releasably attaching the mesh to the tissue; and
contacting the initiated precursor with an initiator to form a second hydrogel after formation of the first hydrogel, the first hydrogel and the second hydrogel forming an interpenetrating network attaching the mesh to the tissue.
2. The method 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 method of claim 1 , wherein the first reactive precursor possesses N-hydroxysuccinimide groups and the second reactive precursor possesses amine groups.
4. The method 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.
5. The method of claim 1 , wherein the initiator is selected from the group consisting of redox initiators, free radical initiators, radiation, and combinations thereof.
6. The method of claim 5 , wherein the radiation is selected from the group consisting of heat, visible light, ultraviolet light, gamma ray, and electron beam.
7. The method of claim 1 , wherein the first hydrogel, the second hydrogel, or both, further comprises a bioactive agent.
8. The method of claim 1 , wherein the first hydrogel has a modulus of from about 5 kPa to about 20 kPa, and the second hydrogel has a modulus of from about 50 kPa to about 500 kPa.
9. The method of claim 1 , wherein the first hydrogel degrades over a period of from about 1 day to about 7 days, and the second hydrogel degrades over a period of at least about 6 months.
10. The method of claim 1 , wherein the first reactive precursor is present in the first hydrogel in an amount from about 10% to about 30% and the second reactive precursor is present in the first hydrogel in an amount from about 70% to about 90%.
11. The method of claim 1 , wherein the first reactive precursor is present in the first hydrogel in an amount from about 70% to about 90% and the second reactive precursor is present in the first hydrogel in an amount from about 10% to about 30%.
12. The method of claim 1 , wherein the first hydrogel permits adherence and re-adherence of the mesh to the tissue surface for at least 10 minutes before the second hydrogel is formed.
13. A method of attaching mesh to tissue comprising:
contacting a mesh possessing an initiated precursor having at least one vinyl group with a first reactive precursor comprising a multi-arm polyether possessing electrophilic groups, and a second reactive precursor comprising nucleophilic groups;
contacting the mesh to tissue;
allowing the first reactive precursor and the second reactive precursor to contact each other and react to form a first hydrogel; and
contacting the initiated precursor with an initiator to form a second hydrogel after formation of the first hydrogel, the first hydrogel and the second hydrogel forming an interpenetrating network attaching the mesh to the tissue.
14. The method of claim 13 , 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.
15. The method of claim 13 , wherein the first reactive precursor possesses N-hydroxysuccinimide groups and the second reactive precursor possesses amine groups.
16. The method of claim 13 , 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.
17. The method of claim 13 , wherein the initiator is selected from the group consisting of redox initiators, free radical initiators, radiation, and combinations thereof.
18. The method of claim 17 , wherein the radiation is selected from the group consisting of heat, visible light, ultraviolet light, gamma ray, and electron beam.
19. The method of claim 13 , wherein the first hydrogel, the second hydrogel, or both, further comprises a bioactive agent.
20. The method of claim 13 , wherein the first hydrogel has a modulus of from about 5 kPa to about 20 kPa, and the second hydrogel has a modulus of from about 50 kPa to about 500 kPa.
21. The method of claim 13 , wherein the first hydrogel degrades over a period of from about 1 day to about 7 days, and the second hydrogel degrades over a period of at least about 6 months.
22. The method of claim 13 , wherein the first reactive precursor is present in the first hydrogel in an amount from about 10% to about 30% and the second reactive precursor is present in the first hydrogel in an amount from about 70% to about 90%.
23. The method of claim 13 , wherein the first reactive precursor is present in the first hydrogel in an amount from about 70% to about 90% and the second reactive precursor is present in the first hydrogel in an amount from about 10% to about 30%.
24. The method of claim 13 wherein the first hydrogel permits adherence and re-adherence of the mesh to the tissue surface for at least 10 minutes before the second hydrogel is formed.