BIOADHESIVE HYDROGELS

• US 20160022862A1
• Filed: 03/07/2014
• Published: 01/28/2016
• Est. Priority Date: 03/07/2013
• Status: Active Grant

• Current Assignee: Case Western Reserve University
• Original Assignee: Case Western Reserve University
• Inventors: Alsberg, Eben
• Granted Patent: US 10,512,708 B2
• Time in Patent Office: Days
• US Class Current: 1/1
• CPC Class Codes: A61L 24/0031 Hydrogels or hydrocolloids
• CPC Class Codes: A61L 24/0042 Materials resorbable by the body
• CPC Class Codes: A61L 24/046 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds A61L24/043 takes precedence

Abstract

A bioadhesive includes a crosslinked biodegradable hydrogel that includes a plurality of oxidized, acrylated or methacrylated, natural polymer. Bioadhesives are natural or synthetic materials that can be used for soft tissue repair to create a seal preventing leakage of biological fluids or to reinforce anatomic integrity as an attractive alternative to sutures and staples. The most widely used bioadhesives are fibrin, cyanoacrylates, and albumin-glutaraldehyde bioadhesives.

Claims

1. A bioadhesive comprising:

a crosslinked biodegradable hydrogel that includes a plurality of oxidized, acrylated or methacrylated, natural polymer macromers crosslinked with a plurality of branched poly(ethylene glycol) macromers.

2. The bioadhesive of claim 1, wherein the oxidized, acrylated or methacrylated, natural polymer macromers include a plurality of aldehyde groups that are crosslinked with the branched poly(ethylene glycol) macromers.

3. The bioadhesive of claim 1, wherein the oxidized, acrylated or methacrylated, natural polymer macromers are polysaccharides, which are oxidized so that about 1% to about 50% of the saccharide units therein are converted to aldehyde saccharide units.

4. The bioadhesive of claim 1, wherein acrylate or methacrylate groups of the natural polymer macromers are crosslinked so that the hydrogel is dual crosslinked.

5. The bioadhesive of claim 1, the oxidized, acrylated or methacrylated, natural polymer macromers comprising oxidized, acrylated or methacrylated, alginates.

6. The bioadhesive of claim 1, wherein the poly(ethylene glycol) macromers are poly(ethylene glycol) amine macromers.

7. The bioadhesive of claim 6, wherein the poly(ethylene glycol) amine macromers are n-arm poly(ethylene glycol) amines, where n is an integer greater than 1.

8. The bioadhesive of claim 1, wherein the hydrogel is cytocompatible and, upon degradation, produces substantially non-toxic products.

9. The bioadhesive of claim 1, wherein the hydrogel is photocrosslinked.

10. A bioadhesive comprising:

a dual crosslinked biodegradable hydrogel that includes a plurality of oxidized, acrylated or methacrylated, polysaccharide macromers crosslinked with a plurality of branched poly(ethylene glycol) macromers.

11. The bioadhesive of claim 10, wherein the oxidized, acrylated or methacrylated, polysaccharide macromers include a plurality of aldehyde groups that are crosslinked with the branched poly(ethylene glycol) macromers.

12. The bioadhesive of claim 10, wherein the oxidized, acrylated or methacrylated, polysaccharide macromers are polysaccharides, which are oxidized so that about 1% to about 50% of the saccharide units therein are converted to aldehyde saccharide units.

13. The bioadhesive of claim 10, wherein acrylate or methacrylate groups of the polysaccharide macromers are cross-linked.

14. The bioadhesive of claim 10, the oxidized, acrylated or methacrylated, polysaccharide macromers comprising oxidized, acrylated or methacrylated, alginates.

15. The bioadhesive of claim 10, wherein the poly(ethylene glycol) macromers are poly(ethylene glycol) amine macromers.

16. The bioadhesive of claim 15, wherein the poly(ethylene glycol) amine macromers are n-arm poly(ethylene glycol) amines, where n is an integer greater than 1.

17. The bioadhesive of claim 10, wherein the hydrogel is cytocompatible and, upon degradation, produces substantially non-toxic products.

18. A bioadhesive comprising:

a dual crosslinked biodegradable hydrogel that includes a plurality of oxidized, acrylated or methacrylated, alginate macromers crosslinked with a plurality of branched poly(ethylene glycol) macromers

19. The bioadhesive of claim 18, wherein the oxidized, acrylated or methacrylated, alginate macromers include a plurality of aldehyde groups that are crosslinked with the branched poly(ethylene glycol) macromers.

20. The bioadhesive of claim 18, wherein the oxidized, acrylated or methacrylated, alginate macromers is an aliginate, which is oxidized so that about 1% to about 50% of the saccharide units therein are converted to aldehyde saccharide units.

21. The bioadhesive of claim 18, wherein acrylate or methacrylate groups of the alginate macromers are photocrosslinked.

22. The bioadhesive of claim 18, the oxidized, acrylated or methacrylated, polysaccharide macromers comprising oxidized, acrylated or methacrylated, alginates.

23. The bioadhesive of claim 18, wherein the poly(ethylene glycol) macromers are poly(ethylene glycol) amine macromers.

24. The bioadhesive of claim 23, wherein the poly(ethylene glycol) amine macromers are n-arm poly(ethylene glycol) amines, where n is an integer greater than 1.

25. The bioadhesive of claim 18, wherein the hydrogel is cytocompatible and, upon degradation, produces substantially non-toxic products.

26-33. -33. (canceled)