Silk-Based Adhesives

Patent metadata

Field	Value
Publication number	US-2018361015-A1
Application number	US-201615780229-A
Country	US
Kind code	A1
Filing date	Nov 29, 2016
Priority date	Nov 30, 2015
Publication date	Dec 20, 2018
Grant date	—

Abstract

In some embodiments, the present invention provides compositions including silk fibroin, at least one hydrophilic agent, and at least one catechol donating agent, wherein the at least one hydrophilic agent and at least one catechol donating agent are conjugated to the silk fibroin. According to various embodiments, at least a portion of the silk fibroin may be crosslinked. In some embodiments, the silk fibroin is at least 50% (e.g., 60%, 70%, 80%, 90%, 95% or more) crosslinked. In some embodiments, the present invention also provides methods for making such compositions.

First claim

We claim:

1 . A composition comprising
silk fibroin; at least one hydrophilic agent; and at least one catechol donating agent, wherein the at least one hydrophilic agent and at least one catechol donating agent are conjugated to the silk fibroin.

2 . The composition of claim 1 , wherein the at least one hydrophilic agent is selected from the group consisting of poly(ethylene glycol), poly(glutamic acid), poly(lysine), sugars, and oligomers of sugars.

3 . The composition of claim 1 or claim 2 , wherein the at least one catechol donating agent is selected from the group consisting of dopamine, norepinephrine, epinephrine, and L-3,4-dihydroxyphenylalanine.

4 . The composition of any one of the above claims, wherein the at least one hydrophilic agent is present in the composition in an amount at or below 10 substitutions per silk fibroin molecule.

5 . The composition of claim 3 , wherein the at least one hydrophilic agent is poly(ethylene glycol) and is present in the composition in an amount at or below 10 poly(ethylene glycol) chains per silk fibroin molecule.

6 . The composition of claim 5 , wherein the at least one hydrophilic agent is poly(ethylene glycol) and is present in the composition in an amount at or below 5 poly(ethylene glycol) chains per silk fibroin molecule.

7 . The composition of any one of the above claims, wherein the silk fibroin is at least 50% crosslinked.

8 . The composition of claim 7 , wherein the crosslinking of the silk fibroin includes at least one of sonication, vortexing, exposure to low pH environment, methanol treatment, exposure to water vapor, exposure to shear stress, exposure to salt, exposure to elevated pressure, and exposure to an electric field.

9 . The composition of any one of the above claims, wherein the composition is characterized in that, upon exposure to an aqueous environment, the composition does not swell more than 50%, relative to its original size.

10 . The composition of claim 9 , wherein the composition does not swell more than 20%, relative to its original size.

11 . The composition of any one of the above claims, wherein the composition is characterized as having an adhesive force of at least about 20 kPa.

12 . The composition of any one of the above claims, wherein the silk fibroin is functionalized through carboxylation of at least a portion of the serine groups in the silk fibroin.

13 . The composition of any one of the above claims, wherein the dopamine is conjugated to the silk fibroin.

14 . The composition of claim 13 , wherein the conjugation is covalent bonding.

15 . A method comprising
providing a silk fibroin solution; associating the silk fibroin solution with at least one hydrophilic agent to form a solubilized silk fibroin solution; and conjugating the solubilized silk fibroin solution with at least one catechol donating agent to form an adhesive silk fibroin composition.

16 . The method of claim 15 , wherein the at least one hydrophilic agent is selected from the group consisting of poly(ethylene glycol), poly(glutamic acid), poly(lysine), sugars, and oligomers of sugars.

17 . The method of claim 15 or claim 16 , wherein the at least one catechol donating agent is selected from the group consisting of dopamine, norepinephrine, epinephrine, and L-3,4-dihydroxyphenylalanine.

18 . The method of claim 15 , wherein the associating step results in not more than 10 substitutions being associated per silk fibroin molecule.

19 . The method of claim 18 , wherein the associating step results in not more than 5 chains being associated per silk fibroin molecule.

20 . The method of claim 17 , wherein the at least one hydrophilic agent is poly(ethylene glycol) and is present in the composition in an amount at or below 10 poly(ethylene glycol) chains per silk fibroin molecule.

21 . The method of claim 20 , wherein the at least one hydrophilic agent is poly(ethylene glycol) and is present in the composition in an amount at or below 5 poly(ethylene glycol) chains per silk fibroin molecule.

22 . The method of any one of claims 15 - 21 , wherein the silk fibroin in the silk fibroin solution is functionalized through carboxylation of at least a portion of the serine groups in the silk fibroin prior to the associating step.

23 . The method of any one of claims 15 - 22 , wherein the adhesive silk fibroin composition is characterized as having an adhesive force of at least about 20 kPa.

24 . The method of any one of 15 - 23 , wherein the adhesive silk fibroin composition does not swell more than 50%, relative to its original size, upon exposure to an aqueous environment.

25 . The method of any one of claims 15 - 24 , wherein the silk fibroin solution is lyophilized prior to the associating step.

26 . The method of any one of claims 15 - 25 , wherein the silk fibroin solution is lyophilized prior to the conjugating step.

27 . The method of any one of claims 15 - 26 , further comprising crosslinking at least a portion of the silk fibroin in the adhesive silk fibroin composition.

28 . The method of claim 27 , wherein the crosslinking occurs after the associating step.

29 . The method of claim 27 , wherein the crosslinking occurs after the conjugating step.

30 . The method of any one of claims 27 - 29 , wherein the crosslinking of the silk fibroin includes at least one of sonication, vortexing, exposure to low pH environment, methanol treatment, exposure to water vapor, exposure to shear stress, exposure to salt, exposure to elevated pressure, and exposure to an electric field.

Assignees

• Tufts College

Inventors

• Burke Kelly A
• Kaplan David L

Classifications

• A61L24/108 Primary

  Specific proteins or polypeptides not covered by groups A61L24/102 - A61L24/106 · CPC title

• A61L24/046

  obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds (A61L24/043 takes precedence) · CPC title

• A61L24/0042

  Materials resorbable by the body · CPC title

• A61L24/0005 Primary

  Ingredients of undetermined constitution or reaction products thereof · CPC title