Biological tissue adhesive composition and method of preparation thereof

Patent metadata

Field	Value
Publication number	US-10568984-B2
Application number	US-201515326420-A
Country	US
Kind code	B2
Filing date	Jul 16, 2015
Priority date	Jul 16, 2014
Publication date	Feb 25, 2020
Grant date	Feb 25, 2020

Abstract

A biological tissue adhesive composition is provided. The biological tissue adhesive composition comprises one or more macromolecules grafted with at least one catechol moiety and comprising at least one cross-linkable functional group, a first cross-linker for cross-linking the at least one catechol moiety, wherein the first cross-linker comprises or consists or a multivalent metal ion, and a second cross-linker for covalently cross-linking the at least one cross-linkable functional group, wherein the one or more macromolecules are cross-linked by (a) complex formation between the at least one catechol moiety and the multivalent metal ion, and (b) covalent bonding of the at least one cross-linkable functional group with the second cross-linker. Fabrication method and working principle of a biological tissue adhesive composition are also provided.

First claim

The invention claimed is:

1. A biological tissue adhesive composition comprising
(i) a gluing macromer comprising one or more macromolecules (a) grafted with a catechol-containing compound comprising at least one catechol moiety and (b) comprising at least one cross-linkable functional group, wherein the catechol-containing compound is selected from the group consisting of dopamine, hydrocaffeic acid, dihydroxyphenylalanine, 3,4-dihydroxylhydrocinnamic acid, and combinations thereof, and wherein amount of catechol moiety in the one or more macromolecules grafted with the catechol-containing compound is in the range of 5% (w/w) to 20% (w/w);
(ii) a first cross-linker for cross-linking the at least one catechol moiety, wherein the first cross-linker comprises a multivalent metal ion; and
(iii) a second cross-linker selected from the group consisting of genipin, polygenipin, genipin-grafted molecule, and combinations thereof for covalently cross-linking the at least one cross-linkable functional group,
wherein the one or more macromolecules are cross-linked by (a) complex formation between the at least one catechol moiety and the multivalent metal ion, and (b) covalent bonding of the at least one cross-linkable functional group with the second cross-linker.

2. The biological tissue adhesive composition according to claim 1 , wherein the one or more macromolecules does not contain an aldehyde group and/or a cyan group.

3. The biological tissue adhesive composition according to claim 1 , wherein the one or more macromolecules is selected from the group consisting of an amino group functionalized polysaccharide, a polyamino acid, and combinations thereof.

4. The biological tissue adhesive composition according to claim 1 , wherein the one or more macromolecules is selected from the group consisting of gelatin, bovine serum albumin (BSA), chitosan, polyethylenimine, hyaluronan, dextran, poly(asparagic acid), poly(glutamic acid), chondroitin sulfate, and combinations thereof.

5. The biological tissue adhesive composition according to claim 1 , wherein the one or more macromolecules comprises a natural macromer.

6. The biological tissue adhesive composition according to claim 1 , wherein the multivalent metal ion is selected from the group consisting of Cu 2+ , Zn 2+ , Al 3+ , Fe 3+ , Cr 3+ , and combinations thereof.

7. The biological tissue adhesive composition according to claim 1 , wherein the second cross-linker comprises a macromolecule grafted with at least one α, β-unsaturated carbonyl or α, β-unsaturated sulfonyl group.

8. The biological tissue adhesive composition according to claim 1 , wherein the one or more macromolecules has a number average molecular weight in the range of about 10,000 g/mol to about 100,000 g/mol.

9. A method of preparing a biological tissue adhesive composition according to claim 1 , the method comprising
a) providing a mixture of a gluing macromer comprising one or more macromolecules (a) grafted with a catechol-containing compound comprising at least one catechol moiety and (b) comprising at least one cross-linkable functional group, and a second cross-linker selected from the group consisting of genipin, polygenipin, genipin-grafted molecule, and combinations thereof, for covalently cross-linking the at least one cross-linkable functional group, wherein the catechol-containing compound is selected from the group consisting of dopamine, hydrocaffeic acid, dihydroxyphenylalanine, 3,4-dihydroxylhydrocinnamic acid, and combinations thereof, and wherein amount of catechol moiety in the one or more macromolecules grafted with the catechol-containing compound is in the range of 5% (w/w) to 20% (w/w); and
b) adding a first cross-linker for cross-linking the at least one catechol moiety, wherein the first cross-linker comprises a multivalent metal ion, to the mixture so as to cross-link the one or more macromolecules by complex formation between the at least one catechol moiety and the multivalent metal ion.

10. The method according to claim 9 , wherein the one or more macromolecules does not contain an aldehyde group and/or a cyan group.

11. The method according to claim 9 , wherein the one or more macromolecules is selected from the group consisting of an amino group functionalized polysaccharide, a polyamino acid, and combinations thereof.

12. The method according to claim 9 , wherein the one or more macromolecules are selected from the group consisting of gelatin, bovine serum albumin (BSA), chitosan, polyethylenimine, hyaluronan, dextran, poly(asparagic acid), poly(glutamic acid), chondroitin sulfate, and combinations thereof.

13. The method according to claim 9 , wherein the one or more macromolecules comprises a natural macromer.

14. The method according to claim 9 , wherein the second cross-linker comprises a macromolecule grafted with at least one α, β-unsaturated carbonyl group or α, β-unsaturated sulfonyl group.

15. The method according to claim 9 , wherein the multivalent metal ion is selected from the group consisting of Cu 2+ , Zn 2+ , Al 3+ , Fe 3+ , Cr 3+ , and combinations thereof.

16. The method according to claim 9 , wherein the one or more macromolecules are cross-linked by complex formation between the at least one catechol moiety and the multivalent metal ion present in the first cross-linker before being cross-linked by covalent bonding between the at least one cross-linkable functional group and the second cross-linker.

17. A method of adhering biological tissues with a biological tissue adhesive composition according to claim 1 , the method comprising
a) applying a mixture of a gluing macromer comprising one or more macromolecules (a) grafted with a catechol-containing compound comprising at least one catechol moiety and (b) comprising at least one cross-linkable functional group, and a second cross-linker selected from the group consisting of genipin, polygenipin, genipin-grafted molecule, and combinations thereof, for covalently cross-linking the at least one cross-linkable functional group on a first biological tissue to form a coating, wherein the catechol-containing compound is selected from the group consisting of dopamine, hydrocaffeic acid, dihydroxyphenylalanine, 3,4-dihydroxylhydrocinnamic acid, and combinations thereof, and wherein amount of catechol moiety in the one or more macromolecules grafted with the catechol-containing compound is in the range of 5% (w/w) to 20% (w/w);
b) adding a first cross-linker for cross-linking the at least one catechol moiety, the first cross-linker comprising a multivalent metal ion, to the coating;
c) contacting a second biological tissue with the resultant coating; and
d) applying pressure to one or both the first biological tissue and the second biological tissue to adhere the first biological tissue to the second biological tissue.

18. The method according to claim 17 , wherein the one or more macromolecules are cross-linked by complex formation between the at least one catechol moiety and the multivalent metal ion present in the first cross-linker before being cross-linked by covalent bonding between the at least one cross-linkable functional group and the second cross-linker.

Assignees

• Univ Nanyang Tech
• Nanyang Technology Univ

Inventors

• Wang Dongan
• Fan changjiang

Classifications

• A61L24/043

  Mixtures of macromolecular materials · CPC title

• A61L24/10

  Polypeptides; Proteins {(A61L24/043 takes precedence)} · CPC title

• A61L24/0031 Primary

  Hydrogels or hydrocolloids · CPC title

• A61L24/104 Primary

  Gelatin · CPC title

• A61L24/02

  containing inorganic materials · CPC title