Adhesion prevention with shear-thinning polymeric hydrogels

Patent metadata

Field	Value
Publication number	US-11969526-B2
Application number	US-201815943358-A
Country	US
Kind code	B2
Filing date	Apr 2, 2018
Priority date	Apr 3, 2017
Publication date	Apr 30, 2024
Grant date	Apr 30, 2024

Abstract

A tissue adhesion prevention hydrogel is provided and engineered with essential features for maintaining separation between tissues and organs in any part of the body, thus preventing adhesion formation, are their shear-thinning, viscoelasticity, and rapid self-healing. A method of using the tissue adhesion prevention hydrogel for tissue adhesion prevention is also provided. A method of interposing the tissue adhesion prevention in between tissue layers for tissue adhesion prevention is further provided.

First claim

What is claimed is:

1. A method comprising:
interposing a dynamically cross-linked supramolecular hydrogel between two animal tissue layers, the dynamically cross-linked supramolecular hydrogel comprising non-covalent interactions between nanoparticles and a hydrophobically modified cellulose derivative; and
preventing formation of tissue adhesion between the two animal tissue layers with the interposed dynamically cross-linked supramolecular hydrogel.

2. The method of claim 1 , wherein the cellulose derivative is hydroxypropylmethylcellulose (HPMC).

3. The method of claim 1 , wherein the nanoparticles are poly(ethyleneglycol)-block-poly(lacticacid) (PEG-PLA) nanoparticles.

4. The method of claim 1 , wherein the dynamically cross-linked supramolecular hydrogel is formed by combining a first aqueous solution that includes three percent weight by volume of the cellulose derivative and a second aqueous solution that includes fifteen percent weight by volume of the nanoparticles, the first and second aqueous solutions being combined in a 1:2 ratio by volume so that a final composition of the dynamically cross-linked supramolecular hydrogel is one percent weight by volume of the cellulose derivative and ten percent weight by volume of the nanoparticles.

5. The method of claim 1 , wherein the dynamically cross-linked supramolecular hydrogel is shear-thinning.

6. The method of claim 1 , wherein the dynamically cross-linked supramolecular hydrogel is self-healing.

7. The method of claim 1 , wherein the dynamically cross-linked supramolecular hydrogel includes polymer chains and non-covalent cross-linking bonds between at least some of the polymer chains.

8. The method of claim 7 , wherein the dynamically cross-linked supramolecular hydrogel is shear-thinning and the shear-thinning of the dynamically cross-linked supramolecular hydrogel is achieved via dissociation of at least some of the non-covalent cross-linking bonds between the non-covalently cross-linked polymer chains.

9. The method of claim 7 , wherein the dynamically cross-linked supramolecular hydrogel is self-healing and the self-healing of the dynamically cross-linked supramolecular hydrogel is achieved via reestablishment of the non-covalent cross-linking bonds between at least some of the non-covalently cross-linked polymer chains.

10. The method of claim 1 , wherein the dynamically cross-linked supramolecular hydrogel further comprises tissue adhesive polymers that act to adhere the dynamically cross-linked supramolecular hydrogel to the two animal tissue layers.

11. The method of claim 1 , wherein the two animal tissue layers are internal to a body of an animal.

12. The method of claim 1 , wherein the interposing comprises spraying the dynamically cross-linked supramolecular hydrogel between the two animal tissue layers.

13. The method of claim 1 , wherein the interposing comprises injecting the dynamically cross-linked supramolecular hydrogel between the two animal tissue layers.

14. A method comprising:
interposing a dynamically cross-linked supramolecular hydrogel between two animal tissue layers to prevent formation of tissue adhesion between the two animal tissue layers, the dynamically cross-linked supramolecular hydrogel being from one to two percent weight by volume hydrophobically modified cellulose derivative, and from five to ten percent weight by volume nanoparticles, wherein the nanoparticles non-covalently interact with the hydrophobically modified cellulose derivative.

15. The method of claim 14 , wherein the dynamically cross-linked supramolecular hydrogel includes polymer chains and non-covalent cross-linking bonds between at least some of the polymer chains.

16. The method of claim 15 , wherein the dynamically cross-linked supramolecular hydrogel is shear-thinning and the shear-thinning of the dynamically cross-linked supramolecular hydrogel is achieved via dissociation of at least some of the non-covalent cross-linking bonds between the non-covalently cross-linked polymer chains.

17. The method of claim 15 , wherein the dynamically cross-linked supramolecular hydrogel is self-healing and the self-healing of the dynamically cross-linked supramolecular hydrogel is achieved via reestablishment of the non-covalent cross-linking bonds between at least some of the non-covalently cross-linked polymer chains.

18. The method of claim 14 , wherein the interposing comprises spraying the dynamically cross-linked supramolecular hydrogel between the two animal tissue layers.

19. The method of claim 14 , wherein the interposing comprises injecting the dynamically cross-linked supramolecular hydrogel between the two animal tissue layers.

20. The method of claim 1 , wherein the hydrophobically modified cellulose derivative is a cellulose derivative modified with a hydrophobic saturated or unsaturated alkyl moiety, or with a hydrophobic aryl moiety.

21. The method of claim 14 , wherein the hydrophobically modified cellulose derivative is a cellulose derivative modified with a hydrophobic saturated or unsaturated alkyl moiety, or with a hydrophobic aryl moiety.

Assignees

• Univ Leland Stanford Junior

Inventors

• Appel Eric Andrew
• Woo Y Joseph
• Stapleton Lyndsay

Classifications

• A61L31/041 Primary

  Mixtures of macromolecular compounds · CPC title

• A61L31/042

  Polysaccharides · CPC title

• A61L31/06

  obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds {(A61L31/041 takes precedence)} · CPC title

• A61L31/145

  Hydrogels or hydrocolloids · CPC title

• A61L2300/424

  Anti-adhesion agents · CPC title