Adhesion prevention with shear-thinning polymeric hydrogels

Patent metadata

Field	Value
Publication number	US-11975123-B2
Application number	US-201916590189-A
Country	US
Kind code	B2
Filing date	Oct 1, 2019
Priority date	Apr 2, 2018
Publication date	May 7, 2024
Grant date	May 7, 2024

Abstract

A method of preventing tissue adhesion includes forming an incision in tissue, applying a hydrogel to tissue through the incision, and closing the incision with the hydrogel therein. The hydrogel includes a polymer non-covalently cross-linked with a plurality of nanoparticles and prevents a formation of adhesions between tissues and/or organs.

First claim

The invention claimed is:

1. A method of preventing tissue adhesion, comprising:
forming an incision in a tissue;
applying a dynamically cross-linked supramolecular hydrogel to the tissue through the incision, the dynamically cross-linked supramolecular hydrogel comprising a hydrophobically modified cellulose derivative non-covalently cross-linked with a plurality of nanoparticles; and
closing the incision with the dynamically cross-linked supramolecular hydrogel therein, wherein the dynamically cross-linked supramolecular hydrogel prevents a formation of adhesions between the tissue and other tissues and/or organs.

2. The method of claim 1 , wherein forming the incision in the tissue is part of a surgical procedure.

3. The method of claim 1 , wherein the hydrophobically modified cellulose derivative comprises hydrophobically modified hydroxypropylmethylcellulose (HPMC).

4. The method of claim 1 , wherein the nanoparticles comprise poly(ethylene glycol)-b-poly(lactic acid) (PEG-PLA).

5. The method of claim 1 , wherein the dynamically cross-linked supramolecular hydrogel remains on the tissue for at least 7 days after closing the incision.

6. The method of claim 1 , wherein the dynamically cross-linked supramolecular hydrogel remains on the tissue for at least 14 days after closing the incision.

7. The method of claim 1 , wherein the dynamically cross-linked supramolecular hydrogel dissipates from the tissue in less than 120 days after closing.

8. The method of claim 1 , wherein the dynamically cross-linked supramolecular hydrogel dissipates from the tissue in less than 30 days after closing.

9. The method of claim 1 , wherein the applying comprises spraying the dynamically cross-linked supramolecular hydrogel onto the tissue.

10. The method of claim 1 , wherein the applying comprises spreading the dynamically cross-linked supramolecular hydrogel onto the tissue.

11. The method of claim 1 , wherein the applying comprises injecting the dynamically cross-linked supramolecular hydrogel onto the tissue.

12. The method of claim 1 , wherein the applying comprises applying a shear to the dynamically cross-linked supramolecular hydrogel to allow the dynamically cross-linked supramolecular hydrogel to achieve a viscous flow so as to conform to and cover the tissue.

13. The method of claim 12 , wherein the dynamically cross-linked supramolecular hydrogel adheres to the tissue without delaminating after conforming to and covering the tissue.

14. The method of claim 12 , wherein the viscous flow stops and the dynamically cross-linked supramolecular hydrogel recovers its mechanical properties within 5 seconds after the applying of the shear.

15. The method of claim 1 , wherein the tissue comprises abdominal tissue.

16. The method of claim 1 , wherein the tissue comprises orthopedic tissue.

17. The method of claim 1 , wherein the tissue comprises thoracic tissue.

18. The method of claim 1 , wherein the tissue comprises cardiac tissue.

19. The method of claim 1 , wherein the tissue comprises gynecologic tissue.

20. The method of claim 1 , wherein a storage modulus of the dynamically cross-linked supramolecular hydrogel is 50-500 Pa.

21. The method of claim 1 , wherein a yield stress of the dynamically cross-linked supramolecular hydrogel is 50-500 Pa.

22. The method of claim 1 , wherein the dynamically cross-linked supramolecular hydrogel maintains a linear viscoelasticity at strains up to at least 0.5%.

23. The method of claim 1 , wherein a tan delta of the dynamically cross-linked supramolecular hydrogel is less than 1.

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

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

26. The method of claim 1 , wherein the dynamically cross-linked supramolecular hydrogel comprises 1 wt % of the hydrophobically modified cellulose derivative or more.

27. The method of claim 1 , wherein the dynamically cross-linked supramolecular hydrogel comprise 5 wt % of the nanoparticles or more.

28. The method of claim 1 , wherein the dynamically cross-linked supramolecular hydrogel comprises approximately 1 wt % of the hydrophobically modified cellulose derivative and 10 wt % of the nanoparticles.

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

• A61L31/145

  Hydrogels or hydrocolloids · CPC title

• A61L31/148

  Materials at least partially resorbable by the body · CPC title

• C08L1/08

  Cellulose derivatives · CPC title