Cell-seeded porous lung hydrogel sealant

Patent metadata

Field	Value
Publication number	US-2019224364-A1
Application number	US-201916371703-A
Country	US
Kind code	A1
Filing date	Apr 1, 2019
Priority date	Oct 6, 2016
Publication date	Jul 25, 2019
Grant date	—

Abstract

Disclosed are a biosealant system and method for treatment of a pulmonary air leak comprising applying the biosealant system to the locus of the air leak.

First claim

What is claimed is:

1 . A biosealant composition comprising an extracellular matrix hydrogel and a thermogel;
wherein the extracellular matrix hydrogel comprises a first extracellular matrix protein, an unbranched polysaccharide, and an elastic protein; and wherein the thermogel comprises a gelatinous material and a cross-linking enzyme in an amount sufficient to result in gelation of the thermogel at a temperature from about 35° C. to 37° C.

2 . The biosealant of claim 1 , wherein the first extracellular matrix protein is collagen, wherein the elastic protein is elastin, and wherein the unbranched polysaccharide is sulfated glycosaminoglycan.

3 . The biosealant of claim 1 , wherein the cross-linking enzyme is transglutaminase.

4 . The biosealant of claim 1 , wherein the extracellular matrix hydrogel also comprises additional therapeutics including cells, microsomes, peptides, or drugs.

5 . The biosealant of claim 1 , wherein the cross-linking enzyme is present in an amount from about 0.5 units/mL to 5 units/mL.

6 . The biosealant of claim 1 , wherein the gelatinous material is gelatin.

7 . The biosealant of claim 1 , wherein the thermogel comprises pores of diameter of about 0.025 mm to 90 mm.

8 . The biosealant of claim 1 , wherein the biosealant composition does not contain fibrin.

9 . The biosealant of claim 1 , wherein the first extracellular matrix protein is present in an amount from about 25% by weight to about 75% by weight of the total weight of the first extracellular matrix protein, unbranched polysaccharide, and elastic protein of the extracellular matrix hydrogel.

10 . The biosealant of claim 1 , wherein the unbranched polysaccharide is present in an amount from about 0.5% by weight to about 15% by weight of the total weight of the first extracellular matrix protein, unbranched polysaccharide, and elastic protein of the extracellular matrix hydrogel.

11 . The biosealant of claim 1 , wherein the elastic protein is present in an amount from about 25% by weight to about 75% by weight of the total weight of the first extracellular matrix protein, unbranched polysaccharide, and elastic protein of the extracellular matrix hydrogel.

12 . A method for sealing a puncture or wound in a tissue comprising applying a biosealant composition directly to the puncture or wound;
wherein the biosealant composition comprising an extracellular matrix hydrogel and a thermogel; wherein the extracellular matrix hydrogel comprises a first extracellular matrix protein, an unbranched polysaccharide, and an elastic protein; and wherein the thermogel comprises a gelatinous material and a cross-linking enzyme in an amount sufficient to result in gelation of the thermogel at a temperature from about 35° C. to 37° C.

13 . The method of claim 12 , wherein the tissue is the lung.

14 . The method of claim 12 , wherein the first extracellular matrix protein is collagen, wherein the elastic protein is elastin, and wherein the unbranched polysaccharide is sulfated glycosaminoglycan.

15 . The method of claim 12 , wherein the gelatinous material is gelatin.

16 . The method of claim 12 , wherein the thermogel comprises pores of diameter of about 0.025 mm to 90 mm.

17 . The method of claim 12 , wherein the cross-linking enzyme is transglutaminase.

18 . A method of making a biosealant according to claim 1 comprising the steps of:
mixing a first extracellular matrix protein, an unbranched polysaccharide, an elastic protein, and a first cross-linking enzyme to form an extracellular matrix hydrogel;
mixing a gelatinous material in saline with a second cross-linking enzyme to form a thermogel;
heating the thermogel to about 52° C. to 55° C.; and
making the thermogel porous.

19 . The method of claim 18 , wherein the step of making the thermogel porous comprises applying a bubbling gas with a bubble generator through the thermogel material.

20 . The method of claim 18 , wherein the first extracellular matrix protein is collagen, wherein the elastic protein is elastin, wherein the unbranched polysaccharide is sulfated glycosaminoglycan, and wherein the first and second cross-linking enzyme is transglutaminase.

Assignees

• Univ Columbia

Inventors

• Bacchetta Matthew
• Guenthart Brandon
• Kim Jinho
• O'Neill John
• Vunjak-Novakovic Gordana

Classifications

• A61L24/102

  Collagen · CPC title

• A61L24/108

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

• A61L24/0094

  containing macromolecular fillers · CPC title

• A61L24/043

  Mixtures of macromolecular materials · CPC title

• A61L24/104

  Gelatin · CPC title