IP Library Granted Patent US 12,734,274
Granted Patent B2
US 12,734,274 · App. 18/044,969 · Granted Sep 15, 2026

Methods for preparation of a terminally sterilized hydrogel or colloidal suspension derived from extracellular matrix, and uses thereof

Inventors: Stephen Francis Badylak (West Lafayette, IN); George S. Hussey (Cranberry Township, PA)
Assignee: University of Pittsburgh—Of the Commonwealth System of Higher Education
A61L27/3633A61L27/52A61L27/54A61L2400/06A61L2430/34
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Quick Facts
Patent No.
US 12,734,274
App. No.
18/044,969
Granted
Sep 15, 2026
Kind
B2
Abstract

A method is disclosed for treating a fistula in a subject, such as, but not limited to, an anal fistula. In some embodiments, the method includes administering locally to the fistula in the subject an effective amount of a composition comprising a mammalian acoustic extracellular matrix (ECM) hydrogel, and optionally trehalose. Compositions of use in these methods are also disclosed.

Claims (32)

1 . A method of treating a fistula in a subject, comprising:

administering locally to the fistula in the subject an effective amount of a composition comprising a mammalian extracellular matrix (ECM) hydrogel, wherein:

a) the mammalian ECM hydrogel is thermoreversible, wherein the mammalian ECM hydrogel is in a gel phase at temperatures below about 37° C. and transitions to a liquid phase at temperatures above about 37° C.,

b) the mammalian ECM hydrogel comprises solubilized ECM at a concentration of about 0.1 mg/mL to about 1,000 mg/mL, and

c) the composition has a storage modulus (G′) to loss modulus (G″) ratio in the range of about 6:1 to about 12:1 at 37° C.,

thereby treating the fistula in the subject.

2 . The method of claim 1 , wherein the composition further comprises a radioprotectant, wherein the radioprotectant comprises 0.1 mg/mL to about 700 mg/mL trehalose.

3 . The method of claim 2 , further comprising sterilizing the composition with ionizing radiation.

4 . The method of claim 3 , wherein the ionizing radiation is e-beam or gamma irradiation.

5 . The method of claim 1 , wherein the mammalian ECM hydrogel comprises urinary bladder ECM, small intestinal submucosal (SIS) ECM, esophageal ECM, tracheal ECM, liver ECM, or dermal ECM.

6 . The method of claim 1 , wherein the mammalian ECM hydrogel comprises porcine ECM.

7 . The method of claim 1 , wherein the mammalian ECM hydrogel does not comprise an exogenous protease or an inactivated exogenous protease.

8 . The method of claim 1 , wherein the subject is a human.

9 . The method of claim 2 , wherein the composition comprises about 50 to about 500 mg/ml trehalose.

10 . The method of claim 1 , wherein the composition further comprises about 1% to about 30% weight per volume comminuted ECM that is not solubilized in the hydrogel.

11 . The method of claim 1 , wherein the composition has a storage modulus (G′) of about 5 Pa to about 15,000 Pa.

12 . The method claim 1 , wherein the fistula is an anal fistula, and wherein the anal fistula is an intersphincteric, transsphincteric, suprasphincteric, extrasphincteric, or submucosal anal fistula.

13 . The method of claim 1 , wherein the composition is administered to fill a tract of the fistula.

14 . A composition comprising:

i) a mammalian extracellular matrix (ECM) hydrogel, wherein:

a) the mammalian ECM hydrogel is thermoreversible, wherein the mammalian ECM hydrogel is in a gel phase at temperatures below about 37° C. and transitions to a liquid phase at temperatures above about 37° C.,

b) the mammalian ECM hydrogel comprises solubilized ECM at a concentration of about 0.1 mg/mL to about 1,000 mg/mL, and

c) the composition has a storage modulus (G′) to loss modulus (G″) ratio of about 6:1 to about 12:1 at 37° C.;

ii) 0.1 mg/mL to about 700 mg/mL trehalose; and

iii) about 1% to about 30% weight per volume of comminuted ECM that is not solubilized in the hydrogel.

15 . The composition of claim 14 , wherein the composition has been gamma irradiated.

16 . The composition of claim 14 , wherein the mammalian ECM hydrogel comprises urinary bladder ECM, small intestinal submucosal (SIS) ECM, esophageal ECM, trachea ECM, liver ECM, or dermal ECM.

17 . The composition of claim 14 , wherein the ECM comprises porcine ECM.

18 . The composition of claim 14 , wherein the mammalian ECM hydrogel does not comprise an exogenous protease or an inactivated exogenous protease.

19 . The composition of claim 14 , wherein the composition comprises about 50 mg/mL to about 500 mg/mL trehalose.

20 . The composition claim 14 , wherein the composition has a storage modulus (G′) of about 5 Pa to about 15,000 Pa.

21 . The method of claim 1 , wherein the fistula is an enterocutaneous fistula, colocutaneous fistula, enteroenteral fistula, vesiconintestinal fistula, vesicocoli fistula, vesicorectal fistula, rectovaginal fistula, vesicovaginal fistula, rectouterine fistula, vesicouterine fistula, uretovaginal fistula, metroperitoneal fistula, enterovaginal fistula, trachea-esophageal fistula, anal fistula, anorectal fistula, biliary-enteric fistula, vesico-intestinal fistula, pancreatic fistula, cryptoglandular fistula, Crohn's fistula, dural-sinus fistula, colo-vesical fistula, colo-enteric fistula, colo-vaginal fistula, recto-urethral fistula, or pharyngo-cutaneous fistula.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 13, 2023
From: BADYLAK, STEPHEN FRANCIS; HUSSEY, GEORGE S
To: UNIVERSITY OF PITTSBURGH - OF THE COMMONWEALTH SYSTEM OF HIGHTER EDUCATION
Reel/Frame 062961/0700 →
Continuity (2)
Provisional Application 63077084 · Sep 11, 2020
Related Publication 20230364301A1 · Nov 16, 2023
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