Methods for Preparation of a Terminally Sterilized Hydrogel Derived from Extracellular Matrix

Patent metadata

Field	Value
Publication number	US-2019374683-A1
Application number	US-201916238826-A
Country	US
Kind code	A1
Filing date	Jan 3, 2019
Priority date	Mar 21, 2014
Publication date	Dec 12, 2019
Grant date	—

Abstract

Provided are methods for preparing sterilized, gelled, solubilized extracellular matrix (ECM) compositions useful as cell growth substrates. Also provided are compositions prepared according to the methods as well as uses for the compositions. In one embodiment a device, such as a prosthesis, is provided which comprises an inorganic matrix into which the gelled, solubilized ECM is dispersed to facilitate in-growth of cells into the ECM and thus adaptation and/or attachment of the device to a patient.

First claim

1 . (canceled)

2 . (canceled)

3 . A gellable extracellular matrix (ECM) composition comprising a decellularized, enzymatically digested, dried, terminally sterilized, intact extracellular matrix, wherein said composition is capable of forming a gel upon hydration, neutralization to pH 7.2-7.8, and warming to a temperature greater than 25° C.

4 . The composition of claim 3 , wherein the composition comprises a protease.

5 . The composition of claim 4 , wherein the protease is pepsin or trypsin.

6 . The composition of claim 3 , wherein the extracellular matrix is bioactive.

7 . The composition of claim 3 , wherein the extracellular matrix is derived from urinary bladder, spleen, liver, heart, pancreases, ovary, small intestine, large intestine, colon, esophagus, central nervous system tissue, adipose tissue, dermis, or bone.

8 . The composition of claim 3 , wherein the extracellular matrix is from a human, monkey, pig, cow, or sheep.

9 . The composition of claim 3 , wherein said composition is capable of forming a gel when warmed to 37° C.

10 . A terminally sterilized extracellular matrix (ECM) digest solution comprising a hydrated, decellularized, enzymatically digested, terminally sterilized, intact extracellular matrix, wherein said digest solution is capable of forming a gel upon neutralization to pH 7.2-7.8 and warming to a temperature greater than 25° C.

11 . The composition of claim 10 , wherein the composition comprises a protease.

12 . The composition of claim 10 , wherein the protease is pepsin or trypsin.

13 . The composition of claim 10 , wherein the extracellular matrix is bioactive.

14 . The composition of claim 10 , wherein the extracellular matrix is derived from urinary bladder, spleen, liver, heart, pancreases, ovary, small intestine, large intestine, colon, esophagus, central nervous system tissue, adipose tissue, dermis, or bone.

15 . The composition of claim 10 , wherein the extracellular matrix is from a human, monkey, pig, cow, or sheep.

16 . A terminally sterilized extracellular matrix (ECM) digest solution comprising a hydrated, decellularized, enzymatically digested, terminally sterilized, intact extracellular matrix, wherein said digest solution has a pH 7.2-7.8 and forms a gel when warmed to a temperature greater than 25° C.

17 . The composition of claim 16 , wherein the composition forms a gel when warmed to 37° C.

18 . The composition of claim 16 , wherein the extracellular matrix is bioactive.

19 . The composition of claim 16 , wherein the extracellular matrix is derived from urinary bladder, spleen, liver, heart, pancreases, ovary, small intestine, large intestine, colon, esophagus, central nervous system tissue, adipose tissue, dermis, or bone.

20 . The composition of claim 16 , wherein the extracellular matrix is from a human, monkey, pig, cow, or sheep.

Assignees

• Univ Pittsburgh Commonwealth Sys Higher Education

Inventors

• Badylak Stephen F
• Dearth Christopher Lee
• Keane Jr Timothy Joseph
• Turner Neill Jordon

Classifications

• A61L27/3633 Primary

  Extracellular matrix [ECM] · CPC title

• A61L27/52 Primary

  Hydrogels or hydrocolloids · CPC title

• A61L2430/02

  for reconstruction of bones; weight-bearing implants · CPC title

• A61L27/50

  Materials characterised by their function or physical properties {, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials} · CPC title

• A61L27/54

  Biologically active materials, e.g. therapeutic substances {(A61L27/227 takes precedence)} · CPC title