Extracellular matrix-derived gels and related methods
Provided are methods for preparing gelled, solubilized extracellular matrix (ECM) compositions useful as cell growth scaffolds. 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.
1. A composition comprising:
an acidic solution comprising an acid protease and solubilized, non-dialyzed, non-crosslinked extracellular matrix from a tissue selected from the group consisting of heart, pancreas, liver, ovary, spleen, and urinary bladder removed of submucosa;
wherein, the acidic solution, when neutralized, forms a gel at a temperature greater than 25° C.
2. The composition of claim 1 , wherein the ECM is from heart tissue.
3. The composition of claim 1 , wherein the ECM is from liver tissue.
4. The composition of claim 1 , wherein the acid protease is pepsin.
5. The composition of claim 1 , wherein the solution is frozen.
6. The composition of claim 1 , wherein the solution has a pH of about 2.
7. A composition comprising:
a hydrogel comprising solubilized, non-dialyzed, non-crosslinked extracellular matrix (ECM) and an acid protease, the hydrogel having a pH in the range of 7.2 to 7.8.
8. The composition of claim 7 , wherein the acid protease is pepsin.
9. The composition of claim 7 , wherein the ECM is derived from a tissue selected from intestine, urinary bladder, liver, esophagus, pancreas, dermis, heart, ovary, or spleen.
10. The composition of claim 9 , wherein the ECM is derived from heart.
11. The composition of claim 9 , wherein the ECM is derived from liver.
12. The composition of claim 7 , wherein the pH is in the range of 7.2 to 7.4.
13. A method of preparing an extracellular matrix-derived gel comprising:
neutralizing an acidic solution comprising solubilized, digested, non-dialyzed, non-crosslinked extracellular matrix (ECM) and an acid protease to produce a neutralized solution, wherein the neutralized solution produces a hydrogel at a temperature greater than 25° C.
14. The method of claim 13 , wherein the neutralized solution has a pH in the range of 7.2 to 7.8.
15. The method of claim 13 , wherein the acid protease is pepsin.
16. The method of claim 13 , wherein the hydrogel forms after 40 minutes at 37° C.
17. The method of claim 13 , wherein the ECM is derived from a tissue selected from intestine, urinary bladder, liver, esophagus, pancreas, dermis, heart, ovary, or spleen.
18. A method of preparing a gelable extracellular matrix composition comprising:
solubilizing non-dialyzed, non-crosslinked extracellular matrix (ECM) in an acidic solution with an acid protease to produce an acidic solution of solubilized, digested, non-dialyzed, non-crosslinked ECM and the acid protease;
wherein, upon neutralizing the acidic solution to produce a neutralized solution having a pH of between 7.2 to 7.8, the solution forms a gel at a temperature greater than 25° C.
19. The method of claim 18 , wherein the ECM is from a tissue selected from the group consisting of intestine, urinary bladder, liver, esophagus, pancreas, dermis, heart, ovary, and spleen.
20. The method of claim 19 , wherein the ECM is from heart tissue.
21. The method of claim 19 , wherein the ECM is from liver tissue.
22. The method of claim 18 , wherein the acid protease is pepsin.
23. The method of claim 18 , wherein the ECM is lyophilized or dried, and then comminuted prior to solubilizing in the acidic solution.
24. The method of claim 18 , wherein the ECM is solubilized by stirring in the acidic solution at room temperature.
25. The method of claim 18 , wherein the pH of the acidic solution is about 2.