Extracellular Matrix-Derived Gels and Related Methods

Abstract

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 method of preparing an extracellular matrix-derived gel comprising: (i) comminuting an extracellular matrix, (ii) solubilizing extracellular matrix that has not been dialyzed, by digestion with an acid protease in an acidic solution to produce a digest solution, (iii) raising the pH of the digest solution to a pH between 7.2 and 7.8 to produce a neutralized digest solution, and (iv) gelling the solution at a temperature greater than 25° C. 
     
     
         2 . The method of  claim 1 , wherein the extracellular matrix further is not dialyzed or subjected to a cross-linking process prior to the solubilizing step. 
     
     
         3 . The method of  claim 1 , wherein the extracellular matrix is derived from mammalian tissue. 
     
     
         4 . The method of  claim 3 , wherein the mammalian tissue is derived from one of urinary bladder, spleen, liver, heart, pancreas, ovary, or small intestine. 
     
     
         5 . The method of  claim 3 , wherein the mammalian tissue is derived from a pig, cow, monkey, or human. 
     
     
         6 .- 7 . (canceled) 
     
     
         8 . The method of  claim 1 , wherein all solutions are maintained at or below 25° C. before gelation. 
     
     
         9 . (canceled) 
     
     
         10 . The method of  claim 1 , wherein the protease is pepsin. 
     
     
         11 .- 18 . (canceled) 
     
     
         19 . The method of  claim 1 , wherein the digest solution is gelled at a pH of about 7.4. 
     
     
         20 .- 21 . (canceled) 
     
     
         22 . The method of  claim 1 , wherein the digest solution is gelled at 30° C. or higher. 
     
     
         23 . The method of  claim 22 , wherein the digest solution is gelled at about 37° C. 
     
     
         24 . The method of  claim 22 , wherein the gel is molded during the gelation step. 
     
     
         25 .- 27 . (canceled) 
     
     
         28 . The method of  claim 1 , further comprising administering the neutralized digest solution to a patient and wherein the gelling takes place in or on the patient. 
     
     
         29 . The method of  claim 28 , wherein the pH of digest solution is raised by mixing the digest solution with a base and/or buffer during administration to the patient. 
     
     
         30 . The method of  claim 28 , wherein the patient is a human patient. 
     
     
         31 . The method of  claim 1 , further comprising integrating one or more of a cell, a drug, a cytokine and a growth factors into the gel. 
     
     
         32 .- 35 . (canceled) 
     
     
         36 . A composition prepared by the process of  claim 1 . 
     
     
         37 .- 69 . (canceled) 
     
     
         70 . A method of preparing a hybrid extracellular matrix scaffold comprising coating a matrix of a biocompatible scaffold a solubilized extracellular matrix and gelling the matrix. 
     
     
         71 .- 84 . (canceled) 
     
     
         85 . A biocompatible device coated with a hybrid scaffold comprising gelled solubilized extracellular matrix embedded into a porous scaffold. 
     
     
         86 .- 88 . (canceled) 
     
     
         89 . The device of  claim 85 , wherein the gelled solubilized extracellular matrix is prepared by a process comprising: (i) comminuting an extracellular matrix, (ii) solubilizing extracellular matrix that has not been dialyzed, by digestion with an acid protease in an acidic solution to produce a digest solution, (iii) raising the pH of the digest solution to a pH between 7.2 and 7.8 to produce a neutralized digest solution, and (iv) gelling the solution at a temperature greater than 25° C. 
     
     
         90 .- 96 . (canceled)