Modified two-component gelation systems, methods of use and methods of manufacture

Abstract

Compositions, methods of manufacture and methods of treatment for post-myocardial infarction are herein disclosed. In some embodiments, the composition includes at least two components. In one embodiment, a first component can include a first functionalized polymer and a substance having at least one cell adhesion site combined in a first buffer at a pH of approximately 6.5. A second component can include a second buffer in a pH of between about 7.5 and 9.0. A second functionalized polymer can be included in the first or second component. In some embodiments, the composition can include at least one cell type and/or at least one growth factor. In some embodiments, the composition(s) of the present invention can be delivered by a dual bore injection device to a treatment area, such as a post-myocardial infarct region.

What is claimed is: 
     
         1 . A composition comprising:
 a first mixture comprising a first functionalized polymer in a first buffer at approximately physiological osmolality;   a second buffer at approximately physiological osmolality;   a second functionalized polymer, wherein the second functionalized polymer is combined with one of the first mixture or the second buffer; and   a substance having at least one cell-adhesion site combined with the first mixture,   wherein the first mixture and the second buffer comprise a gel at pH 7.2 when combined.   
     
     
         2 . The composition of  claim 1 , wherein the first functionalized polymer is one of an activated ester-terminated polyethylene glycol or a vinyl-terminated polyethylene glycol. 
     
     
         3 . The composition of  claim 1 , wherein the second functionalized polymer is one of a thiol-terminated polyethylene glycol or an amino-terminated polyethylene glycol. 
     
     
         4 . The composition of  claim 1 , wherein the substance is a protein selected from the group consisting of gelatin, laminin, elastin, arginine-glycine-aspartic acid peptide sequence and peptide fragments thereof. 
     
     
         5 . The composition of  claim 1 , wherein the first mixture further comprises one of a cell type, a growth factor or a combination thereof. 
     
     
         6 . The composition of  claim 1 , wherein the first functionalized polymer and the second functionalized polymer has a functionality greater than four. 
     
     
         7 . A kit comprising:
 a first syringe including a first functionalized polymer and a substance having at least one cell-adhesion site in a first buffer at physiological osmolality; and   a second syringe including a second buffer at physiological osmolality.   
     
     
         8 . The kit of  claim 7 , wherein the first functionalized polymer is one of an activated ester-terminated polyethylene glycol or a vinyl-terminated polyethylene glycol. 
     
     
         9 . The kit of  claim 7 , wherein the second functionalized polymer is one of a thiol-terminated polyethylene glycol or an amino-terminated polyethylene glycol. 
     
     
         10 . The kit of  claim 7 , wherein the substance is a protein selected from the group consisting of gelatin, laminin, elastin, arginine-glycine-aspartic acid peptide sequence and peptide fragments thereof. 
     
     
         11 . The kit of  claim 7 , wherein the first mixture further comprises one of a cell type, a growth factor or a combination thereof. 
     
     
         12 . A method of treatment comprising:
 simultaneously injecting from a dual bore delivery device (a) a first mixture comprising a first functionalized polymer and a substance having at least one cell-adhesion site in a first buffer at physiological osmolality and (b) a second buffer at physiological osmolality to a post-myocardial infarct region.   
     
     
         13 . The method of  claim 12 , further comprising a second functionalized polymer, wherein the second functionalized polymer is combined with one of the first mixture or the second buffer. 
     
     
         14 . The method of  claim 12 , wherein the first functionalized polymer r is one of an activated ester-terminated polyethylene glycol or a vinyl-terminated polyethylene glycol. 
     
     
         15 . The method of  claim 13 , wherein the second functionalized polymer is one of a thiol-terminated polyethylene glycol or an amino-terminated polyethylene glycol. 
     
     
         16 . The method of  claim 12 , wherein the substance is a protein selected from the group consisting of gelatin, laminin, elastin, arginine-glycine-aspartic acid peptide sequence and peptide fragments thereof. 
     
     
         17 . The method of  claim 12 , wherein the first mixture further comprises one of a cell type, a growth factor or a combination thereof. 
     
     
         18 . The method of  claim 17 , wherein the cell type, the growth factor, or the combination thereof is combined with the first mixture. 
     
     
         19 . The method of  claim 13 , wherein the first functionalized polymer and the second functionalized polymer has a functionality greater than four. 
     
     
         20 . The method of  claim 13 , wherein the first mixture and the second buffer comprise a gel at pH 7.2 when combined.