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

Abstract

A bioscaffolding can be formed from a mixture of gel components of different gelation systems. For example, a bioscaffolding can be formed by mixing at least two different components of at least two different two-component gelation systems to form a first mixture and by mixing at least two different components (other than the components that make up the first mixture) of the at least two different two-component gelation systems to form a second mixture. A treatment agent, such as a cell type or a growth factor, can be added to either the first mixture or the second mixture. In some embodiments, the treatment agent is not added to either mixture. The first mixture can be co-injected with the second mixture to form a bioscaffolding in an infarct region for treatment thereof.

1 . A method comprising:
 combining a first component of a first two-component gel system with a first component of a second two-component gel system to form a first mixture;   combining a second component of a first two-component gel system with a second component of a second two-component gel system to form a second mixture; and   adding a treatment agent to one of the first mixture and the second mixture.   
     
     
         2 . The method of  claim 1 , further comprising simultaneously delivering the first mixture and the second mixture to a post-myocardial infarct region. 
     
     
         3 . The method of  claim 1 , wherein the treatment agent is a cell type selected from the group consisting of localized cardiac progenitor cells, mesenchymal stem cells, bone marrow derived mononuclear cells, adipose stem cells, embryonic stem cells, umbilical cord blood derived stem cells, smooth muscle cells and skeletal myoblasts. 
     
     
         4 . The method of  claim 1 , wherein the treatment agent is selected from the group consisting of vasoendothelial growth factor, fibroblast growth factor, Del 1, hypoxia inducing factor, monocyte chemoattractant protein, nicotine, platelet derived growth factor, insulin-like growth factor 1, transforming growth factor, hepatocyte growth factor, estrogens, follistatin, proliferin, prostaglandin E1 and E2, tumor necrosis factor, interleukin 8, hematopoietic growth factors, erythropoietin, granulocyte-colony stimulating factors and platelet-derived endothelial growth factor. 
     
     
         5 . The method of  claim 1 , wherein the first component of the first two-gel component system is one of an alginate-collagen, an alginate-laminin, an alginate-elastin, an alginate-collagen-laminin, an alginate-hyaluronic acid, an alginate and a self-assembled peptide. 
     
     
         6 . The method of  claim 1 , wherein the first component of the second two-component gel system is one of fibrinogen, a fibrinogen derivative, a fibrinogen conjugate, sodium hyaluronate and a self-assembled peptide. 
     
     
         7 . The method of  claim 1 , wherein the second component of the first two-component gel system is one of sodium chloride, calcium chloride, barium chloride, strontium chloride and sucrose. 
     
     
         8 . The method of  claim 1 , wherein the second component of the second two-component gel system is one of sodium chloride, calcium chloride, barium chloride, strontium chloride, thrombin and sucrose. 
     
     
         9 . The method of  claim 1 , wherein the first component of the first two-component gel system and the second component of the second two-component gel system is mixed in a one-to-one ratio. 
     
     
         10 . The method of  claim 1 , wherein (a) the first component of the first two-component gel system is an alginate-collagen solution and the first component of the second two-component gel system is a fibrinogen solution and (b) the second component of the first two-component gel system is a thrombin solution and the second component of the second two-component gel system is a 2.0% mass per volume calcium chloride solution. 
     
     
         11 . The method of  claim 10 , further comprising human mesenchymal stem cells suspended in one of the first mixture or the second mixture. 
     
     
         12 . The method of  claim 10 , wherein the concentration of alginate-collagen is in a range from between 0.5% mass per volume to 1.0% mass per volume. 
     
     
         13 . The method of  claim 10 , wherein the concentration of fibrinogen is in a range from between 5.0% mass per volume to 7.0% mass per volume. 
     
     
         14 . The method of  claim 10 , wherein the concentration of thrombin is in a range from between 9.5% mass per volume to 10.0% mass per volume. 
     
     
         15 . The method of  claim 10 , wherein the alginate-collagen and fibrinogen are mixed in a one-to-one ratio. 
     
     
         16 . The method of the  claim 10 , wherein the thrombin and calcium chloride are mixed in a one-to-one ratio. 
     
     
         17 . The method of  claim 1 , wherein (a) the first component of the first two-component gel is one of alginate-collagen or fibrinogen and the first component of the second two-component gel is a self-assembled peptide and (b) the second component of the first two-component gel is thrombin and the second component of the second two-component gel is 2.0% mass per volume calcium chloride. 
     
     
         18 . The method of  claim 17 , further comprising platelet derived growth factor combined with the self-assembled peptide in one of the first mixture or the second mixture. 
     
     
         19 . The method of  claim 17 , wherein the self-assembled peptide is selected from the group consisting of RAD 16-II (SEQ ID NO: 1), MAX-1 (SEQ ID NO: 2) and EAK16-II (SEQ ID NO: 3). 
     
     
         20 . The method of  claim 2 , wherein the first mixture and the second mixture is delivered with a dual bore delivery device. 
     
     
         21 . The method of  claim 2 , wherein the first mixture and the second mixture is delivered by one of (a) percutaneously or endoscopically using a dual bore catheter or (b) in an open chest procedure using a dual bore syringe.