Modified two-component gelation systems, methods of use and methods of manufacture
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.
1. A kit for a post-myocardial infarct bioscaffolding gel, the kit separately comprising the following components:
(a) a first mixture comprising a first functionalized polymer in a first buffer, the first buffer having a physiological osmolality;
(b) a second buffer having a concentration of 140 mM to 150 mM and a pH between 7.5 and 9;
(c) a second functionalized polymer different from the first functionalized polymer, the second functionalized polymer capable of being combined with the first mixture or the second buffer; and
(d) a proteinaceous or peptide substance having at least one cell-adhesion site, the substance capable of being combined with the first mixture,
wherein the first functionalized polymer is a functionalized polyethylene glycol selected from the group consisting of an activated ester-terminated polyethylene glycol or a vinyl-terminated polyethylene glycol; wherein the second functionalized polymer is selected from the group consisting of a thiol-terminated polyethylene glycol or an amino-terminated polyethylene glycol; and wherein the components, when combined, form a gel having a pH of 7.2.
2. The kit of claim 1 , wherein the first mixture has a pH of less than 6.5.
3. The kit of claim 1 , wherein the physiological osmolality of the first buffer is from 280 mOsm/kg H 2 O to 300 mOsm/kg H 2 O.
4. The kit of claim 1 , wherein the substance having at least one cell-adhesion site is a protein selected from the group consisting of gelatin, laminin, and elastin or an arginine-glycine-aspartic acid (RGD) peptide sequence.
5. The kit of claim 1 , wherein the first mixture further comprises a cell, a growth factor, or a combination thereof.
6. The kit of claim 5 , wherein the growth factor is selected from the group consisting of vasoendothelial growth factor (VEGF), fibroblast growth factor (FGF), Del 1, hypoxia inducing factor (HIF), monocyte chemoattractant protein (MCP), nicotine, platelet derived growth factor (PDGF), insulin-like growth factor 1 (IGF-1), transforming growth factor (TGF), hepatocyte growth factor (HGF), estrogens, follistatin, proliferin, prostaglandin E1 (PGE1), prostaglandin E2 (PGE2), tumor necrosis factor (TNF), interleukin-8 (IL-8), hematopoietic growth factors, erythropoietin (EPO), granulocyte-colony stimulating factors (G-CSF), and platelet-derived endothelial growth factor (PD-ECGF).
7. The kit of claim 5 , wherein the cell is selected from the group consisting of localized cardiac progenitor cells, mesenchymal stem cells, bone marrow derived mononuclear cells, adipose tissue derived stem cells, embryonic stem cells, umbilical-cord-blood-derived stem cells, smooth muscle cells and skeletal myoblasts.
8. The kit of claim 1 , wherein the first functionalized polymer and the second functionalized polymer have a combined functionality greater than four.