Single step polymerization of covalently bound multilayer matrices

Patent metadata

Field	Value
Publication number	US-9409322-B2
Application number	US-201313794546-A
Country	US
Kind code	B2
Filing date	Mar 11, 2013
Priority date	Mar 10, 2012
Publication date	Aug 9, 2016
Grant date	Aug 9, 2016

Abstract

A method is provided for forming complex tissue using density gradient multilayer polymerization (DGMP) to form strong hydrogels with smooth transitions between layers. The multicompartment hydrogel is formed by co-dissolving a polymer precurser with a constituent in multiple solvent fractions to a create prepolymer solutions with different densities, layering the prepolymer solutions on top of each other from high to low solvent density, and irradiating the prepolymer solutions to form a polymer. The hydrogels may be used as biomimetic matrices.

First claim

What is claimed:

1. A method for preparing a multicompartment hydrogel comprising:
a. co-dissolving a polymer precursor with an inert density modifier in multiple solvent fractions to a create prepolymer solutions with different densities;
b. layering the prepolymer solutions on top of each other in an order proceeding from high to low solvent density; and
c. irradiating the prepolymer solutions to form a polymer.

2. The method of claim 1 , wherein the polymer precursor comprises acrylamide and bisacrylamide.

3. The method of claim 1 , wherein the polymer precursor comprises polyethylene glycol diacrylate (PEGda).

4. The method of claim 1 , wherein co-dissolving further comprises adding an acrylated fluorophore or a conjugated RGD-containing adhesion peptide to the prepolymer solutions.

5. The method of claim 1 , wherein one or more of the layers of the prepolymer solutions are irradiated at different times.

6. The method of claim 1 , wherein the inert density modifier comprises sucrose, iodixanol, or a mixture thereof.

7. The method of claim 1 , wherein the inert density modifier is present in an amount of between about 0% to about 15% or between about 10% to about 50%.

8. The method of claim 1 , further comprising washing out the inert density modifier after the polymer is formed.

9. The method of claim 1 , wherein the multicompartment hydrogel is configured for culturing tissue in a three-dimensional arrangement.

10. The method of claim 1 , wherein co-dissolving comprises serially diluting the polymer precursor with the inert density modifier to progressively create the prepolymer solutions in order of decreasing densities.

11. A method for creating a multicompartment polymer matrix, comprising:
creating a plurality of prepolymer solutions of decreasing densities by serially co-dissolving an inert density modifier with a prepolymer;
progressively layering the plurality of prepolymer solutions in a mold in order of decreasing density, wherein density differences between adjacent layers induce phase separations between layers; and
exposing the layered prepolymer solutions to a polymerizing radiation source to form a polymer.

12. The method of claim 11 , wherein the step of creating further comprises co-dissolving one or more of cells, ligands, proteins and peptides.

13. The method of claim 11 , wherein the prepolymer comprises acrylamide and bisacrylamide.

14. The method of claim 11 , wherein the prepolymer comprises polyethylene glycol diacrylate (PEGda).

15. The method of claim 11 , wherein co-dissolving further comprises adding an acrylated fluorophore or a conjugated RGD-containing adhesion peptide.

16. The method of claim 11 , further comprising washing the polymer to remove the inert density modifier.

17. The method of claim 11 , wherein the inert density modifier comprises sucrose, iodixanol, or a mixture thereof.

18. A method for creating a multicompartment polymer matrix, comprising:
creating a plurality of prepolymer solutions of decreasing densities by serially co-dissolving an inert density modifier with a prepolymer;
layering the plurality of prepolymer solutions in a mold in layers progressing from higher to lower density solutions, wherein density differences between adjacent layers induce phase separations between layers; and
exposing the layered prepolymer solutions to a polymerizing radiation source to form a polymer.

19. The method of claim 18 , wherein the layering is repeated to produce layered combinations of higher to lower density layers.

20. The method of claim 18 , wherein the step of creating further comprises co-dissolving one or more of cells, ligands, proteins and peptides with the prepolymer and the inert density modifier.

Assignees

• Univ California

Inventors

• Almutairi Adah
• Ner Yogesh
• Karpiak Jerome
• Morachis Jose

Classifications

• A61L27/50

  Materials characterised by their function or physical properties {, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials} · CPC title

• A61L27/56

  Porous materials, {e.g. foams or sponges} · CPC title

• A61L27/26

  Mixtures of macromolecular compounds · CPC title

• A61L27/52

  Hydrogels or hydrocolloids · CPC title

• A61L27/18

  obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds · CPC title