Extracellular Matrix Scaffolds

Patent metadata

Field	Value
Publication number	US-2017342374-A1
Application number	US-201715610125-A
Country	US
Kind code	A1
Filing date	May 31, 2017
Priority date	May 31, 2016
Publication date	Nov 30, 2017
Grant date	—

Abstract

A method for micro-tissue encapsulation of cells includes coating a tissue scaffold stamp with an extracellular matrix compound; depositing the tissue scaffold stamp onto a thermoresponsive substrate; seeding the tissue scaffold stamp with a cell culture; incubating the cell culture on the tissue scaffold stamp at a temperature that is specified, wherein the cell culture forms a cell patch that is attached to the extracellular matrix compound; removing the thermoresponsive substrate by lowering the temperature; removing the tissue scaffold stamp from the cell patch to form a micro-tissue structure by dissolving the tissue scaffold stamp in a solvent; folding the micro-tissue structure by suspending the micro-tissue in the solvent to enable the cell patch to fold the micro-tissue structure; collecting the folded micro-tissue structure from the solvent; and administering the folded micro-tissue structure to an organism.

First claim

What is claimed is:

1 . A method for micro-tissue encapsulation of cells comprising:
coating a tissue scaffold stamp with an extracellular matrix compound; depositing the tissue scaffold stamp onto a thermoresponsive substrate; seeding the tissue scaffold stamp with a cell culture; incubating the cell culture on the tissue scaffold stamp at a temperature that is specified, wherein the cell culture forms a cell patch that is attached to the extracellular matrix compound; removing the thermoresponsive substrate by lowering the temperature; removing the tissue scaffold stamp from the cell patch to form a micro-tissue structure by dissolving the tissue scaffold stamp in a solvent; folding the micro-tissue structure by suspending the micro-tissue in the solvent to enable the cell patch to fold the micro-tissue structure; collecting the folded micro-tissue structure from the solvent; and administering the folded micro-tissue structure to an organism.

2 . The method of claim 1 , wherein administering the micro-tissue structure to an organism comprises injecting the micro-tissue structure.

3 . The method of claim 1 , wherein folded micro-tissue structure is configured to protect the cell patch from forces during the injecting.

4 . The method of claim 2 , wherein a size of the micro-tissue structure is proportional to a size of the tissue scaffold stamp, and wherein the size of the micro-tissue structure is a fraction of a diameter of an injecting apparatus.

5 . The method of claim 1 , wherein the tissue scaffold stamp comprises an organosilicon compound.

6 . The method of claim 5 , wherein the organosilicon compound comprises Polydimethylsiloxane.

7 . The method of claim 1 , wherein the extracellular matrix compound comprises a protein comprising one or more of collagen IV, laminin, a fibroblast growth factor protein, and a vascular endothelial growth factor protein.

8 . The method of claim 1 , wherein depositing the tissue scaffold stamp comprises printing the tissue scaffold stamp onto the thermoresponsive substrate.

9 . The method of claim 1 , wherein the thermoresponsive substrate comprises a PIPAAm polymer.

10 . The method of claim 1 , wherein the tissue scaffold stamp forms a regular geometry.

11 . The method of claim 1 , wherein the tissue scaffold stamp comprises a surface dimension of less than or approximately equal to 250 μm 2 .

12 . The method of claim 1 , wherein the cell culture comprises one or more populations of corneal endothelial cells.

13 . The method of claim 1 , wherein the cell culture comprises one or more populations of stem cells.

14 . The method of claim 1 , wherein the cell culture forms a monolayer on the tissue scaffold stamp.

15 . A micro-tissue raft comprising:
a cell patch comprising binders exposed on a first side of the cell patch; and an extracellular matrix compound that is attached to a second side of the cell patch and that forms a base for the cell patch, wherein the extracellular matrix compound is configured to be responsive to one or more tension forces expressed by the cell patch, wherein the one or more tension forces cause the extracellular matrix compound to fold into a specified geometry around the cell patch, wherein the specified geometry substantially conceals the expressed binders of the cell patch.

16 . The micro-tissue raft of claim 15 , wherein the one or more tension forces are expressed by one or more junctions of one or more respective cells that form the cell patch.

17 . The micro-tissue raft of claim 15 , wherein the extracellular matrix compound is configured to fold into the compact geometry in response to removal of an organosilicon compound scaffold from the extracellular matrix compound.

18 . The micro-tissue raft of claim 15 , wherein the extracellular matrix compound is configured to alter a form factor into a planar geometry that exposes the expressed binders of the cell patch, and wherein the extracellular matrix compound is configured to alter the form factor after a delay in response to folding into the specified geometry.

Assignees

• Univ Carnegie Mellon

Inventors

• Simko Rachelle
• Feinberg Adam

Classifications

• C12N5/0656

  Adult fibroblasts · CPC title

• C07F7/0803

  Compounds with Si-C or Si-Si linkages · CPC title

• C12N5/0068

  General culture methods using substrates (for specific animal cell type C12N5/06) · CPC title

• C12N5/0657

  Cardiomyocytes; Heart cells · CPC title

• C12N5/0625

  Epidermal cells, skin cells; Cells of the oral mucosa · CPC title