Polysiloxane substrates with highly-tunable elastic modulus

Patent metadata

Field	Value
Publication number	US-10119119-B2
Application number	US-201314375705-A
Country	US
Kind code	B2
Filing date	Jan 31, 2013
Priority date	Jan 31, 2012
Publication date	Nov 6, 2018
Grant date	Nov 6, 2018

Abstract

A highly tunable bioscaffold is provided, as well as a method of manufacture of the bioscaffold and methods of use of the bioscaffold, for example for drug testing, cell propagation and for optimizing growth of a cell type, for example corneal endothelial cells.

First claim

We claim:

1. A bioscaffold comprising:
a sterile substrate comprising a crosslinked mixture of a first composition comprising a polysiloxane and nanoparticles and a second composition comprising independently a polysiloxane and which does not comprise nanoparticles, and an extracellular matrix (ECM) component deposited on a surface of the crosslinked mixture; and
cells grown or cultured on the sterile substrate.

2. The bioscaffold of claim 1 in which the first composition further comprises polydimethyl siloxane, one or more siloxanes other than polydimethyl siloxane, and silica nanoparticles; and the second composition comprises one or both of a polydimethylsiloxane and a dimethyl, methylhydrogen siloxane.

3. The bioscaffold of claim 1 , in which the polysiloxane of the first and second compositions independently comprise one or more of a dimethyl siloxane; a diphenylsiloxane; a diethylsiloxane; a trifluoropropyl methyl siloxane; a phenylmethylsiloxane; a copolymer of dimethylsiloxane with one or more of a diphenylsiloxane, a diethylsiloxane, a trifluoropropyl methyl siloxane, and/or a phenylmethylsiloxane; and a aminopropylmethylsiloxane-(dimethylsiloxane).

4. The bioscaffold of claim 1 , in which the nanoparticles are silica nanoparticles.

5. The bioscaffold of claim 1 , in which the nanoparticles comprise organically-modified silica.

6. The bioscaffold of claim 5 , in which the organically-modified silica comprises one or more vinyl and/or alkyl groups.

7. The bioscaffold of claim 5 , in which the organically-modified silica comprises one or both of dimethylvinylated silica and trimethylated silica.

8. The bioscaffold of claim 1 , in which the polysiloxane of one or both of the first composition and the second composition is dimethylvinyl-terminated.

9. The bioscaffold of claim 1 in which the first composition comprises dimethylvinyl-terminated dimethyl siloxane, dimethylvinylated and trimethylated silica, and tetra(trimethylsiloxy) silane, and the second composition comprises a polydimethylsiloxane and a dimethyl, methylhydrogen siloxane.

10. The bioscaffold of claim 1 , having an elastic modulus ranging from greater than 5 kPa to less than 1.72 MPa.

11. The bioscaffold of claim 1 , having a mass ratio of the first composition to the second composition of from 50:1 to 1:50.

12. The bioscaffold of claim 1 , in which a weight ratio of polysiloxane to nanoparticles is at least 2.5:1.

13. The bioscaffold of claim 1 , in which the ECM component is patterned on a surface of the bioscaffold.

14. The bioscaffold of claim 1 , in which the ECM component comprises one or more of a glycosaminoglycan; a proteoglycan; a protein; and a glycoprotein.

15. The bioscaffold of claim 1 , formed into a three-dimensional structure.

16. The bioscaffold of claim 1 , formed as a porous mass, a woven mass of fibers or a non-woven mass of fibers.

17. The bioscaffold of claim 1 , in which the cells are selected from the group consisting of a stem cell, a corneal endothelial cell or a progenitor thereof; a muscle cell or a progenitor thereof; a neuronal cell or a progenitor thereof, and a retinal pigment epithelial cell or a progenitor thereof.

18. The bioscaffold of claim 10 , having an elastic modulus of between 5 kPa and 50 kPa.

19. The bioscaffold of claim 1 , wherein the ECM component comprises one or more of a heparan sulfate, a dermatan sulfate, a chondroitin sulfate, a keratin sulfate, a hyaluronic acid, an aggrecan, a versican, a neurocan, a brevican, a decorin, a perlecan, a collagen, an elastin; a laminin, a fibronectin, a vitronectin, an osteopontin and a fibrinogen.

20. The bioscaffold of claim 1 , further comprising a rigid or semi-rigid substrate onto which the sterile substrate is deposited.

Assignees

• Univ Carnegie Mellon
• Univ Of Pittsburgh—Of The Commonwealth System Of Higher Education
• Carnegie Mellon Univ And Univ Of Pittsburgh—Of The Commonwealth System Of Higher Education

Inventors

• Feinberg Adam Walter
• Funderburgh James L
• Simko Rachelle

Classifications

• C08G77/12

  containing silicon bound to hydrogen · CPC title

• B05D7/54

  No clear coat specified · CPC title

• C08K2201/011

  Nanostructured additives · CPC title

• C12M23/20

  Material Coatings (immunocoatings C12M25/00) · CPC title

• C08G77/24

  halogen-containing groups · CPC title