Films for controlled cell growth and adhesion

• US 9,056,125 B2
• Filed: 05/17/2005
• Issued: 06/16/2015
• Est. Priority Date: 05/17/2004
• Status: Active Grant

• Current Assignee: Florida State University Research Foundation, Inc. (State University System of Florida)
• Original Assignee: Florida State University Research Foundation, Inc. (State University System of Florida)
• Inventors: Schlenoff, Joseph B., Salloum, David S., Keller, Thomas C. III, Olenych, Scott G.
• Primary Examiner(s): AHMED, HASAN SYED
• Application Number:
  US11/130,972
• Publication Number:
  US 20050287111A1
• Time in Patent Office: 3,682 Days
• Field of Search: None
• US Class Current: 1/1
• CPC Class Codes: A61K 31/16 Amides, e.g. hydroxamic acids
• CPC Class Codes: A61K 31/785 Polymers containing nitrogen
• CPC Class Codes: A61L 2300/424 Anti-adhesion agents
• CPC Class Codes: A61L 2400/18 Modification of implant surfaces in order to improve biocompatibility, cell growth, fixation of biomolecules, e.g. plasma treatment
• CPC Class Codes: A61L 2420/06 Coatings containing a mixture of two or more compounds
• CPC Class Codes: A61L 2430/00 Materials or treatment for tissue regeneration
• CPC Class Codes: A61L 2430/12 for dental implants or prostheses
• CPC Class Codes: A61L 2430/16 for reconstruction of eye parts, e.g. intraocular lens, cornea
• CPC Class Codes: A61L 27/26 Mixtures of macromolecular compounds
• CPC Class Codes: A61L 27/34 Macromolecular materials
• CPC Class Codes: A61L 27/54 Biologically active materials, e.g. therapeutic substances A61L27/227 takes precedence
• CPC Class Codes: A61L 29/085 Macromolecular materials
• CPC Class Codes: A61L 29/16 Biologically active materials, e.g. therapeutic substances A61L29/048 takes precedence
• CPC Class Codes: A61L 31/10 Macromolecular materials
• CPC Class Codes: A61L 31/16 Biologically active materials, e.g. therapeutic substances A61L31/047 takes precedence
• CPC Class Codes: C12N 2537/00 Supports and/or coatings for cell culture characterised by physical or chemical treatment
• CPC Class Codes: C12N 5/0068 General culture methods using substrates for specific animal cell type C12N5/06

Abstract

An article for controlling the attachment and growth of cells on a surface of the article, and a method for the use of the article is provided. The article comprises a substratum having a surface and a film on the surface, the film comprising a network of a net positively charged composition and a net negatively charged composition, wherein the net positively charged composition comprises a net positively charged polyelectrolyte or the net negatively charged composition comprises a net negatively charged polyelectrolyte, and the net positively charged polyelectrolyte or the net negatively charged polyelectrolyte contain (i) a polymer repeat unit having at least two fluorine atoms, or (ii) a polymer repeat unit having a zwitterion group. The method comprises contacting the article with living tissue, living organisms, or with water in an aqueous system comprising living organisms.

Claims

1. An article adapted for use in combination with living tissue or organisms, the article comprising a polyelectrolyte film, the film comprising a bulk region comprising an interpenetrating network of a net positively charged polyelectrolyte polymer and a net negatively charged polyelectrolyte polymer, the film further comprising a first surface region and a second surface region with a net positively charged polyelectrolyte polymer or net negatively charged polyelectrolyte polymer exposed at each of said first surface region and second surface region wherein (1) the net positively charged polyelectrolyte polymer or the net negatively charged polyelectrolyte polymer exposed in said first surface region contains a polymer repeat unit having at least two fluorine atoms and (2) the net positively charged polyelectrolyte polymer or the net negatively charged polyelectrolyte polymer exposed in said second surface region contains a polymer repeat unit having a zwitterion group and a charged polymer repeat unit that is non-zwitterionic.

2. The article of claim 1 wherein the article comprises the polyelectrolyte film and a metal substratum with the first surface region contacting the metal substratum.

3. The article of claim 1 wherein the article is a membrane having opposing sides, the first surface region being one of the opposing sides and the second surface region being the other opposing side.

4. The article of claim 3 further comprising a film comprising a synthetic elastomeric polymer selected from the group consisting of polyvinyl chloride, polyurethane, polysiloxanes, and combinations thereof said film comprising said synthetic elastomeric polymer in contact with said first surface region.

5. The article of claim 1 wherein the first surface region and the second surface region have substantially planar exposed surfaces wherein the first and second surface regions are substantially contiguous so as to define a pattern of regions having water contact angles that differ by at least 30 degrees.

6. The article of claim 5 wherein the first surface region has a dimensional aspect between 1 micrometer and 1000 micrometers.

7. The article of claim 5 wherein the first surface region is stamped onto the second surface region.

10. The article of claim 1 wherein the polyelectrolyte film is in contact with a substratum selected from the group consisting of stents, catheters, vascular grafts, vascular prostheses, contact lenses, intraocular implants, artificial valves for in vivo use, artificial organs, dental implants, metal implants into bone, corneal implants, Petri dishes, roller bottles, microcarriers, porous structural supports for three dimensional cell growth, synthetic elastomeric polymers, and metal objects adapted for use in aqueous systems containing living organisms.

11. The article of claim 1 wherein the zwitterion group is selected from the group consisting of:

N,N-dimethyl-N-acryloyloxyethyl-N-(3-sulfopropyl)-ammonium betaine, N,N-dimethyl-N-acrylamidopropyl-N-(2-carboxymethyl)-ammonium betaine, N,N-dimethyl-N-acrylamidopropyl-N-(3-sulfopropyl)-ammonium betaine, N,N-dimethyl-N-acrylamidopropyl-N-(2-carboxymethyl)-ammonium betaine, 2-(methylthio)ethyl methacryloyl-S-(sulfopropyl)-sulfonium betaine, 2-[(2-acryloylethyl)dimethylammonio]ethyl 2-methyl phosphate, 2-(acryloyloxyethyl)-2′

-(trimethylammonium)ethyl phosphate, [(2-acryloylethyl)dimethylammonio]methyl phosphonic acid, 2-methacryloyloxyethyl phosphorylcholine (MPC), 2-[(3-acrylamidopropyl)dimethylammonio]ethyl 2′

-isopropyl phosphate, 1-vinyl-3-(3-sulfopropyl)imidazolium hydroxide, (2-acryloxyethyl)carboxymethyl methylsulfonium chloride, 1-(3-sulfopropyl)-2-vinylpyridinium betaine, N-(4-sulfobutyl)-N-methyl-N,N-diallylamine ammonium betaine, N,N-diallyl-N-methyl-N-(2-sulfoethyl)ammonium betaine, N,N-dimethyl-N-(3-methacrylamidopropyl)-N-(3-sulfopropyl)ammonium betaine, N,N-dimethyl-N-acryloyloxyethyl-N-(3-sulfopropyl)-ammonium betaine, N,N-dimethyl-N-acrylamidopropyl-N-(2-carboxymethyl)-ammonium betaine, N,N-dimethyl-N-methacryloyloxyethyl-N-(3-sulfopropyl)-ammonium betaine, N,N-dimethyl-N-(3-methacrylamidopropyl)-N-(3-sulfopropyl)ammonium betaine, and copolymers thereof.

12. The article of claim 1 wherein the net positively charged polyelectrolyte polymer or the net negatively charged polyelectrolyte polymer exposed in said second surface region containing the polymer repeat unit having the zwitterion group further comprises between about 10% and about 90% the non-zwitterionic charged polymer repeat unit.

8. A method for controlling the attachment and growth of cells on a surface of an article, the method comprising contacting the article with living tissue, living organisms, or with water in an aqueous system comprising living organisms wherein the article comprises a substratum having a surface and a film on the surface, the film comprising a bulk region comprising an interpenetrating network of a net positively charged polyelectrolyte polymer and a net negatively charged polyelectrolyte polymer, and wherein the film comprises a first surface region and a second surface region with a net positively charged polyelectrolyte polymer or net negatively charged polyelectrolyte polymer exposed at each of said first surface region and second surface region, wherein (1) the net positively charged polyelectrolyte polymer or net negatively charged polyelectrolyte polymer exposed in said first surface region contains a polymer repeat unit having at least two fluorine atoms and (2) the net positively charged polyelectrolyte polymer or net negatively charged polyelectrolyte polymer exposed in said second surface region contains a polymer repeat unit having a zwitterion group and a charged polymer repeat unit that is non-zwitterionic and wherein the net positively charged polyelectrolyte polymer or net negatively charged polyelectrolyte polymer exposed in said second surface region is a copolymer comprising between about 20 mole % and about 70 mole % of polymer repeat units having zwitterion groups.

9. The method of claim 8 wherein the first surface region of the film promotes the attachment and growth of cells and the second surface region inhibits the attachment and growth of cells.

16. The method of claim 8 wherein the substratum is selected from the group consisting of stents, catheters, vascular grafts, vascular prostheses, contact lenses, intraocular implants, artificial valves for in vivo use, artificial organs, dental implants, metal implants into bone, corneal implants, Petri dishes, roller bottles, microcarriers, porous structural supports for three dimensional cell growth, synthetic elastomeric polymers, and metal objects adapted for use in aqueous systems containing living organisms.

17. The method of claim 8 wherein the article comprises the polyelectrolyte film and a metal substratum with the first surface region contacting the metal substratum.

18. The method of claim 8 wherein the article is a membrane having opposing sides, the first surface region being one of the opposing sides and the second surface region being the other opposing side.

19. The method of claim 8 wherein the article further comprises a film comprising a synthetic elastomeric polymer selected from the group consisting of polyvinyl chloride, polyurethane, polysiloxanes, and combinations thereof, said film comprising said synthetic elastomeric polymer in contact with said first surface region.

20. The method of claim 8 wherein the first surface region and the second surface region have substantially planar exposed surfaces wherein the first and second surface regions are substantially contiguous so as to define a pattern of regions having water contact angles that differ by at least 30 degrees.

13. An article adapted for use in combination with living tissue or organisms, the article comprising a polyelectrolyte film, the film comprising a bulk region comprising an interpenetrating network of a net positively charged polyelectrolyte polymer and a net negatively charged polyelectrolyte polymer, the film further comprising a first surface region and a second surface region with a net positively charged polyelectrolyte polymer or net negatively charged polyelectrolyte polymer exposed at each of said first surface region and second surface region for forming an interface with a cell growth medium at each of said first and second surface regions, wherein (1) the net positively charged polyelectrolyte polymer or the net negatively charged polyelectrolyte polymer exposed in said first surface region contains a polymer repeat unit having at least two fluorine atoms and (2) the net positively charged polyelectrolyte polymer or the net negatively charged polyelectrolyte polymer exposed in said second surface region contains a polymer repeat unit having a zwitterion group and a non-zwitterionic charged polymer repeat unit.

14. An article as set forth in claim 13 wherein said polyelectrolyte film is stable in an aqueous environment having a pH of 7.4.

15. An article adapted for use in combination with living tissue or organisms, the article comprising a polyelectrolyte film that is stable in an aqueous environment having a pH of 7.4, the film comprising a bulk region comprising an interpenetrating network of a net positively charged polyelectrolyte polymer and a net negatively charged polyelectrolyte polymer, the film further comprising a first surface region and a second surface region with a net positively charged polyelectrolyte polymer or net negatively charged polyelectrolyte polymer exposed at each of said first surface region and second surface region wherein (1) the net positively charged polyelectrolyte polymer or the net negatively charged polyelectrolyte polymer exposed in said first surface region contains a polymer repeat unit having at least two fluorine atoms and (2) the net positively charged polyelectrolyte polymer or the net negatively charged polyelectrolyte polymer exposed in said second surface region contains a polymer repeat unit having a zwitterion group and a non-zwitterionic charged polymer repeat unit.