Thin films for controlled cell growth

• US 9,228,169 B2
• Filed: 06/16/2015
• Issued: 01/05/2016
• Est. Priority Date: 05/17/2004
• Status: Expired due to Fees

• 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:
  US14/741,062
• Publication Number:
  US 20150284680A1
• Time in Patent Office: 203 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

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 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.

Claims

1. 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 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, a net positively charged polyelectrolyte or the net negatively charged polyelectrolyte contains (i) a polymer repeat unit having at least two fluorine atoms, or (ii) a polymer repeat unit having a zwitterion group, and the film comprises a surface region at which a net positively charged polyelectrolyte having zwitterion repeat units, a net negatively charged polyelectrolyte having zwitterion repeat units, a net positively charged polyelectrolyte comprising a repeat unit having at least two fluorine atoms, or a net negatively charged polyelectrolyte comprising a repeat unit having at least two fluorine atoms is exposed.

2. The method of claim 1 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.

3. The method of claim 1 wherein the film is deposited by alternately layering the net positively charged composition and the net negatively charged composition and wherein layers 0 through n of the film comprise polyelectrolyte comprising non-fluorinated polymer repeat units and layers n+1 through n+2 of the film comprise polyelectrolyte comprising the polymer repeat unit having at least two fluorine atoms.

4. The method of claim 3 wherein the film promotes the attachment and growth of cells on the surface of the substratum.

5. The method of claim 1 wherein the film comprises a first surface region and a second surface region with a net positively charged or net negatively charged polyelectrolyte exposed at each of said first surface region and second surface region, wherein (1) the net positively charged or net negatively charged polyelectrolyte exposed in said first surface region contains polyelectrolyte comprising non-fluorinated polymer repeat units and (2) the net positively charged or net negatively charged polyelectrolyte exposed in said second surface region contains polyelectrolyte comprising the polymer repeat unit having at least two fluorine atoms.

6. The method of claim 5 wherein the film promotes the attachment and growth of cells on the surface of the substratum.

7. The method of claim 1 wherein the film is deposited by alternately layering the net positively charged composition and the net negatively charged composition and wherein layers 0 through n of the film comprise polyelectrolyte comprising non-zwitterion polymer repeat units and layers n+1 through n+2 of the film comprise polyelectrolyte comprising polymer repeat unit having a zwitterion group.

8. The method of claim 7 wherein the film inhibits the attachment and growth of cells on the surface of the substratum.

9. The method of claim 1 wherein the film comprises a first surface region and a second surface region with a net positively charged or net negatively charged polyelectrolyte exposed at each of said first surface region and second surface region, wherein (1) the net positively charged or net negatively charged polyelectrolyte exposed in said first surface region contains polyelectrolyte comprising non-zwitterion polymer repeat units and (2) the net positively charged or net negatively charged polyelectrolyte exposed in said second surface region contains polyelectrolyte comprising the polymer repeat unit having a zwitterion group.

10. The method of claims 9 wherein the film inhibits the attachment and growth of cells on the surface of the substratum.

11. The method of claim 1 wherein:

the net positively charged composition is a net positively charged polyelectrolyte polymer;

the net negatively charged composition is a net negatively charged polyelectrolyte polymer;

the film comprises a bulk region comprising the net positively charged polyelectrolyte polymer and the net negatively charged polyelectrolyte polymer in an interpenetrating network;

the film further comprises a first surface region and a second surface region with the net positively charged polyelectrolyte polymer or net negatively charged polyelectrolyte polymer exposed at each of said first surface region and second surface region;

the net positively charged polyelectrolyte polymer or the net negatively charged polyelectrolyte polymer exposed in said first surface region contains the polymer repeat unit having at least two fluorine atoms; and

the net positively charged polyelectrolyte polymer or the net negatively charged polyelectrolyte polymer exposed in said second surface region contains the polymer repeat unit having a zwitterion group and a charged polymer repeat unit that is non-zwitterionic.

12. A method as set forth in claim 1 wherein a positively charged polyelectrolyte or a negatively charged polyelectrolyte exposed at said surface region comprises a repeat unit having a zwitterion group.

13. A method as set forth in claim 12 wherein said positively charged electrolyte or negatively charged polyelectrolyte exposed at said surface region comprises a repeat unit having a zwitterion group and a repeat unit that is non-zwitterionic.

14. A method as set forth in claim 13 wherein said positively charged electrolyte or negatively charged electrolyte exposed at said surface region contains between 20 mole % and about 70 mole % of the repeating units that have a zwitterion group.

15. A method as set forth in claim 1 wherein a positively charged polyelectrolyte or a negatively charged polyelectrolyte exposed at said surface region comprises a repeat unit having at least two fluorine atoms.

16. A method as set forth in claim 1 wherein the article has the structure obtained by a process wherein depositing the film comprises alternately layering the net positively charged composition and the net negatively charged composition and wherein layers 0 through n of the film comprise a polyelectrolyte comprising non-fluorinated polymer repeat units and layers n+1 through n+2 of the film comprise a polyelectrolyte comprising the polymer repeat unit having at least two fluorine atoms.

17. A method as set forth in claim 1 wherein the article has the structure obtained by a process wherein depositing the film comprises alternately layering the net positively charged composition and the net negatively charged composition and wherein layers 0 through n of the film comprise a polyelectrolyte comprising non-zwitterion polymer repeat units and layers n+1 through n+2 of the film comprise a polyelectrolyte comprising polymer repeat unit having a zwitterion group.