3-dimensional parylene scaffold cage

• US 9,642,940 B2
• Filed: 01/22/2016
• Issued: 05/09/2017
• Est. Priority Date: 12/05/2011
• Status: Active Grant

• Current Assignee: California Institute of Technology, University of Southern California
• Original Assignee: California Institute of Technology, University of Southern California
• Inventors: Tai, Yu-Chong, Lu, Bo, Humayun, Mark
• Primary Examiner(s): McPherson, John A
• Application Number:
  US15/004,796
• Publication Number:
  US 20160310637A1
• Time in Patent Office: 473 Days
• Field of Search: 430320, 430323, 430324, 430329, 427 224, 4274071, 4272556
• CPC Class Codes: A61F 2/02 Prostheses implantable into the body closure means for urethra or rectum or for artificial body openings therefor A61F2/0004
• CPC Class Codes: A61F 2/04 Hollow or tubular parts of organs, e.g. bladders, tracheae, bronchi or bile ducts A61F2/18, A61F2/20 take precedence; devices, other than stent-grafts, providing patency to, or preventing collapsing of, tubular structures of the body other than stent-grafts, e.g. stents A61F2/82; instruments specially adapted for placement or removal of stents or stent-grafts A61F2/95
• CPC Class Codes: A61F 2240/001 Designing or manufacturing processes
• CPC Class Codes: A61L 2420/02 Methods for coating medical devices
• CPC Class Codes: A61L 2430/16 for reconstruction of eye parts, e.g. intraocular lens, cornea
• CPC Class Codes: A61L 27/025 Other specific inorganic materials not covered by A61L27/04 - A61L27/12
• CPC Class Codes: A61L 27/18 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
• CPC Class Codes: A61L 27/34 Macromolecular materials
• CPC Class Codes: A61L 27/3804 characterised by specific cells or progenitors thereof, e.g. fibroblasts, connective tissue cells, kidney cells
• CPC Class Codes: A61L 27/3839 characterised by the site of application in the body materials for artificial blood vessels A61L27/507; materials for use in artificial skin A61L27/60
• CPC Class Codes: A61L 27/50 Materials characterised by their function or physical properties , e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
• CPC Class Codes: C08L 65/04 Polyxylenes
• CPC Class Codes: C12N 2533/30 Synthetic polymers
• CPC Class Codes: C12N 5/0068 General culture methods using substrates for specific animal cell type C12N5/06
• CPC Class Codes: G03F 7/2002 with visible light or UV light, through an original having an opaque pattern on a transparent support, e.g. film printing, projection printing; by reflection of visible or UV light from an original such as a printed image

Abstract

Thin parylene C membranes having smooth front sides and ultrathin regions (e.g., 0.01 μm to 5 μm thick) interspersed with thicker regions are disclosed. The back sides of the membranes can be rough compared with the smooth front sides. The membranes can be used in vitro to grow monolayers of cells in a laboratory or in vivo as surgically implantable growth layers, such as to replace the Bruch'"'"'s membrane in the eye. The application further provides an implantable cage-like apparatus for culturing cells comprising the parylene membrane.

Claims

1. A method of manufacturing an implantable membrane, the method comprising:

depositing a film material on a first substrate surface to form a supporting film;

creating a plurality of perforations on the supporting film;

removing the supporting film from the first substrate surface;

attaching the supporting film to a second substrate surface;

depositing a parylene layer over the supporting film wherein the parylene layer is sufficient to cover a bottom of each perforation on the supporting film to form a membrane with a smooth first side;

orienting the membrane such that the smooth first side is positioned toward a cell culture; and

diffusing molecules through the membrane.

2. The method of manufacturing of claim 1, wherein the first substrate surface is smooth.

3. The method of manufacturing of claim 1, wherein etching is used to create the plurality of perforations.

4. The method of manufacturing of claim 1, wherein lithography is used to create the plurality of perforations.

5. The method of manufacturing of claim 1, wherein the plurality of perforations extend from a first side of the first supporting film to an opposing, second side of the supporting film.

6. The method of manufacturing of claim 1, wherein the second substrate surface is smooth.

7. The method of manufacturing of claim 1, wherein the parylene layer has a thickness between 0.01 μ

m to 5 μ

m.

8. The method of manufacturing of claim 1, wherein the orientation of the membrane is configured to reduce adherence of cells on the smooth side of the membrane.

9. The method of manufacturing of claim 1, further comprising the mechanical strength of the membrane by attaching a cage-like structure or mesh.

10. A method of manufacturing a structure for providing mechanical strength to an implantable membrane, the method comprising

depositing a first layer of parylene-C on silicone;

depositing a first material on the first layer of parylene-C;

applying a second coating over the first material;

lithographing and wet-etching the first material and the second coating to form a mask for parylene-C etching;

etching the first layer of parylene-C to form a mesh frame;

depositing a second layer of parylene-C on the mesh frame;

lithographing the mesh frame and depositing a layer of photo-resist on the mesh frame;

etching away undesirable regions in the mesh frame; and

removing the mesh frame from the silicone.

11. The method of manufacturing of claim 10, wherein the first layer of parylene C has a thickness of about 1 μ

m to 10 μ

m.

12. The method of manufacturing of claim 10, wherein the first layer of parylene-C has a thickness of about 6 μ

m.

13. The method of manufacturing of claim 10, wherein the deposition of the first layer of parylene-C is performed with a vaporizer at a temperature 180°

C.

14. The method of manufacturing of claim 10, wherein the deposition of the first layer of parylene-C is performed with a furnace at a temperature of 690°

C.

15. The method of manufacturing of claim 10, wherein the deposition of the first layer of parylene-C is performed at a chamber pressure of 35 mTorr.

16. The method of manufacturing of claim 10, wherein the silicone is treated with hexamethyldisilazane.

17. The method of manufacturing of claim 10, wherein the first material is aluminum.

18. The method of manufacturing of claim 10, wherein the second coating is a photoresist spin-coating.

19. The method of manufacturing of claim 10, wherein the etching of the first layer of parylene-C is performed using reactive ion etching.

20. The method of manufacturing of claim 19, further comprising the step of applying hydrofluoric acid to clean residue from the inside of the plurality of circular through holes, wherein the mesh frame comprises a plurality of circular through holes and the second layer of parylene-C has a thickness between 0.15 μ

m and 0.80 μ

m.