Ultrathin parylene-C semipermeable membranes for biomedical applications

Patent metadata

Field	Value
Publication number	US-11318225-B2
Application number	US-201615184934-A
Country	US
Kind code	B2
Filing date	Jun 16, 2016
Priority date	Dec 5, 2011
Publication date	May 3, 2022
Grant date	May 3, 2022

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 thin regions of parylene are semipermeable to allow for proteins in serum to pass through, and the thick regions give mechanical support for handling by a surgeon. The smooth front side allows for monolayer cell growth, and the rough back side helps prevents cells from attaching there.

First claim

What is claimed is:

1. A synthetic semipermeable membrane for cellular therapy, the membrane comprising:
a supporting film having through perforations extending from a first side to an opposing second side; and
a parylene layer produced by chemical vapor deposition (CVD) of parylene over the perforated supporting film while the perforated supporting film is attached to a flat surface, the CVD sufficient to cover walls and a flat surface bottom of each perforation of the supporting film, and removing the supporting film with its parylene layer from the flat surface to form the membrane,
wherein the membrane has a smooth front side with exposed areas of the parylene layer and is configured to facilitate the growth of a monolayer of cells and a rough back side configured to inhibit cell growth.

2. The membrane of claim 1 , wherein the membrane is seeded with a plurality of cells.

3. The membrane of claim 2 , wherein the plurality of cells form a monolayer on the membrane.

4. The membrane of claim 3 , wherein the cells include heart muscle cells, cartilage trabeculae cells, or retinal pigment epithelium (RPE) cells.

5. The membrane of claim 1 , wherein the membrane is composed of parylene C.

6. The membrane of claim 1 , wherein the membrane has a plurality of thick regions that are two times as thick as a plurality of thin regions in the membrane.

7. The membrane of claim 1 , wherein the perforations occur in a random array with an average feature size of about 1 micron to 10 microns.

8. A synthetic semipermeable membrane for cellular therapy, the membrane comprising:
a smooth front side having exposed parylene layer areas and configured to facilitate the growth of a monolayer of cells, wherein the front side has a thickness of 0.15 microns to 0.5 microns and allows passage of molecules having a molecular weight of up to 1,302 kDa;
a rough back side configured to inhibit cell growth and comprising a plurality of thin regions interspersed in a contiguous thick region, wherein the contiguous thick region provides mechanical support and rigidity to the membrane,
the front and back sides having been formed from chemical vapor deposition (CVD) of parylene over a supporting film having perforations while the perforated supporting film is attached to a flat surface, the CVD of parylene at bottoms of the perforations forming the exposed parylene layer areas of the front side,
wherein the plurality of thin regions are a plurality of cylindrical recesses in the membrane.

9. The membrane of claim 8 , wherein the front side is configured to facilitate growth of a monolayer of retinal pigment epithelium (RPE) cells.

10. The membrane of claim 8 , wherein the parylene is parylene C.

11. The membrane of claim 8 , wherein a thickness of the contiguous thick region is constant.

12. The membrane of claim 11 , wherein the thickness of the contiguous thick region is about 1 micron to about 30 microns.

13. The membrane of claim 12 , wherein the thickness of the front side is about 0.15 microns to about 0.8 microns.

14. The membrane of claim 8 , wherein the plurality of thin regions are interspersed in a grid-like pattern.

15. The membrane of claim 8 , wherein the cylindrical recesses each have a diameter of at least about 10 microns.

16. A synthetic semipermeable membrane for cellular therapy, the membrane comprising:
a smooth front side having exposed parylene layer areas and configured to facilitate the growth of a monolayer of cells, wherein the front side has a thickness of 0.15 microns to 0.5 microns and allows passage of molecules having a molecular weight of up to 1,302 kDa;
a rough back side configured to inhibit cell growth and comprising a plurality of thin regions interspersed in a contiguous thick region, wherein the contiguous thick region provides mechanical support and rigidity to the membrane,
the front and back sides having been formed from chemical vapor deposition (CVD) of parylene over a supporting film having perforations while the perforated supporting film is attached to a flat surface, the CVD of parylene at bottoms of the perforations forming the exposed parylene layer areas of the front side,
wherein the plurality of thin regions are interspersed in a grid-like pattern.

17. A synthetic semipermeable membrane for cellular therapy, the membrane comprising:
a smooth front side having exposed parylene layer areas and configured to facilitate the growth of a monolayer of cells, wherein the front side has a thickness of 0.15 microns to 0.5 microns and allows passage of molecules having a molecular weight of up to 1,302 kDa;
a rough back side configured to inhibit cell growth and comprising a plurality of thin regions interspersed in a contiguous thick region, wherein the contiguous thick region provides mechanical support and rigidity to the membrane,
the front and back sides having been formed from chemical vapor deposition (CVD) of parylene over a supporting film having perforations while the perforated supporting film is attached to a flat surface, the CVD of parylene at bottoms of the perforations forming the exposed parylene layer areas of the front side,
wherein the front side of the membrane is seeded with a plurality of cells.

18. The membrane of claim 17 , wherein the plurality of cells form a monolayer on the front side of the membrane.

19. The membrane of claim 18 , wherein the cells are retinal pigmented epithelium (RPE) cells.

20. The membrane of claim 17 , wherein the plurality of thin regions are interspersed in a grid-like pattern.

Assignees

• California Inst Of Techn
• Univ Southern California

Inventors

• Tai Yu-Chong
• Lu Bo
• Humayun Mark

Classifications

• C12N5/0068 Primary

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

• A61L2430/16

  for reconstruction of eye parts, e.g. intraocular lens, cornea · CPC title

• B01D2325/06

  Surface irregularities · CPC title

• A61L27/16 Primary

  obtained by reactions only involving carbon-to-carbon unsaturated bonds · CPC title

• C12N2539/00

  Supports and/or coatings for cell culture characterised by properties · CPC title