Biocompatible substrate for facilitating interconnections between stem cells and target tissues and methods for implanting same

• US 10,188,769 B2
• Filed: 06/25/2014
• Issued: 01/29/2019
• Est. Priority Date: 07/12/2010
• Status: Active Grant

• Current Assignee: California Institute of Technology, Regents of the University of California (University of California), University of Southern California
• Original Assignee: California Institute of Technology, Regents of the University of California (University of California), University of Southern California
• Inventors: Humayun, Mark S., Ahuja, Ashish, Tai, Yu-Chong, Hinton, David R., Grubbs, Robert H., Clegg, Dennis O., Johnson, Lincoln Vallance, Hikita, Sherry T.
• Primary Examiner(s): Claytor, Renee
• Assistant Examiner(s): Clarke, Trent R
• Application Number:
  US14/314,994
• Publication Number:
  US 20150147377A1
• Time in Patent Office: 1,679 Days
• CPC Class Codes: A61K 35/30 Nerves; Brain; Eyes; Corneal cells; Cerebrospinal fluid; Neuronal stem cells; Neuronal precursor cells; Glial cells; Oligodendrocytes; Schwann cells; Astroglia; Astrocytes; Choroid plexus; Spinal cord tissue
• CPC Class Codes: A61K 35/545 Embryonic stem cells; Pluripotent stem cells; Induced pluripotent stem cells; Uncharacterised stem cells
• CPC Class Codes: A61K 47/34 Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers A61K47/10 takes precedence
• CPC Class Codes: A61K 9/0051 Ocular inserts, ocular implants
• CPC Class Codes: A61L 2430/00 Materials or treatment for tissue regeneration
• CPC Class Codes: A61L 2430/16 for reconstruction of eye parts, e.g. intraocular lens, cornea
• 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 27/3808 Endothelial cells
• CPC Class Codes: A61L 27/3813 Epithelial cells, e.g. keratinocytes, urothelial cells
• CPC Class Codes: A61L 27/3834 Cells able to produce different cell types, e.g. hematopoietic stem cells, mesenchymal stem cells, marrow stromal cells, embryonic stem cells
• CPC Class Codes: A61L 27/56 Porous materials, e.g. foams or sponges
• CPC Class Codes: A61P 27/00 Drugs for disorders of the senses
• CPC Class Codes: C08L 65/04 Polyxylenes
• CPC Class Codes: C08L 67/04 Polyesters derived from hydroxycarboxylic acids, e.g. lactones C08L67/06 takes precedence
• CPC Class Codes: C08L 83/08 containing silicon bound to organic groups containing atoms other than carbon, hydrogen and oxygen
• CPC Class Codes: C08L 89/00 Compositions of proteins; Compositions of derivatives thereof foodstuff preparations A23J3/00
• CPC Class Codes: C12N 2533/30 Synthetic polymers thermoreactive polymers, e.g. PNIPAm, C12N2539/10
• CPC Class Codes: C12N 2535/00 Supports or coatings for cell culture characterised by topography
• CPC Class Codes: C12N 5/0621 Eye cells, e.g. cornea, iris pigmented cells photoreceptors C12N5/062
• CPC Class Codes: Y10T 428/24479 : including variation in thickness

Abstract

Disclosed herein are substrates for cell delivery to target tissues requiring treatment for various diseases that induce cell death, damage or loss of function. The substrates are configured to provide seeded cells, including stem cells, with a structural support that allows interconnection with and transmission of biological signals between the cells and the target tissue.

Claims

1. A method for treating retinal degenerative disease comprising:

providing a substrate seeded with cells suitable for implantation into an ocular tissue of a patient, wherein the substrate comprises;

a parylene layer with an apical surface for growth of a population of cells, wherein the parylene layer has a thickness between 0.1 microns and 6 microns;

a plurality of supporting protrusions each extending 1 micron or greater from a basal surface of the parylene layer to a terminating free end of the supporting protrusion;

implanting the substrate into the ocular tissue of the patient; and

positioning the substrate so that the substrate is parallel with an outer nuclear layer of photoreceptors in an eye of the patient.

2. The method of claim 1, wherein the substrate is implanted through an ab-interno surgical approach.

3. The method of claim 1, wherein the substrate is implanted through an ab-externo surgical approach.

4. The method of claim 1, wherein the substrate is implanted into a subretinal space of the eye of the patient.

5. The method of claim 1, wherein the substrate is positioned with the apical surface adjacent to an epiretinal side of a retina of the eye of the patient.

6. The method of claim 1, wherein the substrate is implanted during an open surgical process.

7. The method of claim 1, wherein the substrate is implanted endoscopically.

8. The method of claim 1, wherein the substrate is positioned substantially parallel to a posterior eye wall of the patient.

9. The method of claim 1, wherein the substrate is loaded onto a surgical introducer prior to implantation.

10. The method of claim 1, wherein the supporting protrusions are comprised of parylene.

11. The method of claim 1, wherein the supporting protrusions are distributed in a periodic pattern on the basal surface, columnar in shape, and distributed longitudinally along a long axis of the basal surface, wherein the basal surface is configured to prevent growth of blood vessels through the basal surface to the apical surface.

12. The method of claim 1, wherein the substrate further comprises a handle portion protruding laterally from the substrate.

13. The method of claim 12, wherein the handle portion protrudes from an oval shaped portion of the substrate.

14. The method of claim 12, wherein a length of the handle portion is between 1 mm and 20 mm.

15. The method of claim 14, wherein a length of the handle portion is between 1 mm and 2 mm.

16. The method of claim 12, wherein a width of the handle portion is between 0.2 mm and 6 mm.

17. The method of claim 12, wherein the handle portion was formed by cutting.

18. The method of claim 1, wherein the substrate further comprises a raised lip surrounding the apical surface.

19. The method of claim 18, wherein the raised lip has a height ranging from 10 microns to 1000 microns and a width ranging from 10 microns to 1000 microns.

20. The method of claim 1, wherein each supporting protrusion extends from the parylene layer to the free end such that a height of the substrate from the apical surface to the free end of each supporting protrusion is 3 microns or greater.