Artificial corneal implant

• US 7,857,849 B2
• Filed: 10/04/2005
• Issued: 12/28/2010
• Est. Priority Date: 10/05/2004
• Status: Expired due to Fees

• Current Assignee: Santa Clara University
• Original Assignee: Santa Clara University, Board of Trustees of the Leland Stanford Junior University (Stanford Management Co.)
• Inventors: Koh, Won-Gun, Myung, David, Hu, Yin, Carrasco, Michael R., Smith, Alan J., Ta, Christopher, Frank, Curtis W., Noolandi, Jaan
• Primary Examiner(s): Prebilic; Paul
• Application Number:
  US11/243,952
• Publication Number:
  US 20060083773A1
• Time in Patent Office: 1,911 Days
• Field of Search: 623/5.16, 623/6.56, 424/427, 435/396, 435/180, 351/160.H
• US Class Current: 623/5.16
• CPC Class Codes: A61F 2/142 Cornea, e.g. artificial corneae, keratoprostheses or corneal implants for repair of defective corneal tissue
• CPC Class Codes: A61F 2/145 Corneal inlays, onlays, or lenses for refractive correction
• CPC Class Codes: A61K 35/44 Vessels; Vascular smooth muscle cells; Endothelial cells; Endothelial progenitor cells
• CPC Class Codes: A61L 2300/25 Peptides having up to 20 amino acids in a defined sequence
• CPC Class Codes: A61L 2300/252 Polypeptides, proteins, e.g. glycoproteins, lipoproteins, cytokines
• CPC Class Codes: A61L 2300/602 Type of release, e.g. controlled, sustained, slow
• 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 27/3804 characterised by specific cells or progenitors thereof, e.g. fibroblasts, connective tissue cells, kidney cells
• CPC Class Codes: A61L 27/3813 Epithelial cells, e.g. keratinocytes, urothelial 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 27/52 Hydrogels or hydrocolloids
• CPC Class Codes: A61L 27/54 Biologically active materials, e.g. therapeutic substances A61L27/227 takes precedence
• CPC Class Codes: C08L 33/08 Homopolymers or copolymers of acrylic acid esters
• CPC Class Codes: C08L 71/02 Polyalkylene oxides
• CPC Class Codes: C12N 2533/30 Synthetic polymers thermoreactive polymers, e.g. PNIPAm, C12N2539/10
• CPC Class Codes: C12N 5/0621 Eye cells, e.g. cornea, iris pigmented cells photoreceptors C12N5/062

Abstract

A material that can be applied as implants designed to artificially replace or augment the cornea, such as an artificial cornea, corneal onlay, or corneal inlay (intrastromal lens) is provided. The artificial corneal implant has a double network hydrogel with a first network interpenetrated with a second network. The first network and the second network are based on biocompatible polymers. At least one of the network polymers is based on a hydrophilic polymer. The artificial cornea or implant has epithelialization promoting biomolecules that are covalently linked to the surface of the double network hydrogel using an azide-active-ester chemical linker. Corneal epithelial cells or cornea-derived cells are adhered to the biomolecules. The double network has a physiologic diffusion coefficient to allow passage of nutrients to the adhered cells.

Claims

1. A corneal implant, comprising:

(a) an interpenetrating double network hydrogel of a first network entangled with a second network, wherein said first network is an entangled network of poly(ethylene)glycol-diacrylate macromonomers covalently bonded to themselves or other of said macromonomers in said first network, wherein each of said poly(ethylene)glycol-diacrylate macromonomers has a molecular weight of 3400 Da or higher, and wherein said second network is based on crosslinked poly(acrylic acid);

(b) epithelization promoting biomolecules covalently linked to the surface of said double network hydrogel; and

(c) corneal epithelial cells or cornea-derived cells adhered to said biomolecules.

2. The corneal implant as set forth in claim 1, wherein said first network macromonomers have a molar ratio to said second network monomers lower than 1/100.

3. The corneal implant as set forth in claim 1, wherein said first network macromonomers have a molar ratio to said second network monomers between 1/100 and 1/2000.

4. The corneal implant as set forth in claim 1, wherein the weight ratio between said first network and said second network is in the range of 1/9 to 3/7.

5. The corneal implant as set forth in claim 1, wherein said each of said poly(ethylene)glycol-diacrylate macromonomers has a molecular weight in the range of 3400 Da to 14000 Da.

6. The corneal implant as set forth in claim 1, wherein said biomolecules are linked using an azide-active-ester chemical linker.

7. The corneal implant as set forth in claim 1, wherein said biomolecules are linked using a 5-azido-2-nitrobenzoic acid N-hydroxysuccinimide ester or a derivative thereof.

8. The corneal implant as set forth in claim 1, wherein said biomolecules are selected from the group consisting of collagen, fibronectin, laminin, amino-acids, carbohydrates, lipids, and nucleic acids.

9. The corneal implant as set forth in claim 1, wherein said double network hydrogel has a diffusion coefficient to allow passage of nutrients to said adhered epithelial cells.

10. The corneal implant as set forth in claim 1, wherein said double network hydrogel has a diffusion coefficient in the range of 10⁻

5 cm²/sec to 10<sup>−

7</sup> cm²/sec.

11. A material useful as a artificial cornea, corneal implant, corneal onlay, or corneal inlay, comprising:

an interpenetrating double network hydrogel of a first network entangled with a second network, wherein said first network is an entangled network of poly(ethylene)glycol-diacrylate macromonomers covalently bonded to themselves or other of said macromonomers in said first network, wherein each of said poly(ethylene)glycol-diacrylate macromonomers has a molecular weight of 3400 Da or higher, and wherein said second network is based on crosslinked poly(acrylic acid), wherein said first network macromonomers have a molar ratio to said second network monomers lower than 1/100.

12. The material as set forth in claim 11, wherein said first network macromonomers have a molar ratio to said second network monomers between 1/100 and 1/2000.

13. The material as set forth in claim 11, wherein the weight ratio between said first network and said second network is in the range of 1/9 to 3/7.

14. The material as set forth in claim 11, wherein said each of said poly(ethylene)glycol-diacrylate macromonomers has a molecular weight in the range of 3400 Da to 14000 Da.

15. The material as set forth in claim 11, further comprising epithelization promoting biomolecules covalently linked to the surface of said double network hydrogel.

16. The material as set forth in claim 15, wherein said biomolecules are linked using an azide-active-ester chemical linker.

17. The material as set forth in claim 15, wherein said biomolecules are linked using a 5-azido-2-nitrobenzoic acid N-hydroxysuccinimide ester or a derivative thereof.

18. The material as set forth in claim 15, wherein said biomolecules are selected from the group consisting of collagen, fibronectin, laminin, amino-acids, carbohydrates, lipids, and nucleic acids.

19. The material as set forth in claim 11, further comprising epithelization promoting biomolecules covalently linked to the surface of said double network hydrogel and corneal epithelial cells or cornea-derived cells adhered to said biomolecules.

20. The material as set forth in claim 19, wherein said double network hydrogel has a diffusion coefficient to allow passage of nutrients to said adhered epithelial cells.

21. The material as set forth in claim 19, wherein said double network hydrogel has a diffusion coefficient in the range of 10⁻

5 cm²/sec to 10<sup>−

7</sup> cm²/sec.