Immobilized bioactive hydrogel matrices as surface coatings

• US 8,609,122 B2
• Filed: 11/09/2007
• Issued: 12/17/2013
• Est. Priority Date: 02/21/2002
• Status: Expired due to Fees

• Current Assignee: Pioneer Surgical Technology Incorporated (Surgalign Holdings, Inc.)
• Original Assignee: Pioneer Surgical Technology Incorporated (Surgalign Holdings, Inc.)
• Inventors: Lamberti, Francis V., Klann, Richard Chris, Hill, Ronald Stewart
• Primary Examiner(s): Kwon, Brian-Yong
• Assistant Examiner(s): BECKHARDT, LYNDSEY MARIE
• Application Number:
  US11/937,851
• Publication Number:
  US 20080199508A1
• Time in Patent Office: 2,230 Days
• Field of Search: None
• US Class Current: 424/422
• CPC Class Codes: A61F 2/0063 Implantable repair or support meshes, e.g. hernia meshes
• CPC Class Codes: A61K 47/42 Proteins; Polypeptides; Degradation products thereof; Derivatives thereof, e.g. albumin, gelatin or zein oligopeptides having up to five amino acids A61K47/183; polyamino acids A61K47/34
• CPC Class Codes: A61L 2300/112 Phosphorus-containing compounds, e.g. phosphates, phosphonates
• CPC Class Codes: A61L 2300/412 Tissue-regenerating or healing or proliferative agents
• CPC Class Codes: A61L 2420/04 Coatings containing a composite material such as inorganic/organic, i.e. material comprising different phases
• CPC Class Codes: A61L 2420/06 Coatings containing a mixture of two or more compounds
• CPC Class Codes: A61L 2430/02 for reconstruction of bones; weight-bearing implants
• CPC Class Codes: A61L 27/025 Other specific inorganic materials not covered by A61L27/04 - A61L27/12
• CPC Class Codes: A61L 27/12 Phosphorus-containing materials, e.g. apatite
• CPC Class Codes: A61L 27/20 Polysaccharides
• CPC Class Codes: A61L 27/22 Polypeptides or derivatives thereof , e.g. degradation products
• CPC Class Codes: A61L 27/222 Gelatin
• CPC Class Codes: A61L 27/24 Collagen
• CPC Class Codes: A61L 27/26 Mixtures of macromolecular compounds
• CPC Class Codes: A61L 27/34 Macromolecular materials
• CPC Class Codes: A61L 27/3608 Bone, e.g. demineralised bone matrix [DBM], bone powder
• CPC Class Codes: A61L 27/446 with other specific inorganic fillers other than those covered by A61L27/443 or A61L27/46
• CPC Class Codes: A61L 27/46 with phosphorus-containing inorganic fillers
• 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: A61L 31/10 : Macromolecular materials
• CPC Class Codes: A61P 19/00 : Drugs for skeletal disorders
• CPC Class Codes: A61P 37/00 : Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 7/00 : Drugs for disorders of the blood or the extracellular fluid
• CPC Class Codes: B29C 39/003 : characterised by the choice of material
• CPC Class Codes: B29L 2031/7532 : Artificial members, protheses
• CPC Class Codes: C08L 5/02 : Dextran; Derivatives thereof
• CPC Class Codes: C08L 89/00 : Compositions of proteins; Compositions of derivatives thereof foodstuff preparations A23J3/00
• CPC Class Codes: Y10T 428/29 : Coated or structually defined flake, particle, cell, strand, strand portion, rod, filament, macroscopic fiber or mass thereof
• CPC Class Codes: Y10T 428/2947 : Synthetic resin or polymer in plural coatings, each of different type
• CPC Class Codes: Y10T 428/31551 : Of polyamidoester [polyurethane, polyisocyanate, polycarbamate, etc.]
• CPC Class Codes: Y10T 428/31786 : Of polyester [e.g., alkyd, etc.]

Abstract

The present invention is directed to a stabilized bioactive hydrogel matrix coating for substrates, such as medical devices. The invention provides a coated substrate comprising a substrate having a surface, and a bioactive hydrogel matrix layer overlying the surface of the medical device, the hydrogel matrix comprising a first high molecular weight component and a second high molecular weight component, the first and second high molecular weight components each being selected from the group consisting of polyglycans and polypeptides, wherein at least one of the first and second high molecular weight components is immobilized (e.g., by covalent cross-linking) to the surface of the substrate.

Claims

1. A coated structural implant for providing improved integration with natural tissue, the coated structural implant comprising:

a structural implant having a surface and being formed with a material suitable for repair of bone, ligament, or tendon; and

a bioactive hydrogel matrix layer overlying the surface of the structural implant and immobilized thereon, the hydrogel matrix layer being a solid or semi-solid material at physiological temperature and physiological pH and comprising a polyglycan, a polypeptide, and at least one enhancing agent selected from the group consisting of polar amino acids, divalent cation chelators, and combinations thereof, at least one of the polyglycan and the polypeptide being covalently cross-linked to the surface of the structural implant.

2. The coated structural implant of claim 1, wherein the material is a naturally occurring material.

3. The coated structural implant of claim 1, wherein the material is a synthetic material.

4. The coated structural implant of claim 1, wherein the material is selected from the group consisting of acrylates, polyglycolic-polylactic acid copolymers, polyhydroxybutyrates, polyesters, expanded polytetrafluoroethylene, bioactive glass, ceramics, coralline materials, demineralized bone, polycarbonates, polyurethane or polycarbonate copolymers, metals, and combinations thereof.

5. The coated structural implant of claim 4, wherein the material is a ceramic.

6. The coated structural implant of claim 5, wherein the material is hydroxyapatite.

7. The coated structural implant of claim 1, wherein the structural implant is selected from the group consisting of ligament replacements, bone replacements, tendon replacements, and joint replacements.

8. The coated structural implant of claim 1, wherein the polyglycan is a polysaccharide or a sulfated polysaccharide.

9. The coated structural implant of claim 8, wherein the polysaccharide is selected from the group consisting of dextran, heparan, heparin, hyaluronic acid, alginate, agarose, carrageenan, amylopectin, amylose, glycogen, starch, cellulose, and chitin.

10. The coated structural implant of claim 8, wherein the sulfated polysaccharide is selected from the group consisting of heparan sulfate, chondroitin sulfate, dextran sulfate, dermatan sulfate, and keratan sulfate.

11. The coated structural implant of claim 1, wherein the polypeptide is a tissue-derived polypeptide selected from the group consisting of collagens, gelatins, keratin, decorin, aggrecan, and glycoproteins.

12. The coated structural implant of claim 1, wherein the polyglycan is dextran or oxidized dextran and the polypeptide is gelatin.

13. The coated structural implant of claim 1, wherein the at least one enhancing agent comprises at least one polar amino acid selected from the group consisting of tyrosine, cysteine, serine, threonine, asparagine, glutamine, aspartic acid, glutamic acid, arginine, lysine, histidine, and mixtures thereof.

14. The coated structural implant of claim 1, wherein the at least one enhancing agent comprises a divalent cation chelator selected from the group consisting of ethylenediaminetetraacetic acid and salts thereof.

15. The coated structural implant of claim 1, wherein the polyglycan and polypeptide are covalently cross-linked to each other.

19. The coated structural implant of claim 1, wherein the material is selected from the group consisting of acrylates, polyglycolic-polylactic acid copolymers, polyhydroxybutyrates, polyesters, expanded polytetrafluoroethylene, bioactive glass, ceramics, coralline materials, demineralized bone, polycarbonates, polyurethane or polycarbonate copolymers, metals, and combinations thereof.

16. A coated structural implant for providing improved integration with natural tissue, the coated structural implant comprising:

a structural implant having a surface and being formed with a material suitable for repair of bone, ligament, or tendon; and

a bioactive hydrogel matrix layer overlying the surface of the structural implant and immobilized thereon, the hydrogel matrix layer being a solid or semi-solid material at physiological temperature and physiological pH and comprising a polyglycan and a polypeptide, wherein at least one of the polyglycan and polypeptide is covalently cross-linked to the surface of the structural implant,

wherein the polyglycan is dextran or oxidized dextran and the polypeptide is gelatin.

17. The coated structural implant of claim 16, wherein the material is a naturally occurring material.

18. The coated structural implant of claim 16, wherein the material is a synthetic material.

20. The coated structural implant of claim 16, wherein the material is a ceramic.

21. The coated structural implant of claim 20, wherein the material for bone repair is hydroxyapatite.

22. The coated structural implant of claim 16, wherein the structural implant is selected from the group consisting of ligament replacements, bone replacements, tendon replacements, and joint replacements.

23. The coated structural implant of claim 16, wherein the hydrogel matrix further comprises at least one enhancing agent selected from the group consisting of polar amino acids, divalent cation chelators, and combinations thereof.

24. The coated structural implant of claim 16, wherein the polyglycan and polypeptide are covalently cross-linked to each other.

25. A coated structural implant for providing improved integration with natural tissue, the coated structural implant comprising:

a structural implant having a surface and being selected from the group consisting of ligament replacements, bone replacements, tendon replacements, and joint replacements; and

a bioactive hydrogel matrix layer overlying the surface of the structural implant and immobilized thereon, the hydrogel matrix layer being a solid or semi-solid material at physiological temperature and physiological pH and comprising a polyglycan and a polypeptide;

wherein the structural implant is formed with a material selected from the group consisting of acrylates, polyglycolic-polylactic acid copolymers, polyhydroxybutyrates, polyesters, expanded polytetrafluoroethylene, bioactive glass, ceramics, coralline materials, demineralized bone, polycarbonates, polyurethane or polycarbonate copolymers, metals, and combinations thereof,

wherein the polyglycan is dextran or oxidized dextran and the polypeptide is gelatin.

26. The coated structural implant of claim 25, wherein the material is a ceramic material.

27. The coated structural implant of claim 26, wherein the ceramic material is hydroxyapatite.

28. The coated structural implant of claim 25, wherein at least one of the polyglycan and polypeptide is covalently cross-linked to the surface of the structural implant.

29. The coated structural implant of claim 25, wherein the hydrogel matrix further comprises at least one enhancing agent selected from the group consisting of polar amino acids, divalent cation chelators, and combinations thereof.