Biocompatible coating for solid surfaces

• US 4,979,959 A
• Filed: 05/05/1989
• Issued: 12/25/1990
• Est. Priority Date: 10/17/1986
• Status: Expired due to Term

• Current Assignee: Surmodics Incorporated
• Original Assignee: Bio-Tree Systems, Inc.
• Inventors: Guire, Patrick E.
• Primary Examiner(s): Green, Randall L.
• Assistant Examiner(s): PREBILIC, PAUL B
• Application Number:
  US07/349,884
• Time in Patent Office: 599 Days
• Field of Search: 623/1, 623/11, 623/5, 623/6, 623/66, 128/DIG. 8, 435/176, 435/180, 351/160 R, 351/160 H, 427/2
• US Class Current: 435/176
• CPC Class Codes: A61F 2/0077 Special surfaces of prostheses, e.g. for improving ingrowth A61F2/30767 takes precedence
• CPC Class Codes: A61L 2300/232 Monosaccharides, disaccharides, polysaccharides, lipopolysaccharides
• CPC Class Codes: A61L 2300/236 Glycosaminoglycans, e.g. heparin, hyaluronic acid, chondroitin
• CPC Class Codes: A61L 2300/252 Polypeptides, proteins, e.g. glycoproteins, lipoproteins, cytokines
• CPC Class Codes: A61L 2300/254 Enzymes, proenzymes
• CPC Class Codes: A61L 2300/406 Antibiotics
• CPC Class Codes: A61L 2300/414 Growth factors
• CPC Class Codes: A61L 2300/42 Anti-thrombotic agents, anticoagulants, anti-platelet agents
• CPC Class Codes: A61L 2300/606 Coatings
• CPC Class Codes: A61L 27/34 Macromolecular materials
• CPC Class Codes: A61L 27/54 Biologically active materials, e.g. therapeutic substances A61L27/227 takes precedence
• CPC Class Codes: A61L 33/0011 Anticoagulant, e.g. heparin, platelet aggregation inhibitor, fibrinolytic agent, other than enzymes, attached to the substrate

Abstract

The biocompatibility of biomaterials having solid surfaces is improved through coating the same with biocompatible agents where the biocompatible agents are covalently bonded to the solid surface via a chemical linking moiety. The method for modifying the solid surface to improve biocompatibility employs molecules of a biocompatible agent and a chemical linking moiety possessing a photochemically reactive group capable upon activation of covalently bonding to the solid surface and possessing a different reactive group as capable upon activation of covalently bonding to separate molecules of the biocompatible agent. One of the groups is unresponsive to activation by a stimulus to which the other group is responsive. The method comprises applying stimulus to sequentially activate the groups and covalently bind the different reactive group of the linking moiety to the molecules of the biocompatible agent and to photochemically covalently bind the linking moiety to the solid surface with a sufficient population density to enable the molecules of the biocompatible agent to effectively shield the solid surface and to provide a biocompatible surface.

Claims

1. A biocompatible device comprising a solid surface carrying molecules of a cell attachment factor, and a chemical linking moiety residue covalently binding individual molecules of the cell attachment factor to the solid surface, the chemical linking moiety residue including a residue of a photochemically reactive group covalently bonded to the solid surface, and a residue of a different reactive group covalently bonded to molecules of the cell attachment factor, one of the groups being unresponsive to a stimulus to which the other group responds, the photochemically reactive group residue being bonded to the solid surface so that the individual molecules of the cell attachment factor are positioned sufficiently proximate to one another as to cause said molecules to effectively shield the solid surface and to provide a biocompatible effective surface.

2. The device of claim 1 wherein the cell attachment factor is laminin or fibronectin.

3. A biocompatible device comprising a solid surface carrying molecules of a growth factor, and a chemical linking moiety residue covalently binding individual molecules of the growth factor to the solid surface, the chemical linking moiety residue including a residue of a photochemically reactive group covalently bonded to the solid surface, and a residue of a different reactive group covalently bonded to molecules of the growth factor, one of the groups being unresponsive to a stimulus to which the other group responds, the photochemically reactive group residue being bonded to the solid surface so that the individual molecules of the growth factor are positioned sufficiently proximate to one another as to cause said molecules to effectively shield the solid surface and to provide a biocompatible effective surface.

4. The device of claim 3 wherein the growth factor is endothelial growth factor, epithilial growth factor, osteoblast growth factor, fibroblast growth factor, platelet derived growth factor, neural growth factor, or angiogenin growth factor.

5. A biocompatible device comprising a solid surface carrying molecules of collagen, and a chemical linking moiety residue covalently binding individual collagen molecules to the solid surface, the chemical linking moiety residue including a residue of a photochemically reactive group covalently bonded to the solid surface, and a residue of a different reactive group covalently bonded to molecules of collagen, one of the groups being unresponsive to a stimulus to which the other group responds, the photochemically reactive group residue being bonded to the solid surface so that the individual collagen molecules are positioned sufficiently proximate to one another as to cause said molecules to effectively shield the solid surface and to provide a biocompatible effective surface.

6. A biocompatible device comprising a solid surface carrying molecules of albumin, and a chemical linking moiety residue covalently binding individual albumin molecules to the solid surface, the chemical linking moiety residue including a residue of a photochemically reactive group covalently bonded to the solid surface, and a residue of a different reactive group covalently bonded to molecules of albumin, one of the groups being unresponsive to a stimulus to which the other group responds, the photochemically reactive group residue being bonded to the solid surface so that the individual albumin molecules are positioned sufficiently proximate to one another as to cause said molecules to effectively shield the solid surface and to provide a biocompatible effective surface.

7. A biocompatible device comprising a solid surface carrying molecules of an antimicrobial agent, and a chemical linking moiety residue covalently binding individual molecules of the antimicrobial agent to the solid surface, the chemical linking moiety residue including a residue of a photochemically reactive group covalently bonded to the solid surface, and a residue of a different reactive group covalently bonded to molecules of the antimicrobial agent, one of the groups being unresponsive to a stimulus to which the other group responds, the photochemically reactive group residue being bonded to the solid surface so that the individual molecules of the antimicrobial agent are positioned sufficiently proximate to one another as to cause said molecules to effectively shield the solid surface and to provide a biocompatible effective surface.

8. The device of claim 7 wherein the antimicrobial agent is lysosyme.

9. The device of claim 7 wherein the antimicrobial agent is penicillin.

10. A biocompatible device comprising a solid surface carrying molecules of heparin, and a chemical linking moiety residue covalently binding individual heparin molecules to the solid surface, the chemical linking moiety residue including a residue of a photochemically reactive group covalently bonded to the solid surface, and a residue of a different reactive group covalently bonded to molecules of heparin, one of the groups being unresponsive to a stimulus to which the other group responds, the photochemically reactive group residue being bonded to the solid surface so that the individual heparin molecules are positioned sufficiently proximate to one another as to cause said molecules to effectively shield the solid surface and to provide a biocompatible effective surface.

11. A biocompatible device having a solid surface carrying molecules of albumin joined to one another to form a biocompatible film, said film carrying a chemical linking moiety binding the film to the solid surface, the chemical linking moiety including a residue of a photochemically reactive group covalently bonded to the solid surface and a residue of a different active group bonded to the film of albumin, one of the reactive groups being unresponsive to a stimulus to which the other reactive group responds.

12. A biocompatible device having a solid surface carrying molecules of a synthetic hydrophilic polymer capable of existing in contact with biological fluid to tissue of a living organism with a net beneficial effect on the organism, and a chemical linking moiety residue covalently bonding individual molecules of the synthetic hydrophilic polymer to the solid surface, the chemical linking moiety residue including a residue of a photochemically reactive group covalently bonded to the solid surface, and a residue of a different reactive group covalently bonded to molecules of the hydrophilic polymer, one of the groups being unresponsive to a stimulus to which the other group responds, the photochemically reactive group residue being bonded to the solid surface so that individual molecules of the synthetic hydrophilic polymer are positioned sufficiently proximate to one another as to cause said molecules to effectively shield the solid surface and to provide a biocompatible effective surface.

13. A biocompatible ophthalmic lens having a solid surface, molecules of a hydrophilic polymer biocompatible agent selected from the group consisting of polyethylene glycol, hyaluronic acid, methyl cellulose, collagen and chitsosan, and a chemical linking moiety residue linking individual molecules of the biocompatible agent to the solid surface, the chemical linking moiety residue including a residue of a photochemically reactive group covalently bonded to the solid surface, and a residue of a different reactive group covalently bonded to molecules of the biocompatible agent, one of the groups being unresponsive to a stimulus to which the other reactive group responds, the photochemically reactive group residue being bonded to the solid surface so that the individual molecules of the biocompatible agent are positioned sufficiently proximate to one another as to cause said molecules to effectively shield the solid surface and to provide a biocompatible effective surface.

14. A biocompatible device comprising a solid surface carrying molecules of polyethylene glycol capable of existing in contact with biological fluid or tissue of a living organism with a net beneficial effect on the organism, and a chemical linking moiety residue covalently binding individual molecules of the polyethylene glycol to the solid surface, the chemical linking moiety residue including a residue of a photochemically reactive group covalently bonded to the solid surface, and a residue of a different reactive group covalently bonded to molecules of the polyethylene glycol, one of the groups being unresponsive to a stimulus to which the other group responds, the photochemically reactive group residue being bonded to the solid surface so that the individual molecules of the polyethylene glycol are positioned sufficiently proximate to one another as to cause said molecules to effectively shield the solid surface and to provide a biocompatible effective surface.

15. A biocompatible device comprising a solid surface carrying molecules of a hyaluronic acid capable of existing in contact with biological fluid or tissue of a living organism with a net beneficial effect on the organism, and a chemical linking moiety residue covalently binding individual molecules of the hyaluronic acid to the solid surface, the chemical linking moiety residue including a residue of a photochemically reactive group covalently bonded to the solid surface, and a residue of a different reactive group covalently bonded to molecules of the hyaluronic acid, one of the groups being unresponsive to a stimulus to which the other group responds, the photochemically reactive group residue being bonded to the solid surface so that the individual molecules of the hyaluronic acid are positioned sufficiently proximate to one another as to cause said molecules to effectively shield the solid surface and to provide a biocompatible effective surface.

16. A biocompatible device comprising a solid surface carrying molecules of chitosan capable of existing in contact with biological fluid or tissue of a living organism with a net beneficial effect on the organism, and a chemical linking moiety residue covalently binding individual molecules of the chitosan to the solid surface, the chemical linking moiety residue including a residue of a photochemically reactive group covalently bonded to the solid surface, and a residue of a different reactive group covalently bonded to molecules of the chitosan, one of the groups being unresponsive to a stimulus to which the other group responds, the photochemically reactive group residue being bonded to the solid surface so that the individual molecules of the chitosan are positioned sufficiently proximate to one another as to cause said molecules to effectively shield the solid surface and to provide a biocompatible effective surface.

17. A biocompatible device comprising a solid surface carrying molecules of methyl cellulose capable of existing in contact with biological fluid or tissue of a living organism with a net beneficial effect on the organism, and a chemical linking moiety residue covalently binding individual molecules of the methyl cellulose to the solid surface, the chemical linking moiety residue including a residue of a photochemically reactive group covalently bonded to the solid surface, and a residue of a different reactive group covalently bonded to molecules of the methyl cellulose, one of the groups being unresponsive to a stimulus to which the other group responds, the photochemically reactive group residue being bonded to the solid surface so that the individual molecules of the methyl cellulose are positioned sufficiently proximate to one another as to cause said molecules to effectively shield the solid surface and to provide a biocompatible effective surface.

18. A biocompatible device comprising a solid surface carrying molecules of an antithrombogenic agent capable of existing in contact with biological fluid or tissue of a living organism with a net beneficial effect on the organism, and a chemical linking moiety residue covalently binding individual molecules of the antithrombogenic agent to the solid surface, the chemical linking moiety residue including a residue of a photochemically reactive group covalently bonded to the solid surface, and a residue of a different reactive group covalently bonded to molecules of the antithrombogenic agent, one of the groups being unresponsive to a stimulus to which the other group responds, the photochemically reactive group residue being bonded to the solid surface so that the individual molecules of the antithrombogenic agent are positioned sufficiently proximate to one another as to cause said molecules to effectively shield the solids surface and to provide a biocompatible effective surface.