Method of improving the biocompatibility of solid surfaces

• US 4,973,493 A
• Filed: 10/15/1987
• Issued: 11/27/1990
• Est. Priority Date: 09/29/1982
• 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:
  US07/108,765
• Time in Patent Office: 1,139 Days
• Field of Search: 623/1, 623/6, 623/11, 623/66, 623/901, 427/2, 435/181, 436/532, 436/525, 436/905
• US Class Current: 427/2.24
• CPC Class Codes: A61F 2/0077 Special surfaces of prostheses, e.g. for improving ingrowth A61F2/30767 takes precedence
• CPC Class Codes: A61K 47/68 the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
• 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 2300/406 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 29/085 Macromolecular materials
• CPC Class Codes: A61L 29/16 Biologically active materials, e.g. therapeutic substances A61L29/048 takes precedence
• CPC Class Codes: A61L 33/0011 Anticoagulant, e.g. heparin, platelet aggregation inhibitor, fibrinolytic agent, other than enzymes, attached to the substrate
• CPC Class Codes: G01N 33/531 Production of immunochemical test materials
• CPC Class Codes: G01N 33/543 with an insoluble carrier for immobilising immunochemicals
• CPC Class Codes: Y10S 436/905 Photochemical activation of reactions
• CPC Class Codes: Y10S 623/901 Method of manufacturing prosthetic device

Abstract

A method for modifying the solid surface to improve its biocompatibility is disclosed. The method 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. 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 method of providing a device with an effective biocompatible surface of a growth factor the method employing a solid surface of the device, molecules of the growth factor 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, capable of binding to the molecules of the growth factor, one of the groups being unresponsive to a stimulus to which the other group responds, the method comprising:

activating the different reactive group of the chemical linking moiety in the presence of the molecules of the growth factor to cause the different reactive group to covalently bind the chemical linking moiety to the molecules; and

activating the photochemically reactive group of the chemical linking moiety in the presence of the solid surface of the device to cause the photochemically reactive group to covalently bind to the solid surface and to bind the growth factor molecules to the solid surface in a sufficient population density of the molecules to effectively shield the solid surface and to provide a biocompatible effective surface.

2. A method of providing a device with an effective biocompatible surface of collagen the method employing a solid surface of the device, molecules of collagen 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, capable of binding to the molecules of collagen, one of the groups being unresponsive to a stimulus to which the other group responds, the method comprising:

activating the different reactive group of the chemical linking moiety in the presence of the molecules of collagen to cause the different reactive group to covalently bind the chemical linking moiety to the molecules; and

activating the photochemically reactive group of the chemical linking moiety in the presence of the solid surface of the device to cause the photochemically reactive group to covalently bind to the solid surface and to bind the collagen molecules to the solid surface in a sufficient population density of the molecules to effectively shield the solid surface and to provide a biocompatible effective surface.

3. A method of providing a device with an effective biocompatible surface of albumin the method employing a solid surface of the device, molecules of albumin 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, capable of binding to the molecules of albumin, one of the groups being unresponsive to a stimulus to which the other group responds, the method comprising:

activating the different reactive group of the chemical linking moiety in the presence of the molecules of albumin to cause the different reactive group to covalently bind the chemical linking moiety to the molecules; and

activating the photochemically reactive group of the chemical linking moiety in the presence of the solid surface of the device to cause the photochemically reactive group to covalently bind to the solid surface and to bind the albumin molecules to the solid surface in a sufficient population density of the molecules to effectively shield the solid surface and to provide a biocompatible effective surface.

4. A method of providing a device with an effective biocompatible surface of an antimicrobial agent the method employing a solid surface of the device, molecules of the antimicrobial 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, capable of binding to the molecules of the antimicrobial agent, one of the groups being unresponsive to a stimulus to which the other group responds, the method comprising:

activating the different reactive group of the chemical linking moiety in the presence of the molecules of the antimicrobial agent to cause the different reactive group to covalently bind the chemical linking moiety to the molecules; and

activating the photochemically reactive group of the chemical linking moiety in the presence of the solid surface of the device to cause the photochemically reactive group to covalently bind to the solid surface and to bind the antimicrobial agent molecules to the solid surface in a sufficient population density of the molecules to effectively shield the solid surface and to provide a biocompatible effective surface.

5. The method of claim 4 wherein the antimicrobial agent is lysosyme.

6. The method of claim 4 wherein the antimicrobial agent is penicillin.

7. A method of providing a device with an effective biocompatible surface of heparin the method employing a solid surface of the device, molecules of heparin 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, capable of binding to the molecules of heparin, one of the groups being unresponsive to a stimulus to which the other group responds the method comprising:

activating the different reactive group of the chemical linking moiety in the presence of the molecules of heparin to cause the different reactive group to covalently bind the chemical linking moiety to the molecules; and

activating the photochemically reactive group of the chemical linking moiety in the presence of the solid surface of the device to cause the photochemically reactive group to covalently bind to the solid surface and to bind the heparin molecules to the solid surface in a sufficient population density of the molecules to effectively shield the solid surface and to provide a biocompatible effective surface.

8. A method of providing a device with an effective biocompatible surface of a synthetic hydrophilic polymer capable of existing in contact with biological fluid or tissue of a living organism with a net beneficial effect on the organism, the method employing a solid surface of the device, molecules of the synthetic hydrophilic polymer 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, capable of binding to the molecules of the synthetic hydrophilic polymer, one of the groups being unresponsive to a stimulus to which the other group responds, the method comprising:

activating the different reactive group of the chemical linking moiety in the presence of the molecules of the synthetic hydrophilic polymer to cause the different reactive group to covalently bind the chemical linking moiety to the molecules; and

activating the photochemically reactive group of the chemical linking moiety in the presence of the solid surface of the device to cause the photochemically reactive group to covalently bind to the solid surface and to bind the molecules of the synthetic hydrophilic polymer to the solid surface in a sufficient population density of molecules to effectively shield the solid surface and to provide a biocompatible effective surface.

9. A method of providing a contact lens with an effective biocompatible surface of a hydrophilic polymer selected from the group consisting of polyethylene glycol, hyaluornic acid, methyl cellulose, collagen and chitosan, the method employing a solid surface of the lens, molecules of the hydrophilic polymer 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, capable of binding to the molecules of the hydrophilic polymer, one of the groups being unresponsive to a stimulus to which the other group responds, the method comprising:

activating the different reactive group of the chemical linking moiety in the presence of the molecules of the hydrophilic polymer to cause the different reactive group to covalently bind the chemical linking moiety to the molecules; and

activating the photochemically reactive group of the chemical linking moiety in the presence of the solid surface of the device to cause the photochemically reactive group to covalently bind to the solid surface and to bind the molecules of the hydrophilic polymer to the solid surface in a sufficient population density of molecules to effectively shield the solid surface and to provide a biocompatible effective surface.

10. A method of providing a device with an effective biocompatible surface 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, the method employing a solid surface of the device, molecules of the polyethylene glycol 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, capable of binding to the molecules of the polyethylene glycol, one of the groups being unresponsive to a stimulus to which the other group responds, the method comprising:

activating the different reactive group of the chemical linking moiety in the presence of the molecules of the polyethylene glycol to cause the different reactive group to covalently bind the chemical linking moiety to the molecules; and

activating the photochemically reactive group of the chemical linking moiety in the presence of the solid surface of the device to cause the photochemically reactive group to covalently bind to the solid surface and to bind the molecules of the polyethylene glycol to the solid surface in a sufficient population density of molecules to effectively shield the solid surface and to provide a biocompatible effective surface.

11. A method of providing a device with an effective biocompatible surface of hyaluronic acid capable of existing in contact with biological fluid or tissue of a living organism with a net beneficial effect on the organism, the method employing a solid surface of the device, molecules of the hyaluronic acid 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, capable of binding to the molecules of the hyaluronic acid, one of the groups being unresponsive to a stimulus to which the other group responds, the method comprising:

activating the different reactive group of the chemical linking moiety in the presence of the molecules of the hyaluronic acid to cause the different reactive group to covalently bind the chemical linking moiety to the molecules; and

activating the photochemically reactive group of the chemical linking moiety in the presence of the solid surface of the device to cause the photochemically reactive group to covalently bind to the solid surface and to bind the molecules of the hyaluronic acid to the solid surface in a sufficient population density of molecules to effectively shield the solid surface and to provide a biocompatible effective surface.

12. A method of providing a device with an effective biocompatible surface of chitosan capable of existing in contact with biological fluid or tissue of a living organism with a net beneficial effect on the organism, the method employing a solid surface of the device, molecules of the chitosan 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, capable of binding to the molecules of the chitosan, one of the groups being unresponsive to a stimulus to which the other group responds, the method comprising:

activating the different reactive group of the chemical linking moiety in the presence of the molecules of the chitosan to cause the different reactive group to covalently bind the chemical linking moiety to the molecules; and

activating the photochemically reactive group of the chemical linking moiety in the presence of the solid surface of the device to cause the photochemically reactive group to covalently bind to the solid surface and to bind the molecules of the chitosan to the solid surface in a sufficient population density of molecules to effectively shield the solid surface and to provide a biocompatible effective surface.

13. A method of providing a device with an effective biocompatible surface 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, the method employing a solid surface of the device, molecules of the methyl cellulose 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, capable of binding to the molecules of the methyl cellulose, one of the groups being unresponsive to a stimulus to which the other group responds, the method comprising:

activating the different reactive group of the chemical linking moiety in the presence of the molecules of the methyl cellulose to cause the different reactive group to covalently bind the chemical linking moiety to the molecules; and

activating the photochemically reactive group of the chemical linking moiety in the presence of the solid surface of the device to cause the photochemically reactive group to covalently bind to the solid surface and to bind the molecules of the methyl cellulose to the solid surface in a sufficient population density of molecules to effectively shield the solid surface and to provide a biocompatible effective surface.

14. A method of providing a device with an effective biocompatible surface of a cell attachment factor capable of existing in contact with biological fluid or tissue of a living organism with a net beneficial effect on the organism, the method employing a solid surface of the device, molecules of the cell attachment factor 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, capable of binding to the molecules of the cell attachment factor, one of the groups being unresponsive to a stimulus to which the other group responds, the method comprising:

activating the different reactive group of the chemical linking moiety in the presence of the molecules of the cell attachment factor to cause the different reactive group to covalently bind the chemical linking moiety to the molecules; and

activating the photochemically reactive group of the chemical linking moiety in the presence of the solid surface of the device to cause the photochemically reactive group to covalently bind to the solid surface and to bind the molecules of the cell attachment factor to the solid surface in a sufficient population density of molecules to effectively shield the solid surface and to provide a biocompatible effective surface.

15. A method of providing a device with an effective biocompatible surface 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, the method employing a solid surface of the device, molecules of the antithrombogenic 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 bonding to the solid surface, to the molecules of the antithrombogenic agent, one of the groups being unresponsive to a stimulus to which the other group responds, the method comprising:

activating the different reactive group of the chemical linking moiety in the presence of the molecules of the antithrombogenic agent to cause the different reactive group to covalently bind the chemical linking moiety to the molecules; and

activating the photochemically reactive group of the chemical linking moiety in the presence of the solid surface of the device to cause the photochemically reactive group to covalently bind to the solid surface and to bind the molecules of the antithrombogenic agent to the solid surface in a sufficient population density of molecules to effectively shield the solid surface and to provide a biocompatible effective surface.