Non-fouling, anti-microbial, anti-thrombogenic graft compositions
View Patent ↗The present invention generally relates to articles of manufacture, such as medical devices, having a non-fouling surface comprising a grafted polymer material. The surface resists the adhesion of biological material.
1. A process for the preparation of article of manufacture, the process comprising
(1) depositing a polymeric primer on a substrate, the polymeric primer having a thickness of at least 50 nm comprising and containing at least 5 nanomolar equivalent/cm 2 of a functional group, and
(2) grafting a polymer from the deposited polymeric primer, the deposited polymeric primer being between the grafted polymer and the substrate and having upper and lower surfaces, the lower surface covering at least a portion of the substrate, and the upper surface being bound to the functional group, the polymeric primer and the grafted polymer, in combination, constituting a modified surface having a fibrinogen adsorption of less than about 75 ng/cm 2 in a fibrinogen binding assay in which the modified surface is incubated for 60 minutes at 37° C. in 70 μg/ml fibrinogen derived from human plasma containing 1.4 μg/ml I-125 radiolabeled fibrinogen.
2. The process of claim 1 wherein the polymer is grafted by exposing the functional group to a free radical initiator and a monomer or monomer mixture, the upper surface of the polymeric primer being attached to the grafted polymer through the functional group.
3. The process of claim 2 , wherein the free radial initiator is selected from UV, thermal, and redox initiators.
4. The process of claim 3 wherein the free radical initiator is a redox initiator comprising an oxidant selected from the following: peroxide, hydroperoxide, persulfates, peroxycarbonates, peroxydisulfates, peroxydiphosphate, permanganate, salts of metals such as Mn(III), Ce(IV), V(V), Co(III), Cr(VI) and Fe(III).
5. The process of claim 1 wherein the functional group is selected from the group consisting of glycidyl, isocyanate, amine, benzophenone, bromoisobutyryl, hydroxy, carboxylate and combinations thereof.
6. The process of claim 1 wherein the deposited polymeric primer has a thickness from 50 nm to 500 μm.
7. The process of claim 1 wherein the grafted polymer and the polymeric primer, in combination have a global average dry thickness of at least 500 nm.
8. The process of claim 1 wherein the grafted polymer and the polymeric primer, in combination, have a global average dry thickness that is at least equal to the global average R rms surface roughness of the substrate surface.
9. The process of claim 1 wherein the modified surface has a static contact angle less than 40 degrees.
10. The process of claim 1 wherein the difference between the static contact angle of the polymeric primer, prior to the attachment of the grafted polymer, and the modified surface is at least 10 degrees.
11. The process of claim 1 wherein the polymeric primer contains at least 5 nanomolar equivalents/cm 2 of a functional group that is chemically reactive with a functionality of the grafted polymer or of a moiety from which it is derived.
12. The process of claim 1 wherein covalent bonds are formed between at least one of the following: (a) the grafted polymer and the deposited polymeric primer; or (b) the deposited polymeric primer and the substrate.
13. The process of claim 1 wherein the grafted polymer has a global average dry thickness in the range from about 100 nm to about 1000 nm.
14. The process of claim 1 , wherein the grafted polymer is a homopolymer of sulfobetaine methacrylate, sulfobetaine acrylate, sulfobetaine acrylamide, sulfobetaine methacrylamide, carboxybetaine methacrylate, carboxybetaine acrylate, carboxybetaine acrylamide or carboxybetaine methacrylamide monomers and the grafted polymer has an average dry thickness of at least about 50 nm as measured by SEM under vacuum.
15. The process of claim 1 further comprising pretreating the substrate with an acid, base or chelating agent to remove particles or waxes from the surface of the substrate on which the polymeric primer is deposited thereon, wherein the pretreating occurs prior to the depositing the polymeric primer.
16. The process of claim 1 further comprising mechanically, chemically, or chemomechanically treating the surface of the substrate on which the polymeric primer is deposited thereon to reduce surface defects prior to the depositing the polymeric primer.
17. The process of claim 1 wherein the depositing the polymeric primer includes exposing the substrate to a solution comprising a pre-synthesized polymer and a solvent.
18. The process of claim 1 wherein the depositing the polymeric primer includes exposing the substrate to a solution comprising a monomer, an initiator and a solvent.
19. The process of claim 1 wherein the polymeric primer includes a copolymer comprising: 0-50 mol % lauryl methacrylate (LMA); 0-50 mol % 2-hydroxypropyl methacrylate (HPMA); and
0-25 mol % trimethoxysilyl methacrylate (TMOSMA).
20. The process of claim 1 wherein the grafted polymer includes a copolymer comprising 25-90 mol % sulfobetaine methacrylate (SBMA) and 75-10 mol % 2-hydroxypropyl methacrylate (HPMA).
21. The process of claim 1 further comprising treating the deposited polymeric primer with an initiator prior to the grafting the polymer from the deposited polymeric primer.
22. The process of claim 21 wherein the treating the deposited polymeric primer comprises imbibing an initiator into the deposed polymeric primer.
23. The process of claim 1 wherein the polymeric primer comprises a reactive group that is chemically reactive with a functionality of the substrate to attach the polymeric primer to the substrate.
24. The process of claim 23 wherein the reactive group is selected from the group consisting of an alkyne, primary amine, secondary amine, tertiary amine, anhydride, azide, carboxyl, epoxy, glycidyl, halogen, hydroxyl, isocyanate, peroxide, silanol, thiol, photo-initiator groups, and combinations thereof.