Biomaterials having nanoscale layers and coatings

Abstract

The invention generally relates to surfaces having a protein-resistant hydrogel layer and methods for preparing a protein-resistant hydrogel layer on a surface. The protein-resistant hydrogel layer is formed by a protein-crosslinked water soluble polymer that is contacted with a surface to form a thin protein-resistant hydrogel layer on the surface.

What is claimed is: 
     
         1 . A method for preparing a protein-resistant hydrogel layer on a surface, the method comprising:
 contacting a water soluble polymer with a protein in solution to form a water soluble polymer/protein solution, wherein the water soluble polymer comprises a protein-reactive group; wherein the protein comprises at least one functional group selected from the group consisting of an amino group, a sulfhydryl group, a hydroxyl group, a carboxyl group and a thiol group; and wherein the water soluble polymer reacts with the at least one functional group of the protein to form protein-crosslinked water soluble polymer particles in the water soluble polymer/protein solution; and wherein the protein-crosslinked water soluble polymer particles have a particle size of from about 10 nm to about 1 μm; and   contacting the water soluble polymer/protein solution with a surface to prepare the protein-resistant hydrogel layer on the surface, wherein the protein-resistant hydrogel layer has a thickness of from about 10 nm to about 10 μm.   
     
     
         2 . The method of  claim 1 , wherein the surface is selected from the group consisting of silver, gold, stainless steel, titanium, glass, silicon containing material, cadmium, palladium, platinum, iron, nickel, cobalt, iron oxide, titanium oxide, silicon oxide, copper, quartz and a polymer. 
     
     
         3 . The method of  claim 1 , wherein the protein crosslinked water soluble polymer particles have a particle size of from about 20 nm to about 65 nm. 
     
     
         4 . The method of  claim 1 , wherein the protein-resistant hydrogel layer has a thickness less than 10 μm. 
     
     
         5 . The method of  claim 1 , wherein the surface is silanized. 
     
     
         6 . The method of  claim 5 , wherein the surface is silanized by contacting the surface with 3-aminopropyltriethoxysilane. 
     
     
         7 . The method of  claim 1 , wherein the water soluble polymer is selected from the group consisting of a hydrophilic polymer, a cellulose derivative, a polysaccharide, and a poly(amino acid). 
     
     
         8 . The method of  claim 1 , wherein the water soluble polymer is polyethylene glycol. 
     
     
         9 . The method of  claim 1 , wherein the protein-resistant hydrogel layer comprises a single layer. 
     
     
         10 . The method of  claim 1 , wherein the protein-reactive group is selected from the group consisting of a vinyl sulfone, a maleimide, a diacrylate, and a diamine. 
     
     
         11 . A surface comprising a protein-resistant hydrogel layer having a thickness of from about 10 nm to about 10 μm, wherein the protein-resistant hydrogel layer comprises a water soluble polymer and a protein, wherein the water soluble polymer comprises a protein-reactive group selected from the group consisting of a vinyl sulfone, a maleimide, a diacrylate, and a diamine; and wherein the protein comprises at least one functional group selected from the group consisting of an amino group, a sulfhydryl group, a hydroxyl group, a carboxyl group and a thiol group. 
     
     
         12 . The surface comprising the protein-resistant hydrogel layer of  claim 11 , wherein the water soluble polymer is selected from the group consisting of a hydrophilic polymer, a cellulose derivative, a polysaccharide, and a poly(amino acid). 
     
     
         13 . The surface comprising the protein-resistant hydrogel layer of  claim 11 , wherein the water soluble polymer is polyethylene glycol. 
     
     
         14 . The surface comprising the protein-resistant hydrogel layer of  claim 11 , wherein the surface is selected from the group consisting of silver, gold, stainless steel, titanium, glass, silicon containing material, cadmium, palladium, platinum, iron, nickel, cobalt, iron oxide, titanium oxide, silicon oxide, copper and a polymer. 
     
     
         15 . The surface of  claim 11 , wherein the protein-resistant hydrogel layer further comprises a compound non-covalently bound to the protein-resistant hydrogel layer, the compound selected from the group consisting of a polymer, a protein, a therapeutic molecule, and an adhesion peptide. 
     
     
         16 . A surface comprising a single protein-resistant hydrogel layer, wherein the single protein-resistant hydrogel layer has a thickness of from about 10 nm to about 10 μm. 
     
     
         17 . The surface of  claim 16 , wherein the surface is selected from the group consisting of silver, gold, stainless steel, titanium, glass, silicon containing material, cadmium, palladium, platinum, iron, nickel, cobalt, iron oxide, titanium oxide, silicon oxide, copper, quartz and a polymer. 
     
     
         18 . The surface of  claim 16 , wherein the protein-resistant hydrogel layer further comprises an agent non-covalently bound to the protein-resistant hydrogel layer, the agent selected from the group consisting of a polymer, a protein, a therapeutic molecule, and an adhesion peptide. 
     
     
         19 . The surface of  claim 18 , wherein the therapeutic molecule is selected from the group consisting of an anti-inflammatory agent, a chemotherapeutic agent, an endothelial cell migration promoting agent, an angiogenesis promoting agent, an anticoagulant, an antibacterial agent, an antiparasitic agent, an antifungal agent, an antiviral agent, an analgesic agent, a local anesthetic and an immunomodulatory agent. 
     
     
         20 . The surface of  claim 16 , wherein the surface comprises at least a portion of a medical devices selected from the group consisting of a cardiovascular device, an artificial blood vessel, an artificial bone joint, a tissue growth scaffold, a biosensor, a percutaneous device, a contact lens, an intraocular lens, an ultrafiltration membrane, a container for biological materials and a cell culture dish.