Multi-functional surface coating of implants

Abstract

The invention provides novel surface coatings having surface polymer brushes with zwitterionic and antibiotics-conjugated side chains and synergistic anti-fouling and bactericidal properties. The surface coatings may be prepared using highly efficient surface-initiated “living” polymerization. The design of the surface polymer brushes are highly modular, allowing independent tuning of the anti-fouling and bactericidal properties, e.g., by varying the chemical nature of the zwitterionic motif and the antibiotic agent, the chemistry through which the antibiotic agent is conjugated to the polymer side chains, the molecular weight of the polymer brushes (e.g., thickness of coating and density of respective functional motifs), and the spatial arrangement of the respective functional motifs (e.g., homopolymers, block copolymers, random copolymers) to achieve optimal and sustained anti-infection outcome for a given application.

What is claimed is: 
     
         1 - 29 . (canceled) 
     
     
         30 . An implant substrate having a surface covalently bonded thereto a layer of a co-polymer comprising repeating units having structures of: 
       
         
           
           
               
               
           
         
         wherein 
         R 1 , R 3  each is independently a hydrogen, alkyl, alkyloxy; 
         R 2 , R 4  each is independently a hydrogen, (C 1 -C 15 ) alkyl, (C 1 -C 15 ) alkyloxy; 
         L z  is a linking group; 
         L ab  is a linking group; 
         R z  is a pendant group comprising a zwitterionic group; and 
         R ab  is a pendant group comprising an antibacterial moiety. 
       
     
     
         31 . The implant substrate of  claim 30 , wherein the co-polymer comprises the structure: 
       
         
           
           
               
               
           
         
         wherein each of m, n, p, and q is an integer selected from about 0 to about 500. 
       
     
     
         32 . The implant substrate of  claim 30 , wherein the zwitterionic group is selected from phosphorylcholine, sulfobetaine, and carboxybetaine. 
     
     
         33 . The implant substrate of  claim 30 , wherein the antibacterial moiety is selected from beta-lactam antibiotics, tetracyclines, aminoglycosides, macrolides, chloramphenicol, ivermectin, and rifamycins. 
     
     
         34 . The implant substrate of  claim 30 , wherein the co-polymer comprises repeating units of structures: 
       
         
           
           
               
               
           
         
         wherein 
         L z  is a linking group; and 
         L ab  is a linking group. 
       
     
     
         35 . The implant substrate of  claim 34 , wherein the co-polymer comprises the structure: 
       
         
           
           
               
               
           
         
         wherein each of m, n, p, and q is an integer selected from about 0 to about 500. 
       
     
     
         36 . The implant substrate of  claim 35 , wherein each of R 1 , R 3 , R 2 , and R 4  is hydrogen. 
     
     
         37 . The implant substrate of  claim 36 , wherein each of L z  and L ab  is independently —(CH 2 ) i —, wherein i is an integer from about 1 to about 20. 
     
     
         38 . The implant substrate of  claim 30 , wherein the co-polymer has molecular weight from about 2,000 Da to about 300,000 Da. 
     
     
         39 . The implant substrate of  claim 30 , wherein the implant substrate is a metallic substrate. 
     
     
         40 . The implant substrate of  claim 39 , wherein the metallic substrate comprises stainless steel, titanium, cobalt, chromium, tantalum, magnesium, nickel, or an alloy thereof. 
     
     
         41 - 51 . (canceled)