Antibacterial coatings that inhibit biofilm formation on implants

Abstract

Orthopedic and dental implants coated with an antibacterial coating and methods of making and using, are described herein. The implant can be coated with a hydrophobic, polycationic antibacterial polymer. The polymer can be covalently or non-covalently associated with the surface; however, in particular embodiments, the polymer is non-covalently associated with the surface. As shown in the examples below, clinical observations, digital radiography, and a battery of well-accepted ex vivo analytical methods show that the presence of a hydrophobic polycationic polymer coating, such as N,N-dodecyl,methyl-PEI coating on the surface of a metal implant, was effective in eliminating the clinical signs of infection in vivo in a large animal infection model. Moreover, the coated plates supported bone healing, and in fact decreased healing times, even in the presence of significant bacterial contamination compared to a control.

We claim: 
     
         1 . An implant comprising a coating on one or more surfaces of the implant, wherein the coating comprises an antimicrobial hydrophobic polycationic polymer, wherein the polymer is substantially non-leaching, and wherein the coating does not contain a polyanionic polymer. 
     
     
         2 . The implant of  claim 1 , wherein the implant comprises metallic material, metal oxides, synthetic or natural, cross-linked or non-crosslinked, polymeric materials, ceramics, porcelain, allogenic or xenogenic bone or bone matrix; genetically engineered bone; and combinations thereof. 
     
     
         3 . The implant of  claim 2 , wherein the metallic material is selected from the group consisting of NiTi alloys, stainless steel, titanium or alloys thereof. 
     
     
         4 . The implant of  claim 2 , wherein the polymeric material is non-degradable. 
     
     
         5 . The implant of  claim 4 , wherein the polymeric material is selected from the group consisting of polypropylene (PP), polyethylene (PE), polyacetylene, cross-linked or non-crosslinked polystyrene, styrene-butadiene rubber, TEFLON®, poly(vinyl chloride) (PVC), polyolefin copolymers, poly(methyl methacrylate), polyphenylene, polyacrylonitrile, carbon fiber, and blends or copolymers thereof. 
     
     
         6 . The implant of  claim 2 , wherein the polymeric material is biodegradable. 
     
     
         7 . The implant of  claim 6 , wherein the polymeric material is selected from the group consisting of collagen, cellulosic polymers, polysaccharides, poly(glycolic acid), poly(L-lactic acid) (PLLA), poly(lactide-co-glycolide) (PLGA), a polydioxanone (PDA), or racemic poly(lactic acid), polyurethane (PU), polycarbonates, polyetherketone (PEEK), polyesters, and polyamides (nylon). 
     
     
         8 . The implant of  claim 1 , wherein the implant is a prosthesis. 
     
     
         9 . The implant of  claim 1 , wherein the implant is an orthopedic implant. 
     
     
         10 . The implant of  claim 9  wherein the implant is selected from the group consisting of Kirschner wire, bone plates, screws, pins, tacs, rods, nails, nuts, bolts, washers, spikes, buttons, wires, fracture plates, endo- and exoprostheses, intraosseous transcutaneous prostheses, spacers, mesh, implant abutments, anchors, barbs, clamps, suture, tubes of any geometry, and combinations thereof. 
     
     
         11 . The implant of  claim 1 , wherein the implant is a ear, nose, or throat implant. 
     
     
         12 . The implant of  claim 11 , wherein the implant is selected from the group consisting of ear tubes, endotracheal tubes, ventilation tubes, cochlear implants and bone anchored hearing devices. 
     
     
         13 . The implant of  claim 1 , wherein the implant is a cardiovascular implant. 
     
     
         14 . The implant of  claim 13 , wherein the implant is selected from the group consisting of cardiac valves, alloplastic vessel wall supports, and total artificial heart implants. 
     
     
         15 . The implant  claim 1  wherein said hydrophobic polycation is a N-alkylated branched or linear polyethylenimine (PEI). 
     
     
         16 . The implant of  claim 15  wherein the hydrophobic polycation is N,N-dodecyl,methyl-PEI or N,N-hexyl,methyl-PEI. 
     
     
         17 . The implant of  claim 1 , wherein the weight average molecular weight of the polymer is at least 10,000 g/mol. 
     
     
         18 . The implant of  claim 1 , wherein the thickness of the polymer coating is from about 1 nm to about 1 cm. 
     
     
         19 . The implant of  claim 1 , wherein the polymer is non-covalently associated with one or more surfaces of the implant. 
     
     
         20 . The implant of  claim 1 , wherein the polymer is covalently associated with one or more surfaces of the implant. 
     
     
         21 . A method of preventing infection while treating hard or soft tissue, the method comprising implanting the implant of  claim 1 . 
     
     
         22 . The method of  claim 21 , wherein the coating is applied to the implant immediately prior to implantation. 
     
     
         23 . A method of treating hard or soft tissue in the presence of an infection, the method comprising implanting the implant of  claim 1 . 
     
     
         24 . The method of  claim 23 , wherein the coating is applied to the implant immediately prior to implantation.