Osteopontin coated surfaces and methods of use

Abstract

A novel osteopontin containing implant which increases the rate of osseointegration and the percentage of bone apposition is described. The implant of the invention includes a material suitable for use in vivo within a subject in combination with a releasable form of osteopontin forming an osteopontin containing implant.

What is claimed is:  
     
         1 . An osteopontin containing implant, comprising; 
 a material suitable for use in vivo within a subject in combination with osteopontin forming an osteopontin containing implant.    
     
     
         2 . The implant of  claim 1  wherein the osteopontin is non-covalently attached to the material.  
     
     
         3 . The implant of  claim 2  wherein the non-covalent attachment of osteopontin to the material is via a divalent ion bridge.  
     
     
         4 . The implant of  claim 3  wherein the divalent ion is selected from the group consisting of Ca++, Mg++ and Mn++.  
     
     
         5 . An implant of  claim 4  wherein the non-covalent attachment of osteopontin to the material is via coating of a mucopolysaccharide on to the material.  
     
     
         6 . An implant of  claim 5  wherein the mucopolysaccharide is a chondroitin sulfate or hyaluronic acid.  
     
     
         7 . The implant of  claim 1  wherein the osteopontin is a phosphorylated osteopontin.  
     
     
         8 . An implant of  claim 7  wherein the phosphorylated osteopontin is phosphorylated at Thr138.  
     
     
         9 . An implant of  claim 7  wherein the phosphorylated osteopontin is phosphorylated at Thr152.  
     
     
         10 . An implant of  claim 7  wherein the phosphorylated osteopontin is phosphorylated at Ser26, Ser27, Ser81, Thr138 and Ser308.  
     
     
         11 . An implant of  claim 7  wherein the phosphorylated osteopontin is phosphorylated at Ser26, Ser27, Ser81, Thr152, and Ser308.  
     
     
         12 . The implant of  claim 1  wherein the osteopontin further possesses at least one osteopontin polypeptide possessing chemotactic activity.  
     
     
         13 . The implant of  claim 12  wherein the chemotactic polypeptide comprises the amino acid sequence (SEQ ID NO: 2) or (SEQ ID NO: 3).  
     
     
         14 . An implant of  claim 12  wherein the chemotactic polypeptide comprises the amino acid sequence: 
       XX′DZZ′ 
       wherein 
 X and X′ are hydrophobic amino acids;  
 D is Aspartic Acid;  
 Z is Proline, Glycine, or Serine;  
 Z′ is a basic amino acid.  
 
     
     
         15 . An implant of  claim 14  wherein X and X′ are selected from the group consisting of Leucine, Valine, Isoleucine, Glutamine, and Methionine; Z is selected from the group consisting of Proline, Glycine and Serine; and Z is selected from the group consisting of Lysine and Arginine.  
     
     
         16 . An implant of  claim 15  wherein X is Leucine, X′ is Leucine, Z is Glycine, and Z′ is Lysine.  
     
     
         17 . The implant of  claim 1  wherein the osteopontin further comprises at least one osteopontin polypeptide possessing cell attachment activity.  
     
     
         18 . The implant of  claim 17  wherein the cell attachment peptide comprises the amino acid sequence (SEQ ID NO: 4) or (SEQ ID.NO: 5).  
     
     
         19 . An implant of  claim 18  wherein the cell attachment peptide comprises (SEQ ID NO. 6).  
     
     
         20 . An osteopontin containing titanium implant, comprising: 
 a releasable form of phosphorylated osteopontin or an active fragment thereof in combination with titanium suitable for use in vivo within a subject forming an osteopontin containing titanium implant.    
     
     
         21 . The implant of  claim 20  wherein the titanium implant is a dental implant.  
     
     
         22 . A method of coating an implant with an osteopontin or an active fragment thereof comprising: 
 non-covalently attaching osteopontin or an active fragment thereof to a surface of an implant,    wherein the osteopontin or an active fragment thereof is attached to the surface of the implant such that it is releasable from the surface upon implantation into a subject.    
     
     
         23 . An osteopontin containing implant, comprising; 
 a material suitable for use in vivo within a subject in combination with a releasable form of osteopontin,    wherein the osteopontin is attached to the material such that upon implantation into the subject the osteopontin containing implant induces new bone formation.    
     
     
         24 . An osteopontin containing cell recruitment system comprising: 
 a releasable osteopontin or a fragment thereof in a form which provides a gradient; and    an implant forming a cell recruitment system in the proximity of the implant,    wherein the implant is targeted for cell recruitment by a gradient of osteopontin which forms in the proximity of the implant.    
     
     
         25 . A packaged releasable osteopontin or a fragment thereof for use in a cell recruitment system comprising: 
 a releasable osteopontin or a fragment thereof in a form which provides a gradient in the proximity of an implant which is targeted for cell recruitment by the gradient of osteopontin packaged with instructions for use of said osteopontin or a fragment thereof with the implant targeted for cell recruitment.    
     
     
         26 . A coated osseointegrator capable of implantation, comprising: 
 a coated material which is enhanced for osseointegration by at least about 100% when compared to an uncoated material based on the human osteoblast cell (HOS) attachment assay.    
     
     
         27 . A coated implant, comprising: 
 a coated material which increases the proliferation of osteoblasts by at least about 100% when compared to an uncoated material based on the human osteoblast cell (HOS) proliferation assay.    
     
     
         28 . A method for inducing new tissue formation in a subject at a site where tissue formation is needed comprising: 
 adding osteopontin to a subject at a site where tissue formation is needed, wherein the osteopontin induces new tissue formation about the site.    
     
     
         29 . The method of claim  80  wherein the osteopontin is a recombinant osteopontin.  
     
     
         30 . An osteopontin glue, comprising osteopontin, a mucopolysaccharide and a multivalent metal.