Process for the preparation of bioactive implant surfaces

Abstract

The invention relates to a method for producing bioactive implant surfaces consisting of metallic or ceramic materials, to be used for implants such as artificial joints or very small implants such as so-called stents. The invention also relates to implants produced according to this method.

1 . A process for the production of bioactive implant surfaces of metallic or ceramic materials in which, in a first step, anchor molecules having hydrophobic radicals are covalently bonded to the surface of the implant material and, in a second step, mediator molecules which, as a result of non-covalent interactions between the mediator molecules and the hydrophobic radicals of the anchor molecules, are immobilized, are added to the implant material treated in this way, where in the first step the loading density of the anchor molecules on the implant surface is chosen, depending on the chain length of the hydrophobic radical of the anchor molecule, such that the anchor molecules do not interact with one another themselves and, depending on the covered surface on the implant material, which is covered by an individual mediator molecule absorbed in the second step, at least 10, preferably 15, contact sites are formed between the hydrophobic radicals of the anchor molecules for hydrophobic interaction with the individual mediator molecule.  
     
     
         2 . The process as claimed in  claim 1 , in which the hydrophobic radicals of the anchor molecules are radicals having 1 to 30, preferably 3 to 20, particularly preferably 3 to 8, carbon atoms, which can also be replaced by silicon or heteroatoms such as N, O or S in the chain, where the hydrophobic radicals can also optionally be substituted by one or more substituents from halogen, alkoxy, hydroxyl, thiol, amino, alkyl-amino, dialkylamino or trialkylamino groups, where the alkyl groups of the substituent preferably have 1-6 carbon atoms and can be straight-chain or branched.  
     
     
         3 . The process as claimed in  claim 2 , in which the hydrophobic radicals are branched carbon chains optionally substituted as above and having 1 to 30, preferably 3 to 20, particularly preferably 3 to 8 carbon atoms.  
     
     
         4 . The process as claimed in any of the preceding claims, in which the implant material consists of a material selected from the group consisting of the metals, the metallic alloys, the ceramic materials or combinations thereof.  
     
     
         5 . The process as claimed in any of the preceding claims, in which the mediator molecules used are biologically active substances such as bone growth factors from the class consisting of the BMP proteins, antibiotics or mixtures thereof.  
     
     
         6 . The process as claimed in  claim 5 , in which the bone growth factor used is BMP-2 or BMP-7.  
     
     
         7 . The process as claimed in any of the preceding claims, in which the surface of the implant material is provided with a hydrophilic coating before the covalent bonding of the anchor molecules.  
     
     
         8 . The process as claimed in  claim 7 , in which the hydrophilic coating is a hydrophilic oxide layer.  
     
     
         9 . The process as claimed in  claim 7  or  8 , in which the surface of the implant material, selected from titanium, titanium alloys, aluminum or stainless steel, is provided with an oxide layer before the covalent bonding of the anchor molecules by treatment with chromosulfuric acid for a period of 0.5 up to 3 hours at 100 to 250° C.  
     
     
         10 . The process as claimed in  claim 9 , in which the chromosulfuric acid has a density of more 1.40 g/cm 3 .  
     
     
         11 . The process as claimed in any of the preceding claims, in which, in the first step, as anchor molecules, hydrocarbon radicals, which can be straight-chain or branched, having 1 to 30, preferably 1 to 20 carbon atoms, particularly preferably 1 to 15 carbon atoms, which can also optionally be substituted by one or more substituents from halogen, alkoxy, hydroxyl, thiol, amino, alkyl or dialkylamino groups, are covalently bonded to the surface of the implant material and, in the second step, bone growth factors which, as a result of noncovalent interactions between the bone growth factors and the hydrophobic radicals of the anchor molecules, are immobilized, are added to the implant material treated in this way, where, in the first step, the loading density of the anchor molecules on the implant surface is chosen, depending on the chain length of the hydrophobic radical of the anchor molecule, such that the anchor molecules do not interact with one another themselves and, depending on the covered surface on the implant material, which is covered by an individual bone growth factor molecule absorbed in the second step, at least 10, preferably 15 contact sites are formed between the hydrophobic radicals of the anchor molecules for hydrophobic interaction with the individual bone growth factor molecule.  
     
     
         12 . The process as claimed in  claim 11 , in which the carbon radicals are immobilized in the first step, depending on the degree of branching of the radical used, in a number of at least 3, preferably at least 5 and particularly preferably at least 10 radicals to 10 nm 2  of the implant surface.  
     
     
         13 . The process as claimed in  claim 11  or  12 , in which the carbon radicals are immobilized in the first step, depending on the degree of branching of the radical used, in a number of at most 100, preferably at most 60 radicals per 10 nm 2  of the implant surface.  
     
     
         14 . An implant, obtainable by the process as claimed in any of claims  1 - 13 .  
     
     
         15 . The implant as claimed in  claim 14 , in which the implant material consists of titanium, titanium alloys, aluminum, stainless steel, steel alloys or hydroxyapatite.  
     
     
         16 . The implant as claimed in  claim 14  or  15 , in which the implant is a joint or bone prosthesis, a stent or a dental implant.