Ceramic coating and method of preparation thereof

Abstract

A ceramic coating with gradient density/porosity and/or incorporated biologically active agents can be fabricated on the surface of substrates, including the surface of implantable medical devices.

1 . A method of coating a substrate with a gradient ceramic coating, comprising:
 exposing a portion of a substrate to an aqueous system at a temperature of about 20° C. to about 100° C. to form a gradient ceramic coating on a surface of the substrate having a density of about 75 to about 90% closest to the substrate and a density of about 35 to about 60% at the gradient ceramic coating surface as determined by scanning electron microscope;   wherein the aqueous system comprises water, Ca 2+ , Mg 2+ , Na + , K + , Cl − , SO 4   2− , HPO 4   2− , HCO 3   −  and a buffer system; and   wherein the aqueous system has an initial pH of about 5.5 to about 7.5.   
     
     
         2 . The method of  claim 1 , wherein the buffer system comprises 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid, 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid salts, tris-hydroxymethylaminomethan, piperazine-1,4-bis(2-ethanesulfonic acid), piperazine-1,4-bis(2-ethanesulfonic acid)salts, or combinations thereof. 
     
     
         3 . The method of  claim 1 , wherein the buffer system further comprises an alkali metal carbonate. 
     
     
         4 . The method of  claim 1 , wherein
 Ca 2+  is present in an amount of about 2.5 to about 15.0 mM;   Mg 2+  is present in an amount of about 0.5 to about 5.0 mM;   Na +  is present in an amount of about 50.0 to about 300.0 mM;   K +  is present in an amount of about 2.0 to about 20.0 mM;   Cl −  is present in an amount of about 50.0 to about 350.0 mM;   SO 4   2−  is present in an amount of about 0 to about 2.0 mM;   HPO 4   2−  is present in an amount of about 1.0 to about 10.0 mM; and   HCO 3   −  is present in an amount of about 5.0 to about 100.0 mM.   
     
     
         5 . The method of  claim 1 , wherein the aqueous system further comprises silicate, strontium, zinc, silver, fluoride, or combinations thereof. 
     
     
         6 . The method of  claim 1 , wherein the gradient ceramic coating has a total thickness of about 0.1 micrometers to about 70 micrometers. 
     
     
         7 . The method of  claim 1 , wherein the exposing the substrate to the aqueous system occurs for a time of about 10 hours to about 48 hours. 
     
     
         8 . The method of  claim 1 , wherein the substrate comprises a metal, a ceramic, a polymeric material, or silicon. 
     
     
         9 . The method of  claim 1 , wherein the coating is performed in a sealed container, wherein the sealed container comprises a pressure valve. 
     
     
         10 . The method of  claim 9 , wherein the sealed container has a volume ratio of headspace to aqueous system of about 5 to about 15 at atmospheric pressure. 
     
     
         11 . A method of incorporating a biologically active agent into a ceramic coating on a substrate, comprising:
 exposing a portion of a substrate to an aqueous system at a temperature of about 20° C. to about 100° C. to form a ceramic coating on a surface of the substrate;   wherein the aqueous system comprises water, Ca 2+ , Mg 2+ , Na + , K + , Cl − , SO 4   2− , HPO 4   2− , HCO 3   − , a buffer system, and a biologically active agent;   wherein the aqueous system has an initial pH of about 5.5 to about 7.5;   wherein the ratio of aqueous system volume to the substrate surface area is about 1 mm to about 50 mm; and   wherein the biologically active agent concentration in the aqueous system is less than about 1 mg/ml.   
     
     
         12 . The method of  claim 15 , wherein the buffer system comprises 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid, 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid salts, tris-hydroxymethyl aminomethan, piperazine-1,4-bis(2-ethanesulfonic acid), piperazine-1,4-bis(2-ethanesulfonic acid)salts, or combinations thereof. 
     
     
         13 . The method of  claim 11 , wherein the buffer system further comprises an alkali metal carbonate. 
     
     
         14 . The method of  claim 11 , wherein the concentration of biologically active agent in the aqueous system is less than about 0.5 mg/ml. 
     
     
         15 . The method of  claim 11 , wherein
 Ca 2+  is present in an amount of about 2.5 to about 15.0 mM;   Mg 2+  is present in an amount of about 0.5 to about 5.0 mM;   Na +  is present in an amount of about 50.0 to about 300.0 mM;   K +  is present in an amount of about 2.0 to about 20.0 mM;   Cl −  is present in an amount of about 50.0 to about 350.0 mM;   SO 4   2−  is present in an amount of about 0 to about 2.0 mM;   HPO 4   2−  is present in an amount of about 1.0 to about 10.0 mM; and   HCO 3   −  is present in an amount of about 5.0 to about 100.0 mM.   
     
     
         16 . The method of  claim 11 , wherein the aqueous system further comprises silicate, strontium, zinc, silver, fluoride, or combinations thereof. 
     
     
         17 . The method of  claim 11 , wherein the ceramic coating has a total thickness of about 0.1 micrometers to about 70 micrometers. 
     
     
         18 . The method of  claim 11 , wherein the ratio of the volume of the aqueous system to the surface area of the substrate is about 10 mm to about 40 mm. 
     
     
         19 . The method of  claim 11 , wherein the biologically active agent is a pharmaceutically active agent, an osteogenic factor, a mitogen, a protein, or a gene. 
     
     
         20 . A reactor for coating a substrate with a bioactive ceramic coating, comprising:
 a liquid-holding container with a volume sufficient to allow a ratio of the aqueous system volume to the substrate surface area to be about 5 to about 50; and   a gas valve to control the rate of release of a gas from the container.