Ceramic/structural protein composites and method of preparation thereof

Abstract

Ceramic/structural protein composites and methods of preparation are disclosed, including coatings and films. Ceramic/structural protein coatings can be fabricated on the surface of substrates, including the surface of implantable medical devices.

1 . A method of forming a film, comprising:
 forming an aqueous system comprising a structural protein, a gelation inhibitor agent, a weak acid having a pKa of about 3.0 to about 5.5, water, Ca 2+ , HPO 4   2− , a buffer system, and optionally one or more of Mg 2+ , Na + , K + , Cl − , SO 4   2− ; or HCO 3   − ; wherein the aqueous system has an initial pH of about 5.0 to about 8.0;   placing the aqueous system in a container and allowing for an air-aqueous system interface;   sealing the container; and   allowing a ceramic/structural protein film form at the air-aqueous system interface at a temperature of about 20° C. to about 80° C.   
     
     
         2 . The method of  claim 1 , wherein the structural protein is collagen Type I, II, III, or V. 
     
     
         3 . The method of  claim 1 , wherein the gelation inhibitor agent is urea, histidine, hydroxyproline, thiourea, sodium dodecyl sulfate, lithium dodecyl sulfate, 2-mercaptoethanol, formamide, dithiothreitol, (3-[(3-cholamidopropyl)-dimethylammonio]-1-propanesulfonate), (3-([cholamidopropyl]-dimethyl ammonio)-2-hydroxy-1-propanesulfonate), guanidinium chloride (guanidine hydrochloride), or guanidinium thiocyanate. 
     
     
         4 . The method of  claim 1 , 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. 
     
     
         5 . The method of  claim 1 , wherein the weak acid is an organic carboxylic acid having a pKa of about 3.0 to about 5.5. 
     
     
         6 . A film prepared by the process of  claim 1 . 
     
     
         7 . A device, comprising:
 i) a coated substrate prepared by the process comprising   exposing a portion of a substrate to an aqueous system at a temperature of about 20° C. to about 80° C. to form a ceramic coating on a surface of the substrate;   wherein the aqueous system comprises a structural protein, a gelation inhibitor agent, a weak acid having a pKa of about 3.0 to about 5.5, water, Ca 2+ , HPO 4   2− , a buffer system, and optionally one or more of Mg 2+ , Na + , K + , Cl − , SO 4   2− ; or HCO 3   − ; and   wherein the aqueous system has an initial pH of about 5 to about 8; or   ii) a film prepared by the process comprising   forming an aqueous system comprising a structural protein, a gelation inhibitor agent, a weak acid having a pKa of about 3.0 to about 5.5, water, Ca + , HPO 4   2− , a buffer system, and optionally one or more of Mg 2+ , Na + , K + , Cl − , SO 4   2− ; or HCO 3   − ; wherein the aqueous system has an initial pH of about 5 to about 8;   placing the aqueous system in a container and allowing for an air-aqueous system interface;   sealing the container; and   allowing a ceramic/structural protein film form at the air-aqueous system interface at a temperature of about 20° C. to about 80° C.   
     
     
         8 . The device of  claim 7 , wherein the structural protein is collagen Type I, II, III, or V. 
     
     
         9 . The device of  claim 7 , wherein the gelation inhibitor agent is urea, histidine, hydroxyproline, thiourea, sodium dodecyl sulfate, lithium dodecyl sulfate, 2-mercaptoethanol, formamide, dithiothreitol, (3-[(3-cholamidopropyl)-dimethylammonio]-1-propanesulfonate), (3-([cholamidopropyl]-dimethyl ammonio)-2-hydroxy-1-propanesulfonate), guanidinium chloride (guanidine hydrochloride), or guanidinium thiocyanate. 
     
     
         10 . The device of  claim 7 , 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. 
     
     
         11 . The device of  claim 7 , wherein the device comprises the coated substrate;
 the structural protein is collagen Type I present in an amount of about 0.1 g/L to about 5.0 g/L;   the gelation inhibitor agent is urea present in an amount of about 0.1 M to about 6.0 M;   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.   
     
     
         12 . A coated substrate prepared by the method comprising:
 exposing a portion of a substrate to an aqueous system at a temperature of about 20° C. to about 80° C. to form a ceramic coating on a surface of the substrate;   wherein the aqueous system comprises a structural protein, a gelation inhibitor agent, a weak acid having a pKa of about 3.0 to about 5.5, water, Ca 2+ , HPO 4   2− , a buffer system, and optionally one or more of Mg 2+ , Na + , K + , Cl − , SO 4   2− ; or HCO 3   − ; and   wherein the aqueous system has an initial pH of about 5.0 to about 8.0.   
     
     
         13 . The coated substrate of  claim 12 , wherein the structural protein is collagen Type I, II, III, or V. 
     
     
         14 . The coated substrate of  claim 12 , wherein the gelation inhibitor agent is urea, histidine, hydroxyproline, thiourea, sodium dodecyl sulfate, lithium dodecyl sulfate, 2-mercaptoethanol, formamide, dithiothreitol, (3-[(3-cholamidopropyl)-dimethylammonio]-1-propane sulfonate), (3-([cholamidopropyl]-dimethyl ammonio)-2-hydroxy-1-propanesulfonate), guanidinium chloride (guanidine hydrochloride), or guanidinium thiocyanate. 
     
     
         15 . The coated substrate of  claim 12 , 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. 
     
     
         16 . The coated substrate of  claim 12 , wherein the weak acid is an organic carboxylic acid having a pKa of about 3.0 to about 5.5. 
     
     
         17 . The coated substrate of  claim 12 , wherein
 the structural protein is collagen Type I present in an amount of about 0.1 g/L to about 5.0 g/L;   the gelation inhibitor agent is urea present in an amount of about 0.1 M to about 6.0 M;   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.   
     
     
         18 . The coated substrate of  claim 12 , wherein the exposing the substrate to the aqueous system occurs for a time of about 10 hours to about 48 hours. 
     
     
         19 . The coated substrate of  claim 12 , wherein the substrate comprises a metal, a ceramic, a polymeric material, or silicon. 
     
     
         20 . The coated substrate of  claim 12 , wherein the coating is performed in a sealed container, wherein the sealed container comprises a pressure valve.