US2005058686A1PendingUtilityA1

Bioactive coating for medical devices

40
Priority: Jul 25, 2002Filed: Jul 25, 2003Published: Mar 17, 2005
Est. expiryJul 25, 2022(expired)· nominal 20-yr term from priority
Inventors:Mark E. Van DykeArlene J. Siller-Jackson
B60R 2019/505C09D 189/04C09D 189/06A61L 27/34B60Q 1/2661
40
PatentIndex Score
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Cited by
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References
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Claims

Abstract

A medical device (and method for making same) comprising a passivating coating comprising keratin.

Claims

exact text as granted — not AI-modified
1 . A medical device comprising a substrate comprising a passivating coating comprising keratin, said passivating coating being effective to increase bone matrix formation exhibited by cultured 2T3 mouse osteoblasts cells.  
     
     
         2 . The medical device of  claim 1  selected from the group consisting of tissue engineering constructs, orthopedic implants, dental implants, and ventricular assist devices.  
     
     
         3 . The medical device of  claim 1  comprising a medical implant.  
     
     
         4 . The medical device of  claim 3  wherein said substrate comprises a biocompatible material.  
     
     
         5 . The medical device of  claim 4  wherein the biocompatible material is selected from the group consisting of metals, metal alloys, and ceramics.  
     
     
         6 . The medical device of  claim 5  wherein said biocompatible material is selected from the group consisting of titanium and hydroxyapatite.  
     
     
         7 . The medical device of  claim 1  wherein said passivating coating comprises keratin and one or more bioactive factors selected from the group consisting of bone morphogenetic protein (BMP) and transforming growth factor beta (TGF-β).  
     
     
         8 . The medical device of  claim 2  wherein said passivating coating comprises keratin and one or more bioactive factors selected from the group consisting of bone morphogenetic protein (BMP) and transforming growth factor beta (TGF-β).  
     
     
         9 . The medical device of  claim 3  wherein said passivating coating comprises keratin and one or more bioactive factors selected from the group consisting of bone morphogenetic protein (BMP) and transforming growth factor beta ((TGF-β)).  
     
     
         10 . The medical device of  claim 1  wherein said keratin is derived from a material selected from the group consisting of hair, fur, feathers, horns, hooves, beaks, and feet.  
     
     
         11 . The medical device of  claim 3  wherein said keratin is derived from a material selected from the group consisting of hair, fur, feathers, horns, hooves, beaks, and feet.  
     
     
         12 . The medical device of  claim 9  wherein said keratin is derived from a material selected from the group consisting of hair, fur, feathers, horns, hooves, beaks, and feet.  
     
     
         13 . The medical device of  claim 1  wherein said keratin is derived from hair.  
     
     
         14 . The medical device of  claim 3  wherein said keratin is derived from hair.  
     
     
         15 . The medical device of  claim 9  wherein said keratin is derived from hair.  
     
     
         16 . The medical device of  claim 1  wherein said keratin is human hair keratin.  
     
     
         17 . The medical device of  claim 3  wherein said keratin is human hair keratin.  
     
     
         18 . The medical device of  claim 9  wherein said keratin is human hair keratin.  
     
     
         19 . The medical device of  claim 1  wherein said keratin comprises reduced keratin.  
     
     
         20 . The medical device of  claim 3  wherein said keratin comprises reduced keratin.  
     
     
         21 . The medical device of  claim 9  wherein said keratin comprises reduced keratin.  
     
     
         22 . The medical device of  claim 17  wherein said keratin comprises reduced keratin.  
     
     
         23 . The medical device of  claim 18  wherein said keratin comprises reduced keratin.  
     
     
         24 . The medical device of  claim 1  wherein said keratin comprises high molecular weight keratin (HMWK) having a molecular weight of from about 50 to about 85 kDa.  
     
     
         25 . The medical device of  claim 3  wherein said keratin comprises high molecular weight keratin (HMWK) having a molecular weight of from about 50 to about 85 kDa.  
     
     
         26 . The medical device of  claim 9  wherein said keratin comprises high molecular weight keratin (HMWK) having a molecular weight of from about 50 to about 85 kDa.  
     
     
         27 . The medical device of  claim 18  wherein said keratin comprises high molecular weight keratin (HMWK) having a molecular weight of from about 50 to about 85 kDa.  
     
     
         28 . The medical device of  claim 23  wherein said keratin comprises high molecular weight keratin (HMWK) having a molecular weight of from about 50 to about 85 kDa.  
     
     
         29 . The medical device of  claim 1  wherein said passivating coating is effective to accelerate bone matrix formation by cultured 2T3 mouse osteoblasts.  
     
     
         30 . The medical device of  claim 3  wherein said passivating coating is effective to accelerate bone matrix formation by cultured 2T3 mouse osteoblasts.  
     
     
         31 . The medical device of  claim 9  wherein said passivating coating is effective to accelerate bone matrix formation by cultured 2T3 mouse osteoblasts.  
     
     
         32 . The medical device of  claim 23  wherein said passivating coating is effective to accelerate bone matrix formation by cultured 2T3 mouse osteoblasts.  
     
     
         33 . The medical device of  claim 28  wherein said passivating coating is effective to accelerate bone matrix formation by cultured 2T3 mouse osteoblasts.  
     
     
         34 . A medical implant comprising: 
 a substrate comprising a passivating coating comprising keratin, said passivating coating being effective to increase bone matrix formation by cultured 2T3 mouse osteoblasts, said passivating coating comprising a bonding region and a bioactive region;    said bonding region comprising at least one organosilane compound comprising a silane component bound to a surface of said substrate; and    said bioactive region comprising an organic component of said organosilane bound to a reactive pendant group on said keratin.    
     
     
         35 . The medical implant of  claim 34  wherein said silane component of said organosilane compound is covalently bonded with a surface of the substrate.  
     
     
         36 . The medical implant of  claim 34  wherein said bioactive region comprises reactive pendant groups on said keratin covalently bonded to said organic component of said organosilane.  
     
     
         37 . The medical implant of  claim 35  wherein said bioactive region comprises reactive pendant groups on said keratin covalently bonded to said organic component of said organosilane.  
     
     
         38 . The medical implant of  claim 34  wherein said passivating coating comprises keratin and one or more bioactive factors selected from the group consisting of bone morphogenetic protein (BMP) and transforming growth factor beta ((TGF-β).  
     
     
         39 . The medical implant of  claim 35  wherein said passivating coating comprises keratin and one or more bioactive factors selected from the group consisting of bone morphogenetic protein (BMP) and transforming growth factor beta ((TGF-β).  
     
     
         40 . The medical implant of  claim 36  wherein said passivating coating comprises keratin and one or more bioactive factors selected from the group consisting of bone morphogenetic protein (BMP) and transforming growth factor beta ((TGF-β).  
     
     
         41 . The medical implant of  claim 37  wherein said passivating coating comprises keratin and one or more bioactive factors selected from the group consisting of bone morphogenetic protein (BMP) and transforming growth factor beta ((TGF-β).  
     
     
         42 . The medical implant of  claim 34  wherein said organic component of said organosilane comprises a moiety selected from the group consisting of epoxy groups, alkoxy groups, vinyl groups, amine groups, isocyanate groups, and carboxyl groups.  
     
     
         43 . The medical implant of  claim 34  wherein said organic component of said organosilane comprises a moiety selected from the group consisting of epoxy groups, alkoxy groups, vinyl groups, and amine groups.  
     
     
         44 . The medical implant of  claim 43  wherein said amine groups are alkylamine groups.  
     
     
         45 . The medical implant of  claim 34  wherein said organic component comprises a moiety selected from the group consisting of vinyl groups and epoxy groups.  
     
     
         46 . The medical implant of  claim 36  wherein said organic component of said organosilane comprises a moiety selected from the group consisting of epoxy groups, alkoxy groups, vinyl groups, amine groups, isocyanate groups, and carboxyl groups.  
     
     
         47 . The medical implant of  claim 36  wherein said organic component of said organosilane comprises a moiety selected from the group consisting of epoxy groups, alkoxy groups, vinyl groups, and amine groups.  
     
     
         48 . The medical implant of  claim 51  wherein said amine groups are alkylamine groups.  
     
     
         49 . The medical implant of  claim 36  wherein said organic component comprises a moiety selected from the group consisting of vinyl groups and epoxy groups.  
     
     
         50 . The medical implant of  claim 37  wherein said organic component of said organosilane comprises a moiety selected from the group consisting of epoxy groups, alkoxy groups, vinyl groups, amine groups, isocyanate groups, and carboxyl groups.  
     
     
         51 . The medical implant of  claim 37  wherein said organic component of said organosilane comprises a moiety selected from the group consisting of epoxy groups, alkoxy groups, vinyl groups, and amine groups.  
     
     
         52 . The medical implant of  claim 55  wherein said amine groups are alkylamine groups.  
     
     
         53 . The medical implant of  claim 37  wherein said organic component comprises a moiety selected from the group consisting of vinyl groups and epoxy groups.  
     
     
         54 . The medical implant of  claim 41  wherein said organic component of said organosilane comprises a moiety selected from the group consisting of epoxy groups, alkoxy groups, vinyl groups, amine groups, isocyanate groups, and carboxyl groups.  
     
     
         55 . The medical implant of  claim 41  wherein said organic component of said organosilane comprises a moiety selected from the group consisting of epoxy groups, alkoxy groups, vinyl groups, and amine groups.  
     
     
         56 . The medical implant of  claim 59  wherein said amine groups are alkylamine groups.  
     
     
         57 . The medical implant of  claim 41  wherein said organic component comprises a moiety selected from the group consisting of vinyl groups and epoxy groups.  
     
     
         58 . The medical implant of  claim 34  wherein said organosilane comprises substituents selected from the group consisting of from about 1 to 3 halogens and from about 1 to 3 alkoxy groups.  
     
     
         59 . The medical implant of  claim 36  wherein said organosilane comprises substituents selected from the group consisting of from about 1 to 3 halogens and from about 1 to 3 alkoxy groups.  
     
     
         60 . The medical implant of  claim 37  wherein said organosilane comprises substituents selected from the group consisting of from about 1 to 3 halogens and from about 1 to 3 alkoxy groups.  
     
     
         61 . The medical implant of  claim 41  wherein said organosilane comprises substituents selected from the group consisting of from about 1 to 3 halogens and from about 1 to 3 alkoxy groups.  
     
     
         62 . The medical implant of  claim 54  wherein said organosilane comprises substituents selected from the group consisting of from about 1 to 3 halogens and from about 1 to 3 alkoxy groups.  
     
     
         63 . The medical implant of  claim 57  wherein said organosilane comprises substituents selected from the group consisting of from about 1 to 3 halogens and from about 1 to 3 alkoxy groups.  
     
     
         64 . The medical implant of  claim 34  wherein said passivating coating is effective to accelerate bone matrix formation in cultured 2T3 mouse osteoblasts.  
     
     
         65 . The medical implant of  claim 36  wherein said passivating coating is effective to accelerate bone matrix formation in cultured 2T3 mouse osteoblasts.  
     
     
         66 . The medical implant of  claim 37  wherein said passivating coating is 2 effective to accelerate bone matrix formation in cultured 2T3 mouse osteoblasts.  
     
     
         67 . The medical implant of  claim 41  wherein said passivating coating is 2 effective to accelerate bone matrix formation in cultured 2T3 mouse osteoblasts.  
     
     
         68 . The medical implant of  claim 54  wherein said passivating coating is effective to accelerate bone matrix formation in cultured 2T3 mouse osteoblasts.  
     
     
         69 . The medical implant of  claim 57  wherein said passivating coating is effective to accelerate bone matrix formation in cultured 2T3 mouse osteoblasts.  
     
     
         70 . The medical implant of  claim 63  wherein said passivating coating is effective to accelerate bone matrix formation in cultured 2T3 mouse osteoblasts.  
     
     
         71 . The medical implant of  claim 34  wherein said keratin comprises high molecular weight keratin (HMWK) having a molecular weight of from about 50 to about 85 kDa.  
     
     
         72 . The medical implant of  claim 36  wherein said keratin comprises high molecular weight keratin (HMWK) having a molecular weight of from about 50 to about 85 kDa.  
     
     
         73 . The medical implant of  claim 37  wherein said keratin comprises high molecular weight keratin (HMWK) having a molecular weight of from about 50 to about 85 kDa.  
     
     
         74 . The medical implant of  claim 51  wherein said keratin comprises high molecular weight keratin (HMWK) having a molecular weight of from about 50 to about 85 kDa.  
     
     
         75 . The medical implant of  claim 54  wherein said keratin comprises high molecular weight keratin (HMWK) having a molecular weight of from about 50 to about 85 kDa.  
     
     
         76 . The medical implant of  claim 57  wherein said keratin comprises high molecular weight keratin (HMWK) having a molecular weight of from about 50 to about 85 kDa.  
     
     
         77 . The medical implant of  claim 63  wherein said keratin comprises high molecular weight keratin (HMWK) having a molecular weight of from about 50 to about 85 kDa.  
     
     
         78 . The medical implant of  claim 70  wherein said keratin comprises high molecular weight keratin (HMWK) having a molecular weight of from about 50 to about 85 kDa.  
     
     
         79 . A medical implant comprising: 
 a substrate comprising a biocompatible material selected from the group consisting of metals, metal alloys, and ceramics;    a passivating coating on said substrate comprising HMWK keratin and one or more bioactive factors selected from the group consisting of bone morphogenetic protein (BMP) and transforming growth factor beta ((TGF-β), said passivating coating being effective to increase bone matrix formation by cultured 2T3 mouse osteoblasts said passivating coating comprising an organosilane compound comprising a silane component and an organic component, said passivating coating comprising a bonding region and a bioactive region;    said bonding region comprising said silane component covalently bound to a surface of said substrate; and    said bioactive region comprising said organic component covalently bound to a reactive pendant group on said keratin.    
     
     
         80 . The medical implant of  claim 79  wherein said organic component of said organosilane comprises a moiety selected from the group consisting of epoxy groups, alkoxy groups, vinyl groups, amine groups, isocyanate groups, and carboxyl groups.  
     
     
         81 . The medical implant of  claim 79  wherein said organic component of said organosilane comprises a moiety selected from the group consisting of epoxy groups, alkoxy groups, vinyl groups, and amine groups.  
     
     
         82 . The medical implant of  claim 81  wherein said amine groups are alkylamine groups.  
     
     
         83 . The medical implant of  claim 79  wherein said organic component comprises a moiety selected from the group consisting of vinyl groups and epoxy groups.  
     
     
         84 . The medical implant of  claim 79  wherein said organosilane comprises substituents selected from the group consisting of from about 1 to 3 halogens and from about 1 to 3 alkoxy groups.  
     
     
         85 . The medical implant of  claim 80  wherein said organosilane comprises 2 substituents selected from the group consisting of from about 1 to 3 halogens and 3 from about 1 to 3 alkoxy groups.  
     
     
         86 . The medical implant of  claim 81  wherein said organosilane comprises substituents selected from the group consisting of from about 1 to 3 halogens and from about 1 to 3 alkoxy groups.  
     
     
         87 . The medical implant of  claim 82  wherein said organosilane comprises substituents selected from the group consisting of from about 1 to 3 halogens and from about 1 to 3 alkoxy groups.  
     
     
         88 . The medical implant of  claim 83  wherein said organosilane comprises substituents selected from the group consisting of from about 1 to 3 halogens and from about 1 to 3 alkoxy groups.  
     
     
         89 . The medical implant of  claim 79  wherein the medical implant is selected from the group consisting of a issue engineering construct, an orthopedic implant, a dental implant, and a ventricular assist device.  
     
     
         90 . The medical implant of  claim 79  wherein said biocompatible material is selected from the group consisting of titanium and hydroxyapatite.  
     
     
         91 . A medical implant comprising: 
 a substrate comprising titanium;    a passivating coating on said substrate comprising HMWK keratin and one or more bioactive factors selected from the group consisting of bone morphogenetic protein (BMP) and transforming growth factor beta ((TGF-β), said passivating coating being effective to increase bone matrix formation by cultured 2T3 mouse osteoblasts said passivating coating comprising an organosilane compound comprising a silane component and an organic component, said passivating coating comprising a bonding region and a bioactive region;    said bonding region comprising said silane component covalently bound to a surface of said substrate; and    said bioactive region comprising said organic component covalently bound to a reactive pendant group on said keratin.    
     
     
         92 . The medical implant of  claim 91  wherein said organic component of said organosilane comprises a moiety selected from the group consisting of epoxy groups, alkoxy groups, vinyl groups, amine groups, isocyanate groups, and carboxyl groups.  
     
     
         93 . The medical implant of  claim 91  wherein said organic component of said organosilane comprises a moiety selected from the group consisting of epoxy groups, alkoxy groups, vinyl groups, and amine groups.  
     
     
         94 . The medical implant of  claim 93  wherein said amine groups are alkylamine groups.  
     
     
         95 . The medical implant of  claim 91  wherein said organic component comprises a moiety selected from the group consisting of vinyl groups and epoxy groups.  
     
     
         96 . The medical implant of  claim 91  wherein said organosilane comprises substituents selected from the group consisting of from about 1 to 3 halogens and from about 1 to 3 alkoxy groups.  
     
     
         97 . The medical implant of  claim 92  wherein said organosilane comprises substituents selected from the group consisting of from about 1 to 3 halogens and from about 1 to 3 alkoxy groups.  
     
     
         98 . The medical implant of  claim 93  wherein said organosilane comprises substituents selected from the group consisting of from about 1 to 3 halogens and from about 1 to 3 alkoxy groups.  
     
     
         99 . The medical implant of  claim 94  wherein said organosilane comprises substituents selected from the group consisting of from about 1 to 3 halogens and from about 1 to 3 alkoxy groups.  
     
     
         100 . The medical implant of  claim 95  wherein said organosilane comprises substituents selected from the group consisting of from about 1 to 3 halogens and from about 1 to 3 alkoxy groups.  
     
     
         101 . The medical implant of  claim 100  wherein said halogen is chlorine.  
     
     
         102 . The medical implant of  claim 101  wherein the medical implant is selected from the group consisting of a issue engineering construct, an orthopedic implant, a dental implant, and a ventricular assist devices.  
     
     
         103 . A method of coating a medical device with a passivating coating, said method comprising: 
 bonding a coupling agent to one or more surfaces of said medical device, producing a bonding region; and,    bonding keratin to said bonding region.    
     
     
         104 . The method of  claim 103  further comprising cleaning said one or more surfaces before bonding said coupling agent to said one or more surfaces.  
     
     
         105 . The method of  claim 103  further comprising oxidizing said one or 2 more surfaces before bonding said coupling agent to said one or more surfaces.  
     
     
         106 . The method of  claim 104  further comprising oxidizing said one or more surfaces before bonding said coupling agent to said one or more surfaces.  
     
     
         107 . The method of  claim 104  wherein said cleaning comprises sonicating said one or more surfaces in first anhydrous solvent and sonicating said one or more surfaces in water.  
     
     
         108 . The method of  claim 107  wherein said first anhydrous solvent is selected from the group consisting of methanol, ethanol, isopropyl alcohol, dimethylsulfoxide, acetone, or tetrahydrofuran.  
     
     
         109 . The method of  claim 107  wherein said first anhydrous solvent is dichloromethane.  
     
     
         110 . The method of  claim 106  wherein said cleaning comprises sonicating in said one or more surfaces in first anhydrous solvent and sonicating said one or more surfaces in water.  
     
     
         111 . The method of  claim 110  wherein said first anhydrous solvent is selected from the group consisting of methanol, ethanol, isopropyl alcohol, dimethylsulfoxide, acetone, or tetrahydrofuran.  
     
     
         112 . The method of  claim 110  wherein said first anhydrous solvent is dichloromethane.  
     
     
         113 . The method of  claim 110  wherein said water is deionized water.  
     
     
         114 . The method of  claim 112  wherein said water is deionized water.  
     
     
         115 . The method of  claim 103  wherein bonding keratin to said bonding region comprises: 
 dissolving keratin in a solvent; and    adding second anhydrous solvent to produce a keratin mixture;    exposing said bonding region to said keratin mixture, producing a keratin coated bonding region; and    curing said keratin coated bonding region under conditions effective to produce said bioactive region.    
     
     
         116 . The method of  claim 106  wherein bonding keratin to said bonding region comprises: 
 dissolving keratin in a solvent; and    adding second anhydrous solvent to produce a keratin mixture;    exposing said bonding region to said keratin mixture, producing a keratin coated bonding region; and    curing said keratin coated bonding region under conditions effective to produce said bioactive region.    
     
     
         117 . The method of  claim 110  wherein bonding keratin to said bonding region comprises: 
 dissolving keratin in a solvent; and    adding second anhydrous solvent to produce a keratin mixture;    exposing said bonding region to said keratin mixture, producing a keratin coated bonding region; and    curing said keratin coated bonding region under conditions effective to produce said bioactive region.    
     
     
         118 . The method of  claim 111  wherein bonding keratin to said bonding region comprises: 
 dissolving keratin in a solvent; and    adding second anhydrous solvent to produce a keratin mixture;    exposing said bonding region to said keratin mixture, producing a keratin coated bonding region; and    curing said keratin coated bonding region under conditions effective to produce said bioactive region.    
     
     
         119 . The method of  claim 112  wherein bonding keratin to said bonding region comprises: 
 dissolving keratin in a solvent; and    adding second anhydrous solvent to produce a keratin mixture;    exposing said bonding region to said keratin mixture, producing a keratin coated bonding region; and    curing said keratin coated bonding region under conditions effective to produce said bioactive region.    
     
     
         120 . The method of  claim 103  wherein, when said keratin is reduced/reduced keratin, said solvent is water.  
     
     
         121 . The method of  claim 103  wherein, when said keratin is oxidized/reduced keratin, said solvent comprises an aqueous solution comprising a base.  
     
     
         122 . The method of  claim 121  wherein said base is selected from the group consisting of ammonium hydroxide, sodium hydroxide, potassium hydroxide, and combinations thereof.  
     
     
         123 . The method of  claim 122  wherein said base is ammonium hydroxide.  
     
     
         124 . The method of  claim 115  wherein said second anhydrous solvent is selected from the group consisting of methanol, ethanol, isopropyl alcohol, dimethylsulfoxide, acetone, and tetrahydrofuran.  
     
     
         125 . The method of  claim 115  wherein said second anhydrous solvent is dimethylsulfoxide.  
     
     
         126 . The method of  claim 116  wherein said second anhydrous solvent is selected from the group consisting of methanol, ethanol, isopropyl alcohol, dimethylsulfoxide, acetone, and tetrahydrofuran.  
     
     
         127 . The method of  claim 116  wherein said second anhydrous solvent is @dimethylsulfoxide.  
     
     
         128 . The method of  claim 117  wherein said second anhydrous solvent is selected from the group consisting of methanol, ethanol, isopropyl alcohol, @dimethylsulfoxide, acetone, and tetrahydrofuran.  
     
     
         129 . The method of  claim 117  wherein said second anhydrous solvent is @dimethylsulfoxide.  
     
     
         130 . The method of  claim 118  wherein said second anhydrous solvent is @selected from the group consisting of methanol, ethanol, isopropyl alcohol, dimethylsulfoxide, acetone, and tetrahydrofuran.  
     
     
         131 . The method of  claim 118  wherein said second anhydrous solvent is dimethylsulfoxide.  
     
     
         132 . The method of  claim 119  wherein said second anhydrous solvent is @selected from the group consisting of methanol, ethanol, isopropyl alcohol, @dimethylsulfoxide, acetone, and tetrahydrofuran.  
     
     
         133 . The method of  claim 119  wherein said second anhydrous solvent is dimethylsulfoxide.  
     
     
         134 . The method of  claim 120  wherein said second anhydrous solvent is @selected from the group consisting of methanol, ethanol, isopropyl alcohol, @dimethylsulfoxide, acetone, and tetrahydrofuran.  
     
     
         135 . The method of  claim 120  wherein said second anhydrous solvent is @dimethylsulfoxide.  
     
     
         136 . The method of  claim 121  wherein said second anhydrous solvent is selected from the group consisting of methanol, ethanol, isopropyl alcohol, @dimethylsulfoxide, acetone, and tetrahydrofuran.  
     
     
         137 . The method of  claim 121  wherein said second anhydrous solvent is dimethylsulfoxide.  
     
     
         138 . The method of  claim 115  further comprising mixing the keratin mixture with an activation agent selected from the group consisting of a catalyst and @an initiator.  
     
     
         139 . The method of  claim 138  wherein said activation agent is a vinyl-functional silane and said activation agent is effective to generate free radicals.  
     
     
         140 . The method of  claim 138  wherein said activation agent comprises an @anthraquinone-2-sulfonic acid.  
     
     
         141 . The method of  claim 116  further comprising mixing the keratin mixture with an activation agent selected from the group consisting of a catalyst and @an initiator.  
     
     
         142 . The method of  claim 141  wherein said activation agent is a vinyl-functional silane and said activation agent is effective to generate free radicals.  
     
     
         143 . The method of  claim 141  wherein said activation agent comprises an @anthraquinone-2-sulfonic acid.  
     
     
         144 . The method of  claim 119  further comprising mixing the keratin mixture with an activation agent selected from the group consisting of a catalyst and @an initiator.  
     
     
         145 . The method of  claim 119  wherein said activation agent is a vinyl-functional silane and said reagent is effective to generate free radicals.  
     
     
         146 . The method of  claim 145  wherein said activation agent comprises an anthraquinone-2-sulfonic acid.  
     
     
         147 . The method of  claim 115  wherein said conditions comprises exposing said keratin coated bonding region to an energy source for a period of time effective @to produce said bioactive region.  
     
     
         148 . The method of  claim 119  wherein said conditions comprises exposing said keratin coated bonding region to an energy source for a period of time effective @to produce said bioactive region.  
     
     
         149 . The method of  claim 146  wherein said conditions comprises exposing said keratin coated bonding region to an energy source for a period of time effective @to produce said bioactive region.  
     
     
         150 . The method of  claim 147  wherein said conditions comprises exposing said keratin coated bonding region to an energy source for a period of time effective @to produce said bioactive region.  
     
     
         151 . The method of  claim 146  wherein said conditions comprise the presence of said activation agent.  
     
     
         152 . The method of  claim 150  wherein said conditions comprise the presence of said activation agent.  
     
     
         153 . The method of  claim 149  wherein said period of time is from about 1 to about 24 hours  
     
     
         154 . The method of  claim 150  wherein said period of time is from about 1 to about 24 hours  
     
     
         155 . The method of  claim 151  wherein said period of time is from about 1 to about 24 hours  
     
     
         156 . The method of  claim 152  wherein said period of time is from about 1 to about 24 hours  
     
     
         157 . The method of  claim 149  wherein said period of time is about 24 @hours.  
     
     
         158 . The method of  claim 150  wherein said period of time is about 24 @hours.  
     
     
         159 . The method of  claim 151  wherein said period of time is about 24 @hours.  
     
     
         160 . The method of  claim 152  wherein said period of time is about 24 @hours.  
     
     
         161 . A medical implant comprising: 
 @a substrate comprising a passivating coating comprising keratin, said @passivating coating comprising a bonding region and a bioactive @region; @said bonding region comprising at least one organosilane compound @comprising a silane component bound to a surface of said substrate; and @said bioactive region comprising an organic component of said organosilane @bound to a reactive pendant group on said keratin.    
     
     
         162 . The medical implant of  claim 161  wherein said silane component of said organosilane compound is covalently bonded with a surface of the substrate.  
     
     
         163 . The medical implant of  claim 161  wherein said bioactive region comprises reactive pendant groups on said keratin covalently bonded to said organic component of said organosilane.  
     
     
         164 . The medical implant of  claim 162  wherein said bioactive region comprises reactive pendant groups on said keratin covalently bonded to said organic component of said organosilane.  
     
     
         165 . The medical implant of  claim 161  wherein said organic component of said organosilane comprises a moiety selected from the group consisting of epoxy groups, alkoxy groups, vinyl groups, amine groups, isocyanate groups, and carboxyl groups.  
     
     
         166 . The medical implant of  claim 161  wherein said organic component of said organosilane comprises a moiety selected from the group consisting of epoxy groups, alkoxy groups, vinyl groups, and amine groups.  
     
     
         167 . The medical implant of  claim 166  wherein said amine groups are alkylamine groups.  
     
     
         168 . The medical implant of  claim 162  wherein said organic component 2 comprises a moiety selected from the group consisting of vinyl groups and epoxy groups.  
     
     
         169 . The medical implant of  claim 163  wherein said organic component of said organosilane comprises a moiety selected from the group consisting of epoxy groups, alkoxy groups, vinyl groups, amine groups, isocyanate groups, and carboxyl groups.  
     
     
         170 . The medical implant of  claim 163  wherein said organic component of said organosilane comprises a moiety selected from the group consisting of epoxy groups, alkoxy groups, vinyl groups, and amine groups.  
     
     
         171 . The medical implant of  claim 170  wherein said amine groups are alkylamine groups.  
     
     
         172 . The medical implant of  claim 163  wherein said organic component comprises a moiety selected from the group consisting of vinyl groups and epoxy groups.  
     
     
         173 . The medical implant of  claim 164  wherein said organic component of said organosilane comprises a moiety selected from the group consisting of epoxy groups, alkoxy groups, vinyl groups, amine groups, isocyanate groups, and carboxyl groups.  
     
     
         174 . The medical implant of  claim 164  wherein said organic component of said organosilane comprises a moiety selected from the group consisting of epoxy groups, alkoxy groups, vinyl groups, and amine groups.  
     
     
         175 . The medical implant of  claim 174  wherein said amine groups are alkylamine groups.  
     
     
         176 . The medical implant of  claim 174  wherein said organic component comprises a moiety selected from the group consisting of vinyl groups and epoxy groups.  
     
     
         177 . The medical implant of  claim 161  wherein said organosilane comprises substituents selected from the group consisting of from about 1 to 3 halogens and from about 1 to 3 alkoxy groups.  
     
     
         178 . The medical implant of  claim 162  wherein said organosilane comprises substituents selected from the group consisting of from about 1 to 3 halogens and from about 1 to 3 alkoxy groups.  
     
     
         179 . The medical implant of  claim 163  wherein said organosilane comprises substituents selected from the group consisting of from about 1 to 3 halogens and from about 1 to 3 alkoxy groups.  
     
     
         180 . The medical implant of  claim 169  wherein said organosilane comprises substituents selected from the group consisting of from about 1 to 3 halogens and from about 1 to 3 alkoxy groups.  
     
     
         181 . The medical implant of  claim 170  wherein said organosilane comprises substituents selected from the group consisting of from about 1 to 3 halogens and from about 1 to 3 alkoxy groups.  
     
     
         182 . The medical implant of  claim 171  wherein said organosilane comprises substituents selected from the group consisting of from about 1 to 3 halogens and from about 1 to 3 alkoxy groups.  
     
     
         183 . The medical implant of  claim 172  wherein said organosilane comprises substituents selected from the group consisting of from about 1 to 3 halogens and from about 1 to 3 alkoxy groups.  
     
     
         184 . The medical implant of  claim 175  wherein said organosilane comprises substituents selected from the group consisting of from about 1 to 3 halogens and from about 1 to 3 alkoxy groups.  
     
     
         185 . The medical implant of  claim 176  wherein said organosilane comprises substituents selected from the group consisting of from about 1 to 3 halogens and from about 1 to 3 alkoxy groups.  
     
     
         186 . The medical implant of  claim 161  wherein said keratin comprises high molecular weight keratin (HMWK) having a molecular weight of from about 50 to about 85 kDa.  
     
     
         187 . The medical implant of  claim 162  wherein said keratin comprises high molecular weight keratin (HMWK) having a molecular weight of from about 50 to about 85 kDa.  
     
     
         188 . The medical implant of  claim 163  wherein said keratin comprises high molecular weight keratin (HMWK) having a molecular weight of from about 50 to about 85 kDa.  
     
     
         189 . The medical implant of  claim 169  wherein said keratin comprises high molecular weight keratin (HMWK) having a molecular weight of from about 50 to about 85 kDa.  
     
     
         190 . The medical implant of  claim 170  wherein said keratin comprises high molecular weight keratin (HMWK) having a molecular weight of from about 50 to about 85 kDa.  
     
     
         191 . The medical implant of  claim 171  wherein said keratin comprises high molecular weight keratin (HMWK) having a molecular weight of from about 50 to about 85 kDa.  
     
     
         192 . The medical implant of  claim 172  wherein said keratin comprises high molecular weight keratin (HMWK) having a molecular weight of from about 50 to about 85 kDa.  
     
     
         193 . The medical implant of  claim 175  wherein said keratin comprises high molecular weight keratin (HMWK) having a molecular weight of from about 50 to about 85 kDa.  
     
     
         194 . The medical implant of  claim 177  wherein said keratin comprises high molecular weight keratin (HMWK) having a molecular weight of from about 50 to about 85 kDa.  
     
     
         195 . The medical implant of  claim 178  wherein said keratin comprises high molecular weight keratin (HMWK) having a molecular weight of from about 50 to about 85 kDa.  
     
     
         196 . The medical implant of  claim 182  wherein said keratin comprises high molecular weight keratin (HMWK) having a molecular weight of from about 50 to about 85 kDa.  
     
     
         197 . The medical implant of  claim 183  wherein said keratin comprises high molecular weight keratin (HMWK) having a molecular weight of from about 50 to about 85 kDa.  
     
     
         198 . The medical implant of  claim 184  wherein said keratin comprises high molecular weight keratin (HMWK) having a molecular weight of from about 50 to about 85 kDa.  
     
     
         199 . The medical implant of  claim 185  wherein said keratin comprises high molecular weight keratin (HMWK) having a molecular weight of from about 50 to about 85 kDa.  
     
     
         200 . The medical implant of  claim 161  wherein the substrate comprises one or more biocompatible material is selected from the group consisting of silicon, metals, metal alloys, and ceramics.  
     
     
         201 . The medical implant of  claim 161  wherein said biocompatible material is selected from the group consisting of titanium and hydroxyapatite.  
     
     
         202 . The medical implant of  claim 161  wherein said biocompatible material comprises silicon.  
     
     
         203 . The medical implant of  claim 164  wherein the substrate comprises one or more biocompatible material is selected from the group consisting of silicon, metals, metal alloys, and ceramics.  
     
     
         204 . The medical implant of  claim 164  wherein said biocompatible material is selected from the group consisting of titanium and hydroxyapatite.  
     
     
         205 . The medical implant of  claim 164  wherein said biocompatible material comprises silicon.  
     
     
         206 . The medical implant of  claim 176  wherein the substrate comprises one or more biocompatible material is selected from the group consisting of silicon, metals, metal alloys, and ceramics.  
     
     
         207 . The medical implant of  claim 176  wherein said biocompatible material is selected from the group consisting of titanium and hydroxyapatite.  
     
     
         208 . The medical implant of  claim 176  wherein said biocompatible material comprises silicon.  
     
     
         209 . The medical implant of  claim 184  wherein the substrate comprises one or more biocompatible material is selected from the group consisting of silicon, metals, metal alloys, and ceramics.  
     
     
         210 . The medical implant of  claim 184  wherein said biocompatible material is selected from the group consisting of titanium and hydroxyapatite.  
     
     
         211 . The medical implant of  claim 184  wherein said biocompatible material comprises silicon.  
     
     
         212 . The medical implant of  claim 185  wherein the substrate comprises one or more biocompatible material is selected from the group consisting of silicon, metals, metal alloys, and ceramics.  
     
     
         213 . The medical implant of  claim 185  wherein said biocompatible material is selected from the group consisting of titanium and hydroxyapatite.  
     
     
         214 . The medical implant of  claim 185  wherein said biocompatible material comprises silicon.  
     
     
         215 . The medical implant of  claim 198  wherein the substrate comprises one or more biocompatible material is selected from the group consisting of silicon, metals, metal alloys, and ceramics.  
     
     
         216 . The medical implant of  claim 198  wherein said biocompatible material is selected from the group consisting of titanium and hydroxyapatite.  
     
     
         217 . The medical implant of  claim 198  wherein said biocompatible material 2.  
     
     
         218 . The medical implant of  claim 199  wherein the substrate comprises one or more biocompatible material is selected from the group consisting of silicon, metals, metal alloys, and ceramics.  
     
     
         219 . The medical implant of  claim 199  wherein said biocompatible material is selected from the group consisting of titanium and hydroxyapatite.  
     
     
         220 . The medical implant of  claim 199  wherein said biocompatible material comprises silicon.

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