Plasma modified medical devices and methods

Abstract

Coatings, devices and methods are provided, wherein the contacting surface of a medical device with at least one contacting surface for contacting a bodily fluid or tissue, wherein long-lasting and durable bioactive agents or functional groups are deposited on the contacting surface through a unique two-step plasma coating process with deposition of a thin layer of plasma coating using a silicon-containing monomer in the first step and plasma surface modification using a mixture of nitrogen-containing molecules and oxygen-containing molecules in the second step. The two-step plasma coating process enables the implantable medical device to prevent both restenosis and thrombosis under clinical conditions. The invention also relates to surface treatment of metallic and polymeric biomaterials used for making of medical devices with significantly improved clinical performance and durability.

1 . A medical device adapted for implantation into a human or animal host comprising at least one contacting surface for contacting a bodily fluid or tissue, wherein the contacting surface is has been modified by a two-step plasma treatment process with 1) deposition of a thin layer of a plasma coating using a silicon-containing monomer selected from the silane group that can be vaporized at a temperature of less than 100° C. to produce a plasma surface; and 2) said plasma surface is subsequently modified using a mixture of nitrogen-containing molecules and oxygen-containing molecules. 
     
     
         2 . (canceled) 
     
     
         3 . (canceled) 
     
     
         4 . The device of  claim 1 , wherein the silicon-containing monomers comprise a member selected from the silane group consisting of trimethylsilane (TMS), dimethylsilane, vinyltrichlorosilane, tetraethoxysilane, vinyltriethoxysilane, hexamethyldisilazane, tetramethylsilane, vinyldimethylethoxysilane, vinyltrimethoxysilane, tetravinylsilane, vinyltriacetoxysilane, and methyltrimethoxysilane. 
     
     
         5 . The device of  claim 1 , wherein the silicon-containing monomers comprise a member selected from the silane group consisting of (CH 3 ) 3 —SiH and (CH 3 ) 2 —SiH 2 . 
     
     
         6 . The device of  claim 1 , wherein the nitrogen-containing molecules each comprise no more than six atoms. 
     
     
         7 . The device of  claim 5 , wherein the nitrogen-containing molecules each comprise four or fewer atoms. 
     
     
         8 . The device of  claim 1 , wherein the nitrogen-containing molecules are molecules selected from the group consisting of NH 3 , N 2 O, NO, NO 2  and N 2 O 4 . 
     
     
         9 . The device of  claim 1 , wherein the oxygen-containing molecules are molecules selected from the group consisting of O 2  and O 3 . 
     
     
         10 . The device of  claim 1 , wherein the plasma surface is modified with nitrogen-containing molecules and oxygen-containing molecules simultaneously. 
     
     
         11 . The device of  claim 1 , wherein the plasma-modified contacting surface exhibits increased adhesion of at least some mammalian cells, compared to a similar contacting surface that is not plasma-modified. 
     
     
         12 . The device of  claim 10 , wherein the human or the animal host comprising endothelial cells. 
     
     
         13 . The device of  claim 1 , wherein the medical device is a stent. 
     
     
         14 . The device of  claim 13 , wherein the plasma-modified contacting surface exhibits decreased restenosis subsequent to placement in blood vessel, compared to a similar stent that is not plasma-modified. 
     
     
         15 . The device of  claim 1 , wherein the plasma coating is less than 100 nm. 
     
     
         16 . The device of  claim 15 , wherein the plasma coating is less than 60 nm. 
     
     
         17 . The device of  claim 15 , wherein the plasma coating is less than 20 nm. 
     
     
         18 . The device of  claim 15 , wherein the plasma coating is between 10 and 20 nm. 
     
     
         19 . The device of  claim 1 , wherein the plasma surface is modified for less than about 10 minutes. 
     
     
         20 . The device of  claim 1 , wherein the silicon-containing monomer is (CH 3 ) 3 —SiH. 
     
     
         21 . The device of  claim 1 , wherein the thin layer of plasma coating is a nano-scale (less than 100 nm) plasma coating that is fabricated by a glow discharge plasma deposition process. 
     
     
         22 . The device of  claim 1 , wherein the nitrogen-containing molecules are NH 3  and the oxygen-containing molecules are O 2 . 
     
     
         23 . The device of  claim 1 , wherein the contacting surface is a metallic or polymeric surface. 
     
     
         24 . The device of  claim 1  is a member of selected from the group comprising stents, catheters, balloons, shunts, grafts, valves, pacemakers, pulsed generators, cardiac defibrillators, spinal stimulators, brain stimulators, leads, screws and sensors. 
     
     
         25 . A two-step process for modifying a medical device adapted for implantation into a human or animal host comprising at least one contacting surface for contacting a bodily fluid or tissue, comprising the steps of: 1) depositing of a thin layer of a plasma coating using a silicon-containing monomer onto the contacting surface of the device to produce a plasma surface; and 2) modifying said plasma surface subsequently by using a mixture of nitrogen-containing molecules and oxygen-containing molecules. 
     
     
         26 . The process of  claim 25 , wherein the silicon-containing monomers comprise a member selected from the silane group that are gases at normal conditions. 
     
     
         27 . The process of  claim 25 , wherein the silicon-containing monomers comprise a member selected from the silane group that can be vaporized at a temperature of less than 100° C. 
     
     
         28 . The process of  claim 25 , wherein the silicon-containing monomers comprise a member selected from the silane group consisting of trimethylsilane (TMS), dimethylsilane, vinyltrichlorosilane, tetraethoxysilane, vinyltriethoxysilane, hexamethyldisilazane, tetramethylsilane, vinyldimethylethoxysilane, vinyltrimethoxysilane, tetravinylsilane, vinyltriacetoxysilane, and methyltrimethoxysilane. 
     
     
         29 . The process of  claim 25 , wherein the silicon-containing monomers comprise a member selected from the silane group consisting of (CH 3 ) 3 —SiH and (CH 3 ) 2 —SiH 2 . 
     
     
         30 . The process of  claim 25 , wherein the nitrogen-containing molecules each comprise no more than six atoms. 
     
     
         31 . The process of  claim 25 , wherein the nitrogen-containing molecules are molecules selected from the group consisting of NH 3 , N 2 O, NO, NO 2  and N 2 O 4 . 
     
     
         32 . The process of  claim 25 , wherein the plasma-modified contacting surface exhibits increased adhesion of at least some mammalian cells, compared to a similar contacting surface that is not plasma-modified. 
     
     
         33 . The process of  claim 25 , wherein the medical device is a stent. 
     
     
         34 . The process of  claim 33 , wherein the plasma-modified contacting surface exhibits decreased restenosis subsequent to placement in a blood vessel, compared to a similar stent that is not plasma-modified. 
     
     
         35 . The process of  claim 25 , wherein the plasma surface is modified for less than about 10 minutes. 
     
     
         36 . The process of  claim 25 , wherein the silicon-containing monomer is (CH 3 ) 3 —SiH. 
     
     
         37 . The process of  claim 25 , wherein the thin layer of plasma coating is fabricated by a glow discharge plasma deposition process. 
     
     
         38 . The process of  claim 25 , wherein the nitrogen-containing molecules are NH 3  and the oxygen-containing molecules are O 2 . 
     
     
         39 . The process of  claim 25 , wherein the contacting surface is a metallic or polymeric surface.