Surface modification of substrates

Abstract

Methods of improving the surface characteristics of a medical device or instrument, and the devices and instruments improved thereby, are provided. The disclosed methods involve the chemical attachment of an activated hyaluronic acid, such as hyaluronic acid reacted with a carbodiimide, onto the surface of the device. The hyaluronic acid can be modified to include the presence of Fe +3 or Al +3 cations to prevent calcification of the device and surrounding tissue. The devices and instruments are particularly useful during a surgical procedure.

What is claimed is:  
     
         1 . A method of improving the characteristics of a medical device substrate comprising the steps of: 
 modifying the surface of the substrate to present reactive sites,    preparing an activated hyaluronic acid, and    contacting the modified substrate with the activated hyaluronic acid under conditions sufficient to form a chemical bond between the activated hyaluronic acid and the reactive sites on the substrate surface.    
     
     
         2 . The method of  claim 1  wherein the substrate is a polyalkylene terephthalate.  
     
     
         3 . The method of  claim 2  wherein the substrate is polyethylene terephthalate.  
     
     
         4 . The method of  claim 3  wherein the substrate is a film.  
     
     
         5 . The method of  claim 3  wherein the substrate is a fabric.  
     
     
         6 . The method of  claim 1  wherein the substrate is stainless steel.  
     
     
         7 . The method of  claim 6  wherein the substrate is a tub e.  
     
     
         8 . The method of  claim 6  wherein the substrate is a stent.  
     
     
         9 . The method of  claim 1  wherein the activated hyaluronic acid is contacted with the substrate in an aqueous solution at a temperature in the range of from about 4° C. to about 35° C.  
     
     
         10 . The method of  claim 9  wherein the temperature is in the range of from about 4° C. to about 25° C.  
     
     
         11 . The method of  claim 9  wherein the activated hyaluronic acid is contacted with the substrate for a time period of from about 2 hours to about 24 hours.  
     
     
         12 . The method of  claim 1  wherein the reactive site is a primary or secondary amino group.  
     
     
         13 . The method of  claim 12  wherein the reactive site is a primary amino group.  
     
     
         14 . The method of  claim 13  wherein the activated hyaluronic acid is prepared by reacting the hyaluronic acid with a carbodiimide in an aqueous solution under conditions sufficient to produce said activated hyaluronic acid.  
     
     
         15 . The method of  claim 14  wherein the reaction is carried out at a pH of from about 3.5 to about 7.0.  
     
     
         16 . The method of  claim 15  wherein the hyaluronic acid is present in the solution in a concentration in the range of from about 0.05% w/w to about 2% w/w.  
     
     
         17 . The method of  claim 16  wherein the hyaluronic acid is present in the solution in a concentration in the range of from about 0. 1% w/w to about 1% w/w.  
     
     
         18 . The method of  claim 15  wherein the molar ratio of carbodiimide to hyaluronic acid is in the range of from about 0.5:1 to about 2:1.  
     
     
         19 . The method of  claim 18  wherein the molar ratio of carbodiimide to hyaluronic acid is about 1.5:1.  
     
     
         20 . The method of  claim 14  wherein said carbodiimide is 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide, or 1-ethyl-3-(dimethylaminopropyl) carbodiimide methiodide.