Nanofibers containing latent reactive groups

Abstract

A nanofiber is formed by combining one or more natural or synthetic polymeric materials and one or more than one cross-linking agents having at least two latent reactive activatable groups. The latent reactive activatable nanofiber may be used to modify the surface of a substrate by activating at least one of the latent reactive activatable groups to bond the nanofiber to the surface by the formation of a covalent bond between the surface of the substrate and the latent reactive activatable group. Some of the remaining latent reactive activatable group(s) are left accessible on the surface of the substrate, and may be used for further surface modification of the substrate. Biologically active materials may be immobilized on the nanofiber modified surface by reacting with the latent reactive groups that are accessible on the surface of the substrate.

1 .- 56 . (canceled) 
     
     
         57 . A method of producing a latent reactive nanofiber comprising steps of: (a) preparing a composition comprising a cross-linking agent having at least two latent photochemically reactive groups, and a fiber forming material; and (b) forming a nanofiber from the composition of (a). 
     
     
         58 . The method according to  claim 57  wherein the step of forming a nanofiber comprises electrospinning the composition of (a). 
     
     
         59 . The method according to  claim 57  further comprising a step of treating the formed nanofiber to activate at least some of the latent photochemically reactive groups of the cross-linking agent, thereby forming a crosslinked nanofiber. 
     
     
         60 . The method according to  claim 57  wherein the cross-linking agent is a tri-functional monomeric or polymeric material. 
     
     
         61 . The method according to  claim 57  wherein the cross-linking agent has a formula:
   L-(T-C(R 1 )(XP)CHR 2 GR 3 C(═O)R 4 ) m  
 
 wherein L is a linking group; 
 T is (—CH 2 —) x , (—CH 2 CH 2 —O—) x , (—CH 2 —CH 2 —CH 2 —O—) x , or (—CH 2 —CH 2 —CH 2 —CH 2 —O—) x , ; 
 R 1  is a hydrogen atom, an alkyl, alkyloxyalkyl, aryl, aryloxyalkyl or aryloxyaryl group; 
 X is O, S, or NR 8 R 9 ; 
 P is a hydrogen atom or a protecting group, with the proviso that P is absent when X is NR 8 R 9 ; 
 R 2  is a hydrogen atom, an alkyl, alkyloxyalkyl, aryl, aryloxyalkyl or aryloxyaryl group; 
 G is O, S, SO, SO 2 , NR 10 , (CH 2 ) t —O— or C═O; 
 R 3  and R 4  are each independently an alkyl, aryl, arylalkyl, heteroaryl, or an heteroarylalkyl group or optionally, R 3  and R 4  can be tethered together via (—CH 2 —) q , (—CH 2 —) r C═O(—CH 2 —) s , (—CH 2 —) r S(—CH 2 —) s , (—CH 2 —) r S═O(—CH 2 —) s , (CH 2 —) r S(O) 2 (—CH 2 —) s , or (—CH 2 —) r NR(—CH 2 —) s ; 
 R 10  is a hydrogen atom or an alkyl, aryl or arylalkyl group; 
 R 8  and R 9  are each independently a hydrogen atom, an alkyl, aryl, or arylalkyl group; 
 R is a hydrogen atom, an alkyl or aryl group; 
 q is an integer from 1 to about 7; 
 r is an integer from 0 to about 3; 
 s is an integer from 0 to about 3; 
 m is an integer from 2 to about 10; 
 t is an integer from 1 to about 10; and 
 x is an integer from 1 to about 500. 
 
     
     
         62 . The method according to  claim 57  wherein the cross-linking agent is tris[2-hydroxy-3-(4-benzoylphenoxy)propyl]isocyanurate having formula: 
       
         
           
           
               
               
           
         
       
     
     
         63 . The method according to  claim 57  wherein the fiber forming material is a synthetic or natural polymer. 
     
     
         64 . The method according to  claim 63  wherein the fiber forming material is a biodegradable polymer selected from polyesters, polyamides, polyurethanes, polyorthoesters, polycaprolactone, polyiminocarbonates, aliphatic carbonates, polyphosphazenes, polyanhydrides, and copolymers of these. 
     
     
         65 . The method according to  claim 63  wherein the fiber forming material comprises a polymer having peptide, nucleotide or saccharide monomeric units. 
     
     
         66 . The method according to  claim 63  wherein the fiber forming material is a thermally responsive polymeric material. 
     
     
         67 . The method according to  claim 66  wherein the thermally responsive polymeric material comprises poly(N-isopropylacrylamide) or polyethylene glycol-poly(N-isopropylacrylamide). 
     
     
         68 . The method according to  claim 63  wherein the fiber forming material comprises two or more polymeric materials. 
     
     
         69 . The method according to  claim 57  wherein the nanofiber further comprises a biologically active material or a functional polymer. 
     
     
         70 . A method of coating a surface of a substrate comprising steps of: (a) providing a latent reactive nanofiber according to  claim 57 ; and (b) contacting the surface with the formed nanofiber. 
     
     
         71 . The method according to  claim 70  further comprising a step of treating the surface to activate latent photochemically reactive groups of the cross-linking agent, thereby coupling the nanofiber to the surface via the cross-linking agent. 
     
     
         72 . The method according to  claim 70  wherein the substrate comprises plastic, pyrolytic carbon, glass, ceramic or metal. 
     
     
         73 . The method according to  claim 70  wherein the substrate comprises a catheter, wound drainage tube, arterial graft, soft tissue patch, glove, shunt, stent, wound dressing, sutures, guide wire or prosthetic device. 
     
     
         74 . The method according to  claim 70  wherein the substrate comprises a slide, microliter well, microliter plate, Petri dish, tissue culture slide, tissue culture plate, tissue culture flask, cell culture plate, column support, chromatography media, microscope slide or chip.