Ultrathin Interfacial Layer on a Hydrogel to Direct its Surface Properties and Cell Adhesion

Abstract

A method is disclosed for coating and patterning hydrogels in order to modify surface properties. The method exploits the water content of the hydrogel and the hydrophobicity of the reaction solvent to create a thin oxide adhesion layer on the hydrogel surface. This oxide adhesion layer enables rapid transformation of the hydrophilic, cell non-adhesive hydrogel into either a highly hydrophobic or a cell-adhesive hydrogel by reaction with an alkylphosphonic acid or an α,φ-diphosphonoalkane, respectively. Also disclosed are coated, patterned hydrogels and constructs comprising the coated, patterned hydrogels.

1 - 23 . (canceled) 
     
     
         24 . A method of coating a hydrogel with an inorganic oxide adhesion layer, comprising the steps of:
 a) providing an at least partially hydrated hydrogel;   b) providing a coating mixture comprising an anhydrous hydrophobic solvent containing a water-reactive inorganic compound which is dissolved and/or dispersed in the solvent; and   c) contacting said hydrogel with said coating solution for a time and at a temperature sufficient to form an inorganic oxide coating at the solvent interface on the surface of said hydrogel to provide a coated hydrogel;   wherein said inorganic compound is selected from the group consisting of the alkoxides, alkyls, amides and halides of Ti, Zr, Al, Mg, Si, Zn, Mo, Nb, Ta, Sn, W, and V, and said hydrogel contains at least 10 nmol of water/cm′ at the surface or available to the surface of the hydrogel.   
     
     
         25 . The method of  claim 24 , further comprising:
 d) removing said coated hydrogel from said coating solution; and   e) rinsing with a solvent to provide a rinsed coated hydrogel.   
     
     
         26 . The method of  claim 25 , further comprising:
 f) heating said rinsed coated hydrogel to 30 to 40° C., and removing the optional pattern mask.   
     
     
         27 . The method of  claim 24 , wherein said inorganic compound is selected from the group consisting of the alkoxides of Al, Ti, Zr, Si, Mg and Zn. 
     
     
         28 . The method of  claim 24 , wherein said inorganic compound is an alkoxide selected from the group consisting of methoxide, ethoxide, propoxide, iso-propoxide, butoxide, iso-butoxide, sec-butoxide, and tert-butoxide. 
     
     
         29 . The method of  claim 24 , wherein said inorganic compound is an alkyl, an amide or a halide. 
     
     
         30 . The method of  claim 29 , wherein said halide is chloride. 
     
     
         31 . The method of  claim 24 , wherein said contacting step comprises suspending said hydrogel in said coating solution. 
     
     
         32 . The method of  claim 24 , wherein said adhesion layer comprises a pattern over at least part of the hydrogel surface. 
     
     
         33 . The method of  claim 32 , wherein said pattern comprises continuous stripes spanning at least part of the hydrogel surface. 
     
     
         34 . The method of  claim 24 , wherein said hydrogel comprises a cross-linkable polymer selected from the group consisting of polyethylene glycol, polyacrylate, and polyvinyl alcohol; or a polysaccharide or polysaccharide derivative selected from the group consisting of polysaccharides, alginates, hyaluronic acids, guar gum, xanthan gum, carrageenan, methyl cellulose, carboxymethyl cellulose, ethyl methyl cellulose, hydroxypropyl cellulose, and hypromellose. 
     
     
         35 . The method of  claim 34 , wherein said cross-linkable polymer is cross-linked with fumarate. 
     
     
         36 . The method of  claim 34 , wherein said hydrogel comprises oligo(polyethylene glycol) fumarate (OPF). 
     
     
         37 . The method of  claim 34 , wherein the said hydrogel further comprises a self-assembled monolayer (SAM) bonded to said inorganic oxide adhesion layer, wherein said SAM is selected from organic compounds comprising a phosphonic, carboxylic, sulfonic, phosphinic, phosphoric, sulfinic, or hydroxamic group. 
     
     
         38 . The method of  claim 37 , wherein said SAM comprises a self-assembled monolayer of phosphonates (SAMP). 
     
     
         39 . The method of  claim 38 , wherein said phosphonates are selected from the group consisting of hydrophobic phosphonates and cell-adhesive phosphonates. 
     
     
         40 . The method of  claim 39 , wherein said hydrophobic and cell-adhesive phosphonates are selected from the group consisting of phosphonic acids of structure 
       
         
           
           
               
               
           
         
         wherein the R group is selected from the group consisting of optionally substituted alkyl, optionally substituted heteroalkyl, optionally substituted alkenyl, optionally substituted heteroalkenyl, optionally substituted alkynyl, optionally substituted heteroalkynyl, optionally substituted aryl, optionally substituted arylalkyl, optionally substituted heteroaryl, and optionally substituted heteroarylalkyl, where heteroalkyl, heteroalkenyl, heteroalkynyl, heteroaryl and heteroarylalkyl contain one or more heteroatoms selected from the group consisting of O, N and S. 
       
     
     
         41 . The method of  claim 40 , wherein said hydrophobic phosphonates are selected from the group consisting of R=C 3 -C 30  alkyl, and said cell-adhesive phosphonates are selected from the group consisting of R=C 3 -C 30  alkyl substituted with a further phosphonate group. 
     
     
         42 . The method of  claim 41 , wherein said cell-adhesive phosphonates are selected from the group consisting of C 3 -C 30  α,ω-diphosphonates.