Patterned gradient wound dressing and methods of using same to promote wound healing

Abstract

The present invention provides a wound dressing that includes a patterned gradient of immobilized growth factor molecules that promote directed migration of cells during dermal wound healing. Growth factor is immobilized on a support substrate to present a gradient pattern of increasing growth factor concentration to migrating cells. Methods of promoting wound healing using the patterned gradient wound dressing and fabrication methods of same are also provided.

1 . A patterned gradient wound dressing for promoting directed cell migration during dermal wound healing, comprising: (a) a support substrate for placement at a dermal wound; and (b) a growth factor gradient immobilized to the support substrate, the growth factor gradient characterized by an increasing concentration of growth factor that promotes directed cell migration across said growth factor gradient from low to high growth factor concentration during dermal wound healing. 
     
     
         2 . The patterned gradient wound dressing according to  claim 1 , wherein the growth factor gradient is characterized by an exponentially increasing concentration of growth factor. 
     
     
         3 . The patterned gradient wound dressing according to  claim 1 , wherein said growth factor is selected from the group consisting of epidermal growth factor (“EGF”), insulin-like growth factor 1 (“IGF-1”), basic fibroblast growth factor (“bFGF”), platelet-derived growth factor (“PDGF”), vascular endothelial growth factor (“VEGF”), keratinocyte growth factor (“KGF”), transforming growth factor alpha (“TGF-a”), transforming growth factor beta (“TGF-b”) and mixtures thereof. 
     
     
         4 . The patterned gradient wound dressing according to  claim 1 , wherein said growth factor gradient further comprises an extracellular matrix protein. 
     
     
         5 . The patterned gradient wound dressing according to  claim 1 , wherein said growth factor gradient further comprises an angiogenesis factor. 
     
     
         6 . The patterned gradient wound dressing according to  claim 1 , wherein said support substrate is made of a polymeric material. 
     
     
         7 . The patterned gradient wound dressing according to  claim 6 , wherein said polymeric material is selected from the group consisting of polytetrafluoroethylene, polydimethylsiloxane, poly-vinylidine fluoride, polyethylene, polystyrene, polycarbonate, polyhydroxyethyl methacrylate, polyvinyl alcohol, polyvinyl chloride, polycaproamide, polyetheyleneoxide, polyethyleneterephthalate, polyacrylonitrile, silicones, polysilanes, polysiloxanes, polyurethanes, polylactides, polyglycolic acid, polybeta hydroxybutyrate, polyepisilon caprolactone, polyanhyhdrides, polyorthoesters, polyiminocarbonates, mixtures thereof and copolymers thereof. 
     
     
         8 . The patterned gradient wound dressing according to  claim 1 , wherein said support substrate is made of an interpenetrating polymer network (“IPN”). 
     
     
         9 . The patterned gradient wound dressing according to  claim 1 , wherein said support substrate is made of a sol-gel. 
     
     
         10 . The patterned gradient wound dressing according to  claim 1 , wherein said support substrate is made of a hydrogel. 
     
     
         11 . The patterned gradient wound dressing according to  claim 1 , wherein said support substrate is made of a natural product. 
     
     
         12 . The patterned gradient wound dressing according to  claim 11 , wherein said natural product is selected from the group consisting of alginates, gelatins, collagen, fibrin, hyaluronan, cellulose, polycarbohydates, mycoses, polyxyloses, chitans, polymers of amino glucoses, tragacanths, and latexes. 
     
     
         13 . The patterned gradient wound dressing according to  claim 1 , wherein said growth factor gradient is spatially-oriented relative to the support substrate such that the low concentration of growth factor gradient is located along a periphery of the support substrate, wherein the low concentration of the growth factor gradient is immediately adjacent to the dermal wound when the support substrate is placed at said dermal wound. 
     
     
         14 . The patterned gradient wound dressing according to  claim 1 , wherein said growth factor gradient is in the form of a two dimensional radial pattern. 
     
     
         15 . The patterned gradient wound dressing according to  claim 1 , wherein said growth factor gradient is in the form of a three dimensional radial pattern. 
     
     
         16 . The patterned gradient wound dressing according to  claim 1 , wherein said growth factors are immobilized to the support substrate through covalent linkage formed by a photoactivatable crosslinker. 
     
     
         17 . A method for treating a dermal wound, comprising:
 (a) providing a patterned gradient wound dressing including: (i) a support substrate for placement at the dermal wound; and (ii) a growth factor gradient immobilized to the support substrate, the growth factor gradient characterized by a concentration of growth factor that promotes directed cell migration across said growth factor gradient from low to high growth factor concentration during dermal wound healing; and   (b) applying said patterned gradient wound dressing to the dermal wound in the course of wound management to thereby treat said dermal wound.   
     
     
         18 . The method according to  claim 17 , wherein the dermal wound is an acute dermal wound. 
     
     
         19 . The method according to  claim 17 , wherein the dermal wound is a chronic dermal wound. 
     
     
         20 . A method of screening for agents that promote directed cell migration, comprising:
 (a) providing a support substrate and a test agent gradient immobilized to said support substrate; and   (b) evaluating the ability of cells to migrate across the test agent gradient and comparing to a control that is treated with the same conditions but without the test agent gradient wherein an improvement in migration of cells across the test agent gradient relative to control indicates that the test agent promotes directed cell migration.