Modified wound dressings

Abstract

Embodiments described herein relate to compounds for the detection of wounds, e.g., chronic wounds or infected wounds, including compositions, substrates, kits, dressing materials, and articles, and systems containing such compounds. Further embodiments relate to methods of using these compositions, kits and systems in diagnostic assays, and in the diagnosis and/or detection of chronic or infected wounds based on enzymatic conversion of specific substrates which are contained in the compositions. Additional embodiments relate to methods of characterizing wounds based on expression of a plurality of markers and using such information to treat, manage, and follow-up patients suffering from chronic or infected wounds.

1 . A wound dressing material comprising a compound of Formula I:
   M-L-R  Formula I
   wherein   M is a gel-forming polymer;   R is a reporter molecule;   L is a linker that is either absent or present, and L, when present, connects M and R; and
 wherein the reporter molecule comprises a detectable label. 
   
     
     
         2 . The wound dressing material of  claim 1 , wherein the L is absent. 
     
     
         3 . (canceled) 
     
     
         4 . The wound dressing material of  claim 1 , wherein L is present. 
     
     
         5 . (canceled) 
     
     
         6 . The wound dressing material of  claim 1 , wherein the reporter comprises an enzyme substrate, wherein the enzyme substrate is a sugar, a polysaccharide, a nucleic acid, an amide, a peptide, a protein, a lipid, or a derivative thereof or a combination thereof. 
     
     
         7 . (canceled) 
     
     
         8 . (canceled) 
     
     
         9 . The wound dressing material of  claim 1 , wherein the gel-forming polymer is selected from cellulose, carboxymethylcellulose, pectin, alginate, chitosan, hyaluronic acid, polysaccharide, or gum-derived polymer, or a derivative thereof or any mixture or a combination thereof. 
     
     
         10 . (canceled) 
     
     
         11 . The wound dressing material of  claim 9 , wherein the gel-forming polymer comprises about 200 to about 4000 monomeric units. 
     
     
         12 . The wound dressing material of  claim 11 , wherein the gel-forming polymer comprises about 500 to about 2000 monomeric units. 
     
     
         13 . (canceled) 
     
     
         14 . (canceled) 
     
     
         15 . (canceled) 
     
     
         16 . (canceled) 
     
     
         17 . The wound dressing material of  claim 1 , wherein the detectable label selected from the group consisting of a luminescent molecule, a chemiluminescent molecule, a fluorochrome, a fluorescent quenching agent, a lipid, a colored molecule, a radioisotope, a scintillant, biotin, avidin, streptavidin, protein A, protein G, an antibody or a fragment thereof, a polyhistidine, Ni2+, a Flag tag, a myc tag, a heavy metal, and an enzyme. 
     
     
         18 . The wound dressing material of  claim 17 , wherein the reporter molecule comprises a fluorescent molecule selected from the group consisting of fluorescein, rhodamine, tetramethylrhodamine, R-phycoerythrin, Cy-3, Cy-5, Cy-7, Texas Red, Phar-Red, allophycocyanin (APC), fluorescein amine, eosin, dansyl, umbelliferone, 5-carboxyfluorescein (FAM), 2′7′-dimethoxy-4′5′-dichloro-6-carboxyfluorescein (JOE), 6 carboxyrhodamine (R6G), N,N,N′,N′-tetramethyl-6-carboxyrhodamine (TAMRA), 6-carboxy-X-rhodamine (ROX), 4-(4′-dimethylaminophenylazo) benzoic acid (DABCYL), 5-(2′-aminoethyl)aminonaphthalene-1-sulfonic acid (EDANS), 4-acetamido-4′-isothiocyanatostilbene-2,2′disulfonic acid, acridine, acridine isothiocyanate, r-amino-N-(3-vinylsulfonyl)phenylnaphthalimide-3,5, disulfonate (Lucifer Yellow VS), N-(4-anilino-1-naphthyl)maleimide, anthranilamide, Brilliant Yellow, coumarin, 7-amino-4-methylcoumarin, 7-amino-4-trifluoromethylcouluarin (Coumarin 151), cyanosine, 4′, 6-diaminidino-2-phenylindole (DAPI), 5′,5″-diaminidino-2-phenylindole (DAPI), 5′,5″-dibromopyrogallol-sulfonephthalein (Bromopyrogallol Red), 7-diethylamino-3-(4′-isothiocyanatophenyl)-4-methylcoumarin diethylenetriamine pentaacetate, 4,4′-diisothiocyanatodihydro-stilbene-2,2′-disulfonic acid, 4,4′-diisothiocyanatostilbene-2,2′-disulfonic acid, 4-dimethylaminophenylazophenyl-4′-isothiocyanate (DABITC), eosin isothiocyanate, erythrosin B, erythrosin isothiocyanate, ethidium, 5-(4,6-dichlorotriazin-2-yl)aminofluorescein (DTAF), QFITC (XRITC), fluorescamine, IR144, IR1446, Malachite Green isothiocyanate, 4-methylumbelliferone, ortho cresolphthalein, nitrotyrosine, pararosaniline, Phenol Red, B-phycoerythrin, o-phthaldialdehyde, pyrene, pyrene butyrate, succinimidyl 1-pyrene butyrate, Reactive Red 4, lissamine rhodamine B sulfonyl chloride, rhodamine B, rhodamine 123, rhodamine X, sulforhodamine B, sulforhodamine 101, sulfonyl chloride derivative of sulforhodamine 101, tetramethyl rhodamine, riboflavin, rosolic acid, and terbium chelate derivatives. 
     
     
         19 . The wound dressing material of  claim 17 , wherein the reporter comprises a detectable label and a quencher molecule. 
     
     
         20 . (canceled) 
     
     
         21 . The wound dressing material of  claim 17 , wherein the reporter molecule or a portion thereof is released upon interaction with an enzyme 
     
     
         22 . The wound dressing material of  claim 17 , wherein the reporter comprises a substrate that is specific for a wound-specific enzyme. 
     
     
         23 . The wound dressing material of  claim 22 , wherein the wound-specific enzyme is a protease. 
     
     
         24 . The wound dressing material of  claim 22 , wherein the reporter comprises a substrate that is specific for a wound-specific enzyme selected from the group consisting of MMP-1 (collagenase), MMP-2 (gelatinase A), MMP-3 (stomelysin 1), MMP-8 (neutrophil collagenase), MMP-9 (gelatinase B), human neutrophil elastase (HNE), cathepsin G, urokinase-type plasminogen activator (uPA), and lysozyme or any combination thereof. 
     
     
         25 . (canceled) 
     
     
         26 . (canceled) 
     
     
         27 . (canceled) 
     
     
         28 . (canceled) 
     
     
         29 . (canceled) 
     
     
         30 . (canceled) 
     
     
         31 . A method of diagnosing a status of a wound, comprising the steps of:
 contacting the wound with the wound dressing material of  claim 1  to permit conversion of the reporter molecule into a detectable signal; and,   detecting a signal.   
     
     
         32 . The method of  claim 31 , wherein conversion of the reporter molecule into a detectable signal is carried out by a wound-specific protease. 
     
     
         33 . The method of  claim 32 , wherein the wound specific protease is selected from the group consisting of MMP-1 (collagenase), MMP-2 (gelatinase A), MMP-3 (stomelysin 1), MMP-8 (neutrophil collagenase), MMP-9 (gelatinase B), human neutrophil elastase (HNE), cathepsin G, urokinase-type plasminogen activator (uPA), and lysozyme. 
     
     
         34 . The method of  claim 31 , further comprising the step of determining a presence or absence of a chronic wound or an infected wound,
 wherein the step of determining a presence or absence of a chronic wound or an infected wound comprises the steps of: measuring a parameter in the wound, comparing the measured parameter to a threshold level, and making a determination that the wound is chronic or infected if the level of the parameter in the wound is higher than the threshold level.   
     
     
         35 . (canceled) 
     
     
         36 . The method of  claim 34 , wherein the parameter is an amount or activity of a wound-specific protease is selected from the group consisting of MMP-1 (collagenase), MMP-2 (gelatinase A), MMP-3 (stomelysin 1), MMP-8 (neutrophil collagenase), MMP-9 (gelatinase B), human neutrophil elastase (HNE), cathepsin G, urokinase-type plasminogen activator (uPA), and lysozyme. 
     
     
         37 . The method of  claim 31 , further comprising treating a chronic or an infected wound in a subject, comprising administering the dressing material of  claim 1  topically or dermally to the wound. 
     
     
         38 . (canceled) 
     
     
         39 . (canceled) 
     
     
         40 . (canceled) 
     
     
         41 . A wound dressing material selected from the group consisting of: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
     
     
         42 . (canceled)