Functionalized adhesive medical gel

Abstract

A bioadherent substrate includes a medical gel or medical gel precursor having a plurality of reactive members of a specific binding pair attached on or adapted to be attached to a surface of the medical gel, said reactive members being capable of forming covalent bonds with a plurality of complementary reactive members of the specific binding pair via a reaction selected from a Huisgen cycloaddition reaction, a Diels-Alder reaction and a thiol-ene reaction. A method for adhering a medical gel to biological tissue includes providing a medical gel or a medical gel precursor having a plurality of reactive members of a specific binding pair attached on or adapted to be attached to a surface of the medical gel and providing tissue with a plurality of complementary reactive members of the specific binding pair, wherein upon contact of the reactive members on the medical gel with the complimentary reactive members on the tissue, covalent bonds are formed between the reactive members and the complementary reactive members, thus adhering the medical gel to the tissue.

1 . A bioadherent substrate comprising a medical gel or medical gel precursor having a plurality of reactive members of a specific binding pair adapted to be attached on a surface of the medical gel, said reactive members being capable of forming covalent bonds with a plurality of complementary reactive members of the specific binding pair via a reaction selected from the group consisting of Huisgen cycloaddition reaction, a Diels-Alder reaction and a thiol-ene reaction. 
     
     
         2 . The bioadherent substrate according to  claim 1  wherein the medical gel is a hydrogel. 
     
     
         3 . The bioadherent substrate according to  claim 1  wherein the plurality of reactive members of the specific binding pair are selected from the group consisting of alkynes and azides. 
     
     
         4 . The bioadherent substrate according to  claim 1  wherein the plurality of reactive members of the specific binding pair form covalent bonds via a reaction catalyzed by copper to activate an alkyne and an azide for [3+2] cycloaddition. 
     
     
         5 . The bioadherent substrate according to  claim 1  wherein the plurality of reactive members of the specific binding pair form covalent bonds via a reaction involving a cyclooctyne reagent and an azide for [3+2] cycloaddition. 
     
     
         6 . The bioadherent substrate according to  claim 1  wherein the plurality of reactive members of the specific binding pair are selected from the group consisting of thiols and alkenes. 
     
     
         7 . The bioadherent substrate according to  claim 1  wherein the plurality of reactive members of the specific binding pair are selected from the group consisting of dienes and alkenes. 
     
     
         8 . The bioadherent substrate according to  claim 1  wherein the medical gel is made of a polymer selected from the group consisting of polysaccharides, mucopolysaccharides, polyaminoacids, proteins, collagen-hydroxyethyl-methacrylate (HEMA), polyphosphazines, polyphosphoesters, polyethylene glycol, polyethylene oxide, polyvinyl alcohol, polyvinylpyrrolidone, polyethyloxazoline, polyethylene oxide-co-polypropyleneoxide block copolymers, PGA-PEG-PGA block copolymers, PGA-PEG diblock copolymers, acrylates, PEG-oligoglycolylacrylates, polyacrylonitriles (PAN), carboxy alkyl celluloses, poly(α-hydroxy) acids, polylactones, polycaprolactones, polyanhydrides, polyorthoesters, polydioxanone, styrene, acrolein and copolymers, block copolymers, homoploymers, blends and combinations thereof. 
     
     
         9 . A bioadherent substrate capable of covalently binding to tissue, the bioadherent substrate comprising:
 a hydrogel comprising a plurality of reactive members of a specific binding pair, the plurality of reactive members being present on a surface of the medical gel and capable of forming covalent bonds with a plurality of complementary reactive members of the specific binding pair linked to tissue via a ligand-receptor linkage,   the hydrogel capable of forming covalent bonds via a reaction selected from the group consisting of Huisgen cycloaddition reaction, a Diels-Alder reaction and a thiol-ene reaction.   
     
     
         10 . The bioadherent substrate according to  claim 9  wherein the plurality of reactive members are attached directly to a polymeric backbone of the hydrogel. 
     
     
         11 . The bioadherent substrate according to  claim 9  wherein the hydrogel comprises a polymer selected from the group consisting of polysaccharides, mucopolysaccharides, polyaminoacids, proteins, collagen-hydroxyethyl-methacrylate (HEMA), polyphosphazines, polyphosphoesters, polyethylene glycol, polyethylene oxide, polyvinyl alcohol, polyvinylpyrrolidone, polyethyloxazoline, polyethylene oxide-co-polypropyleneoxide block copolymers, PGA-PEG-PGA block copolymers, PGA-PEG diblock copolymers, acrylates, PEG-oligoglycolylacrylates, polyacrylonitriles (PAN), carboxy alkyl celluloses, poly(α-hydroxy) acids, polylactones, polycaprolactones, polyanhydrides, polyorthoesters, polydioxanone, styrene, acrolein and copolymers, block copolymers, homoploymers, blends and combinations thereof. 
     
     
         12 . The bioadherent substrate according to  claim 9  wherein the hydrogel comprises a chemically cross linked polymer. 
     
     
         13 . The bioadherent substrate according to  claim 9  wherein the hydrogel is an uncured liquid. 
     
     
         14 . The bioadherent substrate according to  claim 9  wherein the hydrogel is configured to be draped over tissue having a plurality of complementary reactive members of the specific binding pair thereon. 
     
     
         15 . The bioadherent substrate according to  claim 9  wherein the hydrogel is injectable. 
     
     
         16 . The bioadherent substrate according to  claim 9  wherein the hydrogel comprises a layer configured to prevent formation of adhesions at a surgical site, the layer having a tissue contacting surface on which the plurality of reactive members are present. 
     
     
         17 . A kit comprising
 a functionalized medical gel or medical gel precursor having a plurality of reactive members of a specific binding pair adapted to be presented on a surface of the gel;   a container containing a mixture which may be a solution or suspension containing complementary reactive members of the specific binding pair, the complementary reactive members having a functionality that will adhere them to biological tissue upon contact; and   at least one applicator adapted to deliver the functionalized medical gel or medical gel precursor or the mixture to biological tissue.