Latent reactive polymers with biologically active moieties

Abstract

A polybifunctional reagent having a polymeric backbone, one or more pendent photoreactive moieties, and two or more pendent bioactive groups. The reagent can be activated to form a bulk material or can be brought into contact with the surface of a previously formed biomaterial and activated to form a coating. The pendent bioactive groups function by promoting the attachment of specific molecules or cells to the bulk material or coated surface. Bioactive groups can include proteins, peptides, carbohydrates, nucleic acids and other molecules that are capable of binding noncovalently to specific and complimentary portions of molecules or cells.

What is claimed is:  
     
         1 . A polybifunctional reagent comprising a plurality of molecules each comprising a polymeric backbone bearing (a) one or more pendent photoreactive moieties capable of being activated by exposure to a suitable energy source, and (b) two or more pendent bioactive groups capable of specific, noncovalent interactions with complimentary groups, the reagent being capable, upon activation of the photoreactive moieties, of forming a bulk material or surface coating in order to promote the attraction of such complimentary groups.  
     
     
         2 . A polybifunctional reagent according to  claim 1 , wherein the photoreactive moieties can be activated to form intermolecular covalent bonds between the reagent molecule and a biomaterial surface in order to form a coating thereon.  
     
     
         3 . A polybifunctional reagent according to  claim 1 , wherein the photoreactive moieties can be activated to form intermolecular covalent bonds between adjacent reagent molecules in order to form a bulk material.  
     
     
         4 . A polybifunctional reagent according to  claim 1 , wherein the bioactive groups participate in a specific binding reaction with complementary molecules or cell receptors.  
     
     
         5 . A polybifunctional reagent according to  claim 4 , wherein the bioactive groups are each, independently, selected from the group consisting of proteins, peptides, amino acids, carbohydrates, and nucleic acids, each being capable of binding noncovalently to specific and complimentary portions of molecules or cells.  
     
     
         6 . A polybifunctional reagent according to  claim 1 , wherein the bioactive groups each have a known or identifiable complementary binding partner and are each, independently, selected from the group consisting of antithrombotic agents, cell attachment factors, receptors, ligands, growth factors, antibiotics, enzymes and nucleic acids.  
     
     
         7 . A polybifunctional reagent according to  claim 6  wherein the bioactive groups comprise antithrombotic agents selected from the group consisting of heparin, hirudin, lysine, prostaglandins, streptokinase, urokinase, and plasminogen activator.  
     
     
         8 . A polybifunctional reagent according to  claim 6  wherein the bioactive groups comprise cell attachment factors selected from the group consisting of surface adhesion molecules and cell-cell adhesion molecules.  
     
     
         9 . A polybifunctional reagent according to  claim 8  wherein the bioactive groups comprise surface adhesion molecules selected from the group consisting of laminin, fibronectin, collagen, vitronectin, tenascin, fibrinogen, thrombospondin, osteopontin, von Willibrand Factor, and bone sialoprotein and active domains thereof.  
     
     
         10 . A polybifunctional reagent according to  claim 8  wherein the bioactive groups comprise cell-cell adhesion molecules selected from the group consisting of N-cadherin and P-cadherin and active domains thereof.  
     
     
         11 . A polybifunctional reagent according to  claim 6  wherein the bioactive groups comprise growth factors selected from the group consisting of fibroblastic growth factors, epidermal growth factor, platelet-derived growth factors, transforming growth factors, vascular endothelial growth factor, bone morphogenic proteins and other bone growth factors, and neural growth factors.  
     
     
         12 . A polybifunctional reagent according to  claim 6  wherein the bioactive groups comprise a ligand or receptor selected from the group consisting of antibodies, antigens, avidin, streptavidin, biotin, heparin, type IV collagen, protein A, and protein G.  
     
     
         13 . A polybifunctional reagent according to  claim 6  wherein the bioactive groups comprise an antibiotic selected from the group consisting of antibiotic peptides.  
     
     
         14 . A polybifunctional reagent according to  claim 6  wherein the bioactive groups comprise enzymes.  
     
     
         15 . A polybifunctional reagent according to  claim 6  wherein the bioactive groups comprise nucleic acid sequences capable of selectively binding complimentary nucleic acid sequences.  
     
     
         16 . A polybifunctional reagent according to  claim 1  wherein the polymeric backbone comprises a synthetic polymer selected from the group consisting of addition type polymers, such as the vinyl polymers.  
     
     
         17 . A polybifunctional reagent according to  claim 1  wherein the photogroups each comprise a photoactivatable ketone.  
     
     
         18 . A polybifunctional reagent comprising a synthetic polymeric backbone bearing (a) one or more pendent photoreactive moieties in the form of photoactivatable ketones, and (b) two or more pendent bioactive groups selected from the group consisting of proteins, peptides, amino acids, carbohydrates, nucleic acids and other molecules that are capable of binding noncovalently to specific and complimentary portions of molecules or cells.  
     
     
         19 . A method of coating a biomaterial surface, the method comprising the steps of (a) providing a polybifunctional reagent comprising a polymeric backbone bearing (i) one or more pendent photoreactive moieties capable of being activated by exposure to a suitable energy source, and (ii) two or more pendent bioactive groups capable of specific, noncovalent interactions with complimentary groups, (b) contacting the surface with the reagent, and (c) activating the photoreactive moieties in order to crosslink the reagent molecules to themselves and/or to the surface.  
     
     
         20 . A method according to  claim 19  wherein the reagent is coated on the surface by spraying, dipping or brushing.  
     
     
         21 . A method for forming a bulk biomaterial, the method comprising the steps of (a) providing a polybifunctional reagent comprising a polymeric backbone bearing (i) one or more pendent photoreactive moieties capable of being activated by exposure to a suitable energy source, and (ii) two or more pendent bioactive groups capable of specific, noncovalent interactions with complimentary groups, and (b) activating the reagent to form a bulk biomaterial.  
     
     
         22 . A coated biomaterial surface, comprising the bound residues of an activated polybifunctional reagent that initially comprised a polymeric backbone bearing (a) one or more pendent photoreactive moieties capable of being activated by exposure to a suitable energy source, and (b) two or more pendent bioactive groups capable of specific, noncovalent interactions with complimentary groups.  
     
     
         23 . A bulk material comprising the bound residues of an activated polybifunctional reagent that initially comprised a polymeric backbone bearing (a) one or more pendent photoreactive moieties capable of being activated by exposure to a suitable energy source, and (b) two or more pendent bioactive groups capable of specific, noncovalent interactions with complimentary groups.