Pegylated fibrinogen precursor molecule

Abstract

The present invention relates to biodegradable scaffolds composed of a naturally-occurring protein backbone cross-linked by a synthetic polymer. Specifically, the present invention provides PEGylated-fibrinogen scaffold and methods of generating and using same for treating disorders requiring tissue regeneration.

What is claimed is: 
     
         1 . A method of generating a scaffold, the method comprising cross-linking precursor molecules to thereby generate the scaffold, wherein said precursor molecules comprise a naturally occurring protein or a fragment of said protein, and at least two synthetic polymers covalently connected to said protein or said fragment of said protein, each of said at least two synthetic polymers having a functional group, and wherein said cross-linking comprises covalently attaching said functional group of a synthetic polymer to said functional group of another of said at least two synthetic polymers. 
     
     
         2 . The method of  claim 1 , wherein said cross-linking comprises polymerization. 
     
     
         3 . The method of  claim 2 , wherein said polymerization comprises free radical polymerization. 
     
     
         4 . The method of  claim 1 , wherein said cross-linking is effected by photoinitiation. 
     
     
         5 . The method of  claim 1 , further comprising cross-linking said precursor molecules with a cross-linker, by covalently attaching said functional group of said synthetic polymer to said cross-linker. 
     
     
         6 . The method of  claim 5 , wherein said cross-linker comprises a synthetic polymer and at least two functional groups capable of covalently attaching to said functional group of said precursor molecules. 
     
     
         7 . The method of  claim 6 , wherein said cross-linker comprises polyethylene glycol (PEG). 
     
     
         8 . The method of  claim 1 , wherein said naturally occurring protein is selected from the group consisting of fibrinogen, collagen, fibronectin, vimentin, laminin and gelatin. 
     
     
         9 . The method of  claim 8 , wherein said fibrinogen comprises plasma-derived fibrinogen. 
     
     
         10 . The method of  claim 1 , wherein said protein or said fragment of said protein is denatured. 
     
     
         11 . The method of  claim 1 , wherein said synthetic polymer is selected from the group consisting of polyethylene glycol (PEG), polyglycolic acid (PGA), poly-L-lactic acid (PLLA), polymethyl methacrylate (PMMA), polyhydroxyalkanoate (PHA), poly-4-hydroxybutyrate (P4HB), polypropylene fumarate (PPF), and polytetrafluoroethylene (PTFE). 
     
     
         12 . The method of  claim 1 , wherein said functional group is selected from the group consisting of acrylate and vinyl sulfone. 
     
     
         13 . The method of  claim 1 , comprising cross-linking said precursor molecules in the presence of chondrocytes, to thereby generate a scaffold seeded with chondrocytes. 
     
     
         14 . The method of  claim 1 , wherein said cross-linking is effected in vivo. 
     
     
         15 . The method of  claim 14 , being for treating a subject having a disorder characterized by tissue damage or loss. 
     
     
         16 . The method of  claim 15 , wherein said tissue comprises cartilage. 
     
     
         17 . A scaffold generated by the method of  claim 1 . 
     
     
         18 . A method of treating a subject having a disorder characterized by tissue damage or loss, the method comprising implanting the scaffold of  claim 17  into a subject in need thereof, thereby treating the disorder. 
     
     
         19 . The method of  claim 18 , wherein said tissue comprises cartilage. 
     
     
         20 . A method of inducing ex vivo formation of a tissue, the method comprising seeding the scaffold of  claim 17  with cells to thereby induce tissue formation.