Compositions and methods for scaffold formation

Abstract

The present invention relates to scaffolds composed of a protein backbone cross-linked by a synthetic polymer. Specifically, the present invention provides PEGylated-thiolated collagen scaffolds and PEGylated albumin scaffolds and methods of generating and using same for treating disorders requiring tissue engineering.

What is claimed is: 
     
         1 . A method of resisting cell spreading, growth and/or invasion in a region of a body characterized by tissue damage, the method comprising:
 administering a composition-of-matter to a subject in need thereof in said region of a body, said composition-of-matter comprising a polymer-protein precursor molecule which comprises albumin and at least two synthetic polymers covalently attached to said albumin, each of said at least two synthetic polymers having a functional group, said functional group being selected capable of cross-linking with a functional group of at least one other synthetic polymer being covalently attached to at least one other polymer-protein precursor molecule so as to form a scaffold; and   cross-linking a plurality of said precursor molecules in vivo to thereby generate said scaffold,   thereby resisting cell spreading, growth and/or invasion.   
     
     
         2 . The method of  claim 1 , wherein said scaffold forms a hydrogel. 
     
     
         3 . The method of  claim 1 , wherein said synthetic polymer is selected from the group consisting of polyethylene glycol (PEG), polycaprolactone (PLC), polyglycolic acid (PGA), poly-L-lactic acid (PLLA), polymethyl methacrylate (PMMA), polyhydroxyalkanoate (PHA), poly-4-hydroxybutyrate (P4HB), polypropylene fumarate (PPF) and polytetrafluoroethylene (PTFE), and copolymers thereof. 
     
     
         4 . The method of  claim 1 , wherein said functional group is selected capable of cross-linking with a functional group of at least one other synthetic polymer by chain polymerization. 
     
     
         5 . The method of  claim 1 , wherein said albumin is denatured. 
     
     
         6 . The method of  claim 1 , wherein said scaffold is biodegradable. 
     
     
         7 . The method of  claim 1 , wherein said scaffold comprises at least 20% albumin by dry weight. 
     
     
         8 . The method of  claim 1 , wherein a concentration of said composition-of-matter is in a range of 1 mg/ml to 200 mg/ml. 
     
     
         9 . The method of  claim 1 , wherein said administering is effected during surgery. 
     
     
         10 . The method of  claim 1 , wherein said cross-linking further comprises cross-linking a plurality of said precursor molecules with a plurality of synthetic polymers, each of said synthetic polymers having at least two functional groups, said functional groups being selected capable of cross-linking with a functional group of said precursor molecules. 
     
     
         11 . The method of  claim 1 , wherein said cross-linking is by ultraviolet illumination. 
     
     
         12 . The method of  claim 11 , wherein said cross-linking further comprises adding a photoinitiator. 
     
     
         13 . A method of resisting cell spreading, growth and/or invasion in a region of a body characterized by tissue damage, the method comprising:
 implanting a scaffold in said region of a body in a subject in need thereof, said scaffold comprising a plurality of albumin molecules and a plurality of synthetic polymers covalently attached to said albumin molecules, each of said albumin molecules being covalently attached to at least two of said synthetic polymers, wherein said synthetic polymers are cross-linked with each other,   thereby resisting cell spreading, growth and/or invasion.   
     
     
         14 . The method of  claim 13 , wherein said scaffold forms a hydrogel. 
     
     
         15 . The method of  claim 13 , wherein said synthetic polymer is selected from the group consisting of polyethylene glycol (PEG), polycaprolactone (PLC), polyglycolic acid (PGA), poly-L-lactic acid (PLLA), polymethyl methacrylate (PMMA), polyhydroxyalkanoate (PHA), poly-4-hydroxybutyrate (P4HB), polypropylene fumarate (PPF) and polytetrafluoroethylene (PTFE), and copolymers thereof. 
     
     
         16 . The method of  claim 13 , wherein said synthetic polymers are cross-linked with each other by chain polymerization. 
     
     
         17 . The method of  claim 13 , wherein said albumin is denatured. 
     
     
         18 . The method of  claim 13 , wherein said scaffold is biodegradable. 
     
     
         19 . The method of  claim 13 , wherein said scaffold comprises at least 20% albumin by dry weight. 
     
     
         20 . The method of  claim 13 , wherein said implanting is effected during surgery.