Pegylated fibrinogen precursor molecule
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.
1. A precursor molecule comprising a fibrinogen protein which is denatured and retains an activity of forming a scaffold and at least two polyethylene glycol (PEG) molecules covalently connected to free thiol groups of said denatured fibrinogen protein, each of said at least two PEG molecules comprising a functional group for cross-linking.
2. The precursor molecule of claim 1 , wherein said PEG is selected from the group consisting of PEG-acrylate (PEG-Ac) and PEG-vinylsulfone (PEG-VS).
3. The precursor molecule of claim 1 , wherein said PEG-Ac is selected from the group consisting of PEG-DA, 4-arm star PEG multi-Acrylate and 8-arm star PEG multi-Acrylate.
4. The precursor molecule of claim 3 , wherein said PEG-DA is a 4-kDa PEG-DA, 6-kDa PEG-DA, 10-kDa PEG-DA, 14-kDa PEG-DA and/or 20-kDa PEG-DA.
5. The precursor molecule of claim 3 , wherein a molar ratio of PEG-DA:fibrinogen is 2-400:1.
6. The precursor molecule of claim 3 , wherein a molar ratio of PEG-DA:fibrinogen is 100-200:1.
7. The precursor molecule of claim 1 , wherein said fibrinogen protein retains an activity of mediating tissue regeneration following in vivo administration.
8. A method of generating a scaffold comprising:
(a) generating the precursor molecules of claim 1 ; and subsequently
(b) cross-linking said precursor molecules to thereby generate the scaffold.
9. A precursor molecule comprising a fibrinogen protein which is denatured and retains an activity of mediating tissue regeneration following in vivo administration, and at least two PEG molecules covalently connected to free thiol groups of said fibrinogen protein, each of said at least two PEG molecules comprising a functional group for cross-linking.