Repairing bruch's membrane with hydrogels

Abstract

The invention provides hydrogels and methods for their use in treating disorders of the retina such as age-related macular degeneration (AMD).

1 . An in situ polymerizable poly(ethylene glycol) (PEG) based diacrylate hydrogel that comprises at least one adhesion ligand. 
     
     
         2 . The hydrogel of  claim 1 , wherein at least one adhesion ligand is covalently attached to the PEG hydrogel through a PEG linker chain. 
     
     
         3 . The hydrogel of  claim 1 , wherein at least one adhesion ligand comprises the amino acid sequence RGDS (SEQ ID NO:1), YIGSR (SEQ ID NO:2), KQAGDV (SEQ ID NO:3), RGDV (SEQ ID NO:4), RGD-HYP (hydroxyproline) (SEQ ID NO:5), RGDT (SEQ ID NO:6) or VTCG (SEQ ID NO:7). 
     
     
         4 . The hydrogel of  claim 3 , wherein at least one adhesion ligand is the amino acid sequence RGDS (SEQ ID NO:1), YIGSR (SEQ ID NO:2) or KQAGDV (SEQ ID NO:3). 
     
     
         5 . The hydrogel of  claim 4 , wherein at least one adhesion ligand is the amino acid sequence RGDS (SEQ ID NO:1). 
     
     
         6 . The hydrogel of  claim 5 , wherein the concentration of the adhesion ligand is about 5.0 μmol/ml. 
     
     
         7 . The hydrogel of  claim 5  that further comprises PHSRN (SEQ ID NO:8). 
     
     
         8 . The hydrogel of  claim 4 , wherein at least one adhesion ligand is the amino acid sequence YIGSR (SEQ ID NO:2). 
     
     
         9 . The hydrogel of  claim 1  that further comprises at least one growth factor. 
     
     
         10 . The hydrogel of  claim 9 , wherein the growth factor is bFGF, PDGF, hepatocyte growth factor (HGF), insulin-like growth factor (IGF) or epidermal growth factor (EGF). 
     
     
         11 . The hydrogel of  claim 1  that further comprises an anti-angiogentic or anti-apoptotic drug or cytokine. 
     
     
         12 . The hydrogel of  claim 1  that is suitable for injection. 
     
     
         13 . The hydrogel of  claim 1  that is a photopolymerizable hydrogel. 
     
     
         14 . A method for preparing a hydrogel, comprising:
 a) combining a PEG diacrylate with an acryloyl-PEG-adhesion ligand and/or an acryloyl-PEG-growth factor in an appropriate solution;   b) filter sterilizing the solution; and   c) adding a photoinitiator to the solution.   
     
     
         15 . The method of  claim 14 , wherein the photoinitiator is 2,2-dimethyl-2-phenyl-acetophenone in n-vinylpyrrolidone. 
     
     
         16 . The method of  claim 14 , further comprising exposing the solution prepared in step c) to UV light. 
     
     
         17 . A hydrogel prepared according to the method of  claim 14 . 
     
     
         18 - 25 . (canceled) 
     
     
         26 . A method for treating a disorder of the retina in a patient in need of such treatment, comprising administering to the patient a therapeutically effective amount of a hydrogel as described in  claim 1  and polymerizing the hydrogel with UV light. 
     
     
         27 . The method of  claim 26 , wherein the disorder of the retina is age-related macular degeneration (AMD), choroidal ruptures, angioid streaks, myopic maculopathy, presumed ocular histoplasmosis, globe ruptures, penetrating injuries, RPE and retinal atropies, degeneration or dystrophy. 
     
     
         28 . The method of  claim 27 , wherein the disorder of the retina is AMD. 
     
     
         29 . The method of  claim 28 , wherein the AMD is dry AMD. 
     
     
         30 . The method of  claim 28 , wherein the AMD is wet AMD. 
     
     
         31 . The method of  claim 26  that further comprises performing a vitrectomy on the patient to remove subretinal scars.