Zwitterionic hydrogels for delivery of biomolecules

Abstract

The invention provides a novel approach in which zwitterionic networks are used to sequester and deliver ionic biomolecules, such as proteins, without compromising their native conformation and bioactivity. Zwitterionic networks are designed to effectively retain and deliver ionic or polar biomolecules for guided tissue regeneration. The invention represents a conceptual advance and enables a novel strategy for the utilization of zwitterionic motifs as therapeutics delivery vehicles and tissue engineering scaffolds.

What is claimed is: 
     
         1 . A composite material comprising a polymer network and a biologically active compound, wherein the 3-dimensioanl polymer network comprises a zwitterionic moiety. 
     
     
         2 . The composite material of  claim 1 , wherein the biologically active compound is a biomacromolecule. 
     
     
         3 . The composite material of  claim 1 , wherein the biomacromolecule is an ionic or polar protein or peptide. 
     
     
         4 . The composite material of  claim 3 , wherein the biomacromolecule is a therapeutic osteogenic protein or anabolic agent for bone formation. 
     
     
         5 . The composite material of  claim 4 , wherein the therapeutic osteogenic protein or anabolic agent or angiogenic factor is selected from BMPs, TGF-beta, EGF, FGF, IGF-1 and VEGF. 
     
     
         6 . The composite material of  claim 5 , wherein the therapeutic osteogenic protein is present in the polymer network at a loading from about 1 ng to about 20,000 ng. 
     
     
         1 . usly Presented) The composite material of  claim 1 , wherein the polymer network is a 3-dimensioanl crosslinked polymer network. 
     
     
         8 . The composite material of claim  7 , wherein the 3-dimensional polymer network is a crosslinked hydrogel of polymethacrylate, polyacrylate or polymethacrylamide, polyacrylamide. 
     
     
         9 . The composite material of claim  7 , wherein the 3-dimensional polymer network is crosslinked with a crosslinker selected from poly(ethylene glycol) dimethacrylate, poly(ethylene glycol) diacrylate, ethylene glycol diacrylate and ethylene glycol dimethacrylate, or derivatives thereof. 
     
     
         10 . The composite material of  claim 1 , wherein the zwitterionic moiety comprises one or more selected from sulfobetaine, phosphorylcholine and carboxybetaine. 
     
     
         11 . The composite material of  claim 1 , wherein the zwitterionic moiety is present in the polymer network as pendant groups to a polymeric backbone. 
     
     
         12 . The composite material of  claim 1 , wherein the zwitterionic moiety is present in the polymer network at a density from about 0.05 mol % to about 10 mol %. 
     
     
         13 . The composite material of claim  7 , wherein the polymer network is crosslinked with a crosslinking density from about 1 mol % to about 100 mol %. 
     
     
         14 . The composite material of  claim 1 , wherein the composite material is biodegradable. 
     
     
         15 . An implant comprising a composite material according to  claim 1 . 
     
     
         16 . An implant comprising a composite material characterized by a 3-dimensional crosslinked polymer network sequestered therein one or more biologically active compounds, wherein the polymer comprises a zwitterionic moiety. 
     
     
         17 - 21 . (canceled) 
     
     
         22 . The implant of  claim 16 , wherein the polymer network is a 3-dimensioanl crosslinked polymer network. 
     
     
         23 . The implant of  claim 22 , wherein the 3-dimensional polymer network is a crosslinked hydrogel of polymethacrylate, polyacrylate, polymethacrylamide or polyacrylamide. 
     
     
         24 . The implant of  claim 22 , wherein the 3-dimensional polymer network is crosslinked with a crosslinker selected from poly(ethylene glycol) dimethacrylate, poly(ethylene glycol) diacrylate, ethylene glycol diacrylate and ethylene glycol dimethacrylate, or derivatives thereof. 
     
     
         25 - 39 . (canceled) 
     
     
         40 . A method for making a composite material useful for tissue engineering, comprising:
 crosslinking, in the presence of a biologically active compound, a polymer comprising a zwitterionic moiety to form a 3-dimensioanl crosslinked polymer network with the biologically active compound encapsulated therein.   
     
     
         41 - 53 . (canceled)