Bioactive polymer for bone regeneration

Abstract

Disclosed herein are biocompatible materials useful for tissue regeneration and repair, wherein the bioactive polymer may be in the form of a hydrogel, for example a thermoresponsive hydrogel. This bioactive polymer and a resulting hydrogel, may be used for the regeneration of bone tissue. Accordingly, also disclosed herein are methods of treating a bone defect in a mammal, the methods comprising administering a therapeutically effective amount of a hydrogel formed by the bioactive polymer to the mammal to treat the bone defect.

1 - 24 . (canceled) 
     
     
         25 . A polymer for forming a hydrogel, the polymer comprising:
 a first monomer for binding water;   a second monomer for imparting mechanical properties to said hydrogel; and   a third monomer for binding to a natural or synthetic peptide or protein (NSPP),   
       wherein the polymer is used to repair or restore bone. 
     
     
         26 . A composition for forming a hydrogel, the composition comprising:
 a natural or synthetic peptide or protein (NSPP); and   a polymer;   
       wherein the polymer includes:
 a first monomer for binding water; and 
 a second monomer that is bindable to said NSPP; 
 
       wherein:
 the binding of said NSPP to the second monomer crosslinks the polymer, thereby enabling formation of said hydrogel when the composition is contacted with water; and 
 the composition is used to repair or restore bone. 
 
     
     
         27 . A hydrogel comprising:
 a natural or synthetic peptide or protein (NSPP); and   a polymer;   
       wherein the polymer includes:
 a first monomer for binding water; and 
 a second monomer that is bindable to said NSPP; 
 
       wherein:
 the binding of said NSPP to the second monomer crosslinks the polymer in the presence of water; and 
 the hydrogel is used to repair or restore bone. 
 
     
     
         28 - 37 . (canceled) 
     
     
         38 . A polymer according to  claim 25 , wherein the NSPP is selected from one or more of the group consisting of: collagen, fibrin, fibronectin, laminin (and isoforms thereof), bone morphogenic natural proteins, bone morphogenic synthetic proteins, and synthetic peptides, with the proviso that α-elastin, β-elastin, animal-derived elastin and/or tropoelastin in any form are not included. 
     
     
         39 . A polymer according to  claim 25 , wherein the proportion of the first monomer in the polymer is between about 2 to 15 mol %. 
     
     
         40 . A polymer according to  claim 25 , wherein the proportion of the second monomer in the polymer is between about 4 to 15 mol %. 
     
     
         41 . A polymer according to  claim 25 , wherein the proportion of the third monomer in the polymer is between about 1 to 20 mol %. 
     
     
         42 . A polymer according to  claim 25 , wherein the first monomer is selected from: polyethers, polyvinyl alcohol (PVA); poly(vinyl pyrrolidone) (PVP); poly(amino acids) and dextran. 
     
     
         43 . A polymer according to  claim 42 , wherein the polyethers are selected from: polyethylene glycol (PEG), oligo(ethylene glycol) (OEG), polyethylene oxide (PEO), polyethylene oxide-co-propylene oxide (PPO), co-polyethylene oxide block or random copolymers thereof. 
     
     
         44 . A polymer according to  claim 25 , wherein the second monomer is a methacrylate, or a random co-polymer comprising a methacrylate. 
     
     
         45 . A polymer according to  claim 25 , wherein the second monomer is selected from: hydroxyethyl methacrylate (HEMA), a hydroxyethyl methacrylate poly(lactic acid) copolymer (HEMA-PLA), poly(lactic acid), poly(caprolactone), poly(glycolide), poly(glycolide-co-lactide) or poly(glycolide-co-caprolactone). 
     
     
         46 . A polymer according to  claim 25 , wherein the third monomer has electrophilic functional groups for binding to said NSPP. 
     
     
         47 . A polymer according to  claim 25 , wherein the third monomer is selected from: N-hydroxysulfosuccinimide (SNHS), N-hydroxyethoxylated succinimido (ENHS), and N-acryloxysuccinimide (NAS). 
     
     
         48 . A polymer according to  claim 25 , wherein the polymer further includes a fourth monomer for imparting phase transition characteristics to a hydrogel for enabling injection at room temperature, and gel formation at body temperature. 
     
     
         49 . A polymer according to  claim 48 , wherein the fourth monomer has a lower critical solution temperature (LCST) less than about 33° C. 
     
     
         50 . A polymer according to  claim 25 , wherein the proportion of the fourth monomer in the polymer is between about 60 to 90 mol %. 
     
     
         51 . A polymer according to  claim 48 , wherein the fourth monomer is poly(N-isopropylacrylamide). 
     
     
         52 . A polymer according to  claim 25 , comprising the monomers: oligo (ethylene) glycol monomethyl ether methacrylate (OEGMA), hydroxyethyl methacrylate poly(lactic acid) (HEMA-PLA), N-acryloxysuccinimide (NAS) and N-isopropylacrylamide (NIPAAm). 
     
     
         53 . A polymer according to  claim 52 , wherein OEGMA is in an amount of about 2-8 mol %, HEMA-PLA is in an amount of about 5-10 mol %, NAS is in an amount of about 14 mol % and NIPAAm is in an amount of about 79 mol %.