Hydrogels for orthopedic repair

Abstract

Hydrogels intended for orthopedic applications, including repair and regeneration of cartilage, bone, joint surfaces and related tissues, must possess greater strength and toughness than hydrogels used in soft tissue repair. A hydrogel formulation is provided which has high strength, toughness, a suitable mechanical modulus and low equilibrium hydration. It may also have controlled porosity or degradation time. It can be made to polymerize in situ with high (“good” to “excellent”) adherence to target tissue or surfaces. A preferred formulation for forming such gels comprises 40 to 80% by weight of a low-molecular weight polar monomer and 30 to 10% of a hydrophilic macromeric crosslinker.

1 . A covalently polymerizable, water-absorbing, hydrogel-forming material, 
 wherein the material has both hydrophilic and hydrophobic regions and is polymerized to form a hydrogel characterized as having the following properties:    a) absorbing water to less than about 300% of its initial weight, on equilibration with water or bodily liquids,    b) having a solids content of at least about 20% after equilibration in water or bodily liquids;    c) having an elongation to failure of at least about 25% hydration to equilibrium; and    d) being sufficiently biocompatible to permit the treatment or repair of biological tissue, or used as an implant in a patient.    
   
   
       2 . The material of  claim 1 , having a molecular weight after polymerization of at least 10 kDa.  
   
   
       3 . The material of  claim 1 , which is covalently crosslinked.  
   
   
       4 . The material of  claim 1 , which is non-covalently crosslinked.  
   
   
       5 . The material of  claim 1 , having a tensile modulus of at least about 50 kPa after equilibrium hydration.  
   
   
       6 . The material of  claim 1 , having an equilibrium water content of at least about 2%.  
   
   
       7 . The material of  claim 1 , being capable of being formed in situ on body tissue or a medical implant by one or both of polymerization and crosslinking.  
   
   
       8 . The material of  claim 1 , adhering to tissue when polymerized thereon.  
   
   
       9 . The material of  claim 1 , being substantially elastic during a 10% elongation and release therefrom.  
   
   
       10 . The material of  claim 1 , further characterized in being lubricious.  
   
   
       11 . The material of  claim 1 , further characterized in comprising, before polymerization or crosslinking, 
 a) at least one component which is a macromer of molecular weight of about 1000 Da or more, at least 20% of the macromer being a hydrophilic block or region and comprising at least one chemical reactive group; and    b) at least one component bearing more than one chemically reactive group.    
   
   
       12 . The material of  claim 1 , further characterized in comprising, before polymerization or crosslinking, at least 20% by weight of at lest one amphiphilic water-soluble monomer of molecular weight less than about 100 Da.  
   
   
       13 . The material of  claim 1 , in which the water absorption at equilibrium hydration is less than about 200%.  
   
   
       14 . The material of  claim 1 , in which the solids content is at least about 25% after equilibrium swelling.  
   
   
       15 . The material of  claim 1 , in which the elongation to failure is at least about 200%.  
   
   
       16 . The material of  claim 1 , in which the tensile modulus is at least 200 kPa.  
   
   
       17 . The material of  claim 1 , further compromising a therapeutic, prophylactic or diagnostic agent.  
   
   
       18 . The material of  claim 1  formed by polymerization of a mixture comprising: 
 a) about 40% to about 100% by weight of one or more polymerizable monomers having a molecular weight of about 1000 Da or less; 
 wherein at lest about 40% by weight of the monomers consists of amphiphilic monomers;  
 wherein no more than about 50% by weight of the monomers consists of functionally hydrophobic monomers;  
   b) 0% to about 40% by weight of a reactive macromer having a molecular weight greater than about 500 Da, which comprises on average more than one polymerizable group per molecule, and which has hydrophilic groups comprising about 20% of the macromer; and    c) 0% to about 40% water.    
   
   
       19 . The material of  claim 1  in the form of a coating on an implant device.  
   
   
       20 . The material of  claim 1  forming an implant or device.  
   
   
       21 - 37 . (canceled)