Cross-linked polymer matrices, and methods of making and using same

Abstract

Functionalized chondroitin sulfate, cross-linked polymer matrices comprising functionalized chondroitin sulfate, and methods of making and using the same are provided. Such polymer matrices may be used for tissue engineering, reconstructing cartilage, and the like. Kits are also provided for detection of cartilage degrading enzymes.

1 . A composition comprising at least one monomeric unit of chondroitin sulfate functionalized by at least one polymerizable moiety. 
     
     
         2 . The composition according to  claim 1 , wherein said composition comprises at least ten monomeric units of chondroitin sulfate. 
     
     
         3 . (canceled) 
     
     
         4 . The composition according to  claim 2 , wherein said polymerizable moiety is selected from the group consisting of methacrylates, ethacrylates, itaconates, acrylamides, and aldehydes. 
     
     
         5 . The composition according to  claim 4 , wherein said polymerizable moiety is methacrylate. 
     
     
         6 . (canceled) 
     
     
         7 . The composition according to  claim 1 , where said monomeric unit of chondroitin sulfate is selected from Formula I, II, or III: 
       
         
           
           
               
               
           
         
       
       wherein R is alkenyl, and R 1  is independently selected from aldehyde or alcohol, wherein at least one R 1  is aldehyde. 
     
     
         8 . The composition of  claim 7 , wherein R is: 
       
         
           
           
               
               
           
         
       
     
     
         9 . The composition of  claim 1 , further comprising at least one monomeric unit of a biocompatible polymer. 
     
     
         10 . The composition of  claim 9 , wherein said biocompatible polymer is polyethylene glycol. 
     
     
         11 . (canceled) 
     
     
         12 . A composition comprising a cross linked polymer matrix, wherein said cross-linked polymer matrix comprises at least one monomeric unit of functionalized chondroitin sulfate. 
     
     
         13 . The composition of  claim 12 , wherein said monomeric unit of chondroitin sulfate is functionalized with an alkenyl moiety. 
     
     
         14 . The composition of  claim 12 , wherein said monomeric unit of chondroitin sulfate is functionalized with an aldehyde moiety. 
     
     
         15 . The composition of  claim 13 , wherein said alkenyl moiety is methacrylate. 
     
     
         16 .- 22 . (canceled) 
     
     
         23 . The composition of  claim 12 , wherein said cross-linked polymer matrix further comprises at least one monomeric unit of a biocompatible polymer. 
     
     
         24 .- 26 . (canceled) 
     
     
         27 . The composition of  claim 23 , wherein said biocompatible polymer is poly(ethylene glycol). 
     
     
         28 .- 37 . (canceled) 
     
     
         38 . A method of producing a composition comprising a cross-linked polymer matrix, said method comprising:
 providing a polymer comprising at least one monomeric unit of functionalized chondroitin sulfate according to  claim 1 ; and   exposing said polymer to at least one polymerizing initiator, thereby producing said cross-linked matrix.   
     
     
         39 .- 44 . (canceled) 
     
     
         45 . A method of restoring a smooth articulation surface to a skeletal joint in need thereof, comprising: administering a composition comprising at least one monomeric unit of functionalized chondroitin sulfate according to  claim 1  to an articular surface of bone in said joint. 
     
     
         46 .- 47 . (canceled) 
     
     
         48 . A method of assessing presence of cartilage degradation activity in a tissue sample, comprising:
 a) providing a composition comprising a cross-linked polymer matrix according to  claim 12  and a detectable agent;   b) providing a tissue sample;   c) contacting said composition with said tissue sample; and,   d) assessing release of said detectable agent from said composition.   
     
     
         49 .- 51 . (canceled) 
     
     
         52 . A method of diagnosing arthritis in a subject, comprising:
 a) providing a cross-linked polymer matrix according to  claim 12 , having entrapped therein a detectable agent;   b) providing a tissue sample derived from skeletal joint biopsy of said subject;   c) contacting said polymer matrix with said tissue sample; and,   d) assessing release of said detectable agent from said polymer matrix, wherein such release indicates the presence of cartilage degrading activity associated with arthritis in said subject.   
     
     
         53 .- 59 . (canceled) 
     
     
         60 . A method for reconstructing cartilage in a subject in need thereof, comprising: administering a composition comprising at least one monomeric unit of functionalized chondroitin sulfate of  claim 1  to a site of desired cartilage formation in said subject. 
     
     
         61 .- 63 . (canceled) 
     
     
         64 . A method for reconstructing cartilage in a subject in need thereof, comprising:
 (a) providing a phototransparent vessel, the interior surface of which defines the external contours of a desired cartilaginous member;   (b) filling said vessel with a composition comprising at least one monomeric unit of functionalized chondroitin sulfate of  claim 1  having viable cartilage forming cells suspended therein;   (c) photoirradiating said filled vessel or further adding a compound comprising an amine group into said vessel, thereby forming a chondroitin sulfate cross-linked polymer matrix having said cells entrapped therein;   (d) releasing said polymer matrix from said vessel; and,   (e) implanting said polymer matrix into said subject at a site in need of said cartilaginous member, whereafter said cells produce cartilaginous extracellular matrix in vivo, thereby forming said cartilaginous member.   
     
     
         65 .- 70 . (canceled) 
     
     
         71 . A method of sealing or filling a wound in a subject in need thereof, the method comprising administering a composition comprising functionalized chondroitin sulfate of  claim 1 . 
     
     
         72 .- 79 . (canceled)