Hyaluronic acid derivative based three-dimensional matrix

Abstract

Use of a biological material containing: e) a three-dimensional matrix based on a hyaluronic acid derivative and optionally f) chondrocytes and/or mesenchymal cells partially or completely differentiated towards chondrocytes for the preparation of a graft to be surgically implanted into a joint cartilage damaged by or to be protected against a degenerative and/or inflammatory pathology.

1 .- 62 . (canceled) 
     
     
         63 . A surgical method for recovering or protecting a joint cartilage from a degenerative and/or inflammatory pathology, associated with the production of IL-1, selected from osteoarthritis, psoriatic and rheumatoid arthritis, said method comprising the step of implanting into a subject in need thereof a graft consisting essentially of a biological material containing:
 a) a three-dimensional matrix based on a hyaluronic acid (HA) derivative selected from the group consisting of
 i) HA salified with organic and/or inorganic bases, 
 ii) HA amides with amine of the aliphatic, araliphatic, cycloaliphatic, aromatic, cyclic and heterocyclic series. 
 iii) O-sulphated derivatives of HA, 
 iv) inner esters of HA with a percentage of esterification that does not exceed 20%, 
 v) deacetylated derivatives of HA obtained by the deacetylation of the N-acetyl-glucosamine fraction, and 
 vi) percarboxylated derivatives of HA obtained by oxidising the primary hydroxyl of the N-acetyl-glucosamine fraction with a degree of percarboxylation ranging between 0.1 and 100%; and optionally 
   b) chondrocytes and/or mesenchymal cells partially or completely differentiated towards chondrocytes.   
     
     
         64 . The method according to  claim 63 , wherein the biological material contains said cells (b), said graft being an in vitro cartilage tissue to be surgically implanted in vivo inside the joint capsule wherein the extracellular cartilage matrix is degraded by said pathology. 
     
     
         65 . The method according to  claim 64 , wherein said graft further comprises the extracellular matrix produced by said b) chondrocytes and/or mesenchymal cells partially or completely differentiated towards chondrocytes, said extracellular matrix being both within said graft and inside the joint cartilage after the graft implantation. 
     
     
         66 . The method according to  claim 63 , wherein said graft is surgically implanted at the beginning of the process of degradation of the extracellular matrix of the cartilage. 
     
     
         67 . The method according to  claim 63 , wherein said graft is surgically implanted at later stages of said pathology. 
     
     
         68 . The method according to  claim 63 , wherein the average molecular weight of hyaluronic acid in the hyaluronic acid derivative range between 1×10 5  Da and 1×10 6  Da. 
     
     
         69 . The method according to  claim 68 , wherein the average molecular weight of hyaluronic acid range between 200,000 and 750,000 Da. 
     
     
         70 . The method according to  claim 63 , wherein the HA derivative of group (i) is obtained by treating hyaluronic acid with sodium hydroxide. 
     
     
         71 . The method according to  claim 63 , wherein the HA derivative of group (ii) has a percentage of amidation from 0.1 to 50% and the remaining portion is salified with organic and/or inorganic bases. 
     
     
         72 . The method according to  claim 71 , wherein said base is sodium hydroxide. 
     
     
         73 . The method according to  claim 63 , wherein the HA derivative of group (iii) has from 1 to 4 —OSO 3 H group per saccharide unit. 
     
     
         74 . The method according to  claim 63 , wherein the HA derivative of group (iv) has a degree of esterification from 0.05 to 10%, and the remaining percentage of non-esterified HA is salified with organic and/or inorganic bases. 
     
     
         75 . The method according to  claim 74 , wherein said base is sodium hydroxide. 
     
     
         76 . The method according to  claim 63 , wherein the HA derivative of group (v) has a percentage of deacetylation from 0.1 to 30% and all the carboxy groups of HA are salified with organic and/or inorganic bases. 
     
     
         77 . The method according to  claim 76 , wherein said base is sodium hydroxide. 
     
     
         78 . The method according to  claim 63 , wherein the HA derivative of group (vi) has a degree of percarboxylation from 25 to 75% and all the carboxy groups are salified with organic and/or inorganic bases. 
     
     
         79 . The method according to  claim 78 , wherein the base is sodium hydroxide. 
     
     
         80 . The method according to  claim 78 , wherein said three-dimensional matrix is in a form selected from the group consisting of non-woven tissue, tissue, microspheres, and sponge.