Composition And Device For In Vivo Cartilage Repair

Abstract

The composition as described serves for in vivo cartilage repair. It basically consists of a naturally derived osteoinductive and/or chondroinductive mixture of factors (e.g. derived from bone) or of a synthetic mimic of such a mixture combined with a nanosphere delivery system. A preferred mixture of factors is the combination of factors isolated from bone, known as BP and described by Poser and Benedict (WO 95/13767). The nanosphere delivery system consists of nanospheres defined as polymer particles of less than 1000 nm in diameter (whereby the majority of particles preferably ranges between 200-400 nm) in which nanospheres the combination of factors is encapsulated. The nanospheres are loaded with the mixture of factors in a weight ratio of 0.001 to 17% (w/w), preferably of 1 to 4% (w/w) and have a release profile with an initial burst of 10 to 20% of the total load over the first 24 hours and a long time release of at least 0.1 per day during at least seven following days. The nanospheres are composed of e.g. ((D,L)lactic acid/glycolic acid)-copolymer (PLGA). The loaded nanospheres are e.g. made by phase inversion. The composition is advantageously utilized as a device comprising any biodegradable matrix in which the nanospheres loaded with the factor combination is contained.

1 - 23 . (canceled) 
   
   
       24 . A composition comprising:
 a chondroinductive protein mixture; and   a delivery system having an initial first release rate (% total protein mixture load/time) greater than a subsequent second release rate (% total protein mixture load/time).   
   
   
       25 . The composition of  claim 24 , wherein the first rate is greater than 10% per day. 
   
   
       26 . The composition of  claim 24 , wherein the second rate is less than 1% per day. 
   
   
       27 . The composition of  claim 24 , wherein the delivery system has a third release rate. 
   
   
       28 . The composition of  claim 27 , wherein the third release rate is greater than 0.1% per day. 
   
   
       29 . The composition of  claim 27 , wherein the third release rate occurs temporally before the second release rate. 
   
   
       30 . The composition of  claim 24 , wherein the protein mixture comprises a bone derived protein. 
   
   
       31 . The composition of  claim 24 , wherein the delivery system comprises nanospheres. 
   
   
       32 . The composition of  claim 24 , further comprising a matrix. 
   
   
       33 . The composition of  claim 32 , wherein the matrix comprises a collagen. 
   
   
       34 . A composition comprising:
 a chondroinductive protein mixture; and   a delivery system having an initial first release rate greater than 10% total protein mixture load per day and a subsequent second release rate less than 1% total protein mixture load per day.   
   
   
       35 . The composition of  claim 34 , wherein the delivery system has a third release rate. 
   
   
       36 . The composition of  claim 35 , wherein the third release rate is greater than 0.1% per day. 
   
   
       37 . The composition of  claim 35 , wherein the third release rate occurs temporally before the second release rate. 
   
   
       38 . The composition of  claim 34 , wherein the protein mixture comprises a bone derived protein. 
   
   
       39 . The composition of  claim 34 , wherein the delivery system comprises nanospheres. 
   
   
       40 . The composition of  claim 34 , further comprising a matrix. 
   
   
       41 . The composition of  claim 40 , wherein the matrix comprises a material selected from the group consisting of type I collagen, type II collagen and hyaluronic acid. 
   
   
       42 . The composition of  claim 40 , wherein the matrix comprises type I collagen. 
   
   
       43 . A composition comprising:
 a bone derived chondroinductive protein mixture;   a biodegradable matrix including collagen; and   a nanosphere delivery system having an initial first release rate greater than 10% total protein mixture load per day and a subsequent second release rate less than 1% total protein mixture load per day.