Amorphous cell delivery vehicle treated with physical/physicochemical stimuli

Abstract

Provided are compositions and methods for in vitro generation and in vivo use of tissue for the repair of defective tissue, especially cartilage. Chondrocytes or other cells are cultured in vitro in a biodegradable amorphous carrier within the confines of a space bounded by a semi-permeable membrane with a molecular weight cut-off of greater than 100 kDa. The culture can be subjected to physical/physicochemical conditions that mimic in vivo conditions of the tissue in need of repair or replacement. In one embodiment the invention provides an amorphous preparation of chondrocytes and their extracellular products, suitable for injection.

1 . A composition comprising a cell/matrix composition produced by contacting a population of cells selected for in vitro culture with a biodegradable amorphous carrier; placing the contacted population of cells in a cell space for receiving the cells, said cell space being bounded at least in part by a semi-permeable membrane having a molecular weight cut-off greater than 100 kDa and up to 1,000 kDa; and periodically applying pressure to the contacted population of cells. 
     
     
         2 . The composition of  claim 1 , wherein the cell/matrix composition comprises chondrocytes and, optionally, precursor cells thereof. 
     
     
         3 . The composition of  claim 1 , wherein cells of the cell/matrix composition consist essentially of chondrocytes. 
     
     
         4 . The composition of  claim 1 , wherein the cell/matrix composition comprises a biodegradable amorphous carrier comprising type I collagen. 
     
     
         5 . The composition of  claim 1 , wherein the cell/matrix composition comprises a biodegradable amorphous carrier comprising dextran beads. 
     
     
         6 . The composition of  claim 1 , wherein the cell/matrix composition comprises a biodegradable amorphous carrier comprising a hydrogel chosen from dextran, chondroitin sulfate, polyethylene glycol, hyaluronan, and any combination thereof. 
     
     
         7 . The composition of  claim 1 , wherein the cell/matrix composition is contained in a cell space for receiving the cells, said cell space being bounded at least in part by a semi-permeable membrane having a molecular weight cut-off greater than 100 kDa and up to 1,000 kDa. 
     
     
         8 . The composition of  claim 7 , wherein the semi-permeable membrane has a molecular weight cut-off of at least 200 kDa. 
     
     
         9 . The composition of  claim 7 , wherein the semi-permeable membrane has a molecular weight cut-off of at least 250 kDa. 
     
     
         10 . The composition of  claim 7 , wherein the semi-permeable membrane has a molecular weight cut-off of at least 500 kDa. 
     
     
         11 . The composition of  claim 7 , wherein the semi-permeable membrane has a molecular weight cut-off of 1,000 kDa.