Intervertebral disc

Abstract

The present invention relates to an engineered biological material comprising or enriched for tissue of intervertebral disc; tissue derived from an engineered biological material; constructs comprising one or more tissues from an engineered biological material; methods for producing the engineered biological materials and constructs; and methods of using the engineered biological materials and constructs.

We claim:  
     
         1 . An engineered biological material comprising one or more tissues of intervertebral disc.  
     
     
         2 . An engineered biological material as claimed in  claim 1  characterized by a continuous layer of nucleus pulposus tissue.  
     
     
         3 . An engineered biological material as claimed in  claim 1  characterized by a continuous layer of annulus fibrosus tissue.  
     
     
         4 . An engineered biological material as claimed in  claim 1 ,  2 , or  3  further characterized by the presence of extracellular matrix, large proteoglycans and collagen.  
     
     
         5 . An engineered biological material as claimed in  claim 2  or  4  wherein the continuous layer of nucleus pulposus tissue is on a substrate.  
     
     
         6 . An engineered biological material as claimed in  claim 3  or  4  wherein the continuous layer of annulus fibrosus tissue is on a substrate.  
     
     
         7 . An engineered biological material as claimed in  claim 5  or  6  wherein the substrate is selected from the group consisting of bone, an engineered biomaterial, preferably an engineered bone substitute, and porous tissue culture inserts.  
     
     
         8 . Nucleus pulposus tissue obtained from an engineered biological material of  claim 2  or  5 .  
     
     
         9 . Annulus fibrosus tissue obtained from an engineered biological material of  claim 3  or  6 .  
     
     
         10 . An intervertebral disc construct comprising nucleus pulposus tissue as claimed in  claim 8  or annulus fibrosus tissue as claimed in  claim 9  fused to a substrate.  
     
     
         11 . An intervertebral disc construct comprising nucleus pulposus tissue as claimed in  claim 8  fused to a continuous layer of cartilage tissue on a substrate.  
     
     
         12 . An intervertebral disc construct as claimed in  claim 11  wherein the nucleus pulposus tissue is surrounded by a continuous layer of annulus fibrosus tissue.  
     
     
         13 . A process for producing an engineered biological material as claimed in  claim 1  comprising: 
 (a) isolating nucleus pulposus cells or annulus fibrosus cells from intervertebral disc;  
 (b) forming a layer of the nucleus pulposus cells or annulus fibrosus cells on a substrate, and;  
 (c) culturing the nucleus pulposus cells or annulus fibrosus cells in growth media under suitable conditions so that the nucleus pulposus cells or annulus fibrosus cells accumulate extracellular matrix and form a continuous layer of nucleus pulposus tissue or annulus fibrosus tissue.  
 
     
     
         14 . A process for producing an engineered biological material as claimed in  claim 1  comprising: 
 (a) isolating nucleus pulposus cells and annulus fibrosus cells from intervertebral disc;  
 (b) forming a layer of the nucleus pulposus cells surrounded by the annulus fibrosus cells on a substrate; and  
 (c) culturing the nucleus pulposus cells and annulus fibrosus cells in growth media under suitable conditions so that the nucleus pulposus cells and annulus fibrosus cells accumulate extracellular matrix and form nucleus pulposus tissue surrounded by annulus fibrosus tissue.  
 
     
     
         15 . A process as claimed in  claim 13  or  14  wherein the substrate is selected from the group consisting of bone, an engineered biomaterial preferably an engineered bone substitute, and porous tissue culture inserts.  
     
     
         16 . An engineered biological material or intervertebral disc construct as claimed in any preceding claim wherein cells of the nucleus pulposus tissue or annulus fibrosus tissue are transformed with recombinant vectors containing an exogenous gene encoding a biologically active protein that corrects or compensates for a genetic deficiency, or stimulates cell growth or stimulates extracellular matrix production by cells, or encodes a drug.  
     
     
         17 . A system for testing a substance that affects nucleus pulposus cells or annulus fibrosus cells comprising: 
 (a) generating or culturing an engineered biological material, or construct as claimed in any preceding claim in the presence of a substance which is suspected of affecting nucleus pulposus tissue or annulus fibrous tissue; and    (b) determining the biochemical composition and/or physiological organization of tissue generated or cultured with the biochemical composition and/or physiological organization of the biological material or construct generated or cultured in the absence of the substance.    
     
     
         18 . A method of using an engineered biological material or construct as claimed in any preceding claim to test pharmaceutical preparations for efficacy in the treatment of diseases of intervertebral disc.  
     
     
         19 . A method of replacing or repairing damaged or deficient intervertebral discs or portions thereof of a patient comprising implanting an engineered biological material, nucleus pulposus tissue, annulus fibrosus tissue, or construct as claimed in any preceding claim into the site of the damaged or deficient intervertebral disc or portions thereof, of the patient.  
     
     
         20 . A method for enhancing healing of an intervertebral disc in a patient which comprises inserting an engineered biological material, nucleus pulposus tissue, annulus fibrosus tissue, or construct as claimed in any preceding claim into the site of a damaged intervertebral disc.  
     
     
         21 . A method for repairing damaged or degenerated intervertebral discs comprising evacuating tissue from a nucleus pulposus portion of a degenerated intervertebral disc space, preparing an engineered biological material in accordance with a process as claimed in  claim 13  using nucleus pulposus cells from the evacuated tissue, and implanting the engineered biological material in the space where the tissue was evacuated.  
     
     
         22 . A method for investigating the metabolism or degeneration of nucleus pulposus or annulus fibrosus cells or tissue using an engineered biological material or construct as claimed in any preceding claim as an in vitro model.  
     
     
         23 . A gene therapy method comprising using an engineered biological material or construct as claimed in any preceding claim.  
     
     
         24 . Use of an engineered biological material, nucleus pulposus tissue, annulus fibrosus tissue, or construct as claimed in any preceding claim as an implant to replace or repair damaged or deficient intervertebral disc.