Engineered intervertebral disc (ivd) for degenerated disc disease

Abstract

The present invention provides a process by which both non-tissue engineered and tissue engineered cartilaginous-like structures can be fabricated. The process of the present invention provides a method to produce electrospun nanofiber-anchored NP gels. The present invention provides a functional design for novel engineered IVD. The present invention provides a method for fabrication of both non-tissue and tissue engineered IVDs. These cartilaginous-like structures can be used to produce replacements for degenerated natural IVD. The method of the present invention uses electrospun PCL nanofiber mesh to anchor the NP. The method of the present invention can create angle-ply AF structure around the circumference of NP to mimic the architecture of native IVD. The method of the present invention anchors the top and bottom sides of NP by using non-woven aligned or random nanofiber mesh to create scaffold for the generation of endplate (EP) tissue.

1 - 29 . (canceled) 
     
     
         30 . A method to produce a cartilaginous-like bio-mechanical structure, said method comprising the steps of:
 producing a gel comprising one of silicone, PEGDA, or a composite of PCL nanofiber and PEGDA, said gel comprising a first surface, a second surface, and a circumferential surface;   applying to said first surface, said second surface, and said circumferential surface nanofibers fabricated by an electrospin process that produces and deposits at least one of aligned or random nanofibers;   encompassing said circumferential surface with a nanofiber structure fabricated by an electrospin process that produces at least one layer of aligned nanofibers said aligned nanofibers being aligned substantially parallel in said at least one layer,   wherein nanofibers encompass all surfaces of said bio-mechanical structure.   
     
     
         31 . The method of  claim 30 , wherein said nanofiber structure is a mesh comprising at least a first layer and a second layer of said aligned nanofibers and wherein said aligned nanofibers in said first layer are oriented at an oblique angle relative to said aligned nanofibers in said second layer. 
     
     
         32 . The method of  claim 31 , wherein said nanofiber structure is bio-mechanically similar to articular cartilage and constructed as a fiber-dense scaffold that exhibits structural characteristics similar to ultrastructure and extracellular matrix. 
     
     
         33 . The method of  claim 31 , wherein said gel is a nucleus pulposus (NP) gel. 
     
     
         34 . The method of  claim 33 , wherein said cartilaginous-like structure is bio-mechanically similar to an intervertebral disc (IVD) and constructed to exhibit structural characteristics similar to native annulus fibrosus (AF) and end plate (EP) in a natural IVD. 
     
     
         35 . The method of  claim 34 , wherein at least one of natural NP, AF or cartilage cells are seeded into said NP scaffold. 
     
     
         36 . A method to produce an engineered nucleus pulposus (NP) gel anchored by electrospun nanofiber scaffold, said method comprising the steps of:
 producing a nucleus pulposus (NP) gel using one of silicone, PEGDA, or a composite of PCL nanofiber and PEGDA, said NP gel comprising a first surface, a second surface, and a circumferential surface;   applying to said first surface, said second surface, and said circumferential surface nanofibers fabricated by an electrospin process that produces and randomly deposits nanofibers;   encompassing said circumferential surface with a nanofiber structure fabricated by an electrospin process that produces at least one layer of aligned fibers said aligned fibers being aligned substantially parallel in said at least one layer,   wherein said engineered NP gel exhibits structural characteristics similar to native annulus fibrosus (AF) and end plate (EP) in a natural intervertebral disc (IVD).   
     
     
         37 . The method of  claim 36 , further comprising fabrication of a non-tissue or a tissue engineered IVD using said anchored NP gel. 
     
     
         38 . The method of  claim 36 , wherein said nanofiber structure is a mesh comprising at least two layers of said aligned nanofibers and wherein said aligned nanofibers in one layer are oriented at an oblique angle relative to said aligned nanofibers in an adjacent layer. 
     
     
         39 . The method of  claim 38 , further comprising fabrication of an engineered IVD using PEGDA and soaking said engineered IVD with PBS or HBSS solution and heating in an incubator to promote disintegration of said PEGDA. 
     
     
         40 . The method of  claim 39 , further comprising seeding NP cell hydrogel material into said engineered IVD. 
     
     
         41 . A method to produce an engineered intervertebral disc (IVD) comprising:
 producing a solid compressible disc consisting of one of swelled or unswelled nucleus pulposus (NP) gel, said disc further comprising a first surface, a second surface, and a circumferential surface;   applying at least one layer of nanofibers on said first surface, said second surface, and said circumferential surface, said nanofibers being one of aligned or randomly oriented and adjoining said first surface, said second surface, and overlapping on said circumferential surface, and   wherein at least one layer of nanofibers is arranged concentrically around said circumferential surface, said nanofibers in each at least one layer being applied as single strips of aligned substantially parallel nanofibers.   
     
     
         42 . The method of  claim 41 , wherein at least a second layer and third layer of nanofibers is applied around said circumferential surface, said nanofibers in each layer directionally alternating relative to fibers in any adjacent layer. 
     
     
         43 . The method of  claim 42 , wherein nanofibers are applied to said circumferential surface by intercepting electrospun nanofibers extended between opposing collectors comprising any one of charged wires, plates, or rotating discs. 
     
     
         44 . The method of  claim 43 , wherein said nanofibers in one layer are angled at an oblique angle in the range of 40 to 80 degrees and preferably 60 degrees with respect to fibers in adjacent layers to mimic natural IVD annual fibrous (AF). 
     
     
         45 . The method of  claim 41 , wherein said solid compressible disc further comprises multiple composite layers of nucleus pulposus (NP) gel and PCL nanofibers. 
     
     
         46 . The method of  claim 45 , wherein said NP gel comprises PEGDA. 
     
     
         47 . The method of  claim 46 , wherein said composite of PCL nanofiber and PEGDA layers form a three-dimensional NP scaffold. 
     
     
         48 . The method of  claim 47 , further comprising soaking said engineered IVD with PBS or HBSS solution and heating in an incubator to promote disintegration of said PEGDA, said three-dimensional NP scaffold remaining stable absent PEGDA when said PEGDA is disintegrated. 
     
     
         49 . The method of  claim 48 , wherein any of natural NP, AF and cartilage cells are seeded into said NP scaffold absent PEGDA.