This invention relates to compositions and methods for activating and promoting mineralization in tissue that does not normally mineralize, specifically intervertebral discs. The composition comprises agents that increase the expression of the gene that encodes TNAP and/or the activation, amount or activity of INAP protein, and agents that decrease the expression of ANK and/or ENPP and/or the activation, amount or activity of these proteins. The composition can be in the form of a cell or cells. The invention also relates to methods of using the composition.

A method of treating soft tissue conditions. A harvesting device is provided. The harvesting device is operably connected to a tissue processing device using tubing. An aperture is formed in a bone. The bone has an interior. The harvesting device is inserted through the aperture in the bone and into the interior of the bone. The harvesting device is manipulated to dissociate connective tissue progenitor cells in the interior of the bone. Tissue is aspirated from the interior of the bone. The connective tissue progenitor cells are separated from the aspirated tissue. The separated connective tissue progenitor cells are injected in a region of a body that is experiencing a soft tissue condition to treat the soft tissue condition.

Disclosed are methods of enhancing regeneration of the nucleus pulposus through enhancement of perispinal perfusion in combination with a regenerative intervention. In one embodiment the invention teaches stimulation of enhancement of perispinal perfusion by administration of angiogenic agents prior to performing a regenerative intervention such as administration of a stem cell therapy. In one specific embodiment perispinal angiogenesis is stimulated by administration of autologous bone marrow mononuclear cells in the perispinal area, preferably into a muscular area, subsequent to which intradiscal administration of regenerative cells, such as mesenchymal stem cells is performed.

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.

Provided is a cell sheet suitable for cartilage repair. The present invention provides a cell sheet for cartilage repair, formed from a culture of cells derived from a cartilage tissue, and the cell sheet is negative for immunostaining using an antibody against type II collagen. The present invention also provides a method for producing a cell sheet for cartilage repair, formed from a culture of cells derived from a cartilage tissue, and the method includes culturing cells derived from a cartilage tissue on a surface of a membrane, where a temperature-responsive polymer is immobilized on the surface, to give the cell sheet. The culturing is stopped before the cell sheet becomes positive for immunostaining using an antibody against type II collagen.

Methods for developing a decellularized tissue and biomaterials for use as biomimetic grafts or in vitro cellular scaffolds formed with the decellularized tissue are described. The biomaterials are particularly well suited for use as an intervertebral disc graft. The decellularized tissue is formed from an intervertebral disc source tissue and can be substantially decellularized and substantially free of potential immunogenic material (e.g., DNA and RNA), while maintaining ECM materials including both glycosaminoglycan and collagen.

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.

The present disclosure describes methods of treating an injury in a subject using placental tissue streamers, engineered tissue placental tissue hybrids, suture placental tissue hybrids, placental tissue patch hybrids, and tissue hybrids, and the use of these compositions to repair, treat, or support an injury or degenerative process in a subject.

Methods and apparatus for treating disc herniation provide a conformable device which assumes a first shape associated with insertion and a second shape or expanded shape to occlude the defect which typically follows partial discectomy. The device may take different forms according to the invention, including patches size to cover the defect or plugs adapted to fill the defect. In a preferred embodiment, however, the device is a gel or other liquid or semi-liquid which solidifies to occlude the defect from within the body of the disc itself. In another preferred embodiment, a mesh screen is collapsed into an elongated form for the purposes of insertion, thereby minimizing the size of the requisite incision while avoiding delicate surrounding nerves. Such a configuration also permits the use of instrumentation to install the device, including, for example, a hollow tube or sheath adapted to hold the collapsed screen, and a push rod to expel the collapsed device out of the sheath for use in occluding the disc defect. A device according to the invention may further include one or more anchors to assist in permanently affixing the device with respect to the defect.

The present invention relates to a tissue-engineered intervertebral disc (IVD) suitable for total disc replacement in a mammal and methods of fabrication. The IVD comprises a nucleus pulposus structure comprising a first population of living cells that secrete a hydrophilic protein and an annulus fibrosis structure surrounding and in contact with the nucleus pulposus structure, the annulus fibrosis structure comprising a second population of living cells and type I collagen. The collagen fibrils in the annulus fibrosis structure are circumferentially aligned around the nucleus pulposus region due to cell-mediated contraction in the annulus fibrosis structure. Also disclosed are methods of fabricating tissue-engineered intervertebral discs.