The invention relates to a method for forming a functional network of human neuronal and glial cells, wherein the cells are introduced into a synthetic hydrogel system with the components polyethylene glycol (PEG) and heparin and are cultivated therein. The cells are introduced into the PEG heparin hydrogel system together with one of the gel components, either PEG or heparin, with which the cells were previously mixed such that the cells are already located in the hydrogel system during the formation of the three-dimensional hydrogel.

The present invention relates to modification of cellulose nanofibrils (CNF) with extracellular matrix components such as collagen, elastin, fibronectin or RGD sequences or growth factors such as TGFBeta using for example EDS-NHS conjugation method and preparation of bioinks for 3D Bioprinting of tissue models such as human skin or neural tissue. Cellulose nanofibrils provide excellent printing fidelity which is crucial for diffusion of oxygen and diffusion of nutrients into the 3D bioprinted constructs. The surface conjugated extracellular matrix components induce biological activity by providing adhesion sites or inducing differentiation process. 3D Bioprinted bioinks based on CNF bioinks showed great ability inducing adhesion of human fibroblasts and stimulating Collagen I production. Such bioinks are thus suitable for 3D Bioprinting of tissue models.

Disclosed are systems, methods, and devices for tissue regenerative implants. In some aspects, a nerve tissue regeneration implant article includes an exterior shell; a plurality of fascicle structures disposed in an interior region of the exterior shell, where each fascicle structure includes a hollow region between a proximal end and a distal end, such that a fascicle structure is configured to facilitate and guide axonal growth along at least a portion of the fascicle structure between the proximal end and the distal end; and a plurality of vascularizable passages along the exterior shell, wherein the vascularizable passages are configured to allow vascular tissue to infiltrate the implant article, such that the implant article is able to facilitate nerve regeneration by enabling exchange of nutrients, oxygen, and/or waste to axons within the plurality of fascicle structures via the vascular tissue that infiltrates the implant article through the plurality of vascularizable passages.

The present disclosure provides fasciculated nerve grafts of customizable lengths and diameters, and methods of preparing the same. The grafts are made by digesting native extracellular matrix (ECM) around the nerve fascicles of a nerve tissue, and the epineurial sheath. One or more of the individual fascicles may then be entubulated in an entubulation material, embedded in or coated with a coating material, or both, to form a fasciculated nerve graft. The fasciculated nerve grafts are customizable and designed to bridge nerve gaps; the modularity of the fasciculated nerve graft allows for restoring continuity to nerve defects of virtually any length and allows for matching the diameter of the patient's recipient nerve.

The invention is directed to methods for treating nervous system injury and disease, in particular traumatic brain injury and degenerative nervous system disease. Such methods utilize novel compositions, including but not limited to trophic factor-secreting extraembryonic cells (herein referred to as TSE cells), including, but not limited to, amnion-derived multipotent progenitor cells (herein referred to as AMP cells) and conditioned media derived therefrom (herein referred to as amnion-derived cellular cytokine solution or ACCS), each alone or in combination with each other and/or other agents.

The invention relates to a cell sheet construct for neurovascular reconstruction. The cell sheet construct has a vascular endothelial cell layer and a neural stem cell layer, and the two layers are physically in direct contact with each other, where the vascular endothelial cell layer forms branching vasculatures, and the neural stem cell layer differentiates into neurons. The invention also relates to a method for manufacturing the cell sheet construct, having the following steps: culturing vascular endothelial cells on a substrate to form a vascular endothelial cell layer, seeding neural stem cells on the vascular endothelial cell layer to make the neural stem cells be physically in direct contact with the vascular endothelial cell layer, and culturing the neural stem cells and the vascular endothelial cell layer to differentiate into neurons and branching vasculatures to form a cell sheet construct.

A medical device for repairing a lesion in a spinal cord or in a peripheral nerve is provided. The medical device has a flexible support made of expanded polytetrafluoroethylene. Stem cells suitable for being oriented along a first growth direction or a second growth direction are at least partially embedded on the flexible support that is suitable for taking an extended configuration and a wound configuration. In the wound configuration, the flexible support is suitable for being wound around the spinal cord so that the first and second growth directions are substantially statistically parallel to a neuronal extension direction of neurons of the spinal cord. Surgical methods of treating a spinal injury involving using the medical device are also provided.

In various aspects and embodiments the present disclosure provides a construct comprising a pre-formed neural network, the construct comprising a micro-column comprising an outer sheath comprising a hyaluronic acid (HA) hydrogel, and a core comprising an extracellular matrix (ECM); a plurality of neurons within the micro-column. The present disclosure further provides methods of making and using the same.

Neurosupportive materials that possess strong tissue adhesion were synthesized by photocrosslinking two polymers, gelatin methacryloyl (GelMA) and methacryloyl-substituted tropoelastin (MeTro). The engineered materials exhibited tunable mechanical properties by varying the GelMA/MeTro ratio. In addition, GelMA/MeTro hydrogels exhibited 15-fold higher adhesive strength to nerve tissue ex vivo compared to traditionally used fibrin-based materials. Furthermore, the composites were shown to support Schwann cell (SC) viability and proliferation, as well as neurite extension and glial cell participation in vitro, which are essential cellular components for nerve regeneration. Finally, subcutaneously implanted GelMA/MeTro hydrogels exhibited slower degradation in vivo compared with pure GelMA, indicating its potential to support the growth of slowly regenerating nerves. Thus, GelMA/MeTro composites may be used as clinically relevant biomaterials to regenerate nerves and reduce the need for microsurgical suturing during nerve reconstruction.

A method for making a culture medium for culturing neural cells is provided. An original carbon nanotube structure is provided. The original carbon nanotube structure includes a drawn carbon nanotube film including a number of carbon nanotubes joined end to end by van der Waals force. The carbon nanotubes are substantially oriented along the same direction. A carbon nanotube structure including a number of carbon nanotube wires spaced from each other is formed by treating the original carbon nanotube structure. The carbon nanotube structure is fixed on a substrate.