The impact of graphene on neural regenerative medicine

There is increasing interest in studying carbon-based nanomaterials（CBNs）for use in regenerative medicine.Some carbon crystalline structures,such as graphene,carbon nanotubes/nanofibers,boron nitride nanosheets/nanotubes and fullerenes,as well as disordered structures,such as diamond-like carbon,glasslike carbon,and amorphous carbon,are now being considered as promising scaffolds（Ferreira et al.,2015;Kabiri et al.,2015）,

Graphene platform for neural regenerative medicine

Graphene is a material composed of a single layer of carbon atoms arranged in a two-dimensional honeycomb lattice. The unique elec- trical, optical, thermal, and mechanical properties of graphene are extensively exploited for various applications in electronics, energy, and sensors.

Novel advancements in threedimensional neural tissue engineering and regenerative medicine

Neurological diseases and injuries present some of the great- est challenges in modern medicine, often causing irrevers- ible and lifelong burdens in the people whom they afflict. Conditions of stroke, traumatic brain injury, spinal cord injury, and neurodegenerative diseases have devastating con- sequences on millions of people each year, and yet there are currently no therapies or interventions that can repair the structure of neural circuits and restore neural tissue function in the brain and spinal cord. Despite the challenges of over- coming these limitations, there are many new approaches under development that hold much promise. Neural tissue engineering aims to restore and influence the function of damaged or diseased neural tissue generally through the use of stem cells and biomaterials. Many types of biomaterials may be implemented in various designs to influence the survival, differentiation, and function of developing stem cells, as well as to guide neurite extension and morphological architecture of cell cultures. Such designs may aim to reca- pitulate the cellular interactions, extracellular matrix char- acteristics, biochemical factors, and sequences of events that occur in neurodevelopment, in addition to supporting cell survival, differentiation, and integration into innate neural tissue.

Material and mechanical factors:new strategy in cellular neurogenesis

Since damaged neural circuits are not generally self-recovered, developing methods to stimulate neurogenesis is critically required. Most studies have examined the effects of soluble pharma- cological factors on the cellular neurogenesis. On the other hand, it is now recognized that the other extracellular factors, including material and mechanical cues, also have a strong potential to induce cellular neurogenesis. This article will review recent data on the material （chemical patterning, micro/nano-topography, carbon nanotube, graphene） and mechanical （static cue from substrate stiffness, dynamic cue from stretch and flow shear） stimulations of cellular neuro- genesis. These approaches may provide new neural regenerative medicine protocols. Scaffolding material templates capable of triggering cellular neurogenesis can be explored in the presence of neurogenesis-stimulatory mechanical environments, and also with conventional soluble factors, to enhance axonal growth and neural network formation in neural tissue engineering.

Stem cells:a promising candidate to treat neurological disorders

Neurologic impairments are usually irreversible as a result of limited regeneration in the central nervous system.Therefore,based on the regenerative capacity of stem cells,transplantation therapies of various stem cells have been tested in basic research and preclinical trials,and some have shown great prospects.This manuscript overviews the cellular and molecular characteristics of embryonic stem cells,induced pluripotent stem cells,neural stem cells,retinal stem/progenitor cells,mesenchymal stem/stromal cells,and their derivatives in vivo and in vitro as sources for regenerative therapy.These cells have all been considered as candidates to treat several major neurological disorders and diseases,owing to their self-renewal capacity,multi-directional differentiation,neurotrophic properties,and immune modulation effects.We also review representative basic research and recent clinical trials using stem cells for neurodegenerative diseases,including Parkinson＇s disease,Alzheimer＇s disease,and age-related macular degeneration,as well as traumatic brain injury and glioblastoma.In spite of a few unsuccessful cases,risks of tumorigenicity,and ethical concerns,most results of animal experiments and clinical trials demonstrate efficacious therapeutic effects of stem cells in the treatment of nervous system disease.In summary,these emerging findings in regenerative medicine are likely to contribute to breakthroughs in the treatment of neurological disorders.Thus,stem cells are a promising candidate for the treatment of nervous system diseases.