Nanostructure Mediated Stem Cell Differentiation For Tissue Repair

With the increasing development of tissue engineering,the combination of cell biology and materials science has become one of the most important strategies for the effective treatment of nerve injury.This therapeutic strategy goes beyond the traditional treatments of the past by providing an extracellular matrix structure suitable for the body to build a neuroregenerative microenvironment for tissue repair.The properties of neural stem cells offer new ideas for neural regeneration and are therefore used as seed cells for neural tissue engineering.Neural stem cells are capable of selfrenewal and have the potential to differentiate into neurons,astrocytes and oligodendrocytes.There are many more applications for neural stem cells to be explored,and as research continues to be explored,it will lead to new therapeutic options for the clinical management of neurodegenerative diseases.The high cost,short half-life and complexity of biologic modulation of stem cell differentiation have hindered its clinical application.In addition,chemical and physical modulation methods have become promising new modulation methods,which can open up the signalling pathways related to stem cell differentiation and achieve the targeted differentiation of stem cells.Chemical and physical regulation is more reliable and less costly than regulation by biological factors.In recent years,researchers have designed low-cost,well-moulded,biocompatible nanomaterials as excellent tissue engineering scaffolds with unique physicochemical properties that can be used to build microenvironments suitable for cell growth and differentiation.Firstly,stem cell differentiation can be induced using chemical microenvironmental conditions.The controlled release of metal ions from nanomaterials can effectively regulate the directed differentiation of stem cells.Ions can regulate cell fate in a number of ways,such as by affecting cell membrane potential,ion channels and transporters,to name a few.One of the more prevalent ion signalling molecules is calcium ion,which plays an important role as an intracellular signalling molecule.Many signalling pathways are regulated by calcium ions,such as the Wnt signalling pathway,the Notch signalling pathway and the Hedgehog signalling pathway.In tissue engineering,stem cells are combined with calcium ions in nanomaterials and the mechanism of calcium ion action is used for targeted differentiation of stem cells.Secondly,stem cell differentiation can also be induced through the physical microenvironment,using the physical properties of nanomaterials or using nanomaterialmediated physical signals to regulate stem cell fate.Physical factors are easier to achieve localised stimulation and are more biosafe than chemical and biological factors.Some physical factors can directly or indirectly influence the initiation of intracellular signalling pathways,thereby affecting stem cell proliferation and differentiation.In neural tissue engineering,electrical stimulation has been shown to have the ability to induce stem cell differentiation by affecting the extracellular membrane potential and thus causing changes in signalling pathways,triggering biochemical reactions associated with stem cell differentiation,making electrical stimulation a very promising therapeutic strategy.Due to the unique physical properties of piezoelectric materials,the use of nano-biomaterials with piezoelectric properties allows for non-invasive electrical stimulation,which is safer and more reliable than implantable electrodes and eliminates the appearance of inflammatory reactions on the trauma surface.Organic piezoelectric materials have been found to be more flexible and easier to prepare than inorganic piezoelectric materials,making them ideal for microfabrication and very suitable for use in nerve repair.This thesis focuses on the regulation of stem cell fate by two factors,chemical and physical,and selects suitable nanomaterial scaffolds to combine with neural stem cells to investigate the effects of two different regulatory factors on the differentiation of neural stem cells towards nerves.This thesis has two main parts:1.An antimicrobial silver phosphate-loaded nano-hydroxyapatite paper induces differentiation of neural stem cells.Hydroxyapatite is prepared by hydrothermal synthesis and subsequently doped with silver ions to undergo in situ ion replacement to obtain silver phosphate hydroxyapatite nanowires,which are passed through an extraction device to obtain soft and unbreakable antibacterial hydroxyapatite paper.These paper films are easy to prepare,unbreakable,antibacterial and biocompatible,and slowly release calcium ions in solution.Calcium ions can affect the activation and inhibition of many signalling pathways.Neural stem cells were selected as seed cells and the modulation of neural stem cells by antibacterial hydroxyapatite was investigated.2.Regulation of neural stem cell fate by ultrasound-driven piezoelectric nanostructuresPVDF membranes with ordered nanoarray columns were prepared by hot pressing and their piezoelectric properties were significantly enhanced.The unique piezoelectric properties of the piezoelectric material were exploited to stimulate the material with ultrasound,thereby generating electrical stimulation around the cells and stimulating the initiation of calcium channels to promote neural differentiation.The longer nano-array columns allow for the natural purification of the neuroglia due to the easy shedding of differentiated neurons on this structure.This non-invasive approach to radio signal stimulation is clearly suitable for further clinical research and development.The effect of piezoelectric flexible membranes with V-shaped arrays on cell behaviour such as adhesion,proliferation and differentiation of neural stem cells was investigated.In summary,this thesis provides new ideas and approaches for future work in neural repair and regenerative medicine through the properties of nano-biomaterials for the targeted differentiation of neural stem cells in a chemical and physical factor-regulated manner.