Piezoelectric Nanocomposites Driven By Ultrasound Regulate Neural Differentiation Of Stem Cells

Neurodegenerative disease is one of the main causes of disability and morbidity worldwide,which affects human health and quality of life.At present,drug therapy is mainly used to treat neurodegenerative diseases all over the world,but drug therapy is expensive and ineffective,and can only improve symptoms but not completely treat them.Stem cells have attracted people’s attention because of their ability to differentiate into other types of cells.Especially in the field of treatment of neurodegenerative diseases,stem cell therapy has played a new role superior to traditional drug treatment,which has opened up a new road for the treatment of neurodegenerative diseases.Mesenchymal stem cells(MSCs)are pluripotent stem cells that can differentiate across germ layers.They have a wide range of cell sources and no risk of teratoma,and have become the third cell type that has been widely studied after embryonic stem cells(ESCs)and induced pluripotent stem cells(i PSCs).It also has many preclinical studies in the field of nerve regeneration,and has surprising performance in nerve cell regeneration.The main factors affecting the fate of stem cells are biological factors,chemical factors and physical factors.Physical factors are the use of sound,light,electricity and other physical signals to regulate the fate of stem cells.Bioelectricity exists widely in organisms,and the transmission of nerve signals also depends on electrical signals,which can be repaired by electrical stimulation of nerve cells.In clinic,electrical stimulation is mainly realized by external leads.The equipment used in this way occupies a large area,is expensive and complicated to operate.In addition,external leads will cause tissue trauma and increase the risk of infection,so a noncontact electrical stimulation treatment is needed.Piezoelectric materials have piezoelectric properties that meet the above requirements.Piezoelectric materials can generate electrical signals under external force,including non-contact ultrasonic stimulation.Nano-materials are closer to the size of cells in size,and can be used as a platform to realize multifunctional loading while inducing stem cell differentiation.In this paper,a kind of piezoelectric nanoparticles(NPs)material is proposed based on the above-mentioned effects of piezoelectric materials on nano-materials.Based on the barium titanate nanoparticles(BT NPs),a piezoelectric barium titanate nanocrystal-based composite was developed,and its effect on neural differentiation of mesenchymal stem cells was studied.The main research contents are as follows:1.Piezoelectric Barium Titanate Nanocrystalline Matrix Composite promotes the differentiation of stem cells into nerves.Based on the piezoelectric properties of barium titanate nanoparticles and the biocompatibility and adhesion of poly-dopamine(PDA),we constructed a core-shell structure of barium titanate nanocrystalline matrix composite(BT-PDA)coated with PDA film.The successful preparation of BT-PDA nanoparticles was proved by scanning electron microscope,atomic force microscope,X-ray diffractometer,Fourier transform infrared spectrum and Raman spectrum.The survival rate of live/dead stained cells is over 99%,and the cell proliferation rate in CCK-8 test shows an increasing trend,which proves that the material has good biocompatibility.The 5-day immunofluorescence staining proved that BT promoted Nestin secretion in cells,and the 10-day immunofluorescence staining proved that BT promoted GFAP in cells.Q-PCR proved that BT could promote the secretion of Nestin at 5 days.Immunofluorescence staining and q-PCR showed that BT-PDA had the ability to induce stem cells to differentiate into nerves in vitro.Therefore,it is inferred that piezoelectric nanoparticles have the ability to generate electrical stimulation by cell force in vivo,so as to realize intracellular electrical stimulation.2.Ultrasonic-driven piezoelectric barium titanate nanocrystal-based composites promote neural differentiation of stem cells.Due to the good piezoelectricity of barium titanate nanoparticles,in vitro electrical stimulation of cells without external wires can be realized by ultrasound.In this chapter,we successfully constructed barium titanate nanoparticles(BT-GQDs)with graphene quantum dots(GQDs)attached.The successful preparation of BT-GQDs was proved by scanning electron microscope,oscilloscope and X-ray diffractometer.The living/dead staining and cytocompatibility test showed that the material had good biocompatibility.Immunofluorescence staining and q-PCR showed that BTGQDs significantly promoted the differentiation of stem cells into nerves in vitro under ultrasonic conditions.After 10 days of immunofluorescence staining,it was proved that BT-GQDs could significantly promote the secretion of intracellular GFAP under ultrasonic conditions.It is inferred that the composite BT-GQDs can improve the piezoelectricity of piezoelectric nanoparticles and further promote the differentiation of mesenchymal stem cells into nerves under the stimulation of ultrasound.The electrical stimulation without external wires is realized.