Triboelectric Stimulator And Its Applications In Tissue Engineering

With the rapid development of medical technology and health level,people’s demand for highly efficient and safe medical treatment continues to increase.Among them,electrical stimulation,as a non-invasive treatment with controllable parameters,effective and good tolerance and compliance,has shown unique advantages in tissue engineering and regenerative medicine,and has become a research direction that has attracted much attention.However,current commercial electrical stimulation devices are usually very large in size.The power supply and the Joule heating effect of long-term direct current and alternating current stimulation processes on tissues need to be considered urgently.Triboelectric nanogenerator(TENG)is a new type of energy converter that uses the coupling effect of triboelectric and electrostatic induction to convert tiny mechanical energy into electrical energy and output current,and has self-powered characteristics.Its pulsed output characteristics of high voltage and low current can greatly reduce or even avoid adverse reactions caused by thermal effects on skin and other tissues.The feasibility and benefits of TENG as a high-voltage low-frequency pulsed electrical stimulation device for regenerative medicine,such as tissue repair and tumor treatment from the cell to the in vivo model level,have been extensively studied in recent years,but research on the mechanism of TENG in body tissues is lagging behind.On the other hand,the current electrical output performance of wearable and implantable TENGs is limited,thereby limiting its effectiveness and efficiency in the treatment of more complex diseases.Therefore,this paper explores the application and mechanism of pulsed electrical stimulators based on triboelectric nanogenerators(i.e.,triboelectric stimulators)in tissue engineering,including the mechanism of high-frequency pulsed current stimulation based on turntable TENG in inhibiting tumor metastasis,and the therapeutic effect of TENG based electrical stimulation synergistic triboelectrical response of controllable drug delivery hydrogels in promoting chronic wound healing of bacterial infections.Therefore,this thesis will discuss the application and mechanism of pulsed electrical stimulators based on triboelectric nanogenerators(i.e.,triboelectric stimulators)in tissue engineering.Studying the mechanism of high-frequency pulse current stimulation based on turntable TENG in inhibiting tumor metastasis is the first focus of this thesis.The second research point of this thesis is to design a therapeutic system of pulse electrical stimulation based on TENGs combined with triboelectric responsive drug delivery hydrogels and verify its therapeutic effect in promoting chronic wound healing of bacterial infection.Based on the above research focuses,this thesis designs a rotatory disc-shaped triboelectric nanogenerator(RD-TENG)and discusses the effect of pulse current on inhibiting cancer cell migration and tumor metastasis.Subsequently,a therapeutic system of pulse electrical stimulation based on TENGs combined with triboelectric responsive drug delivery hydrogels was constructed,aiming to improve the utilization of curcumin and realize the controllable and efficient release process of curcumin,which ultimately significantly promoted the healing rate of bacterial infection wounds and provided an efficient,convenient and safe treatment strategy for the treatment of chronic wounds,the main research results are as follows:(1)Rapid metastasis of cancer cells to the whole body is the leading cause of more than 90%of cancer-related deaths.Inhibiting the migration and invasion of cancer cells is considered as an important strategy to defeat metastatic cancer.Although agents and nanomedicines have been developed to delay the migration of cancer cells,the insensitivity of cells to antagonists and the frequent occurrence of side effects such as drug resistance limit their widespread application.Therefore,we developed a rotatory disc-shaped triboelectric nanogenerator(RD-TENG)as a novel high-frequency pulse electrotherapy strategy to achieve a more effective and tolerated therapeutic strategy by generating pulse electrical stimulation to slow cell migration in vitro and tumor metastasis in vivo without causing significant changes in normal organs and tissues.Firstly,we found that cell proliferation can be significantly inhibited at a promotion rate of～15%when the TENG output current reaches to 150 μA.Subsequently,a pulse current stimulation of 150 μA was revealed by a two-dimensional scratch assay that can partially inhibit cell migration in vitro by inducing shortening of cellular cilia and structural disruption of cytoskeletons such as actin and tubulin.The results of qRT-PCR analysis showed that TENG-based electrical stimulation could regulate cell migration by affecting the cytoskeleton through affecting F-actin and a tubulin-related signaling pathways,which was manifested as significantly inhibiting the expression of MAPs protein,Vinculin protein,Talin protein and Src protein associated with cell migration.Finally,by using mice inoculated with 4T1-LUC cells as an in vivo model for tumor metastasis,we found that 150 μA galvanic stimulation slows the spread of early cancer cells to other body parts(e.g.,lungs)without significant side effects and good tissue safety.The above results show the great potential of RD-TENG-based pulsed current stimulation as a novel electrotherapy strategy to inhibit cell migration and tumor metastasis and in cancer treatment.(2)Pulse electrical stimulation alone has been reported to be effective for wounds healing,but the effect of electrical stimulation alone is limited for wounds with bacterial infection.Curcumin has a certain antibacterial effect,but curcumin has the defect of low utilization,and the developed curcumin nanoparticles delivery system and skin penetration enhancer can improve the availability,but its effect as a passive drug delivery method is limited and cannot achieve controllable release.Therefore,in order to improve the healing rate and effect of bacterial infected wounds,we developed a wearable triboelectric stimulator(WTS)and constructed a synergistic therapeutic system based on a wearable TENG(W-TENG)with the triboelectric-responsive drug delivery hydrogel(TR-DDH).The W-TENG with microstructures significantly improves the electrical output performance of the device compared to the W-TENG without microstructures,achieving an open circuit voltage of 240 V,a short-circuit current of 4 μA,and a transfer charge of 40 nC at a contact separation frequency of 2.5 Hz.By preparing polypyrrole/curcumin composite nanoparticles and using the polyvinyl alcohol as a dispersant,the UV absorbance of polypyrrole/curcumin nanoparticles remained basically unchanged within 14 days under light and the size relatively uniform,which improved the stability of curcumin nanoparticles.The TR-DDH can form a stable and reversible adhesion interface with the skin due to its lower Young’s modulus and good adhesion,thereby ensuring the stability and efficiency of electrical signal transmission during electrical stimulation.The release rate of curcumin nanoparticles under pulsed electrical stimulation is about twice that of the group without electrical stimulation.The system significantly increases the rate of wound healing for bacterial infections and has good antimicrobial effect and tissue safety without causing thermal damage to the skin.Therefore,the therapeutic system of electrical stimulation combined with triboelectric responsive drug delivery hydrogels provides an efficient and safe treatment strategy for chronic wound healing of bacterial infection and the controllable drug delivery process.