| BackgroundAt present,millions of people rely on implantable medical devices such as pacemakers to maintain normal vital signs.In the past half century,pacemaker technology has made a great progress,such as the Internet-based remote monitoring.However,there is a lack of innovative development in the basic system example of an extravascular pulse generator connected to a lead passing through the venous system to contact myocardial tissue.In addition,the basic power supply method is still highly dependent on the batteries.Many complications,such as infection,pneumothorax,lead failure and invalid pacing,are related to this basic structure.Besides,regular battery replacement surgery is inevitable to ensure adequate power supply,which greatly increases the health risks of patients with high morbidity and potential mortality.Therefore,it has become a main focus to develop leadless or battery-free pacemakers.Researchers have made great efforts to develop the battery-free medical equipment.The most promising method is to directly convert biomechanical energy into electrical energy,such as muscle stretching,heartbeat,blood flow and air flow generated by breathing.The mechanisms of biomechanical energy conversion include electromagnetic induction,triboelectric,electrostatic and piezoelectric methods.Because of its high power density,high output stability and flexibility,piezoelectric method is more promising for implantable battery-free medical devices.Biomechanical energy conversion in vivo is firstly realized by a flexible piezoelectric transducer based on zinc oxide nanowire film.Flexible polyvinylidene fluoride is adopted to develop an implantable piezoelectric transducer.Subsequently,the flexible transducer based on piezoelectric ceramics(lead zirconate titanate)can achieve an in vivo output current of about 0.1 A in a large animal model.While providing three pieces of evidence for the possibility of realizing the transformation from biomechanical energy to electrical energy,it proves that piezoelectric ceramic method can generate a large amount of electrical energy from the movement of internal organs.However,the commercial pacemakers are still difficult to drive with implantable piezoelectric transducers.Adequate power supply is a key obstacle of implantable piezoelectric transducer pacemaker,which is related to the material,manufacture,structural design,implantation position,and conversion mode.There are two different methods to develop leadless pacemaker,which are the single-component system and multi-component system.For the one-component system,the whole pacemaker(battery,electronic equipment,stimulation electrode and sensor)is integrated into a small capsule implanted into the heart.For the multi-component system,the transducer is placed in the heart cavity.The chest part emits energy(ultrasonic or radio waves)to the transducer.However,endocardial energy conversion is not easy to obtain enough energy.These two methods are realized by placing the integrated components in the heart cavity,which not only greatly limits the size and weight of the equipment,but also increases the difficulty and risk of maintenance(e.g.thrombosis,infection and sensitivity to environmental interference).In this study,we put forward a strategy of pacemaker without battery and lead.In the process of contraction and relaxation of pig's heart,a capsule piezoelectric transducer was applied to utilize the mechanical energy of heart compression,and the converted electrical energy was used to directly power the commercial pacemaker circuit to verify whether the energy supply of the sensor is sufficient.By puncturing the epicardial tissue,the pacing probe could achieve effective pacing and avoid the lead passing through the venous system.Since the battery-free pacemaker based on piezoelectric transducer is in a direct contact with epicardium,the lead can be removed.This study may provide new insights for the rational design and development of battery-free and leadless pacemakers or other biomedical devices.ObjectiveThis study has three objectives:1.To design and prepare a piezoelectric transducer for rat heart,and characterize its current output capability: The extract of piezoelectric transducer was co-cultured with myocardial cells,and the toxicity of piezoelectric transducer to cells was detected.Piezoelectric transducer was implanted into rats,and its biocompatibility and safety in vivo for up to 3 months were investigated.It lays an experimental foundation for the next preparation of pig heart piezoelectric transducer.2.To design and manufacture a piezoelectric transducer for pig heart,which has the characteristics of no battery and no lead and can drive the heart to pace: The in vivo experiments were conducted to detect the output current capacity of the modified piezoelectric transducer implanted in pigs.3.To summarize the whole paper,put forward the preparation method,biocompatibility and safety in vivo and in vitro,and show the prospect of clinical application in the future.Methods1.The assembly and packaging of piezoelectric transducer: We packaged devices with core/shell packaging technology.PDMS coating was applied to piezoelectric transducer,and parylene-C film was used as the second protective layer to prepare piezoelectric transducer.2.Verification of the safety,effectiveness and histocompatibility of long-term implantation of cardiac piezoelectric transducer in rats: The prepared extract of rat heart piezoelectric transducer was co-cultured with cardiomyocytes in vitro.Then,MTT assay was used to analyze the cell proliferation,and the cell proliferation rate of the extract group and the control group was analyzed.Furthermore,the piezoelectric transducer was implanted into rats.Immediately after implantation,1 week,2 weeks,4 weeks and 12 weeks after implantation,the position of piezoelectric transducer in rats was examined by CT scanning,and the cardiac function of rats was examined by echocardiography.After12 weeks,the rats were treated,serum was extracted and biochemical indexes were detected.3.Preparation of a battery-free leadless piezoelectric transducer for pigs,which can convert the mechanical energy of heart beat into electrical energy and provide energy for the battery-free pacemaker.4.Test on the electrical energy conversion ability of the pig piezoelectric transducer after its implantation into the body.Results1.The rat heart transducer was successfully fabricated by core/shell packaging technologyTwo piezoelectric composite materials were symmetrically bonded on the top surface and the bottom surface of the elastic skeleton to realize switchable output.Copper wires were pre-packaged in medical silica gel as electrical leads,and then spun on PDMS film.In this way,the deformation process of i PEG could be divided into four states:initial state,compressed state,compressed state and expanded state.During this process,alternating current was generated,and the output reached a positive maximum in the compressed state and a negative maximum in the expanded state.2.Piezoelectric transducer for rats has good biocompatibility and safety in vivo and in vitroAs shown by the result of the cell experiments,the piezoelectric transducer used in rats had no adverse effects on myocardial tissue and normal proliferation of myocardial cells.Twelve weeks after the implantation,CT revealed that the position of the self-powered pacemaker did not change.Although the implantation of the device into the thoracic cavity of rats had a certain effect on cardiac function,it had no significant effect on blood biochemical indexes of rats.The electrical performance of the piezoelectric transducer for rats was tested.The electrical performance of the piezoelectric vibration energy harvester prepared by us in vitro was: the average voltage was about 3.5 m V,and the average current was about 60 n A.After being implanted into rats,the average voltage and current were measured immediately at about 3.2 m V and 54 n A,respectively.After one week in vivo,the average voltage was about 3.0 m V and the average current was about 48 n A.After 12 weeks in vivo,the average voltage was about 2.1 m V and the average current was about 31 n A.3.Piezoelectric transducers for pigs were successfully preparedWe designed a piezoelectric transducer for pigs,which is composed of an elastic skeleton and two piezoelectric composite materials(including piezoelectric,metal and polymer layers).Furthermore,the PMM-PT was cut into rectangular blocks by UV laser cutting process,and then bonded and hot pressed in vacuum.Then,by mechanical grinding and magnetic sputtering,the thinned PMM-PT piezoelectric film was polarized and bonded with adhesive,and the piezoelectric transducer for pigs was successfully prepared.4.In vivo transduction ability of pig piezoelectric transducerWe evaluated the mechanical and electrical properties of piezoelectric transducers for pigs.The maximum short-circuit current output of 30?A could be achieved when implanted in adult pigs,which was more than 15 times higher than that of the same type of research.The pacing effect was achieved by implanting piezoelectric transducer for pigs to drive pacemaker to generate electric pulse and to directly stimulate myocardial tissue through epicardium.It proves the feasibility of in-situ epicardium pacing strategy,avoids placing devices or leads in the heart cavity,and is expected to realize leadless pacing.ConclusionThis paper focuses on the preparation of cardiac piezoelectric transducer and its application in animals.It proposes to convert heartbeat kinetic energy into electrical energy using piezoelectric transducer,and explore the output characteristics of energy collector and its performance in realizing self-powered pacemaker.At the same time,the epicardial in-situ pacing strategy is put forward to explore the realization method of self-powered leadless pacemaker.The specific conclusions are as follows:(1)The heart transducer for rats was successfully fabricated by core/shell packaging technology,which showed good biocompatibility and safety in vivo and in vitro.(2)The cardiac transducer for rats has certain electrical characteristics.After the rat was implanted with heart transducer for 12 weeks,the average output voltage and current were measured to be about 2.1 m V and 31 n A,respectively.(3)Based on the preparation technology of cardiac transducer for rats,piezoelectric transducer for pigs was successfully prepared,which has no obvious biological toxicity to cells and tissues.(4)The maximum short-circuit current output of 30?A could be achieved when the piezoelectric transducer for pigs was implanted in adult pigs,which was over 15 times higher than that of the same type of research.The output electrical energy is connected to the commercial pacemaker with the battery removed.Through the obtained electrical pulse signal,it is verified that the heartbeat kinetic energy collected by the implanted flexible buckling piezoelectric energy collector is enough to maintain the normal operation of the commercial pacemaker,showing the feasibility of the implanted piezoelectric energy collection technology in realizing the self-powered pacemaker.To sum up,the leadless and self-powered pacing is being explored as the basic structural forms of cardiac pacemakers.Sustainable energy supply and effective pacing are the two key parts of this leadless self-powered pacing strategy,which not only provide more possibilities for the future development of pacemakers but also have a great significance for the development of new pacemaker strategies. |
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