Like the bacteriophage, many organs contain macromolecules which give them piezoelectric properties. Organs with piezoelectric properties can be viewed as amorphous organic material containing structured fibers which give them their piezoelectric properties [ 19 , 28 ]. Often these fibrils will grow in a helix shape, preventing them from having centrosymmetric symmetry [ 29 ]. The overall strength of the piezoelectric effect will depend on the ordering, quantity or composition of these fibers.
Bones and tendons have hexagonal symmetry and contain the following piezoelectric constant d ij in the form of Eq. For example, examination of the epidermis, horny layer, and dermis of the skin revealed that each layer had its own piezoelectric coefficient, the highest being the horny layer. The structure of the keratin horny layer simplified its ability to produce piezoelectric tensors, giving them the form of Eq.
The values of piezoelectric coefficients varied based on temperature; however, the highest were seen in the horny layer, on the order of 0. The lack of consistency in these measurements is due to the variety in how the molecules were ordered in each sample [ 28 ]. Similarly, piezoresponse force measurements PFM studies of collagen proved that collagen is the main source of piezoelectricity in the bone and reveal different ordering of collagen fibers results in different piezoresponses, as seen in Figure 2 [ 32 ].
In collagen, there are alternating sections of overlap and gap regions. The collagen fibers are arranged in a staggered way that result in the gap region having one less microfiber. In addition, the molecules in the gap region have less uniform symmetry, and therefore that region does not have as high of a piezoresponse [ 32 ]. These two studies indicate the piezoelectric response is not merely dependent on the molecular structure, but the structure of the entire organ.
Table 1 gives a description of organs with tested piezoelectric properties and their attributed molecule. The images show a the topology of the collagen and b the piezoresponse force microscopy PFM image where the collagen can be distinguished from the surrounding tissues and how the gap and overlap regions differ in piezoelectric response. Despite many measurements, it is sometimes difficult for the scientific community to come to a consensus on the exact nature and relevance of in situ piezoelectric characteristics. For example, in the case of bone, two groups found contradicting results on the dependency of piezoelectricity in terms of hydration [ 14 , 37 ].
Some studies on the aorta indicate that it has piezoelectric properties, though results were varied. Two studies, taken over forty years apart showed different orders of magnitude for the studied properties [ 17 , 38 ]. A lab attempting to verify either of these studies found that there was no piezoelectric response from the aorta [ 39 ]. However, later research proved streaming potentials, fluid and ions driven by mechanical loading, may have a greater impact in determining bone properties [ 41 ].
However, Ahn et al. Furthermore, the generation of electric fields has been shown to increase bone healing during fracture [ 42 , 43 ]. Even if the exact purpose for piezoelectric properties in the body is not known, they still can be used for developing biomedical solutions on both microscopic and macroscopic levels. For example, knowing that amino acids and macromolecules composed of them have piezoelectric properties has inspired the use of biomaterials for human sensors [ 44 ].
Using peptides to build piezoelectric sensors eliminates the need for developing other biocompatible materials. For example, the knowledge of previously mentioned virus, M13, led to the alignment of its phages into nanopillars for enhanced piezoelectric properties [ 45 ]. The outer hair cell is another structure that piezoelectric properties can be attributed to. The motions of the outer hair cell alter how the organ of Corti vibrates, and changes how the inner hairs receive stimulation [ 36 ]. Recently, the development of a piezoelectric cochlear implant to mimic the conversion of sound vibration into an electrical signal has been undertaken and will be covered in a later section of this review [ 47 ].
Biological structures can serve as examples for the development of piezoelectric structures and biocompatible piezoelectric materials. In addition, the knowledge of piezoelectric properties can help in disease detection or injury analysis. With the knowledge that piezoelectric tissue properties are determined by proteins, diseases that affect the amount or distribution of these proteins can be detected by piezoelectric sensors.
One group proposed that the electromechanical coupling factor, controlled by collagen, could aid in detecting breast cancer [ 35 ]. In this paper, they claimed the PFM amplitude increased as a function of advancing atherosclerosis and could help with early detection of the disease. Finally, once the effect of piezoelectricity on the body have been studied, piezoelectric materials can be used to promote disease healing. Though the exact reason for piezoelectric qualities have not been fully discovered, studies into bone related injuries have revealed that induced electrical fields can accelerate bone repair and promote the growth of neurons [ 49 , 50 ].
Because of this, increasing the piezoelectric properties of a synthetic bone material has potential to increase the speed of osteoconduction and subsequently bone repair [ 51 ]. Lead free ceramics can be used in conjunction with synthetic bone; however, these materials have problems with ion diffusion which can be controlled by embedding in a ceramic or polymer matrix [ 50 ]. In terms of regenerating damaged bone or cartilage, a piezoelectric scaffold may provide the necessary stimulation for cell regrowth, and diminish the need for other growth factors [ 43 ].
Typically, scaffolds are made out of polymers, such as PVDF, and can also promote the growth of neurons and wound healing [ 50 ]. Many biomedical piezoelectric applications exceed the aforementioned purposes of mimicking or employing biological piezoelectric phenomena. In some cases, the choice of material depends mostly on the strength of the piezoelectric effect and the cost of the material. PZT lead zirconium titanate and quartz are common piezoelectric materials used in industry. PZT is cheaper, has higher piezoelectric coupling coefficients, and can be manipulated by changing the composition.
Quartz, however, is more stable and has consistent properties over a broader temperature range [ 4 ]. Developing implants or technology involving direct human contact has more constraints. Ceramics, like quartz, barium titanate, and potassium sodium niobate, are more biocompatible because they do not contain lead [ 50 ]. In addition, many biomedical devices require higher flexibility than ceramics can provide, due to the dynamic nature of human motion. Biocompatible polymers include most biological materials and PVDF copolymers. So far, polymer applications of PVDF have included, but are not limited to, biomechanical energy harvesting systems, sensors, and wound scaffolds [ 50 , 52 ].
Piezoelectric materials can be employed in monitoring many bodily signals because they convert mechanical energy into an electrical signal. They are especially applicable to monitoring dynamic pressure changes; many human vital signs consist of rhythmic activities like the heartbeat or breathing. In the higher end of that range are intraocular pressure and cranial pressure.
Piezoelectric sensors can be tailored by structure or material to match the pressure range of the desired quality [ 54 ]. Implanted or wearable medical sensors have greater applicability, as the Internet of Things becomes more fully developed. A medical professional or computer algorithm can monitor a patient for early warning signs that may have been missed between scheduled check-ups through their implanted device [ 55 ]. Table 2 lists some literature studies of piezoelectric sensors and their tested applications.
The variety of applications for piezoelectric sensors in the biomedical industry is promising, however much of this technology is still in the research and development phase. Before reaching the market, these devices need to have scalable manufacturing and guaranteed quality for every device [ 52 ].
A specific application for piezoelectric pressure sensing is synthetic skin. As a bare minimum, synthetic skin should provide the magnitude of contact force and approximate location of contact with the sensitivity of normal skin [ 53 ].
Piezoelectric Materials for Medical Applications
Ideally, it would also provide information about temperature changes or humidity [ 68 ]. Human skin itself acts as a vibrational sensor; it is structured to amplify tactile stimulation [ 69 ]. Piezoelectric force transducers offer a solution to quantifying and locating contact forces [ 53 ]. The use of polymers for synthetic skin is popular because of their similarity in texture and flexibility to human skin [ 70 ]. Polymers can be molded to emulate human characteristics, such as fingerprints to enhance their sensitivity [ 69 ]. Processing techniques, such as electrospinning, can increase response by aligning the molecular dipoles [ 25 ].
In a similar way, using hybrid materials or structuring ceramics and polymers can yield higher piezoelectric properties [ 71 , 72 ]. Though there are many materials, which can be used for this purpose, most are structured in arrays. A unit in the array will send an electrical signal describing the characteristic of the force.
In prosthetics, the electric signal will arrive at a location which still can perceive tactile senses [ 53 ]. One of the problems with arrays is interference between signals, otherwise known as crosstalk. During crosstalk, neighboring units are affected by the unit undergoing force and send their own signal. This can lead to an ill-defined contact region, which can be fixed using the installation of transistors or through triangulation of the signal [ 53 , 68 ].
One other interesting application of piezoelectric sensors is the detection of disease or odor through a change in chemical composition of a sensor. The quartz microbalance is used for a variety of purposes, such as gas detection [ 73 ], composition analysis, and chirality classification [ 74 ]. It can also sense changes in liquid density or viscosity [ 75 ]. This method relies on mass changes in a coating film around the crystal. An increase in mass indicates a decrease in the frequency of quartz vibration [ 76 ].
In this type of sensor, biological molecules are imbedded or attached to piezoelectric materials. This technology can also be used for detection of bacteria and biomolecules. The detection of bacteria or biomolecules usually involves the incorporation of a biomolecule in an exterior film. One method of detecting glucose uses the enzyme hexokinase embedded in a polymer matrix.
The glucose binds to the enzymes at a rate proportional to its concentration in solution [ 77 ]. In another glucose detection system, the frequency of the quartz was increased. The sensor was coated with dextran and Concanavalin A. The dextran preferentially binds to the glucose, therefore the presence of glucose causes the release of Concanavalin A.
Glucose has a lower molecular weight, and therefore the frequency increased with its detachment. This method of glucose detection is advantageous because it does not involve the use of enzymes; however has a lower detection range [ 78 ]. The quartz microbalance may also be applicable to developing bioelectronic olfactory replacements.
It has been used to detect hazardous odorants such as diacetyl, which can cause damage to the lung if inhaled, and could be used to measure other odors [ 79 ]. Unfortunately, some of the quartz microbalance equipment is bulky and requires complicated molecules as indicators. If the synthetic nose to be used for many compounds, the size may be too large to be practical. In addition, sensors based on biomolecules, such as the glucose have problems with biological stability [ 78 ]. These problems need to be fixed before they can be viewed as commercially viable.
The destruction of inner ear cells results in severe hearing loss and is most commonly treated by cochlear implants. Though the current technology allows for recovery from deafness, it is incompatible with water and has very high-power requirements [ 81 ]. Piezoelectric materials can be used for creating an artificial basilar membrane ABM. The membrane performs mechanical frequency selectivity for the cochlea. Varying physical rigidity and thickness of the basilar membrane allows it to perform its duty, and likewise piezoelectric materials can filter out frequency based on their physical properties [ 82 ].
Ceramics, such as PZT or AlN films, can be fabricated in beam or cantilever arrays with lengths corresponding with different resonance frequencies [ 81 , 83 ].
Piezoelectricity - Engineering LibreTexts
Many experimental cochlear ABMs need increased sensitivity, stability, and size reduction to be practically used [ 83 ]. In addition to creating implants, piezoelectricity can be used in a variety of medical treatments, most of which depend on the vibrational properties of the piezoelectric device. Unlike implanted devices, piezoelectric devices needed for surgery do not need to be biocompatible, because they do not come in contact with human cells.
Therefore, many external devices will make use of lead zirconate titanate PZT , as it is easier to produce [ 86 ]. The typical piezosurgical devices will consist of stacked rings which are given an applied voltage. The stacked actuator design increases the actuator efficiency because the electric field is determined by the applied voltage and the thickness Eq. The strain is proportional to the electric field if the thickness of the actuator is decreased, a higher strain can be generated for the same amount of voltage.
The resulting vibration will be transduced to the tip, which is installed in such a way that it will amplify vibrations, because traditionally ceramics are more brittle and do not display much displacement [ 88 ]. In surgery, piezoelectric devices, such as the ultrasonic lancet, are used for delicate operations to preserve surrounding tissue. By controlling the micromovements of the oscillating device, damage to soft tissues can be avoided, and the separation between interfaces is easily accomplished. Alternatives to piezosurgery, such as a chisel and hammer or rotating saw are seen as more invasive, have potential to lacerate non-discriminatorily [ 89 ].
There are no macrovibrations which may cause discomfort to the patient or disturbance of surrounding tissue [ 90 ]. The first use of piezosurgery was the dental industry, with applications like removal of implants, bone harvesting, and inferior alveolar nerve detachment [ 91 ]. Many such surgeries require working in small spaces and do not require larger incisions on the bone material.
This reduces the adhesion forces and allows the implant to be removed with fewer incisions. In a similar way, the collection of graft material is another excellent use of an ultrasonic lancet. After making preliminary cuts with a saw, the ultrasonic vibrations reduce the need for chisel strikes [ 91 ]. In surgery performed on the lower jawline, protecting the inferior alveolar nerve is important to patient recovery [ 92 ]. As said previously, the use of piezosurgery prevents the damage of these nerve tissues. Another benefit in all surgeries is particle breakdown caused by ultrasonic activity, which makes visibility easier [ 92 ].
Piezosurgery has some other applications in neurosurgery and orthopedic surgery; however, it is limited in equipment fragility and associated expenses [86, 90].
It is noted that elongated PLLA films have no spontaneous polarization, unlike poled polymers such as PVDF, but still have a large shear piezoelectric constant. Therefore, the piezoelectric constant of a PLLA film can be engineered and improved by increasing crystallinity and molecular orientation.
The piezoelectric effect in collagen comes from polar and charged groups in the molecule. Together, these effects result in the overall piezoelectric effect in collagen. Silk is known to have a combination of amorphous and crystalline phases. Biomedical applications of 2D materials like graphene are rapidly growing.
New classes of composite piezoelectric materials tend to combine different advantages of inorganic materials e. Recent developments in piezoelectric nanocomposite—based biomedical devices have shown various applications for these materials.
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Figure 2 provides a comparison of piezoelectric coefficients for different biocompatible piezoelectric materials. Nanoribbons of PZT have been developed by Dagdeviren et al. The device is made by a stacking and microcontact transferring method Figure 3 a. An array of actuators is laminated on the skin and stimulated to generate tissue deformations that are measured by another set of the PZT sensors to provide information on the mechanical properties of skin Figure 3 b. Unlike conventional characterization methods which are invasive and tailored only for specific regions of the body, their systems achieved conformal contact with the underlying complex topography and texture of the targeted skin.
The group then validated their piezoelectric actuator—sensor pairs by applying them on a variety of soft biological tissues and organ systems in animal models. Figure 3 c—f shows the ex vivo measurements from the apex of the bovine heart, left ventricle LV and right ventricle RV , and lung. Studies on human subjects established the clinical significance of these devices for rapid and noninvasive characterization of skin mechanical properties.
In another work, Nguyen et al. They transferred arrays of PZT nanoribbons onto a silicone elastomer and measured mechanical deformations of an explanted cow lung during simulated respiration Figure 3 g,h. The PZT nanoribbons provide a minimally invasive and scalable stage for electromechanical biosensing. Dagdeviren et al. A schematic, an optical microscope image, and a photograph of the device are illustrated in Figure 3 i—k. In vivo testing involved attaching the device to the RV, LV base, and free wall of bovine and ovine hearts. The results showed that the piezoelectric energy harvester can store significant electrical power from motions of internal organs at levels that meet requirements for practical applications.
Hwang et al. The animal experiment was conducted to implant the energy harvester in the cardiac muscle of a live rat to detect deformations from the heart and power the pacemaker. The reported results describe a high electric power that can be used as an additional energy source for a pacemaker. Nanogenerators based on other piezoelectric materials such as ZnO and GaN have also been studied to harvest the biomedical energy.
Some specific biomolecules and proteins can be detected through piezoelectric biosensors. Piezoelectric materials with high acoustic velocity are a very good candidate for this application. On one of the faces of the piezoelectric resonator, acetylcholinesterase enzyme is attached as the sensitive coating. From the reduction of the frequency shift compared with the levels found in their absence, traces of organophosphorus pesticides in the solution can be detected. The AlN biosensor exhibits a remarkably low detection limit, a linear response, and good reproducibility.
This method can be extended to detect a wide variety of biological reactions, such as antigen—antibody binding, protein—ligand interactions, and genetic hybridizing, which could provide information for the studies of biological reaction kinetics. Organic piezoelectric materials are more flexible than their inorganic counterparts, therefore they can deform under smaller applied forces.
This behavior makes them suitable for biomedical pressure sensing applications. Polyimide substrates are attached to the ends of a ribbon shaped sample of fiber arrays, as depicted in Figure 4 a. The result of a cyclic bending test is presented in Figure 4 c. The collective results suggest that the capabilities of the sensor could be valuable for a range of applications in biomedical and wearable electronics.
The first completely biodegradable piezoelectric force sensor was developed by Curry et al. For instance, the group demonstrated the PLLA piezosensor can be implanted inside the abdominal cavity of a mouse to monitor the pressure of diaphragmatic contraction Figure 4 g,h. The device has a wide range of measurable pressures 0—18 kPa. PVDF has been studied recently as a sensing element in endovascular catheters due to its flexibility, stretchability, and biocompatibility.
A thin film of copper is deposited to create the external electrode. Highly aligned nanofibers were fabricated to significantly boost device sensitivity and flexibility Figure 5 b. The process is fully compatible with existing micromachining fabrication processes without additional mechanical stretching and electrical poling. This sensor Figure 5 f demonstrated great potential for flow direction measurements as an implantable biomedical device owing to its fast recovery time 0.
Piezoelectric PVDF nanofibers have shown great promise for the realizations of more robust, reliable, flexible sensors on catheters to revolutionize the field of minimally invasive surgeries. Over the last few years, noninvasive biosensors demonstrated unique capabilities for physiological signal monitoring, disease diagnosis, and health assessment. Schematic diagrams of the sensor array are depicted in Figure 6 a. By placing gold electrode arrays on the top and bottom of the film, the temperature variation of a human hand can be mapped by the temperature sensor Figure 6 a.
The structure of the piezoelectric sensor is illustrated in Figure 6 c. Gold films are employed as electrodes to compactly sandwich both the surfaces of the compressed PVDF film and a silicone substrate is used to enhance the flexibility of the whole device. The sensor has been placed in different parts of body for different pressure sensing applications. It can be used as a physiological signal recording system to measure respiration signals, or as a detector for human gestures and vocal cord vibrations.
Since the piezoelectric sensor can detect subtle muscle movements, it has promising applications in the recovery of stroke patients who have suffered paralysis. Human physiological monitoring systems based on other piezoelectric materials such as silk 69 , and collagen , have also been studied recently Figure 6 d,e. PVDF : Tissue stimulators that are biocompatible, biodegradable, small, and flexible have been used in various biomedical applications. Several studies have shown that organic piezoelectric actuators, for example, PVDF can be used for tissue engineering scaffolds to promote tissue regeneration.
Frias et al.
Piezoelectric Biomaterials for Sensors and Actuators
The actuator consists of a thin film of PVDF, printed with silver ink on both sides as electrodes Figure 7 a. Osteoblasts were grown on the surface of the piezoelectric material and the cellular response of the osteoblasts was studied. These results suggest that the both static and dynamic substrates affect cell viability and proliferation.
Damaraju et al. Figure 7 d,e shows the testing device used to measure the electrical output from the bulk scaffold. Piezoelectric scaffolds that exhibit high output voltage helped osteogenic differentiation. On the other hand, piezoelectric scaffolds with a low voltage output helped chondrogenic differentiation. Results show that cell differentiation under electromechanical actuation is greater than mechanical actuation alone. The epithelial cells showed intact nuclei in the areas surrounding the fibers, thus indicating their cytocompatibility Figure 7 j.
The effect of electrospinning parameters on the piezoelectricity of PVDF nanofiber actuators is investigated by Wang et al. The pressed fibrous mat was sputtered with Au electrodes on both the surfaces and then poled in a silicon oil bath under an electric field to obtain high piezoelectricity Figure 7 m.
The fabricated actuator under optimized electrospinning conditions was then used for implanted energy harvesting in rats Figure 7 n. Since electrospun PVDF—TrFE nanofibers have excellent biocompatibility and a large piezoelectric effect, fibroblast cells developed perfectly along the fiber direction, and the proliferation rate was promoted by 1. Using wireless stimulations to induce piezoelectricity in polymers to promote differentiation of neuronal cells can create a new road for contactless, controlled neuroregenerative therapies.
The results showed that the ultrasound is capable of inducing polarization in the piezoelectric polymers, hence, initiating differentiation of PC12 cells Figure 7 r. This study demonstrates that using a combination of ultrasonic actuation and piezoelectric polymers is promising for the differentiation of neuronal cells and deserves further investigation.
Recent developments in tissue engineering have shown the application of PVDF scaffolds to preserve the contractility of cardiomyocytes and promote cell—cell communication. Overall, the scaffold promotes rat and human cardiac cell attachment but future studies should further investigate the effect of piezoelectric materials in cardiomyocyte function. PLLA : Tajitsu et al. Figure 8 a illustrates the operating principle of this simple tweezer.
The PLLA tweezer was then inserted into a blood vessel to demonstrate its ability to grasp a blockage due to thrombosis Figure 8 b—d , and then remove it Figure 8 e—g.
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The tweezer also demonstrated its potential to release and grasp a silica bead Figure 8 h,i. Due to the biocompatibility, biodegradability, and high sensitivity of the PLLA tweezers, PLLA will find applications in cellular biology, tissue engineering, nanomedicine, and cell delivery. There are also numerous attempts to use the biocompatible and biodegradable piezoelectric PLLA polymer as a tissue stimulator to promote the proliferation and differentiation of cells.
This finding strongly suggests that the drawn PLLA can provide improved fracture fixation devices, because they are resorbable in the body, making a second surgery unnecessary. The fact that tissue regeneration benefits from the use of piezoelectric PLLA might be because polarized PLLA shows greater protein adsorption and enhances cellular adhesion and proliferation. It is obvious that a significantly higher quantity of proteins is adsorbed on the surface of the poled PLLA samples.
Specifically, higher adhesion and proliferation of cells was observed in negatively charged PLLA. Santos et al. It is important to note that electrospinning PLLA nanofibers have been shown to be piezoelectric Figure 1 d. In summary, piezoelectric biomaterials are a class of functional materials that can convert mechanical deformation into electricity and vice versa. Those materials are or can be biocompatible for use in many different biodevices. We have reviewed the working principle of the different types of piezoelectric biomaterials used in biosensors, bioactuators, and tissue stimulators.
A comparison between the different piezoelectric biomaterials including organic and inorganic piezoelectric biomaterials has also been presented. Each of these materials must be chosen based on the application, and further developments are needed to transform them into useful biomedical devices.
While inorganic piezoelectric materials have been widely explored, organic piezoelectric biomaterials offer a unique choice, particularly in biosensing applications owing to their excellent properties of being mechanically flexible and biocompatible. Several challenges need to be overcome for better use of both inorganic piezoelectric and organic piezoelectric in medicine.
These include 1 how to make highly efficient piezoelectric inorganics such as PZT more biocompatible, 2 how to improve modest piezoelectric constants of organic materials, and 3 how to obtain a robust control over dissolution rate of some biodegradable piezoelectric polymers e.
Despite such challenges, the field of piezoelectric biomaterials is gaining interest at a fast pace with growing applications in the development of biosensors and other biomedical devices. Meysam T. Chorsi received his B.
He is currently working toward his Ph. Eli J. Curry is currently pursuing his Ph. He also received his B.
Related Piezoelectric Materials and Devices: Applications in Engineering and Medical Sciences
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