Piezoelectricity

In brief

What piezoelectricity is, and what it is not

Take a crystal whose repeating structure has no center of symmetry, press it, and its two faces acquire opposite electric charge in direct proportion to the force; let go and the charge disappears. That is the direct piezoelectric effect, which Jacques and Pierre Curie demonstrated in quartz and several other crystals in 1880, and the modern definition is still the Curies' in one sentence: a linear relationship between stress and induced electrical charge ^1,2,3. The following year Gabriel Lippmann argued from thermodynamics that the effect had to run backward, so that a voltage applied across the crystal must make it change shape, and the Curies confirmed this converse effect ^2,4. The two directions are one property. An ultrasound probe makes a picture because a voltage makes a ceramic disk ring and the returning echo squeezes the same disk into a signal ⁵.

The size of the effect is given by a coefficient, written d, in picocoulombs of charge per newton of force (pC/N); because of the way the units cancel, that is the same number as picometers of movement per volt (pm/V), and the two are used interchangeably ³. Biological materials sit at the bottom of the scale, typically 0.1 to 10 pm/V, while the engineered ceramics barium titanate and lead zirconate titanate sit near 178 pm/V and above ³; a curved barium titanate ceramic printed in 2023 reached 275 pC/N ⁶. Single collagen fibrils from tendon measure about 1 pm/V ³⁶, and intact human cortical bone less than 1 pm/V ¹¹. Keep the ratio in mind, roughly a hundred to a thousand to one, whenever a sentence moves from a ceramic to a tissue.

Three things that are routinely confused with piezoelectricity are not it. The first is mechanosensation by cells. In 2010 Bertrand Coste and Ardem Patapoutian identified two large membrane proteins, Piezo1 and Piezo2, as the components of the ion channels that open when a cell membrane is stretched, in a line of mouse nerve-tumor (neuroblastoma) cells; they named them from the Greek for pressure ¹⁶. Mice lacking Piezo2 in their sensory neurons lose almost all light-touch sensation ³⁷, and the 2021 Nobel Prize in Physiology or Medicine was shared by David Julius, for the heat-sensing channel TRPV1, and Patapoutian, for Piezo1 and Piezo2, with both credited for the cold-sensing channel TRPM8 ²⁸. A Piezo channel is a protein pore that lets ions through when pulled; it generates no charge by itself and has nothing to do with crystals ¹⁶. The shared root has made it easy to write sentences in which the body's 'piezo' sensors and the crystal effect blur into one thing, and one 2026 scaffold paper invokes Piezo1 as the receiver of its material's charge ³⁰ while another designs its material to stand in for a missing PIEZO2 signal ³⁸, which are hypotheses about a hand-off, not an identity.

The second confusion is the streaming potential: when salt water is forced past a surface that carries fixed charge, as the fluid in bone's tiny channels is forced when the bone bends, the moving ions make a voltage. It looks like piezoelectricity from outside, which is why it took twenty years to separate the two in bone, and the separation is the subject of its own section below ^12,13. The third is flexoelectricity, the voltage that any material, symmetric or not, produces when strained unevenly rather than uniformly; in bone it was measured in 2018 and found comparable in bone and in its mineral ³⁹. Piezoelectricity needs asymmetry; flexoelectricity does not; streaming potentials need water. Of the three, streaming potentials are the one that has been recorded in living bone ^40,41.

The whole history, including the reversals

The history of piezoelectricity in medicine is the history of one good measurement being asked to carry more weight than it could bear. Fukada and Yasuda measured it in dried bone in 1957 ^7,9, and by 1959 Fukada was demonstrating phonograph pickups built from a piece of bone or tendon, a party trick that was also a proof ⁵². Bassett and Becker's 1962 Science paper turned the measurement into a physiological theory: bent bone makes potentials, compressed areas are negative, and the potentials probably act on bone cells and may even direct how the matrix assembles ⁴³. The same 1962 paper also attributed the effect to the mineral, since removing it abolished the signal; Fukada and Yasuda placed it in collagen in 1964 ⁸ and Becker's own laboratory agreed in 1971 ⁵³, the first and smallest of the field's reversals.

From theory to treatment took a decade. Bassett passed currents through dog femurs in 1964 ⁵⁴; Yasuda grew 'electrical callus', the bridge of new bone that forms around a break, at the cathode, the negative electrode, in rabbits and, with Fukada, wrapped rat femurs in a permanently charged Teflon film and got callus in 9 of 10 animals ^44,55,56. In 1974 Bassett switched from implanted electrodes to coils outside the skin that induced fields in surgical cuts through dogs' bones (osteotomies), and the same year the founders were debating human use and its ethics at a New York Academy of Sciences panel ^57,58. Brighton's group at the University of Pennsylvania took electrodes into patients instead: a 1971 case report described a nonunion, a fracture that had failed to heal, of the medial malleolus, the inner knob of the ankle, healed with direct current ⁵⁹, and a 1981 multicenter study reported solid union in 149 of 178 nonunions (83.7%) treated at Pennsylvania with four cathodes each delivering 20 microamperes for twelve weeks, and in 58 of 80 (72.5%) at other centers, without a control group ⁶⁰. Bassett's coil series followed: 127 ununited tibial fractures with 87% healing, no controls ⁶¹, and in 1982 a worldwide registry of 1,007 ununited fractures with success rates of 76% to 81%, in a JAMA paper that records the Food and Drug Administration's approval of the method in November 1979 ¹⁸.

The scientific correction arrived while the clinical program was expanding. Anderson and Eriksson had examined wet collagen and wet bone in 1968 and 1970 ^62,63, and the water problem was quantified in 1975 and 1976: the piezoelectric constants of bone and tendon fell with hydration, tendon's exponentially and bone's more slowly ¹⁰, and the constants of oriented collagen holding more than 25% water fell away as it warmed, which the authors put down to ions conducting the charge away ³¹. Then Gross and Williams in 1982 showed that streaming potentials dominate in wet bone ¹², and Pienkowski and Pollack in 1983 that the potentials follow the salt and viscosity of the fluid and reverse with high salt, the signature of streaming potentials, not crystals ¹³. Otter and Cochran recorded the pulse itself as a voltage across living dog bone in 1990 and changed bone's electrical response with an injected protein in 1993 ^40,41. The first blinded trial of the pulsed-field devices, in which neither patients nor assessors knew which machines worked, reported interim results in 1984: 5 of 9 active and 5 of 7 dummy nonunions (here, fractures that had failed to heal for at least a year) healed ⁶⁴.

The devices nonetheless multiplied. Low-intensity pulsed ultrasound entered with a 67-fracture trial in 1994 and a 61-fracture trial in 1997, each with a company author ^20,65, and was reversed by the 501-patient TRUST trial in 2016 and a BMJ rapid recommendation against it in 2017 ^21,22. In 2019 a load sensor in mouse bone was found to be a channel that responds to fluid flow ¹⁵. In the laboratory, meanwhile, the crystal effect itself got interesting again: glycine crystals with coefficients similar in magnitude to the ceramics in 2018 ³, rabbits regrowing cartilage on a scaffold charged by their own exercise in 2022 ²⁹, and a 2026 nanoscale dissection of human bone that put the mineral's contribution near zero and collagen's at a fraction of a picometer per volt ¹¹. Each of those is real; none of them restores the 1962 theory.

Bone's piezoelectricity: collagen, dry, and small

What Fukada and Yasuda found in 1957 is not in dispute: a slab of dried bone, cut so that its collagen fibers run at an angle to the applied shear, produces a measurable charge, and the effect is a shear effect, written d14, because the fibers are aligned and squeezing them straight on does little ^7,9,10. Where it comes from took a few years to settle. Bassett and Becker's demineralized specimens lost their signal, which they read as mineral ⁴³, but Fukada and Yasuda's 1964 collagen paper ⁸, Becker's own 1971 study ⁵³, and the behavior of collagen films that stayed piezoelectric even when poorly organized ⁴² placed it in the protein, at the level of the tropocollagen molecule or aggregates under 50 ångströms (5 nanometers); Becker's laboratory went on measuring it in human bone by age and, in a 1974 title, named the hypothesis outright, 'piezoelectricity and autoinduction' ^84,85. Hydroxyapatite, the calcium phosphate mineral of bone, is centrosymmetric in its usual crystal form, which should rule piezoelectricity out ¹¹; yet piezoelectricity has been reported in synthetic hydroxyapatite ³, and a 2013 piezoresponse study, noting earlier reports of strong piezoelectricity in nanocrystalline synthetic hydroxyapatite films, showed that their polarization could be reversed by an electric field, the property called ferroelectricity ⁸⁶. In 2026 the question was tested in bone directly: human cortical bone whose organic matrix had been reduced with sodium hypochlorite, the active ingredient of household bleach, gave an effective coefficient of -0.0138 ± 0.0074 pm/V, near zero and, in the authors' words, approaching the symmetry-limited behavior of centrosymmetric hydroxyapatite, while intact bone gave sub-picometer values and collagen's inferred share was 0.2 to 0.4 pm/V ¹¹.

The numbers are small by any standard. Netto and Zimmerman's dry bovine bone gave d14 of 0.2 × 10^-14 m/V, that is 0.002 pm/V, and dry tendon 2.0 × 10^-14 m/V, 0.02 pm/V ¹⁰. Fukada's bacterial polymer of 1988 had a bending coefficient of the order of 10^-18 coulomb-meters per newton, a different measure that cannot be set directly beside the pm/V figures, which he noted was similar to bone ⁸⁷. Nanoscale probes read higher, about 1 pm/V on a single tendon fibril, because a single fibril has one polarity along its length while a whole tendon contains fibrils pointing both ways that cancel each other; the 2017 tensor measurement on rat tail tendon put the fibril's longitudinal coefficient roughly an order of magnitude above the macroscopic tendon value for exactly that reason ^36,88. Set beside the 178 pm/V of a glycine crystal or a ceramic ³, or the 275 pC/N of a printed barium titanate sheet ⁶, bone is a feeble piezoelectric.

Then there is the water. The piezoelectric constants of bone and tendon fall as the tissue takes up water; in tendon the fall is exponential with a characteristic hydration of 7% by weight, and in bone it is relatively slow ¹⁰. In oriented collagen holding more than 25% water by weight, measured at ten cycles per second, the constants fell away once the temperature rose above -50 °C, which the authors attributed to ionic conduction in the water around the piezoelectric collagen ³¹; Marino and Becker tried to preserve the effect by freezing hydrated bone and tendon ⁸⁹, and Maeda and Fukada mapped the water dependence systematically in 1982 ⁹⁰. The electric double layer, the thin film of ions that clings to a charged surface in salt water, complicates even dry measurements at the fluid-matrix interface, since charged species remain on the matrix after drying ⁶⁷. The nanoscale is kinder: lateral piezoresponse microscopy of rat tail collagen from 10% to 70% relative humidity, spanning the 40 to 50% the authors equate with physiological bone moisture, still found a response in 2023, though the same paper records that macroscale hydrated tendon shows an insignificant effect, while nanoscale probes have detected the effect in both dry and wet bone ⁹. A fibril under a tip in humid air is not a femur full of blood.

A newer candidate deserves its own sentence. Flexoelectricity, the polarization any material produces when strained unevenly, was measured in bone and in pure hydroxyapatite in 2018 and found to be of the same order of magnitude, which led the authors to propose the mineral's flexoelectricity, not collagen's piezoelectricity, as the main source of bending-induced polarization in cortical bone, and to calculate that the field at a crack tip could be large enough to kill nearby osteocytes and so trigger repair ³⁹. Mouse bone cells grown on microcracked hydroxyapatite and strained did die near the crack and two weeks later showed more attachment and mineralization around it ⁴⁹. That is a physics measurement and a culture dish; it has not been shown in a living bone, and unlike piezoelectricity it does not require a crystal that lacks a center of symmetry ³⁹. A 2025 review of flexoelectricity across biological materials, from cell membranes and hearing to bone, calls the field relatively new and still developing ⁹¹.

The reversal: living bone's signals are mostly fluid flow

The 1962 theory needed living bone to make a voltage when loaded, and it does; the question was what kind. Bone is riddled with microscopic channels, the canaliculi and the Haversian canals, filled with salty fluid, and the channel walls carry fixed negative charge ^13,40,67. When bone bends, fluid is squeezed from the compressed side toward the tension side, and the moving ions produce a voltage, the streaming potential, whose size depends on the fluid's conductivity and viscosity and whose sign depends on the sign of the wall charge ^13,67. Williams's group had first built ceramic models of piezoelectricity in dry bone ⁹², and then Gross and Williams made the decisive logical point in 1982: a piezoelectric bone and a streaming-potential bone would both give a current proportional to strain rate and a voltage that depends in the same way on the strain gradient from the compressed face to the stretched one, so the bending experiments of the 1960s could not tell the two apart no matter how carefully they were done ¹². They then measured the streaming potential directly, forcing electrolytes of varied concentration and viscosity through a flat disk of bone, and concluded that in physiologically moist bone streaming potentials dominate ¹².

Pienkowski and Pollack settled it the following year with an experiment that piezoelectricity cannot pass. They soaked cortical bone from humans and cattle in solutions in which sodium chloride and sucrose were varied systematically, so that conductivity and viscosity changed while the bone did not, and recorded the stress-generated potentials and their decay times under load, with macroscopic electrodes and with a microelectrode. The potentials tracked the fluid, and solutions of high salt consistently reversed the polarity of the signal ¹³. A crystal's charge does not change sign because the bath got saltier; a double layer's does, and the zeta potential of bone, the charge at its fluid-matrix interface, was shown to reverse at high sodium or potassium chloride the next year ⁶⁷. Their sentence is the one to quote: although fluid-saturated bone may retain some piezoelectric properties, stress-generated potentials are predominantly caused by streaming potentials ¹³.

The living animal made the same point with less apparatus. Otter and Cochran, recording across the cortex, the dense outer wall, of a dog's tibia in vivo, found a voltage that rose and fell with every heartbeat, the periosteal (outer) surface going positive as pressure in the medullary (marrow) cavity rose, which is what outward fluid flow through a negatively charged matrix predicts; clamping the femoral artery stopped both pressure and voltage, and epinephrine (adrenaline) reduced both by the same fraction ⁴⁰. Protamine, a strongly positively charged protein, injected into the femoral artery of anesthetized dogs reduced the bending-generated potentials and in several cases reversed their sign, the first demonstration that a circulating protein alters bone's electromechanical response, which no crystal property allows ⁴¹. The same group's comparison of in vivo and excised bone at one site found that excised, soaked strips gave streaming potentials per unit periosteal strain 6.5 times larger on average, at one cycle per second (1 Hz), than the same site in vivo, though per unit of strain difference across the cortex the two were similar; the authors warned against extrapolating either number to the field a cell experiences ⁶⁹.

So where did that leave the theory that bone's electricity steers its remodeling, the mechanistic reading of Wolff's law, the nineteenth-century observation that bone is laid down where stress is greatest? Ahn and Grodzinsky's 2009 critical review traces the arc: collagen piezoelectricity was invoked in the 1960s as the way osteocytes could detect stress, diminished in importance as streaming potentials were identified, and was made to seem obsolete by accumulating evidence that fluid-related shear stress, not voltage, is what osteocytes sense ⁴⁷. Riddle and Donahue's review of the same year carries the verdict in its title, from streaming potentials to shear stress: interstitial fluid flow produced by deformation is the signal, and the molecular cascades it activates are the subject ¹⁴. In 2019 a sensor was identified in mice: Piezo1, the stretch-gated channel, was required for the gene expression that fluid shear induces in cultured osteocytes; mice lacking it in osteoblasts, the bone-forming cells, and osteocytes had less and weaker bone, and a small-molecule Piezo1 agonist given to adult mice increased bone mass, mimicking exercise ^15,77. On the mouse evidence, the loop runs through a channel, not a crystal: load moves fluid, fluid shears the osteocyte, the osteocyte's Piezo1 opens, and the cell signals. Later mouse work places the channel in a network rather than alone: its loss stunts the osteocytes' branching network of connections through YAP, a protein that carries mechanical signals to the cell nucleus (2025) ⁴⁸, and in aged bone it acts through connexin 43 hemichannels, pores in the osteocyte membrane (2026) ¹⁷. The voltage that rides along with the fluid is, on present evidence, a byproduct.

Two honest caveats. First, Ahn and Grodzinsky end not by burying piezoelectricity but by proposing hypotheses under which it might still matter at the nanoscale, and the 2023 humidity work and the 2026 human bone study are in that spirit ^9,11,47; nobody has shown that a 0.3 pm/V collagen effect does anything to a cell in a wet bone, and nobody has shown it cannot. Second, flexoelectricity, which does not need asymmetry, is a live candidate for crack-sensing with a 2018 measurement and a 2020 cell-culture result behind it ^39,49. What is not live is the 1962 picture of bone as a piezoelectric crystal running its own remodeling, and any device, scaffold or wellness product whose rationale is that picture is standing on a reversed finding.

What came of it: pulsed electromagnetic fields for fractures that will not heal

A fracture that has not healed in months is a nonunion, and the orthopedic answer is usually another operation. Bassett's pulsed electromagnetic field (PEMF) coils, worn over a cast and switched on for hours a day, offered something non-invasive, and the pitch was the piezoelectric loop: coils on the cast induce weak electric currents in bone ¹⁸, standing in for the signal loading was thought to make. The early human evidence was all of one kind. 127 ununited tibial fractures treated with the fields alone healed in 87%, with success unaffected by age, sex, prior disability, previous operations or infection ⁶¹; a registry of 1,007 ununited fractures and 71 failed arthrodeses (operations to fuse a joint) reported 81% success at Bassett's own center, 79% internationally and 76% elsewhere in the United States, and 75% in a subset of 332 patients who had averaged 4.7 years of disability and 3.4 failed operations ¹⁸; 147 patients with external fixation, a frame of pins outside the limb, plus fields united in 73% ⁹³; and in congenital pseudarthrosis of the tibia, a childhood condition, 72% of the milder type I and II lesions but only 19% of the atrophic type III lesions, in which the bone ends have thinned and wasted, healed and 18% of limbs were amputated over the series ⁹⁴. None of these had a control group, and the Food and Drug Administration's approval of November 1979 preceded any blinded trial ¹⁸.

The blinded trials, when they came, were small and pointed in different directions. The Sheffield interim report of 1984 randomized tibial nonunions of at least a year to active or dummy stimulators in full-leg casts for 24 weeks: 5 of 9 healed on working machines and 5 of 7 on dummies, a difference whose confidence limits ran from 33% better to 61% worse, and the authors observed that the high healing rate on the dummies suggested conservative management itself explained much of what had been credited to the fields ⁶⁴. Sharrard's 1990 trial of 45 tibial fractures with union delayed 16 to 32 weeks found a blinded radiologist reading union or progress in 10 of 20 active and 2 of 25 dummy fractures (p = 0.002) and a blinded surgeon reading union in 9 of 20 against 3 of 25 (p = 0.02), though the two readers did not agree on the count; the groups differed in age, but age did not affect outcome ⁶⁸. Scott and King's capacitive-coupling trial, a different device, healed 6 of 10 nonunions against 0 of 11 on placebo ⁵⁰. Those three trials, with one more, are most of what the systematic reviews, formal searches that gather and pool all eligible trials, have to work with.

Pooled, they are inconclusive. Mollon and colleagues' 2008 meta-analysis, a statistical pooling of trials, opened with the observation that bone stimulation was a $500 million market in the United States, found eleven eligible trials and, in four of them, 106 delayed or ununited fractures, a relative risk of healing (the chance of healing with the device divided by the chance without, 1 meaning no difference) of 1.76 (95% confidence interval, or CI, the range of values compatible with the data, 0.8 to 3.8; p = 0.15) with 60.4% heterogeneity (I², the share of the variation between trials beyond what chance would produce) ⁷⁴. The 2011 review from Cochrane, the international collaboration that produces standardized systematic reviews, found four blinded placebo-controlled trials, 125 participants, three of pulsed fields and one of capacitive coupling, mostly tibial nonunion: risk ratio for union 1.96 (0.86 to 4.48), 1.61 (0.74 to 3.54) at 24 weeks, no reduction in pain in the two trials that measured it, no functional outcomes in any, and a verdict of inconclusive and insufficient to inform practice ¹⁹. Aleem and colleagues in 2016, pooling fifteen trials of all electrical devices against inactive (sham) devices for any bone healing, found radiographic nonunion reduced by 35% (19 to 47%; number needed to treat 7, that is, seven patients treated for each nonunion prevented) and pain 7.7 mm lower on a 100 mm scale, with no difference in function in the two trials that measured it ⁹⁵. The outcome that moves is the X-ray; the ones a patient would choose are either unmeasured or unmoved.

For fresh fractures the case is weaker still. Hannemann's 2014 meta-analysis of 737 patients in 13 trials of pulsed fields or ultrasound found no difference in the proportion of nonunion and a time-to-union benefit in some subgroups ⁹⁶; Picelli's 2024 update found three randomized trials from 2014 to 2022, 197 patients, none showing an effect on acute healing, and did not support the use of the fields for acute fractures ⁹⁷. The 2022 network meta-analysis of nonunion treatments, which compares many treatments at once through shared comparators, is the one place the fields look worse than nothing: a higher risk of adverse events than control, odds ratio (the odds of an event with the treatment divided by the odds without, 1 meaning no difference) 13.21 (1.58 to 110.40), an interval so wide it says mostly that the data are thin ⁹⁸. The 2025 network meta-analysis of 39 trials and 2,379 fracture patients pooled seven different physical agents together and found faster healing by 21.58 days (-31.05 to -12.11) and more complete healing (risk ratio 1.37, 1.17 to 1.60) for the group, while nearly every comparison between agents crossed the null ⁹⁹; the 2026 network meta-analysis of 37 trials and 3,325 subjects restricted to electrical devices found a risk ratio of 1.18 (1.09 to 1.28) for bone healing overall and 1.20 (1.02 to 1.41) for pulsed fields, ranked pulsed fields second for functional recovery without giving a pooled size for that effect, and still called for high-quality trials ⁷⁹. Read together, forty years of trials leave a device that may raise the chance of a healed radiograph modestly, has not convincingly been shown to change function (one small trial in the 2024 update found a transitory gain in strength and range of motion ⁹⁷), and whose piezoelectric rationale was corrected in 1982-1983, a correction that by itself neither proved nor disproved that induced currents act on bone ^12,13.

Two footnotes on the current literature. The 2013 Cochrane review of electromagnetic fields for osteoarthritis, a different indication, rests its background explicitly on Wolff's law, the piezoelectric effect and streaming potentials, and finds nine trials, 636 participants, pain 15.10 points lower on a 100-point scale (9.08 to 21.13) with no effect on function or quality of life and no radiographic data ⁴⁶; the rationale is the reversed one and the benefit, if real, must have another explanation. And the mechanism papers of the last decade have quietly dropped piezoelectricity: in Fukada's own late collaborations, intermittent pulsed fields keep the mTOR pathway, a master switch for cell growth, active in mouse osteoblast-like and prechondrocyte cell lines, a cell-signaling story with no crystal in it ^100,101. A newer, stronger device, extracorporeal magnetotransduction, a more intense pulsed magnetic field applied from outside the body, arrives in 2026 on two in vitro studies, six case reports and one pilot ¹⁰², a 20-patient matched comparison with named commercial machines ¹⁰³, and a randomized trial of a supplement added to the fields whose authors concede that without a no-field arm the field's own effect cannot be known ¹⁰⁴. The uncontrolled literature on the older devices continues too. In 2026 a retrospective study at two centers of type II odontoid fractures, breaks at the base of the bony peg of the second neck vertebra, in patients with a median age of 80 reported union in 68.4% of 19 patients given a pulsed-field stimulator against 13% of 29 matched patients without, with pain, disability, complications and deaths no different; the matching was by propensity score, a statistical pairing on measured characteristics, and the authors call for a prospective study ¹⁰⁵. A retrospective multicenter series of 56 nonunions of the fifth metatarsal, the long bone on the outer edge of the foot, treated with a commercial pulsed-field device reported 91.1% healed by 12 months, with no comparison group ¹⁰⁶. And a 2026 orthopedic review tells surgeons that the devices have been shown to accelerate healing and recommends integrating them into trauma protocols ¹⁰⁷. The pattern of 1979 is being repeated with better abstracts.

Low-intensity pulsed ultrasound: the trial that reversed a product

Ultrasound is the converse effect put to work: a voltage rings a piezoelectric disk, the disk pushes a pressure wave into tissue, and the echo squeezes the disk into a signal ⁵. Low-intensity pulsed ultrasound (LIPUS), aimed at a fracture, was proposed as a way to deliver the mechanical load that healing bone wants, and the device arrived in 1994 with a prospective, randomized, double-blind trial of 67 tibial shaft fractures in casts, closed or open with only a small, clean wound (grade I), 33 active and 34 placebo units: clinical healing in 86 ± 5.8 against 114 ± 10.4 days (p = 0.01) and overall clinical-plus-radiographic healing in 96 ± 4.9 against 154 ± 13.7 days (p = 0.0001) ²⁰. A second trial in 1997, 61 distal radius fractures in casts, found union at 61 ± 3 against 98 ± 5 days (p < 0.0001) and less loss of position ⁶⁵. Both trials list J. P. Ryaby, of the device company, as second author, which is not a flaw in the arithmetic but is the sort of thing the house notes.

For twenty years those two trials carried the device. The 2014 Cochrane review of ultrasound for acute fractures found twelve studies, 622 participants and 648 fractures, with no significant reduction in time to union (standardized mean difference, the difference between groups in units of their spread, -0.47, 95% CI -1.14 to 0.20) under 90% heterogeneity and no difference in delayed or nonunion (10 of 168 against 13 of 165), and called the evidence insufficient for routine use ¹⁰⁸; the 2014 meta-analysis of pulsed fields and ultrasound in fresh fractures found no difference in nonunion, a heterogeneous benefit in time to radiographic union limited to non-operatively treated or upper-limb fractures, and faster clinical union in fractures of the shaft of a long bone (diaphyseal fractures) ⁹⁶. The decisive test was designed by the McMaster group with Heckman himself as a coauthor, piloted in 51 patients in 2014 ¹⁰⁹, and reported in the BMJ in 2016 as TRUST, for its title, Re-evaluation of low intensity pulsed ultrasound in treatment of tibial fractures: 501 patients at 43 North American academic trauma centers, tibial fractures fixed with intramedullary nails, metal rods placed down the marrow cavity, randomized between October 2008 and September 2012 to daily self-administered ultrasound or an identical inactive (sham) device until healing or one year ²¹. There was no difference in the SF-36 physical component score, a standard 36-question measure of physical health (mean difference 0.55, 95% CI -0.75 to 1.84; P = 0.41, against a minimal important difference, the smallest change patients notice, of 3 to 5 points), none in any other functional measure, and none in time to radiographic healing (hazard ratio, the relative rate of healing with 1 meaning no difference, 1.07, 0.86 to 1.34; P = 0.55); 73% of patients delivered at least half the prescribed treatments ²¹.

The reversal was then made formal. A systematic review of 26 randomized trials, median size 30, found that ultrasound did not shorten return to work (2.7% later, 7.7% earlier to 14.3% later) or reduce reoperation (risk ratio 0.80, 0.55 to 1.16), and that for pain, weight bearing and radiographic healing the trials at low risk of bias showed no benefit while the trials at high risk of bias did, with the interaction significant at P < 0.001; restricted to low-risk trials, radiographic healing was 1.7% earlier (11.2% earlier to 8.8% later) ⁷⁵. The BMJ Rapid Recommendation panel, which included patients, recommended against the device for fractures ²². The economic analysis of TRUST put the device at C$3,995, the added cost per patient at C$3,647 from a payer's perspective, the gain at 0.023 quality-adjusted life years (-0.035 to 0.069), and the price of a year of full health at C$155,433, all in 2015 Canadian dollars ⁷⁶. The 2023 Cochrane update, 21 studies and 1,543 fractures in 1,517 participants, 20 of them of ultrasound, found quality of life unchanged (SF-36 mean difference 0.06, -3.85 to 3.97; very low certainty), return to work 1.96 days later with the device (-2.13 to 6.04; low certainty), delayed or nonunion risk ratio 1.25 (0.50 to 3.09; moderate certainty), and could not pool time to union for unexplained heterogeneity; its sentence is that ultrasound probably makes little or no difference to delayed or nonunion ⁷⁸.

The remaining claim is for established nonunion, where the device's makers argue randomized trials are impractical. A 2017 meta-analysis of thirteen mostly uncontrolled studies and 1,441 nonunions pooled healing at 82% (77 to 87%) with 71% heterogeneity and called the findings compelling; two of its six authors were employees of Bioventus, the device's manufacturer, and the paper is best read as the company's case ¹¹⁰. The 2026 systematic review that searched to May 2025 found the same shape in the observational literature, 30 studies and 3,437 participants pooling to 0.79 (0.73 to 0.85) with 92% heterogeneity and very low certainty, but the three randomized trials, 264 participants, gave a risk ratio of 1.13 (0.93 to 1.37; P = .23) and a healing-time difference of 14.99 days (95% CI -120.37 to 150.35; P = .83); it does not support ultrasound as a first-line treatment for nonunion ⁸⁰. Two network meta-analyses of nonunion treatments, which compare many treatments at once through shared comparators, credit ultrasound with shorter healing time than cancellous bone graft, standardized mean differences of -9.26 (-14.64 to -3.87) in 2022 and -9.33 (-12.94 to -5.73) in 2026 ^98,111. A difference of nine standard deviations would be enormous for any treatment, so these figures say more about how a few small trials were combined than about ultrasound; the 2026 authors themselves rate the quality of their evidence low ¹¹¹. An uncontrolled 80% is the kind of number the 1981 tibial series produced for the coils, and it has the same problem: nobody knows what the same fractures would have done in a cast ^61,64. Two 2026 reports add to the same picture. A double-blind randomized trial in two South African hospitals, of 94 adults with surgically treated lower-limb fractures, found no difference between ultrasound and standard care in callus, bridging of the fracture, fracture gap or overall radiographic healing at 6, 12 or 18 weeks, though heavy loss to follow-up weakened it ⁸¹. A British hospital's registry of 46 established nonunions in 44 patients treated with the Exogen ultrasound device found union in 54.4%, which its authors say falls short of the success rates cited in guidance from the United Kingdom's National Institute for Health and Care Excellence (NICE) but is in line with other single-center series ⁸².

Bone-growth stimulators after spinal fusion

The third clinical descendant of the 1962 theory is the stimulator worn or implanted after spinal fusion, an operation in which two vertebrae are bridged with bone graft and hardware and in which failure of the graft to knit, pseudarthrosis, is common enough to make any adjunct attractive. Three designs exist: a direct-current implant with a cathode laid in the graft, a capacitive-coupling pad on the skin, and the inductive coils of pulsed electromagnetic fields ⁵¹. Proponents' reviews summarize the trial literature as union of 80% to 90% with stimulation against 65% to 75% with placebo ¹¹². A 2013 pooled fusion rate of 85% (79 to 90%) across 21 studies and 1,381 patients, 85% for direct current and 90% for the single capacitive study, is often quoted, but it is a single-arm figure with no comparator and cannot say whether the devices did anything ¹¹³.

The randomized trials say something, and what they say depends on how they are pooled. A 2014 systematic review found six randomized trials of lumbar fusion with fusion rates spanning 35.4% to 90.6% in stimulated patients and 33.3% to 81.9% in controls over 9 to 24 months, too heterogeneous to combine, and could not conclude benefit; it graded the strength of evidence low ¹¹⁴. Cottrill's 2019 cross-disciplinary review pooled eleven animal studies (257 animals, odds of fusion 4.79) and thirteen clinical studies (2,144 patients, odds 2.26), found that direct current worked in both species and inductive coupling only in patients, and that capacitive coupling did not work on its single trial ⁵¹. Akhter's 2020 meta-analysis of seven randomized trials and 941 patients, 487 stimulated and 454 on control or sham, gave odds of radiographic fusion of 2.53 (1.86 to 3.43), moderate quality, with no difference by device, smoking or number of levels ²⁴. Luo's 2024 meta-analysis searched to September 2023 for related articles, without limiting itself in its abstract to randomized trials: odds 2.66 (1.79 to 3.97), fusion in 86.8% against 73.7%, direct current 2.33 (1.37 to 3.96), pulsed fields 2.60 (1.29 to 5.27), capacitive coupling 3.44 (1.75 to 6.75), with the authors concluding that effectiveness still needs study ²³.

That is a more consistent signal than the fracture literature gives, and it should be stated as such: in randomized trials, stimulation after spinal fusion roughly doubles the odds that the fusion will look solid on imaging. Three things keep it modest. The outcome is radiographic fusion, and none of the pooled estimates above is of pain, disability or return to work. The randomized trials are few, seven in the 2020 analysis ²⁴, and the 2014 review graded their strength of evidence low and found them too inconsistent to pool ¹¹⁴. The often-quoted 80% to 90% union with stimulation comes from a narrative review by the devices' proponents ¹¹². Neither recent pooled analysis lists a stimulator maker among its authors' affiliations: the 2020 one includes authors at OrthoEvidence, an evidence-summary company, and North Inc., a wearable-electronics firm ²⁴, and the 2024 one comes from hospital spine departments in China ²³. And the rationale on the device literature remains the reversed one, bone's own piezoelectric signal ^46,115, while the mechanisms the field now studies are cell-signaling pathways in culture that owe nothing to crystals ¹⁰⁰. A device can work for a reason other than the one on its label; the trials so far cannot tell whether this one does.

Where piezoelectric materials really work in medicine

None of the uncertainty above touches the places where the physics itself is the tool. Nearly every diagnostic ultrasound image is made by a piezoelectric transducer, a ceramic driven by voltage to emit a pressure wave and squeezed by the echo into a signal, and the same elements, focused and run at high intensity, heat and ablate tissue in tumors and uterine fibroids, open the blood-brain barrier for drugs, and modulate nerves ⁵. Diagnostic ultrasound entered clinical medicine with reports such as Donald, MacVicar and Brown's 1958 Lancet paper on investigating abdominal masses by pulsed ultrasound ¹¹⁶. The polymer side has its own history: Fukada's own account runs from bone pickups in 1959 to the discovery in 1969 that polyvinylidene fluoride (PVDF), a plastic, becomes piezoelectric once poled, that is, once its molecular dipoles have been aligned by a strong electric field, and on to PVDF ultrasonic transducers in 1972 and headphones in 1975 ⁵². Flexible piezoelectric polymers, lead-free ceramics and composites now make wearable ultrasound patches, with integrated arrays reaching focal spots near 200 μm and cardiovascular monitoring demonstrated to 164 mm depth for 12 hours ¹¹⁷. Ultrasound is also one way power is now sent through tissue to implants, with bulk piezoelectrics, micromachined transducers and polymer films all in play ¹¹⁸.

Shock-wave lithotripsy, which breaks kidney stones from outside the body, is the second great application and a useful corrective to the word's glamour. The first report, from Munich in 1980, passed fragments in 96% of 60 dogs with implanted stones and in 20 of 21 patients with renal pelvic stones, with hematuria (blood in the urine) and ureteral colic (the pain of fragments passing down the ureter) as the costs ¹¹⁹; that machine made its shock with an underwater spark, not a crystal. Piezoelectric lithotripters came later, an array of ceramic elements on a bowl all firing toward one focus, and the bench comparisons are not flattering: of ten commercial machines measured with an underwater microphone (hydrophone), the piezoelectric generators produced pulses with less energy than the spark-gap (electrohydraulic) and electromagnetic ones ³², and on standard artificial stones (phantoms) the piezoelectric machine removed the least volume per shock, cutting narrow, deep craters ³³. On the bench, then, the piezoelectric machine delivers the least energy per shock of the three designs. In patients it works. In a 2023 double-blind trial, 135 adults with a single 1 to 2 cm stone in the renal pelvis, the funnel where urine collects inside the kidney, were randomized to a narrow (2 mm) or wide (8 mm) focus on a piezoelectric lithotripter: 79.2% and 69.1% were stone-free after one session and 86.6% and 86.8% after three, with more pain and more severe bleeding into the urine at the narrow focus ¹²⁰. A 2025 Indonesian series of 40 patients with 5 to 20 mm kidney stones on a newer piezoelectric machine reported 75% stone-free at four weeks, without a comparison group ¹²¹.

Piezoelectric surgery is the third, and the one with the most modest and most honest evidence. An ultrasonic bone cutter driven by a piezoelectric handpiece vibrates at a frequency that cuts mineralized tissue and spares soft tissue. The technique entered implant dentistry with a 2000 case report by T. Vercellotti describing widening of the jaw's bony ridge with modulated-frequency piezoelectric scalpels ¹²²; the randomized evidence came later. In five randomized trials of lower third molar (wisdom tooth) extraction, 402 patients, it gave less pain at days 6 to 7 (standardized mean difference -0.33, -0.56 to -0.10), less swelling at day 7 (standardized mean difference -1.95, -3.22 to -0.67) and better mouth opening on day 1, at the cost of 6.23 more minutes (3.32 to 9.14) of operating time ¹²³; in dental implant site preparation it made no difference to implant survival (risk ratio 0.98, 0.94 to 1.03) and a small difference to early stability scores ¹²⁴. Those are the effects of a better saw, and they are stated as such.

The workhorse material in nearly all of this is lead zirconate titanate, PZT, a ceramic that contains lead, and the search for a lead-free replacement has run for more than twenty years. The 2024 stock-taking from the transducer community is candid: the main lead-free families, barium titanate, potassium sodium niobate and bismuth sodium titanate, are less universally applicable than PZT, though medical imaging transducers and other low-power devices have been demonstrated and commercialization waits on availability, reproducibility and sample size ²⁵; textured lead-free ceramics can in some cases rival or surpass PZT ¹²⁵, and reviews of implantable piezoelectrics single out potassium sodium niobate as the composition to watch inside the body ¹¹⁵. The transducer literature frames that search as a sustainability question ¹²⁵; neither review raises exposure of patients to lead from a sealed probe as the concern. The scaffold field has gone the other way, putting the lead-free ceramics, barium titanate above all, unsealed into animals ^{38,126,127,128}; there the open question is not lead but what becomes of the particles.

Piezoelectric and 'self-powered' implants: animal data, stated as such

The newest use of the word takes the 1962 loop and builds it into a material: if bone cells respond to electricity, make the implant generate electricity from the body's own movement, no battery or wire required. The idea is old. Fukada wrapped rat femurs in a film of poly-gamma-methyl-L-glutamate in the early 1980s and reported new bone ¹³⁰, and the electret callus of 1977 was the same wager with a permanently charged film ⁵⁶. The 2020 review that organizes the modern field lists the candidate materials, piezoelectric ceramics such as barium titanate and the lead-free potassium sodium niobate, and polymers such as PVDF, polylactic acid and collagen, and accepts bone's own piezoelectricity as the rationale, which, as the sections above show, is the reversed finding ¹¹⁵. That does not make the implants wrong; an implant that generates charge under load is generating it in a wet tissue by its own ceramic physics, not borrowing bone's. It means the rationale and the evidence have to be judged separately.

The evidence is cells and animals, and some of it is well controlled. In 2015 tetragonal barium titanate nanoparticles on neuron-like cells produced calcium and sodium fluxes when ultrasound was applied, while cubic particles of the same chemistry, which are not piezoelectric, did nothing, a control that isolates the effect ¹³¹; by 2024 the particles had become 20 μm two-faced microparticles steerable by magnets and driven by focused ultrasound to stimulate primary neurons, taken directly from animal tissue, still in a dish ¹³². The best animal study is the 2022 rabbit work: a biodegradable piezoelectric polylactic acid nanofiber scaffold was placed in critical-sized osteochondral defects, holes through joint cartilage into the bone beneath that are too large to heal on their own, and the rabbits were exercised, and after one to two months of exercise the defects had filled with hyaline cartilage, the smooth, glassy cartilage that lines joints, rich in type II collagen, while rabbits given an otherwise identical non-piezoelectric scaffold and the same exercise had unfilled defects ²⁹. That is a material control, a functional stimulus and a histological outcome in one experiment, and it is the standard the rest should be held to.

The 2025-2026 literature is large and almost entirely rodent. A PVDF nerve conduit doped with liquid metal and zinc oxide raised its coefficient from 0.9 to 4.6 pC/N and improved sciatic nerve recovery in Sprague-Dawley rats, the version coupled to a nanogenerator being tested only in cells ¹³³; a two-layer conduit with barium titanate in a hydrogel outside and aligned conductive fibers inside, charged by ultrasound, approached a graft of the animal's own nerve (autologous graft), the clinical standard, in animals, through a mechanism traced to ferroptosis, an iron-dependent form of cell death, in Schwann cells, the cells that wrap and support peripheral nerves ¹²⁶. In bone, a gelatin cryogel loaded with piezoelectric whitlockite, the magnesium-bearing calcium phosphate that is bone's second mineral, bridged a critical-size rat radial defect completely and, in culture, triggered calcium influx through Piezo1 in marrow stromal cells, the authors naming the channel as the receiver of the material's charge ^30,134; zinc oxide nanofibers carrying icariin, a plant-derived compound, under low-intensity ultrasound accelerated bone in defects drilled in the rat skull (calvaria) ¹³⁵; a black phosphorus–carbon nitride hydrogel coating 3D-printed titanium prostheses, activated by light and ultrasound, was antibacterial and promoted nerve-guided bone regeneration in infected defects in animals ¹³⁶; and a 2026 rat skull study of barium titanate in a printed scaffold found its piezoelectric response 'detectable but mild' and said that its contribution to bone formation had not been separated from the ceramic's other effects ¹³⁷. In joints and tendons, potassium sodium niobate nanoparticles with engineered apoptotic bodies, membrane packets shed by dying cells and loaded here with signals, in an injectable hydrogel, activated by ultrasound, reduced cartilage degeneration in an osteoarthritis model ¹²⁷, and barium titanate in a hydrogel built around a human transcriptomic finding of reduced PIEZO2 in diabetic rotator cuff tissue restored the tendon-bone interface in diabetic animals ³⁸. In the spinal cord, barium titanate particles coated to release zinc under ultrasound matured mouse neural stem cells in 5 days instead of 10 and aided recovery after injury ¹²⁸. A bioresorbable glycine-film device driven by ultrasound shortened wound healing by about 40% in animal models ¹³⁸. The same idea is now aimed at tumors. In sono-piezoelectric dynamic therapy, ultrasound makes piezoelectric nanoparticles, most often barium titanate, generate reactive oxygen species, chemically aggressive forms of oxygen that damage cells; a 2026 study used bismuth-based piezoelectric nanosheets in an injectable peptide hydrogel to suppress residual osteosarcoma, a bone cancer, and regrow bone in an animal model of bone cancer after surgery, which its title calls 'real-world-matched' ¹³⁹.

Three things are true of all of it at once. First, several of these designs do not generate their own charge from body movement at all: they are ultrasound-driven, which means an external transducer, a technician and a schedule, and 'wireless' is the honest word, not 'self-powered' ^{126,127,128,135}. Second, the material inside is usually barium titanate or a niobate ceramic, whose coefficients are a hundred times or more those of bone's collagen ^3,11; that a laboratory adds a ceramic is itself a comment on how little the tissue supplies. Third, as of October 2026 there is no randomized human trial of a piezoelectric scaffold or implant for any indication in this literature, and the field's own reviews describe translation as the open problem ^115,134. The right sentence is the one the 2022 rabbit paper earns and the 2026 rat papers approach: a load- or ultrasound-charged implant can improve tissue repair in animals against a non-piezoelectric control, and whether it does so in a person is untested.

Tendon, dentin, hair, amino acids and viruses: what a measurable effect means

Once the method existed, piezoelectricity turned up in nearly every dried, oriented biological solid, and the 1967 Nature paper that announced it as 'a fundamental property of biological tissues' measured cartilage, dentin, skin and bone from cats, pigs and people ⁶⁶. Fukada and Yasuda reported the effect in collagen in 1964 ⁸, and Anderson and Eriksson examined wet collagen from human Achilles tendon in 1968 ⁶²; in dry bovine tendon the coefficient was ten times bone's and fell exponentially as the tissue took up water, with a characteristic hydration of 7% by weight, while bone's fell relatively slowly ¹⁰; at the nanometer scale a single tendon fibril is a shear piezoelectric of about 1 pm/V with a single polarity along its length, and the whole tendon reads an order of magnitude lower because its fibrils point both ways ^36,88. Dentin, the bulk of a tooth, shows the effect in its collagen-rich intertubular matrix and not at all in the peritubular dentin around each tubule, which supports the view that the latter is non-collagenous ⁷². Keratin, the protein of hair, horn and nail, is piezoelectric when dry and oriented; the measurement cited here is from cattle horn, where its heat denaturation can be followed by the signal ¹⁴⁰, and chitin, the polymer of lobster shell, joined the list in 1977 ¹⁴¹; Fukada's 1968 review already ranged over bone, tendon, wood and synthetic peptides ¹⁴².

The amino acids are the newest and most striking entries, and the ones most easily misread. Beta-glycine crystals grown in the laboratory show a shear piezoelectricity of 178 pm/V, similar to barium titanate or lead zirconate titanate, with a predicted voltage constant of 8 V·m/N, an order of magnitude above any ceramic or polymer in use ³; films of beta-glycine assembled under an electric field reach 11.2 pm/V and survive to 192 °C ¹⁴³, and gamma-glycine in polyvinyl alcohol gives 10.4 pC/N and a bioresorbable device ¹³⁸. Acetylated tryptophan assemblies are predicted at 47 pm/V and light a diode at over 1.4 volts ³⁴; water-layered tryptophan assemblies conduct charge through their water ¹⁴⁴. Even a virus will do: films of the M13 bacteriophage reach 7.8 pm/V, the coat protein can be engineered to tune the dipole, and a phage generator delivering 6 nA at 400 mV ran a liquid-crystal display ¹⁴⁵. A whole engineering literature now builds nanogenerators from cellulose, silk, collagen, keratin, peptides and phage ¹⁴⁶.

What any of this means for physiology is, with one exception taken up below, nothing yet, and the reasons are the ones the bone story already taught. The glycine that reaches 178 pm/V is a crystal of pure glycine packed in one particular lattice ³; glycine in a person is dissolved in water, built into proteins, or, in collagen, one residue in every three of a triple helix whose whole-fibril coefficient is about 1 pm/V ³⁶. A virus film is a material that happens to be made of viruses ¹⁴⁵. The millivolts estimated for a sheared fibril are estimated for an isolated fibril in air ³⁶, and the one in vivo comparison on this page found excised bone gave potentials per unit surface strain 6.5 times larger than the living site, though similar per unit strain difference across the cortex, and warned against reading any of it as the field a cell feels ⁶⁹. The 2026 whitlockite review and scaffold papers show the honest route: when a laboratory wants a tissue to feel piezoelectric charge, it adds a piezoelectric material ^30,134, and the tissue's own supply, a fraction of a picometer per volt in human bone, is small ¹¹.

The exception is in the ear. The outer hair cells of the cochlea, the hearing organ, change length when the voltage across their membrane changes, and in 2000 the motor protein responsible was identified and named prestin; cultured human kidney cells given the gene changed shape with voltage too ⁷⁰. In 2002, stretching guinea pig outer hair cells with a known force moved charge across their membranes in the reciprocal way piezoelectricity requires, with an efficiency of about 20 femtocoulombs of charge per nanonewton of force, which the authors calculated was four orders of magnitude greater than the coefficient of the best man-made material ³⁵. Mice whose prestin gene was deleted lost that movement and 40 to 60 decibels of cochlear sensitivity ⁷¹, and 2025 work in mouse outer hair cells still describes the motor's response to membrane tension as piezoelectric-like ¹⁴⁷. Prestin is a protein motor in a living, wet membrane, not a crystal, and it has nothing to do with collagen or bone; but it is the clearest case in which a coupling of voltage and mechanical force of this kind does essential physiological work, and it shows that water by itself does not rule such a coupling out.

The speculative route has a long history too. A 1990 hypothesis paper proposed that collagen, keratin and the cytoskeleton, all piezoelectric, form a unitary 'bioelectronic connectional system' for coherent communication among cells by piezoelectric interaction and photon-phonon transduction, consistent with 'bioplasma' ¹⁴⁸. No measurement supported it then, and nothing since has; it is cited here because every sentence that moves from 'collagen is piezoelectric' to 'the body is a crystal network' is a paraphrase of it, and because its vocabulary reappears in the energy-medicine literature of the next section.

• Piezoresponse force microscopyThe needle-sharp tip of an atomic-force microscope, an instrument that feels a surface at the scale of molecules, applies an alternating voltage to the surface and records how much it moves, the converse effect run at the nanometer scale; this is how single collagen fibrils, dentin and intact human bone have been mapped ^11,36,72.Research only; it is how the 2009 fibril coefficient (about 1 pm/V) and the 2026 human bone values were obtained ^11,36Resolution of about 10 nm in dentin ⁷²; values vary several-fold between laboratories with preparation and humidity, which the 2026 authors acknowledge ^9,11It probes a surface in air or controlled humidity, not bone in a living limb; a fibril coefficient says nothing about what a whole bone does when its fibrils point both ways ⁸⁸
• Macroscopic piezoelectric constants (d) by charge or interferometryA cut, oriented block of dried bone or tendon is stressed between electrodes and the charge measured, or driven by voltage and its movement measured by laser interferometry; Fukada's 1957 method and its descendants ^7,10,31.The source of every textbook number for bone piezoelectricity ^10,31Repeatable on dry specimens; values collapse as hydration rises, so the number depends on how dry the sample was ^10,90It cannot be done on living bone, and in a wet specimen the electric double layer, the thin film of ions that clings to any charged surface in salt water, at the fluid-matrix interface contaminates the reading ⁶⁷
• Stress-generated and streaming potential measurementElectrodes on a bent, wet bone specimen or on a living bone record the voltage, while the soaking fluid's salt and viscosity are varied, or fluid is forced through a disk of bone under known pressure ^12,13,69.The experiments of 1982-1993 that reassigned bone's signals to fluid flow ^12,13,40In dogs, potentials per unit of surface (periosteal) strain in excised, soaked bone were on average 6.5 times larger than at the same site in the living animal at one cycle per second (1 Hz), though per unit of strain difference across the bone's wall (cortex) the two were similar ⁶⁹Electrical shunting through soft tissue makes in vivo values hard to interpret, and the authors warn against extrapolating any of it to the field strength a cell actually feels ⁶⁹
• Acoustically stimulated electromagnetic (ASEM) imagingUltrasound drives bone's collagen piezoelectricity at radio frequency and an antenna tuned to the same frequency picks up the emitted field, giving a map of the piezoelectric response ¹²⁹.Experimental; in 2026 it distinguished femurs of diabetic and immobilized rats from controls, with the difference surviving decalcification ¹²⁹Correlation with mechanical breaking displacement r = 0.499, p = 0.058, in a small rat series ¹²⁹Excised rat bone only, and the authors are affiliated with the companies developing the method ¹²⁹
• Radiographic union, the endpoint the devices are judged byPlain films or computed tomography read for bridging callus or fusion mass, usually by assessors blinded to the device ^21,68.The primary outcome of nearly every stimulator and ultrasound trial and meta-analysis ^19,24In the 1990 tibial trial a radiologist and a surgeon reading the same films reached different counts, 5 against 9 unions in the active group ⁶⁸; in the 501-patient TRUST trial the hazard ratio for radiographic healing, the relative rate of healing with 1 meaning no difference, was 1.07 (0.86 to 1.34) and function did not move ²¹A fused X-ray is not a patient who works, walks or stops hurting; the 2017 review found benefit only in trials at high risk of bias ⁷⁵

Quartz, biofields and grounding, at their true strength

Because quartz was the Curies' crystal, and because bone is piezoelectric, the word has become a bridge by which a wellness claim walks from physics to physiology without passing through evidence. The physics is not in dispute: a quartz crystal, squeezed, makes a voltage ^1,2. What a crystal held in the hand or laid on the body does is a different question, and it has been put to a randomized, placebo-controlled test at least once. In 2025, 138 adults classified as believers or non-believers in crystal healing were randomized to a rose quartz or a visually matched placebo for a standardized 14-day protocol with anxiety measured on two validated scales: anxiety fell only among believers, equally whether they held the quartz or the placebo, improvements did not exceed the usual size of placebo responses, and a Bayesian analysis, which weighs how strongly the data favor one hypothesis over another, favored no specific effect of the crystal ²⁶. A person pressing a crystal separates a minute quantity of charge across the crystal's own faces for as long as the pressure changes; it stays on the crystal, and nothing in that physics reaches a cell.

'Biofield' therapies, practices in which a practitioner places hands on or near the body to adjust an energy field that has never been measured, such as Reiki, therapeutic touch and healing touch, do not usually invoke piezoelectricity explicitly, but their literature leans on the same move, from the body's real electrical phenomena to an unmeasured field that a practitioner can adjust. The best evidence synthesis is from 2010: 66 clinical studies of medium quality, with strong evidence for reduced pain intensity in pain populations, moderate evidence for hospitalized and cancer patients, and equivocal evidence for fatigue and quality of life ¹⁴⁹. A 2026 scoping review, which maps a literature without pooling its results, of touch-based, biofield and hypnosis interventions for pain, 14 studies and 1,001 patients from 2004 to December 2025, found consistent effects for hypnosis and 'potential' improvements for the other two, and called the safety and effectiveness evidence preliminary ¹⁵⁰. The field's own 2024 reporting guideline, a 15-item checklist developed because systematic reviews had complained of poor reporting, is an admission from inside ¹⁵¹. Relief in these trials may come from attention, expectation and touch, which designs that rarely blind the practitioner cannot separate ¹⁴⁹; it is not evidence of a field, and no study in this literature has measured a field that a practitioner adjusts. Devices sold to read or tune the body's fields have fared no better when tested blind. In a double-blind trial published in 1997, 32 children hospitalized with atopic dermatitis (eczema) were randomized to an active or a sham bioresonance device, also called biophysical information therapy, on top of usual care; both groups improved, the device added nothing measurable, and the authors concluded it had no place in treatment ¹⁵². In 2026 a study of biofield images made by gas discharge visualization, a photographic method its users say records the field, reported 99.12% accuracy in sorting diabetic from nondiabetic people with a neural network; one author is from an institute of biofield evaluation, the result rests on cross-validation within the study's own images, and the authors say larger data sets and expert validation are needed ¹⁵³. The field also has a retraction. In 2026 a journal withdrew a 2024 randomized trial of remote biofield energy treatment because it was essentially the same as another paper the group had published that year without saying so, and because it contained physiologically implausible data and statistical anomalies; the authors disagree with the retraction ⁸³. That group publishes from its own companies, Trivedi Global and Trivedi Science Research Laboratory, including a 2026 report that 'blessing/biofield energy treatment' improved the eggs and meat of laying hens ¹⁵⁴. The most serious new claim is preclinical. In 2026 a group at the University of Texas MD Anderson Cancer Center reported that three biofield therapists using a standardized procedure, compared with sham and incubator controls, slowed the growth of mouse and human pancreatic cancer cells in dishes and of tumors and liver metastases in mice ¹⁵⁵. That is a cell and mouse result from one center, it identifies no physical agent passing from therapist to cells, and it should be held to exactly that.

Grounding, or earthing, is the claim that conductive contact with the ground lets the Earth's electrons into the body and quells inflammation, and its literature is unusual in how visibly it is written by its sellers. The founding 2012 review proposed disconnection from the Earth as a major contributor to unwellness and promised better sleep and less pain ¹⁵⁶; a 2017 summary of more than twelve of the same authors' reports, some of them blinded, concluded that all studies discussed had shown significant outcomes ¹⁵⁷. A 2023 paper calling grounding 'the universal anti-inflammatory remedy' and 'one of the greatest kept secrets', and asserting that inflammation is the root cause of almost all diseases, lists one author's affiliation as Grounded.com, a seller of grounding products, and another is written from a private company whose author promises 'a profound healing state' from joining a planetary direct-current circuit ^27,158; both appeared in a journal special section introduced by a freelance journalist alongside an article linking sunspots to pandemics ¹⁵⁹. The clinical data are small. A case series of ten hypertensive patients in one practice reported systolic pressure down 8.6% to 22.7%, with no control group ¹⁶⁰. Sixteen massage therapists at the Chopra Center, in a six-week trial its authors call double-blind and stepped-wedge (every participant switches from control to treatment, at staggered times), reported better self-rated pain, mood and energy while grounded ¹⁶¹. The sham-controlled studies are also small, and two of the three include Gaétan Chevalier, an author of the founding review ¹⁵⁶. Forty adults, double-blinded, grounded or sham-grounded for one hour in a recliner, reported better mood (2015) ¹⁶². Thirty-two young men randomly divided after 200 half-knee bends had no significant rise in creatine kinase, a blood marker of muscle damage, when grounded, while the sham group's rose, though both groups had pain on every day afterward (2015) ¹⁶³. In mild Alzheimer's disease, a 12-week sham-controlled pilot at a Taiwanese hospital enrolled 22 patients, finished with 15, and found better sleep-questionnaire scores but no change in anxiety or depression (2022) ¹⁶⁴. A randomized crossover test of grounding running shoes in ten elite runners, four of whose authors worked for the shoe company adidas, found no difference in oxygen use, heart rate, lactate or perceived fatigue (2022) ¹⁶⁵. A 2025 narrative review proposes grounding for Alzheimer's disease, calls the evidence preliminary, asks for robust trials, and still suggests integrating grounding into standard care ¹⁶⁶. The newest work is in a dish and in rats. Mitochondria, the cell's power plants, wired to ground in a laboratory preparation made 5% to 11% more ATP, the molecule cells use to carry energy, and 22% to 33% less reactive oxygen species than sham-wired ones, in a study one of whose two authors is at a private company, North American Science Associates (2025) ¹⁶⁷. Rats grounded around the clock through a skull electrode for 21 to 28 days did better in memory tests, a result whose authors say should not be read as evidence of a direct electrical mechanism (2026) ¹⁶⁸. Nothing in grounding involves piezoelectricity at all, and the house rule applies: the body is electrical, every cell holds a membrane voltage, and that is not a license for any claim that uses the word.

The common error is a confusion of scale and of medium. Piezoelectricity is a property of a dry, asymmetric solid, measured in picometers per volt, and the one biological material that has it in quantity, collagen, has it weakly and loses much of it to the water it lives in ^10,31; the one place a living body is known to put an electromechanical coupling of this kind to essential use, the prestin motor of the ear, is a protein, not a crystal ^35,71. The devices that work, ultrasound and lithotripsy, work by putting engineered ceramics outside the body and driving them hard ^5,32. The claims that do not work put a crystal, a hand or a wire on the skin and invoke the physics as metaphor. Between the two sit the stimulators and scaffolds, where the physics is used honestly and the evidence is still being gathered ^21,29.

What was believed, and is not

The page's reversals, in one place. Bone's piezoelectricity was believed in 1962 to come from its mineral, because demineralized bone lost the signal ⁴³; it comes from collagen, and the mineral's own coefficient is near zero ^8,11,53. The potentials of bent living bone were believed to be piezoelectric and to direct remodeling ⁴³; in wet bone they are predominantly streaming potentials from fluid flow, they reverse with salt, they beat with the pulse and they shrink when a protein is injected into the artery ^12,13,40,41. The signal bone cells use was believed to be a voltage; it is fluid shear, sensed in mice at least partly through the Piezo1 channel ^14,15,17. Pulsed electromagnetic fields were approved in November 1979, before any blinded trial, and the uncontrolled series published in 1981-1982 reported 76% to 87% success ^18,61; the first blinded trial healed 5 of 7 nonunions on dummy machines ⁶⁴, and four blinded trials in 125 patients give a risk ratio of 1.96 (0.86 to 4.48) ¹⁹. Low-intensity pulsed ultrasound shortened tibial healing by a month in 67 patients in 1994 ²⁰; in 501 patients in 2016 it changed nothing ²¹, and the guideline is against it ²². Its 80% success in nonunion from uncontrolled series ¹¹⁰ becomes a risk ratio of 1.13 (0.93 to 1.37) in randomized trials ⁸⁰.

And the ones that were never believed by anyone who measured. That a crystal held against the skin does anything a matched placebo does not ²⁶. That bone's piezoelectricity makes the body a crystal communication network ¹⁴⁸. That grounding is a universal anti-inflammatory remedy, on the word of its vendors ²⁷. That 'self-powered' describes every piezoelectric implant; several are driven by ultrasound and need an external transducer and someone to run it ^{126,127,128,135}. Each borrows a true sentence from the top of this page and spends it at the bottom.

The 2023-2026 literature, verified, and what is still unknown

What the last four years add, each checked against its PubMed record. On the physics of bone: collagen piezoresponse survives to physiological humidity at the nanoscale, in rat tail tendon ⁹; human cortical bone probed intact and with its organic matrix reduced gives collagen about 0.2 to 0.4 pm/V and mineral near zero ¹¹; an ultrasound-driven antenna method reads a reduced piezoelectric signal in diabetic and immobilized rat femurs, with company-affiliated authors and a correlation that missed significance ¹²⁹; in mice, Piezo1 turns out to work through connexin 43 hemichannels and YAP signaling rather than alone ^17,48; and the ear's prestin motor is still described as piezoelectric-like ¹⁴⁷. On the clinic: the 2023 Cochrane review finds ultrasound probably makes little or no difference to delayed union or nonunion ⁷⁸; a 2026 double-blind trial finds no radiographic benefit from ultrasound after lower-limb fracture surgery, and a British registry reports 54.4% union in nonunions ^81,82; the 2024 update of pulsed fields for acute fractures finds three trials and no effect on healing ⁹⁷; the 2024 spinal fusion meta-analysis holds the odds at 2.66 ²³; the 2025 and 2026 network meta-analyses pool unlike devices into modest, significant, heterogeneous benefits for radiographic healing ^79,99; the 2026 nonunion review finds the observational 80% for ultrasound does not survive randomization ⁸⁰; uncontrolled pulsed-field series in neck and foot fractures continue ^105,106; and a newer magnetic device is being introduced on case reports ^102,103. On materials: glycine and tryptophan assemblies reach 10 to 47 pm/V in the laboratory, the 47 predicted ^34,138,143, short of the 178 pm/V of 2018's beta-glycine crystals, which match the ceramics ³; lead-free transducers remain less universal than PZT after twenty years ^25,125; wearable and through-tissue ultrasound are engineering reviews ^117,118. On implants: ten animal studies (rat or mouse where the abstract names the species) of barium titanate, niobate, zinc oxide, whitlockite and other piezoelectric materials driven by load, light or ultrasound, one naming Piezo1 as the receiver and one designed around a PIEZO2 deficit, none in people ^{30,38,126,127,128,133,135,136,137,139}. On the fringe: one randomized test of a healing crystal, negative ²⁶; grounding reviews written from the trade ^27,158 and new laboratory work in mitochondria and rats ^167,168; a biofield reporting checklist ¹⁵¹, a biofield trial retracted for duplication and implausible data ⁸³, and a single-center study of biofield therapy in pancreatic cancer cells and mice ¹⁵⁵.

What is not known. Whether the sub-picometer collagen effect that survives humidity at the nanoscale does anything to any cell in a living bone, which is the question Ahn and Grodzinsky left open in 2009 and which no experiment since has answered ^9,11,47. Whether flexoelectricity at crack tips, measured in bone mineral and shown to kill cells on a synthetic substrate, operates in a fracture ^39,49. Whether any electrical stimulator changes a patient-important outcome after fracture or fusion, since the pooled estimates are of radiographs and function, where measured, has barely moved ^21,95,97. Why ultrasound, which has no plausible piezoelectric target in bone, appeared to work in small company-authored trials and not in a large independent one, a question the 2017 review answers with risk of bias ⁷⁵. Whether a piezoelectric scaffold charged by a patient's own walking, the one design that is genuinely self-powered and the one that worked in rabbits, would work in a knee ²⁹. And what becomes, over years, of the barium titanate, niobate and zinc oxide particles that the animal implants leave in tissue. These implants are lead-free, so the lead question raised by the transducer literature does not apply to them ^25,125, but none of the implant abstracts cited here reports the long-term fate or safety of its particles ^{38,126,127,128,135}.

The house verdict. Piezoelectricity is real, it is in bone, and it is small and dry; the clearest electromechanical coupling of this kind in a living body is not in bone at all but in a protein motor of the inner ear ³⁵. The theory built on it in 1962 was reversed in 1982-1983 and replaced by fluid flow and, in mice in 2019, by a channel ^12,13,15. The devices built on the theory have, after forty years, one modest and radiographic signal in spinal fusion, an inconclusive one in nonunion, and a negative one in fresh fractures treated with ultrasound ^19,21,24. The materials built on the physics image the body, ablate fibroids and break kidney stones ^5,120. The implants built on the physics have repaired cartilage, bone and nerve defects in rabbits and rats and have not been tried in a person ^29,30,133. And the crystals, mats and devices sold on the word have a handful of small sham-controlled tests: grounding studies of mood, muscle damage and sleep, two of them coauthored by one of the practice's founding proponents ^162,163,164; grounding shoes that made no difference ¹⁶⁵; a bioresonance device no better than a sham ¹⁵²; and the one randomized test of a healing crystal on this page, which found that believers improved whichever object they held ²⁶.

Where it connects

Sources

168 sources, numbered as they are cited. Every one was checked against PubMed or its publisher before it was cited here; the note under each says what it shows and what it does not.

1. 1
   Curie J, Curie P. Développement par compression de l'électricité polaire dans les cristaux hémièdres à faces inclinées.Bulletin de la Société minéralogique de France · 1880 · 3:90-93

   Primary nineteenth-century document, not indexed in PubMed and not held by it; cited for the existence and date of the discovery of the direct effect in quartz and other crystals. Not opened in this session; the citation is the standard one reproduced in the indexed literature.

2. 2
   Gill M, Máthé MT, Salamon P, Gleeson JT, Jákli A. From solid to liquid piezoelectric materials.Materials Horizons · 2025 · 12(21):8920-8942doi:10.1039/d5mh00917k · PMID 40765300

   Review of the history of piezoelectricity from the Curie brothers' discovery of pressure electricity onward, defining direct piezoelectricity (stress-induced polarization) and converse piezoelectricity (field-induced stress) as a linear coupling in materials lacking inversion symmetry. An indexed secondary source for the definitions and the Curies' priority; its abstract does not itself give the 1880 date or describe Lippmann's prediction.

3. 3
   Guerin S, Stapleton A, Chovan D, Mouras R, Gleeson M, McKeown C, Noor MR, Silien C, Rhen FMF, Kholkin AL, Liu N, Soulimane T, Tofail SAM, Thompson D. Control of piezoelectricity in amino acids by supramolecular packing.Nature Materials · 2018 · 17(2):180-186doi:10.1038/nmat5045 · PMID 29200197

   Defines piezoelectricity as the linear relationship between stress and induced charge; notes biological coefficients are typically 0.1 to 10 pm/V; reports a shear coefficient of 178 pm/V in crystals of beta-glycine, similar to barium titanate or lead zirconate titanate, and a predicted voltage constant of 8 V·m/N. Crystals grown in the laboratory, not glycine in the body.

4. 4
   Lippmann G. Principe de la conservation de l'électricité, ou second principe de la théorie des phénomènes électriques.Annales de chimie et de physique · 1881 · 24:145-178

   Primary nineteenth-century document, not indexed in PubMed; cited for the thermodynamic prediction of the converse effect (voltage producing strain), which the Curies confirmed in 1881. Not opened in this session; standard citation.

5. 5
   Bachu VS, Kedda J, Suk I, Green JJ, Tyler B. High-Intensity Focused Ultrasound: A Review of Mechanisms and Clinical Applications.Annals of Biomedical Engineering · 2021 · 49(9):1975-1991doi:10.1007/s10439-021-02833-9 · PMID 34374945

   Review describing the history of diagnostic and therapeutic ultrasound, both delivered by piezoelectric transducers, and the uses of focused high-intensity beams for ablation, drug delivery and neuromodulation. Cited for the transducer and for the fact that the same physics heats and destroys tissue at high intensity.

6. 6
   Wang Z, Ma D, Wang Y, Xie Y, Yu Z, Cheng J, Li L, Sun L, Dong S, Wang H. Kirigami-Origami-Inspired Lead-Free Piezoelectric Ceramics.Advanced Science (Weinheim) · 2023 · 10(17):e2207059doi:10.1002/advs.202207059 · PMID 37096841

   Printed, curved barium titanate ceramics with a piezoelectric constant of 275 pC/N, 45% higher than conventionally sintered sheets, able to detect a pulse at the wrist. Cited for the scale of an engineered ceramic against a collagen fibril.

7. 7
   Fukada E, Yasuda I. On the piezoelectric effect of bone.Journal of the Physical Society of Japan · 1957 · 12(10):1158-1162

   Primary physics-journal paper, not indexed in PubMed; the first measurement of piezoelectricity in dried bone. Not opened in this session; the 1957 date and attribution are confirmed by indexed sources on this page.

8. 8
   Fukada E, Yasuda I. Piezoelectric effects in collagen.Japanese Journal of Applied Physics · 1964 · 3(2):117-121

   Primary physics-journal paper, not indexed in PubMed; the paper that placed bone's piezoelectricity in collagen rather than mineral. Not opened in this session; standard citation.

9. 9
   Bazaid A, Zhang F, Zhang Q, Neumayer S, Denning D, Habelitz S, Marina Ferreira A, Rodriguez BJ. Electromechanical Coupling in Collagen Measured under Increasing Relative Humidity.Materials (Basel) · 2023 · 16(17):6034doi:10.3390/ma16176034 · PMID 37687727

   Lateral piezoresponse force microscopy of rat tail tendon collagen from 10% to 70% relative humidity; piezoresponse measurable across the range, including the 40-50% humidity the authors equate with the 12% moisture of physiological bone. Nanoscale only; the abstract itself notes that macroscale hydrated tendon shows insignificant piezoelectricity. Dates the discovery in bone to 1957.

10. 10
    Netto TG, Zimmerman RL. Effect of water on piezoelectricity in bone and collagen.Biophysical Journal · 1975 · 15(6):573-6doi:10.1016/S0006-3495(75)85839-5 · PMID 1148359

    Interferometric measurement in bovine bone and tendon: the piezoelectric strain constant d14 fell with hydration from dry values of 0.2 × 10^-14 m/V (bone) and 2.0 × 10^-14 m/V (tendon); in tendon the fall was exponential with a characteristic hydration of 7% by weight. Dry, excised tissue.

11. 11
    Gharibi Keit M, Davletkildeev N. Decoupling collagen and mineral contributions to piezoelectricity in human cortical bone via piezoresponse force microscopy.Biomedical Physics & Engineering Express · 2026 · (epub 23 Sep)doi:10.1088/2057-1976/aeaba8 · PMID 42777739

    Human cortical bone probed intact and after sodium hypochlorite removal of the organic matrix: intact bone responded in the sub-picometer-per-volt range; the deproteinized, mineral-dominated specimen gave an effective coefficient of -0.0138 ± 0.0074 pm/V, near zero, consistent with centrosymmetric hydroxyapatite; the collagen contribution was inferred at about 0.2 to 0.4 pm/V. Two-author nanoscale study on excised bone; the page's most recent direct measurement.

12. 12
    Gross D, Williams WS. Streaming potential and the electromechanical response of physiologically-moist bone.Journal of Biomechanics · 1982 · 15(4):277-95doi:10.1016/0021-9290(82)90174-9 · PMID 7096383

    Points out that piezoelectricity and streaming potentials depend in the same way on the strain gradient and both give a current proportional to strain rate, so bending wet bone cannot by itself tell them apart; then forces electrolytes of varied concentration and viscosity through a bone disk, measures the potential directly, and concludes that streaming potentials dominate piezoelectricity in wet bone bending. The first half of the reversal.

13. 13
    Pienkowski D, Pollack SR. The origin of stress-generated potentials in fluid-saturated bone.Journal of Orthopaedic Research · 1983 · 1(1):30-41doi:10.1002/jor.1100010105 · PMID 6679573

    Human and bovine cortical bone soaked in solutions of varied sodium chloride and sucrose; the magnitude and time course of stress-generated potentials followed the fluid's conductivity and viscosity, and high salt consistently reversed their polarity, which piezoelectricity cannot do. Conclusion: although fluid-saturated bone may retain some piezoelectric properties, stress-generated potentials are predominantly streaming potentials. The second half of the reversal.

14. 14
    Riddle RC, Donahue HJ. From streaming-potentials to shear stress: 25 years of bone cell mechanotransduction.Journal of Orthopaedic Research · 2009 · 27(2):143-9doi:10.1002/jor.20723 · PMID 18683882

    Review of how interstitial fluid flow, produced when bone deforms, became the accepted biophysical signal for bone cells, with the signaling cascades it activates. The title is the field's own summary of the reversal.

15. 15
    Li X, Han L, Nookaew I, Mannen E, Silva MJ, Almeida M, Xiong J. Stimulation of Piezo1 by mechanical signals promotes bone anabolism.eLife · 2019 · 8:e49631doi:10.7554/eLife.49631 · PMID 31588901

    Piezo1 was required for the gene-expression response of cultured osteocytes to fluid shear stress; deleting it in osteoblasts and osteocytes reduced bone mass and strength in mice, and a Piezo1 agonist given to adult mice increased bone mass, mimicking loading. Mouse and cell work: the load sensor in bone is a channel responding to fluid flow, which is where the streaming-potential story leads.

16. 16
    Coste B, Mathur J, Schmidt M, Earley TJ, Ranade S, Petrus MJ, Dubin AE, Patapoutian A. Piezo1 and Piezo2 are essential components of distinct mechanically activated cation channels.Science · 2010 · 330(6000):55-60doi:10.1126/science.1193270 · PMID 20813920

    Identification, in a mouse neuroblastoma cell line, of Piezo1 (Fam38A) as required for mechanically activated currents, with Piezo2 (Fam38B) a related channel; both are multipass membrane proteins with homologs in invertebrates, plants and protozoa. These are ion channels that open under membrane tension; they are not piezoelectric materials and share with the effect only a Greek root.

17. 17
    Zhao D, Fu J, Liu H, Liang S, Song M, Zhang A, Wang DE, Guo Q, Zhang Y, Wu J, Xu H. Piezo1 Activation Rescues Anabolic Response to Mechanical Loading in Aged Bone via Connexin 43 Hemichannels.Aging Cell · 2026 · 25(9):e70687doi:10.1111/acel.70687 · PMID 42630044

    In 19-month-old male mice the bone-building response of the tibia to loading was blunted; activating osteocyte Piezo1 with the agonist Yoda1 rescued it, with Piezo1 co-localizing with connexin 43 and opening its hemichannels to release prostaglandin E and suppress sclerostin. Mouse study; places Piezo1 within a signaling network.

18. 18
    Bassett CA, Mitchell SN, Gaston SR. Pulsing electromagnetic field treatment in ununited fractures and failed arthrodeses.JAMA · 1982 · 247(5):623-8PMID 7054564

    States that the method was approved by the Food and Drug Administration in November 1979, and reports 1,007 ununited fractures and 71 failed arthrodeses worldwide: 81% success at Columbia-Presbyterian, 79% internationally, 76% elsewhere in the United States; 75% in a subset of 332 patients averaging 4.7 years of disability and 3.4 failed operations. Uncontrolled registry data from the inventor's center. No DOI in the record.

19. 19
    Griffin XL, Costa ML, Parsons N, Smith N. Electromagnetic field stimulation for treating delayed union or non-union of long bone fractures in adults.Cochrane Database of Systematic Reviews · 2011 · 2011(4):CD008471doi:10.1002/14651858.CD008471.pub2 · PMID 21491410

    Four blinded, randomized, placebo-controlled trials, 125 participants, three of pulsed fields and one of capacitive coupling, mostly tibial nonunion: pooled risk ratio for union 1.96 (95% CI 0.86 to 4.48) with I² 58%, and 1.61 (0.74 to 3.54) at 24 weeks; no reduction in pain in two trials and no functional outcomes reported. Judged inconclusive and insufficient to inform practice.

20. 20
    Heckman JD, Ryaby JP, McCabe J, Frey JJ, Kilcoyne RF. Acceleration of tibial fracture-healing by non-invasive, low-intensity pulsed ultrasound.Journal of Bone and Joint Surgery (American) · 1994 · 76(1):26-34doi:10.2106/00004623-199401000-00004 · PMID 8288661

    67 closed or grade I open tibial shaft fractures in casts, 33 active and 34 placebo devices: clinical healing 86 ± 5.8 against 114 ± 10.4 days (p = 0.01) and overall healing 96 ± 4.9 against 154 ± 13.7 days (p = 0.0001). The pivotal trial; the second author was with the device company.

21. 21
    TRUST Investigators writing group; Busse JW, Bhandari M, Einhorn TA, Schemitsch E, Heckman JD, Tornetta P, Leung KS, Heels-Ansdell D, Makosso-Kallyth S, Della Rocca GJ, Jones CB, Guyatt GH. Re-evaluation of low intensity pulsed ultrasound in treatment of tibial fractures (TRUST): randomized clinical trial.BMJ · 2016 · 355:i5351doi:10.1136/bmj.i5351 · PMID 27797787

    501 patients at 43 North American trauma centers, tibial fractures fixed with intramedullary nails, randomized to daily LIPUS or a sham device until healing or one year: no difference in SF-36 physical component scores (mean difference 0.55, 95% CI -0.75 to 1.84; P = 0.41) or time to radiographic healing (hazard ratio 1.07, 0.86 to 1.34; P = 0.55); 73% of patients delivered at least half the prescribed treatments. The trial that reversed the 1994 result.

22. 22
    Poolman RW, Agoritsas T, Siemieniuk RA, Harris IA, Schipper IB, Mollon B, Smith M, Albin A, Nador S, Sasges W, Schandelmaier S, Lytvyn L, Kuijpers T, van Beers LW, Verhofstad MH, Vandvik PO. Low intensity pulsed ultrasound (LIPUS) for bone healing: a clinical practice guideline.BMJ · 2017 · 356:j576doi:10.1136/bmj.j576 · PMID 28228381

    The BMJ Rapid Recommendation, written with patient panel members, that followed the TRUST trial and the systematic review. No abstract in the record; cited for the existence and date of the guideline against LIPUS for fractures.

23. 23
    Luo M, Zeng X, Jiang L, Yi Q, Zhang L, Wang H, Huang J, Zhang Z, Tang S, Xiao Z. Effect of electrical stimulation on the fusion rate after spinal surgery: a systematic review and meta-analysis.Neurosurgical Review · 2024 · 47(1):618doi:10.1007/s10143-024-02874-3 · PMID 39278993

    Searched to 30 September 2023: stimulation raised the odds of fusion, odds ratio 2.66 (95% CI 1.79 to 3.97), 86.8% against 73.7%; direct current odds ratio 2.33 (1.37 to 3.96), PEMF odds ratio 2.60 (1.29 to 5.27), capacitive coupling odds ratio 3.44 (1.75 to 6.75). The authors still say effectiveness needs further study. The abstract says it searched for 'related articles' and does not restrict itself to randomized trials.

24. 24
    Akhter S, Qureshi AR, Aleem I, El-Khechen HA, Khan S, Sikder O, Khan M, Bhandari M, Aleem I. Efficacy of Electrical Stimulation for Spinal Fusion: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.Scientific Reports · 2020 · 10(1):4568doi:10.1038/s41598-020-61266-x · PMID 32165697

    Seven randomized trials, 941 patients (487 stimulated, 454 control or sham): odds of radiographic fusion 2.53 (95% CI 1.86 to 3.43), moderate quality, no difference by device type, smoking or levels fused. Fusion on imaging, not pain or function; two authors list commercial affiliations, OrthoEvidence (an evidence-summary company) and North Inc. (a wearable-electronics company), neither a stimulator maker.

25. 25
    Ringgaard E, Levassort F, Wang K, Vaitekunas J, Nagata H. Lead-Free Piezoelectric Transducers.IEEE Transactions on Ultrasonics, Ferroelectrics, and Frequency Control · 2024 · 71(1):3-15doi:10.1109/TUFFC.2023.3340950 · PMID 38060358

    Stock-taking of more than twenty years of lead-free piezoelectric research: the main material families are less universally applicable than lead zirconate titanate, but medical imaging transducers and other low-power devices have been demonstrated, with commercialization still limited by availability, reproducibility and sample size.

26. 26
    Escolà-Gascón Á, Dagnall N, Drinkwater K, Denovan A, Benito-León J. Placebo effects in alternative medical treatments for anxiety: false hope or healing potential?CNS Spectrums · 2025 · 30(1):e70doi:10.1017/S1092852925100515 · PMID 40855750

    138 adults classified as believers or non-believers in crystals, randomized to rose quartz or a visually matched placebo for 14 days: anxiety fell only among believers and equally with either object; Bayesian analysis favored no specific effect. The one randomized test of a healing crystal on this page.

27. 27
    Sinatra ST, Sinatra DS, Sinatra SW, Chevalier G. Grounding - The universal anti-inflammatory remedy.Biomedical Journal · 2023 · 46(1):11-16doi:10.1016/j.bj.2022.12.002 · PMID 36528336

    Calls grounding 'one of the greatest kept secrets' and asserts that inflammation is the root cause of almost all diseases; one author's listed affiliation is Grounded.com, a seller of grounding products. A commercial conflict visible on the paper itself.

28. 28
    Donoso M F, Sagredo M P, García-Huidobro T JP. [D. Julius y A. Patapoutian. 2021 Nobel Prize Awardees discover new ionic channels that detect temperature and mechanical stimuli].Revista Médica de Chile · 2022 · 150(1):88-92doi:10.4067/S0034-98872022000100088 · PMID 35856969

    Spanish-language account of the 2021 Nobel Prize in Physiology or Medicine: Julius for the heat channel TRPV1 and the cold channel TRPM8, Patapoutian for TRPM8 and for Piezo1 and Piezo2, the mechanosensors of touch and proprioception. Cited for the prize and what it was for.

29. 29
    Liu Y, Dzidotor G, Le TT, Vinikoor T, Morgan K, Curry EJ, Das R, McClinton A, Eisenberg E, Apuzzo LN, Tran KTM, Prasad P, Flanagan TJ, Lee SW, Kan HM, Chorsi MT, Lo KWH, Laurencin CT, Nguyen TD. Exercise-induced piezoelectric stimulation for cartilage regeneration in rabbits.Science Translational Medicine · 2022 · 14(627):eabi7282doi:10.1126/scitranslmed.abi7282 · PMID 35020409

    A biodegradable piezoelectric poly(L-lactic acid) nanofiber scaffold charged by joint loading: rabbits with critical-sized osteochondral defects given the scaffold plus exercise regrew hyaline cartilage with type II collagen after 1 to 2 months of exercise, while a non-piezoelectric scaffold plus exercise left the defect unfilled. Rabbit study with a material control; no human data.

30. 30
    Wang C, Zhang T, Liu J, Wang X, Gao C, Chen J, Feng J, Dong Z, Wang X, Li Y, Zhao M, Li F, Yu Y, Cai Q, Tian H. Biodegradable Mg-releasing piezoelectric scaffold for segmental bone defect repair.Bioactive Materials · 2026 · 61:743-757doi:10.1016/j.bioactmat.2026.02.017 · PMID 41799954

    A gelatin methacryloyl cryogel loaded with piezoelectric whitlockite nanoparticles, generating potentials under load and releasing calcium and magnesium; in a rat critical-size radial defect it achieved complete bridging, and in culture it triggered Piezo1-mediated calcium influx in marrow stromal cells. Rat study; the authors themselves invoke the Piezo1 channel as the receiver of their material's charge.

31. 31
    Fukada E, Ueda H, Rinaldi R. Piezoelectric and related properties of hydrated collagen.Biophysical Journal · 1976 · 16(8):911-8doi:10.1016/S0006-3495(76)85741-4 · PMID 938730

    Oriented collagen measured at 10 Hz from -150 to 50 °C at several hydration levels; above 25% water by weight the piezoelectric constants fell above -50 °C, which the authors attribute to ionic conduction around the piezoelectric phase. Excised, oriented samples.

32. 32
    Buizza A, Dell'Aquila T, Giribona P, Spagno C. The performance of different pressure pulse generators for extracorporeal lithotripsy: a comparison based on commercial lithotripters for kidney stones.Ultrasound in Medicine & Biology · 1995 · 21(2):259-72doi:10.1016/s0301-5629(94)00104-9 · PMID 7571134

    Hydrophone measurements of ten commercial lithotripters of the three technologies, electrohydraulic, electromagnetic and piezoelectric: the piezoelectric generators produced pulses with less energy than the others. Bench measurement.

33. 33
    Chuong CJ, Zhong P, Preminger GM. A comparison of stone damage caused by different modes of shock wave generation.Journal of Urology · 1992 · 148(1):200-5doi:10.1016/s0022-5347(17)36553-9 · PMID 1613869

    Standard stone phantoms under electrohydraulic, electromagnetic and piezoelectric lithotripters: for the same number of shocks, volume loss was greatest with electrohydraulic, then electromagnetic, then piezoelectric; piezoelectric craters were narrow and deep. Bench study.

34. 34
    Wang Y, Liu S, Li L, Li H, Yin Y, Rencus-Lazar S, Guerin S, Ouyang W, Thompson D, Yang R, Cai K, Gazit E, Ji W. Manipulating the Piezoelectric Response of Amino Acid-Based Assemblies by Supramolecular Engineering.Journal of the American Chemical Society · 2023 · 145(28):15331-15342doi:10.1021/jacs.3c02993 · PMID 37392396

    Acetylated tryptophan assemblies with a predicted piezoelectric tensor of 47 pm/V and voltage constant of 1719 mV·m/N; a nanogenerator from the crystals gave over 1.4 V under pressure and lit a light-emitting diode. Laboratory crystals.

35. 35
    Dong XX, Ospeck M, Iwasa KH. Piezoelectric reciprocal relationship of the membrane motor in the cochlear outer hair cell.Biophysical Journal · 2002 · 82(3):1254-9doi:10.1016/S0006-3495(02)75481-7 · PMID 11867442

    Stretching guinea pig outer hair cells with known force displaced charge, with a maximum efficiency of about 20 fC/nN for a 50 μm lateral membrane, consistent with the reciprocal relationship characteristic of piezoelectricity; the authors calculate this coefficient as four orders of magnitude greater than that of the best man-made material. Isolated living cells.

36. 36
    Minary-Jolandan M, Yu MF. Nanoscale characterization of isolated individual type I collagen fibrils: polarization and piezoelectricity.Nanotechnology · 2009 · 20(8):085706doi:10.1088/0957-4484/20/8/085706 · PMID 19417467

    Piezoresponse force microscopy of single collagen fibrils about 100 nm across from bovine Achilles tendon: shear piezoelectric coefficient of the order of 1 pm/V with unipolar polarization along the fibril; the authors estimate potentials up to tens of millivolts under reasonable shear. An estimate for an isolated fibril in air, not a measurement in tissue.

37. 37
    Ranade SS, Woo SH, Dubin AE, Moshourab RA, Wetzel C, Petrus M, Mathur J, Bégay V, Coste B, Mainquist J, Wilson AJ, Francisco AG, Reddy K, Qiu Z, Wood JN, Lewin GR, Patapoutian A. Piezo2 is the major transducer of mechanical forces for touch sensation in mice.Nature · 2014 · 516(7529):121-5doi:10.1038/nature13980 · PMID 25471886

    Mice lacking Piezo2 in sensory neurons and Merkel cells lost almost all light-touch sensation while pain sensation remained; the channel sits at the endings of low-threshold mechanoreceptors in hairy and glabrous skin. Mouse genetics.

38. 38
    Hua Y, Duan W, Liu R, Shu Y, Peng J, Xu W, Zhao Q, Xu S, Cui H, Hao X, Hao L. Energy-responsive multi-catalytic nanogenerator hydrogels synergistically enhance diabetic tendon-to-bone healing via the ages/RAGE/PIEZO2 axis.Biomaterials · 2026 · 336:124443doi:10.1016/j.biomaterials.2026.124443 · PMID 42442283

    Barium titanate nanocrystals in a thermosensitive hydrogel with a gold-palladium nanozyme, designed around a human transcriptomic dataset showing reduced PIEZO2 in diabetic rotator cuff tissue; in a diabetic animal model of rotator cuff repair the tendon-bone interface regained structure and strength on micro-computed tomography and mechanical testing. Animal study; the material is meant to substitute for a missing mechanosensor.

39. 39
    Vasquez-Sancho F, Abdollahi A, Damjanovic D, Catalan G. Flexoelectricity in Bones.Advanced Materials · 2018 · 30(9)doi:10.1002/adma.201705316 · PMID 29345377

    Measures flexoelectricity, the voltage any material produces under a strain gradient, in bone and in pure hydroxyapatite and finds them of the same order of magnitude; argues that mineral flexoelectricity, not collagen piezoelectricity, is the main source of bending-induced polarization in cortical bone, and calculates that fields at cracks are theoretically large enough to kill nearby osteocytes. A physics measurement plus a calculation, not a biological demonstration.

40. 40
    Otter MW, Palmieri VR, Cochran GV. Transcortical streaming potentials are generated by circulatory pressure gradients in living canine tibia.Journal of Orthopaedic Research · 1990 · 8(1):119-26doi:10.1002/jor.1100080115 · PMID 2293626

    In living dog tibia the periosteal surface became positive relative to the endosteal surface with each pulse as medullary pressure rose; occluding the femoral artery stopped both pressure and potential, and epinephrine reduced both by the same fraction. Streaming potentials from blood flow, with no bending at all.

41. 41
    Otter MW, Wu DD, Bieber WA, Cochran GV. Intraarterial protamine sulfate reduces the magnitude of streaming potentials in living canine tibia.Calcified Tissue International · 1993 · 53(6):411-5PMID 8293355

    Nine anesthetized dogs, tibia bent sinusoidally at 2 Hz to about 200 microstrain; protamine injected into the femoral artery reduced the streaming potentials and sometimes reversed their sign. A circulating protein changed bone's electrical response, which is impossible for a crystal property. No DOI in the record.

42. 42
    Marino AA, Spadaro JA, Fukada E, Kahn LD, Becker RO. Piezoelectricity in collagen films.Calcified Tissue International · 1980 · 31(3):257-9doi:10.1007/BF02407190 · PMID 6781732

    Collagen films made by evaporation and by electrodeposition; the more organized electrodeposited films had higher coefficients, but even evaporated films were piezoelectric, placing the origin at the tropocollagen molecule or aggregates no larger than 50 ångströms (5 nanometers). In vitro films.

43. 43
    BASSETT CA, BECKER RO. Generation of electric potentials by bone in response to mechanical stress.Science · 1962 · 137(3535):1063-4doi:10.1126/science.137.3535.1063 · PMID 13865637

    The paper that launched the clinical program. Amplitude depended on rate and magnitude of deformation, polarity on direction of bending, compression negative; results were the same in living and dead bone; removing the inorganic fraction abolished the potentials, an attribution to mineral that later work reversed. The authors call it probable that the potentials influence bone cells directly, which was a hypothesis, not a finding.

44. 44
    Yasuda I. Electrical callus and callus formation by electret.Clinical Orthopaedics and Related Research · 1977 · (124):53-6PMID 598093

    Callus formed by passing current through bone (electrodynamic callus) grows first at the negative pole; a Teflon electret film laid near bone produces electrostatic callus, more when the bone is wrapped. No DOI in the record; animal and in vitro work.

45. 45
    BECKER RO. The bioelectric factors in amphibian-limb regeneration.Journal of Bone and Joint Surgery (American) · 1961 · 43-A:643-56PMID 14448529

    No abstract and no DOI in the record. Cited for the origin of Becker's wider program, in which electricity measured on salamander limbs was proposed as the control signal for regeneration.

46. 46
    Li S, Yu B, Zhou D, He C, Zhuo Q, Hulme JM. Electromagnetic fields for treating osteoarthritis.Cochrane Database of Systematic Reviews · 2013 · 2013(12):CD003523doi:10.1002/14651858.CD003523.pub2 · PMID 24338431

    Nine trials, 636 participants: pain 15.10 points lower on a 0-100 scale (95% CI 9.08 to 21.13) after 4 to 26 weeks, no significant effect on function (mean difference 4.55, -2.23 to 11.32) or quality of life (standardized mean difference 0.09), no radiographic data, no serious adverse events. The background explicitly rests the rationale on Wolff's law, the piezoelectric effect and streaming potentials.

47. 47
    Ahn AC, Grodzinsky AJ. Relevance of collagen piezoelectricity to "Wolff's Law": a critical review.Medical Engineering & Physics · 2009 · 31(7):733-41doi:10.1016/j.medengphy.2009.02.006 · PMID 19286413

    The critical review of the whole question: collagen piezoelectricity was invoked in the 1960s as the way bone cells sense load, diminished as streaming potentials were identified, and was made to seem obsolete by evidence for fluid shear stress as the osteocyte's signal; the authors propose hypotheses under which it might still matter. First author affiliated with a Harvard complementary-medicine division, which is relevant to reading its even-handedness.

48. 48
    Hu YJ, Wu X, Wang F, Jin Y, Jin Y, Liu Y, Cong Q, Yang Y. Piezo1-mediated mechanotransduction controls osteocyte maturation and dendrite development via a YAP-CCN-Src signaling axis.Nature Communications · 2025 · 16(1):10859doi:10.1038/s41467-025-65636-9 · PMID 41315189

    Deleting Piezo1 in late osteoblasts and osteocytes of mice reduced bone mass and disrupted osteocyte maturation, with fewer and shorter dendrites and a poorer network; reduced YAP activity was responsible, and overexpressing the YAP targets CCN1/2 in the liver rescued the defects. Mouse genetics.

49. 49
    Núñez-Toldrà R, Vasquez-Sancho F, Barroca N, Catalan G. Investigation of The Cellular Response to Bone Fractures: Evidence for Flexoelectricity.Scientific Reports · 2020 · 10(1):254doi:10.1038/s41598-019-57121-3 · PMID 31937885

    Mouse MC3T3-E1 cells differentiated on microcracked hydroxyapatite and subjected to a strain gradient died near the crack, and two weeks later showed more attachment, mineralization and osteocalcin around it. Cell culture on a synthetic substrate; consistent with the flexoelectric hypothesis, not proof of it in bone.

50. 50
    Scott G, King JB. A prospective, double-blind trial of electrical capacitive coupling in the treatment of non-union of long bones.Journal of Bone and Joint Surgery (American) · 1994 · 76(6):820-6doi:10.2106/00004623-199406000-00005 · PMID 8200888

    23 patients with established long-bone nonunion, 21 completing: healed in 6 of 10 actively treated and 0 of 11 on placebo units (p = 0.004). Capacitive coupling, not PEMF; very small.

51. 51
    Cottrill E, Pennington Z, Ahmed AK, Lubelski D, Goodwin ML, Perdomo-Pantoja A, Westbroek EM, Theodore N, Witham T, Sciubba D. The effect of electrical stimulation therapies on spinal fusion: a cross-disciplinary systematic review and meta-analysis of the preclinical and clinical data.Journal of Neurosurgery: Spine · 2019 · 32(1):106-126doi:10.3171/2019.5.SPINE19465 · PMID 31593923

    Eleven preclinical studies (257 animals) and 13 clinical studies (2,144 patients): odds ratio 4.79 for fusion in animals and 2.26 in patients; direct current worked in both (clinical odds ratio 2.13, p = 0.03), inductive coupling only clinically (odds ratio 2.45), capacitive coupling not at all on one study. Mixes trial designs; the animal-to-human concordance is its main point.

52. 52
    Fukada E. History and recent progress in piezoelectric polymers.IEEE Transactions on Ultrasonics, Ferroelectrics, and Frequency Control · 2000 · 47(6):1277-90doi:10.1109/58.883516 · PMID 18238673

    Fukada's own history: shear piezoelectricity studied in cellulose and collagen since the 1950s; phonograph pickups using a piece of bone or tendon demonstrated in 1959; piezoelectricity in poled polyvinylidene fluoride found in 1969; PVDF ultrasonic transducers in 1972 and headphones marketed in 1975. A retrospective review.

53. 53
    Marino AA, Becker RO, Soderholm SC. Origin of the piezoelectric effect in bone.Calcified Tissue Research · 1971 · 8(2):177-80doi:10.1007/BF02010135 · PMID 5145213

    No abstract in the record; indexed under collagen, minerals and human bone. Cited for the attribution of the effect to collagen rather than mineral by Becker's own group, reversing the 1962 reading.

54. 54
    BASSETT CA, PAWLUK RJ, BECKER RO. EFFECTS OF ELECTRIC CURRENTS ON BONE IN VIVO.Nature · 1964 · 204:652-4doi:10.1038/204652a0 · PMID 14236279

    No abstract in the record; dog femur, electric stimulation, histology. Cited for the first in vivo attempt to grow bone with applied current on the piezoelectric rationale.

55. 55
    Yasuda I. Mechanical and electrical callus.Annals of the New York Academy of Sciences · 1974 · 238:457-65doi:10.1111/j.1749-6632.1974.tb26812.x · PMID 4531275

    No abstract in the record; rabbit femur, electric stimulation and vibration. Cited for Yasuda's own account of callus produced by current.

56. 56
    Inoue S, Ohashi T, Yasuda I, Fukada E. Electret induced callus formation in the rat.Clinical Orthopaedics and Related Research · 1977 · (124):57-8PMID 598094

    A Teflon electret wrapped around the rat femoral shaft produced bony callus in 9 of 10 animals. No DOI in the record. A permanently charged film is not a piezoelectric one, but this is the earliest passive electrical implant on the page.

57. 57
    Bassett CA, Pawluk RJ, Pilla AA. Augmentation of bone repair by inductively coupled electromagnetic fields.Science · 1974 · 184(4136):575-7doi:10.1126/science.184.4136.575 · PMID 4821958

    Pulsing electromagnetic fields coupled across skin to canine fibular osteotomies; the induced field appeared to increase the organization and strength of repair at 28 days. Dogs, short follow-up; the paper that moved the field from implanted electrodes to external coils.

58. 58
    Bassett CA, Becker RO, Brighton CT, Lavine L, Rowley BA. Panel discussion: To what extent can electrical stimulation be used in the treatment of human disorders?Annals of the New York Academy of Sciences · 1974 · 238:586-93doi:10.1111/j.1749-6632.1974.tb26824.x · PMID 4548340

    No abstract in the record; indexed under medical ethics, human experimentation, fractures and neoplasms. Cited for the fact that the field's founders were debating human use, and its ethics, in 1974.

59. 59
    Friedenberg ZB, Harlow MC, Brighton CT. Healing of nonunion of the medial malleolus by means of direct current: a case report.Journal of Trauma · 1971 · 11(10):883-5doi:10.1097/00005373-197110000-00010 · PMID 5094761

    No abstract in the record; a single case from Brighton's group. Cited for the existence and date of an early direct-current treatment of a human nonunion.

60. 60
    Brighton CT, Black J, Friedenberg ZB, Esterhai JL, Day LJ, Connolly JF. A multicenter study of the treatment of non-union with constant direct current.Journal of Bone and Joint Surgery (American) · 1981 · 63(1):2-13PMID 7005239

    Study begun at the University of Pennsylvania in 1970 and widened in 1977: four cathodes delivering 20 microamperes of constant direct current for twelve weeks, with cast immobilization; solid union in 149 of 178 nonunions (83.7%) at Pennsylvania and 58 of 80 (72.5%) at participating centers. No control group; the authors compare the rate with bone-graft surgery. No DOI in the record.

61. 61
    Bassett CA, Mitchell SN, Gaston SR. Treatment of ununited tibial diaphyseal fractures with pulsing electromagnetic fields.Journal of Bone and Joint Surgery (American) · 1981 · 63(4):511-23PMID 7217117

    125 patients with 127 ununited tibial shaft fractures treated with PEMF alone; 87% healed; success not affected by age, sex, duration, prior operations, infection or metal. No control group, so the 87% cannot be separated from what casting alone would have done. No DOI in the record.

62. 62
    Anderson JC, Eriksson C. Electrical properties of wet collagen.Nature · 1968 · 218(5137):166-8doi:10.1038/218166a0 · PMID 5645288

    No abstract in the record; indexed under human Achilles tendon, pH and electrophoresis. Cited as the first of the papers that examined collagen wet rather than dry and found electrokinetic behavior, the seed of the streaming-potential correction.

63. 63
    Anderson JC, Eriksson C. Piezoelectric properties of dry and wet bone.Nature · 1970 · 227(5257):491-2doi:10.1038/227491a0 · PMID 5428466

    No abstract in the record; indexed under bovine femur, pH and hydroxyapatite. Cited for the existence and date of the dry-versus-wet comparison.

64. 64
    Barker AT, Dixon RA, Sharrard WJ, Sutcliffe ML. Pulsed magnetic field therapy for tibial non-union. Interim results of a double-blind trial.Lancet · 1984 · 1(8384):994-6doi:10.1016/s0140-6736(84)92329-8 · PMID 6143970

    Tibial fractures ununited for at least 52 weeks, randomized to active or dummy stimulators in full-leg casts for 24 weeks: 5 of 9 healed with working machines and 5 of 7 with dummies, a difference compatible with anything from +33% to -61%. The authors say the high control success suggests conservative management explains much of the success attributed to the fields. Tiny, interim, but the first blinded test.

65. 65
    Kristiansen TK, Ryaby JP, McCabe J, Frey JJ, Roe LR. Accelerated healing of distal radial fractures with the use of specific, low-intensity ultrasound. A multicenter, prospective, randomized, double-blind, placebo-controlled study.Journal of Bone and Joint Surgery (American) · 1997 · 79(7):961-73doi:10.2106/00004623-199707000-00002 · PMID 9234872

    60 patients, 61 dorsally angulated distal radius fractures in casts, 30 active and 31 placebo devices 20 minutes daily for ten weeks: time to union 61 ± 3 against 98 ± 5 days (p < 0.0001) and less loss of reduction (20 ± 6% against 43 ± 8%). The second pivotal trial, with the same company author.

66. 66
    Shamos MH, Lavine LS. Piezoelectricity as a fundamental property of biological tissues.Nature · 1967 · 213(5073):267-9doi:10.1038/213267a0 · PMID 6030604

    No abstract in the record; indexed under cartilage, dentin, skin, cat, swine and human tissue. Cited for the 1967 claim that piezoelectricity is general to oriented biological tissue, which is true of dried, oriented samples and says nothing about function.

67. 67
    Pollack SR, Salzstein R, Pienkowski D. The electric double layer in bone and its influence on stress-generated potentials.Calcified Tissue International · 1984 · 36 Suppl 1:S77-81doi:10.1007/BF02406138 · PMID 6430528

    The zeta potential of bone, the charge at the fluid-matrix interface, reverses at high sodium or potassium chloride; the authors note the double layer may even contaminate dry-bone piezoelectric measurements because charged species remain on the matrix after drying.

68. 68
    Sharrard WJ. A double-blind trial of pulsed electromagnetic fields for delayed union of tibial fractures.Journal of Bone and Joint Surgery (British) · 1990 · 72(3):347-55doi:10.1302/0301-620X.72B3.2187877 · PMID 2187877

    45 conservatively treated tibial fractures with union delayed 16 to 32 weeks; 20 active and 25 dummy units for 12 weeks in casts. Blinded radiologist: union in 5, progress in 5, no progress in 10 of the active group against 1, 1 and 23 in controls (p = 0.002); blinded surgeon: union 9 of 20 against 3 of 25 (p = 0.02). Small but properly blinded; the groups differed in age, though the paper reports that age did not affect the outcome and the treatment effect was consistent in each age group.

69. 69
    Otter MW, Palmieri VR, Wu DD, Seiz KG, MacGinitie LA, Cochran GV. A comparative analysis of streaming potentials in vivo and in vitro.Journal of Orthopaedic Research · 1992 · 10(5):710-9doi:10.1002/jor.1100100513 · PMID 1500983

    Streaming potentials at one site on intact canine tibia in vivo compared with the same site excised and soaked: in vitro signals per periosteal strain were larger in 13 tibias, by an average of 6.5 times at 1 Hz. The authors warn against extrapolating either measurement to field strengths at the cellular level.

70. 70
    Zheng J, Shen W, He DZ, Long KB, Madison LD, Dallos P. Prestin is the motor protein of cochlear outer hair cells.Nature · 2000 · 405(6783):149-55doi:10.1038/35012009 · PMID 10821263

    Identification of prestin, expressed specifically in outer hair cells; cultured human kidney cells expressing it change shape with voltage and show the nonlinear capacitance (gating charge) of the outer hair cell motor. The protein that lets these cells change length with voltage.

71. 71
    Liberman MC, Gao J, He DZ, Wu X, Jia S, Zuo J. Prestin is required for electromotility of the outer hair cell and for the cochlear amplifier.Nature · 2002 · 419(6904):300-4doi:10.1038/nature01059 · PMID 12239568

    Mice with prestin deleted lost outer hair cell electromotility in vitro and 40-60 dB of cochlear sensitivity in vivo, with mechano-electrical transduction intact; heterozygotes had halved electromotility and about 6 dB higher thresholds. Mouse genetics.

72. 72
    Habelitz S, Rodriguez BJ, Marshall SJ, Marshall GW, Kalinin SV, Gruverman A. Peritubular dentin lacks piezoelectricity.Journal of Dental Research · 2007 · 86(9):908-11doi:10.1177/154405910708600920 · PMID 17720865

    Piezoresponse force microscopy of human dentin at 10 nm resolution: the intertubular matrix is piezoelectric, fibril by fibril, while the peritubular dentin around each tubule gives no response, supporting the view that it is a non-collagenous tissue. Piezoelectricity used as a probe for collagen, not as a function.

73. 73
    Minary-Jolandan M, Yu MF. Uncovering nanoscale electromechanical heterogeneity in the subfibrillar structure of collagen fibrils responsible for the piezoelectricity of bone.ACS Nano · 2009 · 3(7):1859-63doi:10.1021/nn900472n · PMID 19505115

    High-resolution piezoresponse microscopy showing that piezoelectricity varies along a collagen fibril with its gap and overlap periodicity, and that the pattern persists in fibrils embedded in bone. Structural observation; the roles proposed are the authors' implications.

74. 74
    Mollon B, da Silva V, Busse JW, Einhorn TA, Bhandari M. Electrical stimulation for long-bone fracture-healing: a meta-analysis of randomized controlled trials.Journal of Bone and Joint Surgery (American) · 2008 · 90(11):2322-30doi:10.2106/JBJS.H.00111 · PMID 18978400

    Opens by sizing bone stimulation as a $500 million market in the United States; eleven eligible trials, and in four trials of 106 delayed or ununited fractures a pooled relative risk of 1.76 (95% CI 0.8 to 3.8; p = 0.15; I² 60.4%). Concludes the effect on healing remains uncertain.

75. 75
    Schandelmaier S, Kaushal A, Lytvyn L, Heels-Ansdell D, Siemieniuk RA, Agoritsas T, Guyatt GH, Vandvik PO, Couban R, Mollon B, Busse JW. Low intensity pulsed ultrasound for bone healing: systematic review of randomized controlled trials.BMJ · 2017 · 356:j656doi:10.1136/bmj.j656 · PMID 28348110

    26 trials, median size 30 (range 8 to 501): no effect on return to work (2.7% later, 95% CI 7.7% earlier to 14.3% later) or reoperation (risk ratio 0.80, 0.55 to 1.16); among trials at low risk of bias, no effect on weight bearing, pain or radiographic healing (1.7% earlier, 11.2% earlier to 8.8% later), while high-risk trials suggested benefit, interaction P < 0.001. The review behind the rapid recommendation.

76. 76
    Tarride JE, Hopkins RB, Blackhouse G, Burke N, Bhandari M, Johal H, Guyatt GH, Busse JW. Low-intensity pulsed ultrasound for treatment of tibial fractures: an economic evaluation of the TRUST study.Bone & Joint Journal · 2017 · 99-B(11):1526-1532doi:10.1302/0301-620X.99B11.BJJ-2017-0737 · PMID 29092994

    At a device cost of $3,995 (2015 Canadian dollars) LIPUS added a mean $3,647 per patient from the payer perspective (95% CI $3,244 to $4,070) and gained 0.023 quality-adjusted life years (-0.035 to 0.069), an incremental cost of $155,433 per quality-adjusted life year: not cost-effective for fresh tibial fractures.

77. 77
    Haelterman N, Lim J. Sensing the load.eLife · 2019 · 8:e50210doi:10.7554/eLife.50210 · PMID 31588900

    Commentary on the Piezo1 bone papers asking how the skeleton detects and adapts to the load it carries. A comment, not data.

78. 78
    Searle HKC, Lewis SR, Coyle C, Welch M, Griffin XL. Ultrasound and shockwave therapy for acute fractures in adults.Cochrane Database of Systematic Reviews · 2023 · 3(3):CD008579doi:10.1002/14651858.CD008579.pub4 · PMID 36866917

    Update to March 2022: 21 studies, 1,543 fractures in 1,517 participants, 20 of LIPUS; quality of life mean difference 0.06 on SF-36 (95% CI -3.85 to 3.97; very low certainty), return to work 1.96 days later with LIPUS (-2.13 to 6.04; low certainty), delayed or nonunion risk ratio 1.25 (0.50 to 3.09; moderate certainty), time to union not pooled for unexplained heterogeneity. Probably little or no difference.

79. 79
    Liu G, Sun J, Xie W, Li H, Yang G, Ji B, Yao Y, Li Y, Yang X, Xiao W. Comparative Efficacy of Electrical Stimulation Therapies for Bone Healing: A Network Meta-analysis of Randomized Controlled Trials.American Journal of Physical Medicine & Rehabilitation · 2026 · (epub 7 Oct)doi:10.1097/PHM.0000000000003169 · PMID 42839336

    37 randomized trials, 3,325 subjects, searched to 2 January 2025: electrical stimulation overall risk ratio 1.18 (95% CI 1.09 to 1.28) for bone healing, PEMF risk ratio 1.20 (1.02 to 1.41), combined magnetic fields risk ratio 1.49 (1.14 to 1.95); the authors still call for high-quality trials. Published this month.

80. 80
    Côté-Picard C, Dupuis F, Gagnon M, Côté AA, Ducharme É, Lantier P, Morin M, Massé-Alarie H. The use of low-intensity pulsed ultrasound for the treatment of established nonunion fractures: A systematic review and meta-analysis.Medicine (Baltimore) · 2026 · 105(24):e49098doi:10.1097/MD.0000000000049098 · PMID 42299555

    Searched to 6 May 2025: 30 observational studies (3,437 participants) pooled to a healing proportion of 0.79 (95% CI 0.73 to 0.85) with I² 92% and very low certainty, but the three randomized trials (264 participants) gave risk ratio 1.13 (0.93 to 1.37; P = .23) and a healing-time difference of 14.99 days (-120.37 to 150.35). Does not support LIPUS as first-line treatment for established nonunion; the uncontrolled 80% figure does not survive randomization.

81. 81
    Magida N, Myezwa H, Mudzi W, Musenge E, Mohamed Khan SA, Graham MA. Efficacy of low-intensity pulsed ultrasound in surgically managed lower limb fractures: a randomised controlled trial.Acta Orthopaedica Belgica · 2026 · 92(1)doi:10.52628/92.1.12938 · PMID 42012031

    Double-blind randomized trial in two hospitals in Gauteng, South Africa: 94 adults with lower-limb fractures given 20-minute LIPUS sessions on alternate days for 20 days in hospital, or standard care; no difference in callus, cortical bridging, fracture gap or overall radiographic healing at 6, 12 or 18 weeks. Heavy loss to follow-up and missing radiographs reduced its power.

82. 82
    Haque ARA, Hali NZ, Khan ZA, Zain-Ur-Rehman M, Quadri STAA, Mathur K. Exogen Therapy for the Treatment of Non-unions: A Single-Centre UK Experience.Indian Journal of Orthopaedics · 2026 · 60(9):2452-2460doi:10.1007/s43465-026-01771-9 · PMID 42824624

    Retrospective review of a UK hospital device registry: 44 patients with 46 nonunions treated with the Exogen LIPUS device; union in 54.4% (25 of 46), 57.6% after fractures and 46.2% after osteotomies or fusions, better when the site had been plated than nailed. The authors say this falls short of the success rates cited in NICE guidance and systematic review but matches other single-center series. Uncontrolled.

83. 83
    Retraction: Assessment of Cognitive-Motor Functions in Adults With Perceived Neuropsychological Problems Using NIH Toolbox After Remote Biofield Energy Treatment as Non-Pharmacological Intervention: A Randomized Double-Blind Placebo Controlled Trial.Neuropsychopharmacology Reports · 2026 · 46(1):e70098doi:10.1002/npr2.70098 · PMID 41703379

    Retraction notice for Trivedi MK, Branton A, Trivedi D, Mondal S, Jana S, Neuropsychopharmacol Rep 2024;44(4):749-761: its design, methods, results and conclusions were essentially the same as another article by the same group published that year without attribution, and it contains physiologically implausible data and statistical anomalies; the editors consider its results invalid, and the authors do not agree with the retraction.

84. 84
    Marino AA, Becker RO. Piezoelectricity in bone as a function of age.Calcified Tissue Research · 1974 · 14(4):327-31doi:10.1007/BF02060307 · PMID 4527112

    No abstract in the record; indexed under human femur and tibia, aging, osteosarcoma and paleontology. Cited for its existence as part of the dry-bone measurement program.

85. 85
    Marino AA, Becker RO. Piezoelectricity and autoinduction.Clinical Orthopaedics and Related Research · 1974 · (100):247-9PMID 4838405

    No abstract and no DOI in the record; indexed under bone matrix, collagen, hydrochloric acid, nitrates and osteogenesis in cattle. Cited for the hypothesis in its title: that bone's own electricity induces bone.

86. 86
    Lang SB, Tofail SA, Kholkin AL, Wojtaś M, Gregor M, Gandhi AA, Wang Y, Bauer S, Krause M, Plecenik A. Ferroelectric polarization in nanocrystalline hydroxyapatite thin films on silicon.Scientific Reports · 2013 · 3:2215doi:10.1038/srep02215 · PMID 23884324

    Piezoresponse force microscopy showing that the polarization of nanocrystalline synthetic hydroxyapatite films can be reversed by an electric field (ferroelectricity), building on earlier reports of strong piezoelectricity and pyroelectricity in such films. Synthetic thin films on silicon, not bone mineral.

87. 87
    Fukada E, Ando Y. Bending piezoelectricity in a microbially produced poly-beta-hydroxybutyrate.Biorheology · 1988 · 25(1-2):297-302doi:10.3233/bir-1988-251-239 · PMID 3196826

    A bacterial storage polymer showed a bending piezoelectric coefficient of the order of 10^-18 C·m/N, which the authors note is similar to the value reported for bone. Cited to show how small bone's coefficient is on an absolute scale.

88. 88
    Denning D, Kilpatrick JI, Fukada E, Zhang N, Habelitz S, Fertala A, Gilchrist MD, Zhang Y, Tofail SAM, Rodriguez BJ. Piezoelectric Tensor of Collagen Fibrils Determined at the Nanoscale.ACS Biomaterials Science & Engineering · 2017 · 3(6):929-935doi:10.1021/acsbiomaterials.7b00183 · PMID 33429565

    Rat tail tendon sectioned at 0, 59 and 90 degrees to the fibril axis and probed by piezoresponse force microscopy; the longitudinal coefficient of a single fibril is roughly an order of magnitude greater than that reported for whole tendon, because oppositely oriented fibrils cancel. Fukada, then in his nineties, is a coauthor.

89. 89
    Marino AA, Becker RO. Piezoelectricity in hydrated frozen bone and tendon.Nature · 1975 · 253(5493):627-8doi:10.1038/253627a0 · PMID 1113852

    No abstract in the record; bovine femur and tendon, frozen while hydrated. Cited as the attempt to rescue a piezoelectric signal from wet tissue by freezing the water that otherwise conducts it away.

90. 90
    Maeda H, Fukada E. Effect of water on piezoelectric, dielectric, and elastic properties of bone.Biopolymers · 1982 · 21(10):2055-68doi:10.1002/bip.360211010 · PMID 7171727

    No abstract in the record; bovine bone. Cited for its existence as the systematic water study from Fukada's laboratory.

91. 91
    Mohammadkhah M, Slavkovic V, Klinge S. Flexoelectricity in Biological Materials and Its Potential Applications in Biomedical Research.Bioengineering (Basel) · 2025 · 12(6):579doi:10.3390/bioengineering12060579 · PMID 40564396

    Review of flexoelectric effects in cells and cell membranes, hearing mechanisms and bone, with emphasis on bone remodeling; the authors call the field relatively new and still developing. Engineering review.

92. 92
    Johnson MW, Williams WS, Gross D. Ceramic models for piezoelectricity in dry bone.Journal of Biomechanics · 1980 · 13(7):565-73doi:10.1016/0021-9290(80)90057-3 · PMID 7400185

    No abstract in the record; bovine bone compared with ceramic models. Cited for its existence as the dry-bone modeling that preceded the wet-bone correction from the same group.

93. 93
    Marcer M, Musatti G, Bassett CA. Results of pulsed electromagnetic fields (PEMFs) in ununited fractures after external skeletal fixation.Clinical Orthopaedics and Related Research · 1984 · (190):260-5PMID 6488642

    147 patients, average 3.3 failed operations, treated with external fixation plus PEMF: 107 united (73%); femur 81%, tibia 75%, humerus 5 of 13. No control group. No DOI in the record.

94. 94
    Bassett CA, Schink-Ascani M. Long-term pulsed electromagnetic field (PEMF) results in congenital pseudarthrosis.Calcified Tissue International · 1991 · 49(3):216-20doi:10.1007/BF02556121 · PMID 1933587

    91 patients with congenital pseudarthrosis of the tibia treated since 1973: 43 of 60 (72%) type I and II lesions healed, only 6 of 31 (19%) type III, and 16 of 91 limbs (18%) were ultimately amputated. Uncontrolled series; the authors' claim of no known risk is an assertion.

95. 95
    Aleem IS, Aleem I, Evaniew N, Busse JW, Yaszemski M, Agarwal A, Einhorn T, Bhandari M. Efficacy of Electrical Stimulators for Bone Healing: A Meta-Analysis of Randomized Sham-Controlled Trials.Scientific Reports · 2016 · 6:31724doi:10.1038/srep31724 · PMID 27539550

    Fifteen sham-controlled trials: pain lower by 7.7 mm on a 100 mm scale (95% CI -13.92 to -1.43; four trials), no difference in function (two trials), and radiographic nonunion reduced by 35% (95% CI 19 to 47%; number needed to treat 7), all graded moderate quality. A radiographic endpoint with little patient-important data behind it.

96. 96
    Hannemann PF, Mommers EH, Schots JP, Brink PR, Poeze M. The effects of low-intensity pulsed ultrasound and pulsed electromagnetic fields bone growth stimulation in acute fractures: a systematic review and meta-analysis of randomized controlled trials.Archives of Orthopaedic and Trauma Surgery · 2014 · 134(8):1093-106doi:10.1007/s00402-014-2014-8 · PMID 24895156

    737 patients in 13 trials of PEMF or LIPUS for fresh fractures: no difference in the proportion of nonunion; time to radiographic union favored the devices only in non-operatively treated or upper-limb fractures, with heterogeneous results.

97. 97
    Picelli A, Di Censo R, Tomasello S, Scaturro D, Letizia Mauro G, Smania N, Filippetti M. Effects of pulsed electromagnetic fields on bone fractures: a systematic review update.European Journal of Physical and Rehabilitation Medicine · 2024 · 60(6):989-994doi:10.23736/S1973-9087.24.08226-1 · PMID 39387850

    Three randomized trials from 2014 to 2022, 197 patients in all: none found a significant effect of PEMF on healing of acute fractures, with contradictory results on pain. Does not support PEMF for acute fractures.

98. 98
    Yang J, Zhang X, Liang W, Chen G, Ma Y, Zhou Y, Fen R, Jiang K. Efficacy of adjuvant treatment for fracture nonunion/delayed union: a network meta-analysis of randomized controlled trials.BMC Musculoskeletal Disorders · 2022 · 23(1):481doi:10.1186/s12891-022-05407-5 · PMID 35597937

    Thirty randomized trials: ultrasound shortened healing time against cancellous bone graft (standardized mean difference -9.26, 95% CI -14.64 to -3.87), while electromagnetic fields (odds ratio 13.21, 95% CI 1.58 to 110.40) and shock wave (odds ratio 4.90, 1.38 to 17.43) carried a higher risk of adverse events than control. Network meta-analysis, wide intervals.

99. 99
    Li L, Yang L, Yang Y, Zhu J, Shi R, Deng Q, Wang J, Sun F. Evaluation of the efficacy of physical agent modalities in patients with fractures: a systematic review and network meta-analysis.Frontiers in Medicine (Lausanne) · 2025 · 12:1646903doi:10.3389/fmed.2025.1646903 · PMID 41244766

    39 randomized trials, 2,379 participants, to April 2025, seven modalities pooled together: pain relief mean difference 1.30 (95% CI 0.61 to 1.99), healing time 21.58 days shorter (-31.05 to -12.11), complete healing risk ratio 1.37 (1.17 to 1.60); but nearly every head-to-head comparison in the network crossed the null. Pooling unlike devices is the main weakness.

100. 100
     Miyamoto H, Sawaji Y, Iwaki T, Masaoka T, Fukada E, Date M, Yamamoto K. Intermittent pulsed electromagnetic field stimulation activates the mTOR pathway and stimulates the proliferation of osteoblast-like cells.Bioelectromagnetics · 2019 · 40(6):412-421doi:10.1002/bem.22207 · PMID 31338867

     Mouse osteoblast-like MC3T3-E1 cells: intermittent PEMF (10 minutes on, 20 off) sustained mTOR phosphorylation and favored proliferation over differentiation. Cell line; the proposed mechanism does not involve piezoelectricity at all.

101. 101
     Iwaki T, Sawaji Y, Masaoka T, Fukada E, Date M, Yamamoto K. Investigation of the effectiveness of intermittent electromagnetic field stimulation for early internal cartilaginous ossification in prechondrocytic ATDC5 cells.Bioelectromagnetics · 2024 · 45(5):226-234doi:10.1002/bem.22501 · PMID 38546158

     Mouse prechondroblast cells: intermittent PEMF kept the mTOR pathway active and increased proliferation. Cell line only; cited for the mechanism claim and for Fukada's name on a 2024 paper, 67 years after his bone measurement.

102. 102
     Charles R, Vlasak A, Turner T, Romero J, Bondi E. Extracorporeal magnetotransduction therapy as an adjunctive and primary modality for bone healing: a scoping review of current evidence.Electromagnetic Biology and Medicine · 2026 · 45(3):313-320doi:10.1080/15368378.2026.2648306 · PMID 41885227

     Nine studies of a newer, stronger magnetic device: two in vitro, six case reports and one pilot trial, with faster union and pain relief reported. The evidence base is case reports; the authors acknowledge small samples, publication bias and confounding co-treatments. PubMed's record mis-parses the author names with their degrees (for example 'Rohan Charles BS'); the authors are at the Mayo Clinic Department of Orthopedic Surgery.

103. 103
     Saxena A, Bondi E, Gerdesmeyer L, Leal C, Knobloch K, Maffulli N, Gerdesmeyer L, Tenforde AS. Focused shock wave therapy (ESWT) and electromagnetic transduction therapy (EMTT) may improve post-operative bone healing in selective foot and ankle surgeries: a case-control pilot study.Journal of Orthopaedic Surgery and Research · 2025 · 20(1):1018doi:10.1186/s13018-025-06420-9 · PMID 41267064

     Ten foot and ankle surgery patients given shock wave plus magnetic transduction, matched to ten controls: pain at weight bearing 0.2 ± 0.4 against 3.1 ± 1.3, return to activity 13.2 ± 2.9 against 22.4 ± 9.2 weeks, radiographic healing at four weeks 8 of 10 against 2 of 10. Unblinded, matched, twenty patients, named commercial devices.

104. 104
     Scaturro D, Tomasello S, Barberi MT, Re GL, Mauro GL. Combined Nutraceutical Supplementation and Pulsed Electromagnetic Field Therapy Enhances Early Pain Reduction and Bone Callus Formation After Distal Radius Fracture: A Randomized Controlled Trial.Nutrients · 2026 · 18(12):2010doi:10.3390/nu18122010 · PMID 42356396

     Sixty women after distal radius fracture randomized to PEMF alone or PEMF plus a supplement; the authors state that without a non-PEMF arm the independent effect of PEMF cannot be determined. Cited for that admission.

105. 105
     Enriquez-Marulanda A, Sakthiyendran NA, Gonzalez-Salido J, Perkins T, Sconzo D, Ramirez-Velandia F, Berube M, Avery MA, Powers AY, Im J, Yazdanian F, Alwakaa O, Terry-Escalante F, Syed BA, Stippler M, Papavassiliou E, Moses ZB, Binello E. Pulsed Electromagnetic Field Bone Growth Stimulation Improves Union Outcomes in Type II Odontoid Fractures: Insights from a Multicenter Propensity-Matched Pilot Study.Spine (Phila Pa 1976) · 2026 · (epub 24 Jun)doi:10.1097/BRS.0000000000005778 · PMID 42390981

     Retrospective cohort at two Boston centers, 2014-2024: 321 patients (median age 80), 20 given a PEMF stimulator; in the propensity-matched cohort union was 68.4% (19 patients) against 13% (29 patients), with no difference in pain, modified Rankin Scale, complications or mortality. Small and nonrandomized; the authors call for a prospective, adherence-tracked study.

106. 106
     Adams W, Bromson MS, Lin D, Perez D, Gonzalez O. Pulsed Electromagnetic Field (PEMF) Stimulation for the Treatment of Fifth Metatarsal Fracture Nonunion.Orthopedic Reviews (Pavia) · 2026 · 18:150312doi:10.52965/001c.150312 · PMID 42305571

     Multicenter retrospective series of 56 fifth-metatarsal nonunions (89.3% women, mean age 59.7) treated with the PhysioStim device: 62.5% healed by 4 months, 75.0% by 6 and 91.1% by 12; nicotine use was associated with longer healing. No comparison group.

107. 107
     Sheaffer K. Bone Growth Stimulators in Orthopedic Trauma: History, Mechanisms, and Clinical Applications.Orthopedic Clinics of North America · 2026 · 57(3):211-221doi:10.1016/j.ocl.2026.02.004 · PMID 42270187

     Narrative review stating that pulsed electromagnetic field, capacitive coupling, combined magnetic field, direct current and LIPUS devices have been shown to accelerate healing, and recommending their integration into trauma protocols. Cited as an example of the pre-TRUST view persisting in 2026, not for its conclusions.

108. 108
     Griffin XL, Parsons N, Costa ML, Metcalfe D. Ultrasound and shockwave therapy for acute fractures in adults.Cochrane Database of Systematic Reviews · 2014 · 2014(6):CD008579doi:10.1002/14651858.CD008579.pub3 · PMID 24956457

     Twelve studies, 622 participants, 648 fractures: no significant reduction in time to union with LIPUS (standardized mean difference -0.47, 95% CI -1.14 to 0.20; I² 90%), delayed or nonunion 10 of 168 against 13 of 165 (risk ratio 0.75, 0.24 to 2.28). Insufficient to support routine use, before TRUST reported.

109. 109
     Busse JW, Bhandari M, Einhorn TA, Heckman JD, Leung KS, Schemitsch E, Tornetta P, Walter SD, Guyatt GH. Trial to re-evaluate ultrasound in the treatment of tibial fractures (TRUST): a multicenter randomized pilot study.Trials · 2014 · 15:206doi:10.1186/1745-6215-15-206 · PMID 24898987

     51 adults in a blinded sham-controlled pilot: recruitment about 0.8 patients per center per month, 84% follow-up at one year, device timers showing 76% fully compliant. Feasibility study that set up the definitive trial; Heckman, author of the 1994 trial, is a coauthor.

110. 110
     Leighton R, Watson JT, Giannoudis P, Papakostidis C, Harrison A, Steen RG. Healing of fracture nonunions treated with low-intensity pulsed ultrasound (LIPUS): A systematic review and meta-analysis.Injury · 2017 · 48(7):1339-1347doi:10.1016/j.injury.2017.05.016 · PMID 28532896

     Thirteen mostly uncontrolled studies, 1,441 nonunions: pooled healing 82% (95% CI 77 to 87%) with I² 71. Two of the six authors are employees of Bioventus, the device's maker, and the paper argues that randomized trials of nonunion are hard to do; a commercial conflict stated on the paper.

111. 111
     Wang Y, Zhuang W, Lei B, Zhang D, Ma S, Wang H, Han Q. Efficacy and safety of biological agents and physical therapies for delayed union or nonunion of fractures: a network meta-analysis of randomized controlled trials.BMC Musculoskeletal Disorders · 2026 · 27(1)doi:10.1186/s12891-026-09973-w · PMID 42210142

     27 randomized trials, 1,495 patients, 15 interventions: LIPUS shortened healing time against cancellous bone graft (standardized mean difference -9.33, 95% CI -12.94 to -5.73), while bone marrow aspirate plus graft had the best healing rate (odds ratio 8.14 against graft alone, 1.69 to 39.32). The authors rate the evidence low.

112. 112
     Aaron RK, Ciombor DM, Simon BJ. Treatment of nonunions with electric and electromagnetic fields.Clinical Orthopaedics and Related Research · 2004 · (419):21-9doi:10.1097/00003086-200402000-00005 · PMID 15021127

     Review by proponents: in spine fusion trials union averaged 80% to 90% with active treatment against 65% to 75% with placebo; uncontrolled cohorts of delayed and nonunions report 75% to 85% union. The PubMed record lists an affiliation only for the first author (Brown Medical School); read as the case for the devices, not an independent appraisal.

113. 113
     Tian NF, Wu YS, Zhang XL, Mao FM, Xu HZ, Chi YL. Efficacy of electrical stimulation for spinal fusion: a meta-analysis of fusion rate.Spine Journal · 2013 · 13(10):1238-43doi:10.1016/j.spinee.2013.06.056 · PMID 23993034

     21 studies, 1,381 patients: pooled fusion 85% (95% CI 79 to 90) with direct current (14 studies) 85%, capacitive coupling (1 study) 90% and inductive coupling (10 studies) 85%. A pooled single-arm rate with no comparator, so it cannot show the devices do anything.

114. 114
     Park P, Lau D, Brodt ED, Dettori JR. Electrical stimulation to enhance spinal fusion: a systematic review.Evidence-Based Spine-Care Journal · 2014 · 5(2):87-94doi:10.1055/s-0034-1386752 · PMID 25278882

     Six randomized trials of lumbar fusion (three direct current, three PEMF, one capacitive): fusion 35.4% to 90.6% with stimulation against 33.3% to 81.9% in controls over 9 to 24 months, too heterogeneous to pool; unable to conclude benefit, overall strength of evidence low.

115. 115
     Khare D, Basu B, Dubey AK. Electrical stimulation and piezoelectric biomaterials for bone tissue engineering applications.Biomaterials · 2020 · 258:120280doi:10.1016/j.biomaterials.2020.120280 · PMID 32810650

     Review of piezo-, pyro- and ferroelectric responses in bone and of piezoelectric bioceramics (barium titanate, magnesium silicate) and polymers (PVDF, collagen) as implants, singling out potassium sodium niobate as the implantable composition with the most attractive properties. Review written from the materials side; it accepts bone's own piezoelectricity as functional.

116. 116
     Donald I, MacVicar J, Brown TG. Investigation of abdominal masses by pulsed ultrasound.Lancet · 1958 · 1(7032):1188-95doi:10.1016/s0140-6736(58)91905-6 · PMID 13550965

     No abstract in the record. Cited for the existence and date of an early clinical report of diagnostic pulsed ultrasound.

117. 117
     Zhao J, Huang Y, Zhang Y, Xie Y, Guo W, Li Y, Wang S. Ultrasound Patches Toward Intelligent Theranostics: From Flexible Materials to Closed-Loop Biomedical Systems.Bioengineering (Basel) · 2026 · 13(3):345doi:10.3390/bioengineering13030345 · PMID 41899876

     Review of wearable ultrasound patches built on flexible piezoelectric polymers, lead-free ceramics and composites: transducer arrays with focal spots near 200 μm, continuous cardiovascular monitoring to 164 mm depth for 12 hours, drug delivery and neuromodulation demonstrations. Engineering review, mostly preclinical.

118. 118
     Chu Y, Naderi A, Wu H, Xue X, Oelze ML, Jiang X. Recent advances in transducers for through-tissue ultrasonic power transfer.Progress in Biomedical Engineering (Bristol) · 2026 · 8(2)doi:10.1088/2516-1091/ae5f8a · PMID 41983539

     Review of transducers that send power through tissue to implants by ultrasound, from bulk piezoelectrics including lead-free options to micromachined and polymer devices, with attenuation, misalignment and packaging as the open problems. Engineering review.

119. 119
     Chaussy C, Brendel W, Schmiedt E. Extracorporeally induced destruction of kidney stones by shock waves.Lancet · 1980 · 2(8207):1265-8doi:10.1016/s0140-6736(80)92335-1 · PMID 6108446

     The first report of shock-wave lithotripsy: fragments passed in 96% of 60 dogs with implanted stones and in 20 of 21 patients with renal pelvic stones, with hematuria and ureteral colic as side effects. The Munich machine used an electrohydraulic spark, not a piezoelectric source; piezoelectric lithotripters came later.

120. 120
     Noureldin YA, Abdel Halim WA, Elnahif E, El Shaer A, Shaher H, Abdel Fattah AAE, Hashem A, El-Dakhakhny AS, Zahran AA, El Hamshary SA. The effect of piezoelectric shockwave lithotripsy with 2- and 8-mm focus sizes on stone disintegration and renal injury.BJU International · 2023 · 132(4):404-410doi:10.1111/bju.16083 · PMID 37216189

     Double-blind randomized trial in 135 adults with a solitary 1-2 cm renal pelvic stone treated by piezoelectric shock-wave lithotripsy: stone-free 79.2% (narrow 2 mm focus) and 69.1% (wide 8 mm) after one session, 86.6% and 86.8% after three; the narrow focus caused more pain, more high-grade hematuria and a larger early rise in a urinary kidney-injury marker. A clinical outcome for piezoelectric lithotripsy.

121. 121
     Sihombing AT, Wijayanti Z, Steven S, Stefanus D. Uncovering New Horizons: Update to Quadruple-D Score to Predict Stone-Free Rate with Advanced Non-invasive Lithotripsy Technology.Urology Research & Practice · 2025 · 51(1):38-42doi:10.5152/tud.2025.24152 · PMID 40434748

     Prospective observational study in Bandung, Indonesia, in 2023: 40 patients with 5-20 mm kidney stones treated on a Piezolith 3000 Plus piezoelectric lithotripter; 75% stone-free at four weeks. No comparison group; the paper's aim is a predictive score.

122. 122
     Vercellotti T. Piezoelectric surgery in implantology: a case report--a new piezoelectric ridge expansion technique.International Journal of Periodontics & Restorative Dentistry · 2000 · 20(4):358-65PMID 11203575

     Single case: modulated-frequency piezoelectric scalpels used to split and widen a 2-3 mm ridge of jawbone so implants could be placed in one stage; the ridge had mineralized at 5 mm at three months. A technique report, not a trial. No DOI in the record.

123. 123
     Liu J, Hua C, Pan J, Han B, Tang X. Piezosurgery vs conventional rotary instrument in the third molar surgery: A systematic review and meta-analysis of randomized controlled trials.Journal of Dental Sciences · 2018 · 13(4):342-349doi:10.1016/j.jds.2016.09.006 · PMID 30895143

     Five randomized trials, 402 patients: with the piezoelectric bone cutter, pain at days 6 to 7 lower (standardized mean difference -0.33, 95% CI -0.56 to -0.10), swelling at day 7 lower (standardized mean difference -1.95, -3.22 to -0.67), mouth opening at day 1 better (standardized mean difference 0.84), but operation time 6.23 minutes longer (3.32 to 9.14). Modest, consistent, and about a tool rather than a biological effect.

124. 124
     Li X, Lin X, Guo J, Wang Y. The Stability and Survival Rate of Dental Implants After Preparation of the Site by Piezosurgery vs Conventional Drilling: A Systematic Review and Meta-Analysis.International Journal of Oral & Maxillofacial Implants · 2020 · 30(3):e51-e56doi:10.11607/jomi.5913 · PMID 32406651

     Five prospective studies: implant survival no different (risk ratio 0.98, 95% CI 0.94 to 1.03), stability scores higher at 8 weeks (mean difference 4.24, 1.36 to 7.12) and 12 weeks (mean difference 3.33, 0.59 to 6.08) with piezoelectric site preparation. Small literature.

125. 125
     Zate TT, Abdurrahmanoglu C, Esposito V, Haugen AB. Textured Lead-Free Piezoelectric Ceramics: A Review of Template Effects.Materials (Basel) · 2025 · 18(3):477doi:10.3390/ma18030477 · PMID 39942142

     Review of textured barium titanate, potassium sodium niobate and bismuth sodium titanate ceramics as sustainable alternatives to lead-based systems such as PZT, some reaching properties that rival or surpass it. Materials science, not medicine.

126. 126
     Wang Z, Jiang A, Wang F, Yang Z, Zhong Y, Yang Y, Tan J, Han W, Li X, He X, Zhang X, Wang J, Han X, Bai D. A programmable spatiotemporal bioelectrical conduit promotes peripheral nerve regeneration by suppressing ferroptosis through modulation of ER-mitochondria coupling in Schwann cells.Bioactive Materials · 2026 · 68:734-757doi:10.1016/j.bioactmat.2026.08.024 · PMID 42781229

     A two-layer nerve conduit, barium titanate in a gelatin hydrogel outside for ultrasound-triggered charge and an aligned conductive fiber tube inside; in vivo repair approached autologous nerve grafting, with mechanisms traced through Schwann cell ferroptosis. Animal proof of concept, the species not named in the abstract.

127. 127
     Zhang Z, Guan X, Zhai Y, Lin H, Ying A, Lin J, Zhu C, Huang B, Chen N, Zhang K, Liu X, Ying J. An ultrasound-responsive hydrogel with piezoelectric-enhanced bioelectric-vesicular coupling alleviates mitochondrial dysfunction and inflammation for osteoarthritis therapy.Bioactive Materials · 2026 · 69:86-104doi:10.1016/j.bioactmat.2026.09.018 · PMID 42861280

     Potassium sodium niobate nanoparticles and engineered apoptotic bodies in an injectable hydrogel, activated by low-intensity ultrasound; in a destabilized-meniscus model of osteoarthritis, cartilage degeneration and subchondral bone changes were reduced. Animal model; a lead-free piezoelectric used as an ultrasound-driven stimulator.

128. 128
     Han S, Zhang D, Kao Y, Zhou X, Guo X, Zhang W, Liu M, Chen H, Kong X, Wei Z, Liu H, Feng S. Trojan Horse Strategy for Wireless Electrical Stimulation-Induced Zn2+ Release to Regulate Neural Stem Cell Differentiation for Spinal Cord Injury Repair.ACS Nano · 2024 · 18(47):32517-32533doi:10.1021/acsnano.4c08863 · PMID 39527695

     Barium titanate nanoparticles coated with polydopamine and zinc, taken up by mouse neural stem cells and driven by ultrasound to release zinc; neurons matured in 5 days instead of 10, and transplanted cells aided recovery after spinal cord injury in vivo. Mouse cells and an animal model.

129. 129
     Kojima Y, Niimi N, Ikushima K, Yabe Y, Hagiwara Y. Detection of Osteoporotic Changes in Rat Femoral Bone Using the Acoustically Stimulated Electromagnetic (ASEM) Method.Ultrasound in Medicine & Biology · 2026 · 52(12):2845-2854doi:10.1016/j.ultrasmedbio.2026.08.019 · PMID 42778440

     Ultrasound drives bone's collagen piezoelectricity at radio frequency and an antenna picks up the resulting field; signal was lower in femurs of diabetic Goto-Kakizaki rats and of cast-immobilized rats, and the reduction persisted after decalcification; correlation with breaking displacement r = 0.499, p = 0.058. Excised rat bone; authors affiliated with three companies developing the method.

130. 130
     Fukada E. Electro-biorheology.Biorheology · 1984 · 21(1-2):75-84doi:10.3233/bir-1984-211-212 · PMID 6466798

     Review by Fukada: piezoelectric anisotropy used to map collagen orientation in fish skin; a film of poly-gamma-methyl-L-glutamate wrapped around a rat femur produced new bone. The rat result is the ancestor of every 'self-powered' scaffold on this page.

131. 131
     Marino A, Arai S, Hou Y, Sinibaldi E, Pellegrino M, Chang YT, Mazzolai B, Mattoli V, Suzuki M, Ciofani G. Piezoelectric Nanoparticle-Assisted Wireless Neuronal Stimulation.ACS Nano · 2015 · 9(7):7678-89doi:10.1021/acsnano.5b03162 · PMID 26168074

     Tetragonal (piezoelectric) barium titanate nanoparticles on SH-SY5Y neuron-like cells produced calcium and sodium fluxes when ultrasound was applied, blocked by channel blockers, while cubic (non-piezoelectric) particles did nothing. Cell culture with a built-in material control; the origin of ultrasound-driven piezoelectric stimulation.

132. 132
     Han M, Yildiz E, Bozuyuk U, Aydin A, Yu Y, Bhargava A, Karaz S, Sitti M. Janus microparticles-based targeted and spatially-controlled piezoelectric neural stimulation via low-intensity focused ultrasound.Nature Communications · 2024 · 15(1):2013doi:10.1038/s41467-024-46245-4 · PMID 38443369

     20 μm two-faced particles, one half barium titanate and one half magnetic, steered by magnetic fields and driven by low-intensity focused ultrasound to stimulate primary neurons, with antibodies targeting dopaminergic cells. Cell culture; a design study.

133. 133
     Li J, Wu Y, Huang X, Zhang S, Chang S, Wang P. Liquid metal-ZnO enhanced piezoelectric PVDF Nanofibrous nerve guidance conduit: Self-powered electrical stimulation for accelerated peripheral nerve regeneration.Biomaterials Advances · 2025 · 180:214566doi:10.1016/j.bioadv.2025.214566 · PMID 41166962

     Electrospun PVDF conduits with liquid metal and zinc oxide raised the piezoelectric coefficient from 0.9 to 4.6 pC/N; in Sprague-Dawley rats with sciatic nerve injury, functional recovery improved and the neurotrophic factor neurotrophin-3 (NT-3) rose. Rat study; the 'self-powered' version pairs the conduit with a nanogenerator and was tested only in cells.

134. 134
     Li Y, Shi Y, Pak YL, Liu Q, Gao X, Meng F, Liang J, Ma W, Wang Z, Wang P, Luo Y. Whitlockite: A biomineral from bone to bone repair.Biomaterials Advances · 2026 · 188:215049doi:10.1016/j.bioadv.2026.215049 · PMID 42413389

     Review of whitlockite, the magnesium-bearing calcium phosphate that is the second most abundant mineral in human bone after hydroxyapatite, including its intrinsic piezoelectricity and its use in 'self-powered' scaffolds. Review from the materials side.

135. 135
     Ma Z, Zou C, Zhang M, Zheng S, Liu Y, Jin Z, Feng H, Chen K, Wang L, Zhang J, Xu X, Li G, Sun X, Wu G. Ultrasound-responsive polydopamine-functionalized piezoelectric membranes for vascularized bone regeneration.Colloids and Surfaces B: Biointerfaces · 2026 · 268(Pt 2):116107doi:10.1016/j.colsurfb.2026.116107 · PMID 42647967

     Zinc oxide in polycaprolactone nanofibers with icariin attached; under low-intensity pulsed ultrasound the membrane promoted osteogenic and angiogenic behavior in culture and accelerated new bone in a rat calvarial defect. Rat study.

136. 136
     Ai Z, Li D, Tian Y, Zheng Y, Zhang C. The photothermal-piezoelectric dual-responsive antibacterial prosthesis interface regulates Schwann cell phenotypic conversion to promote the repair of infectious bone defects.Biomaterials · 2026 · 336:124494doi:10.1016/j.biomaterials.2026.124494 · PMID 42531892

     Black phosphorus quantum dots on graphitic carbon nitride in a hydrogel coating 3D-printed titanium prostheses; photothermal plus sonodynamic antibacterial effect; Schwann cells shifted to a repair phenotype and nerve-guided bone regeneration in infected defects. Animal study; species not named in the abstract.

137. 137
     Liu X, Zhang J, Xu B, Xu Y, Wang Y, Huang Z, Liu B, Song F. 3D-printed BaTiO3-modified PCL/β-TCP scaffolds with multimodal optimization for enhanced critical-size bone regeneration.Biomaterials Advances · 2026 · 189:215079doi:10.1016/j.bioadv.2026.215079 · PMID 42492350

     Polycaprolactone and beta-tricalcium phosphate scaffolds with 0 to 8% barium titanate: piezoresponse microscopy found a 'detectable but mild' local piezoelectric response whose bone-forming contribution 'was not isolated from other BT-related material effects'; the 4% scaffold gave more bone in a rat calvarial critical-size defect at 12 weeks. PubMed lists the first seven authors with given name and surname reversed (for example 'Xuanhao L'). Rat study.

138. 138
     Xue H, Jin J, Tan Z, Chen K, Lu G, Zeng Y, Hu X, Peng X, Jiang L, Wu J. Flexible, biodegradable ultrasonic wireless electrotherapy device based on highly self-aligned piezoelectric biofilms.Science Advances · 2024 · 10(22):eadn0260doi:10.1126/sciadv.adn0260 · PMID 38820150

     Gamma-glycine in polyvinyl alcohol films, 10.4 pC/N with a voltage coefficient of 324 × 10^-3 V·m/N, built into a bioresorbable device driven by ultrasound that shortened wound healing by about 40% in preclinical (animal) wound models. Animal data.

139. 139
     Wu Q, Wang T, Guo H, Zhu C, Chen Y, Xiao L, Cui H, Hu J, Xu S, Jia R, Fang C, Yang J, Zhang K. Stromal Cells Recruitment by Sono-Piezoelectric/Pyroelectric Peptide Hydrogels Promotes Bone Regeneration After Postsurgical Osteosarcoma Recession: A Real-World-Matched Study.Advanced Materials · 2026 · 38(56):e74522doi:10.1002/adma.74522 · PMID 42554109

     Bismuth-based nanosheets in an injectable peptide hydrogel that generate reactive oxygen species under ultrasound by piezoelectric and pyroelectric catalysis; the authors note that barium titanate dominates sono-piezoelectric dynamic therapy. In a model of postsurgical osteosarcoma with a bone defect, residual tumor was repressed and bone regenerated. Animal work despite the 'real-world-matched' title; species not named in the abstract.

140. 140
     Fukada E, Zimmerman RL, Mascarenhas S. Denaturation of horn keratin observed by piezoelectric measurements.Biochemical and Biophysical Research Communications · 1975 · 62(2):415-8doi:10.1016/s0006-291x(75)80154-9 · PMID 1167451

     No abstract in the record; cattle horn keratin heated until it denatured, followed by its piezoelectric signal. Cited for the fact that keratin, the protein of hair and horn, is piezoelectric when dry and oriented.

141. 141
     Ando Y, Fukada E, Glimcher MJ. Piezoelectricity of chitin in lobster shell and apodeme.Biorheology · 1977 · 14(4):175-9doi:10.3233/bir-1977-14404 · PMID 912046

     No abstract in the record. Cited for chitin, the shell polymer, joining the list of piezoelectric biological solids. PubMed lists the third author as 'Glimicher MJ'; the author is Melvin J. Glimcher.

142. 142
     Fukada E. Piezoelectricity in polymers and biological materials.Ultrasonics · 1968 · 6(4):229-34doi:10.1016/0041-624x(68)90132-7 · PMID 5717476

     No abstract in the record; indexed under bone, tendons, wood, peptides and polymers. Cited for the breadth of materials in which Fukada had by then measured the effect.

143. 143
     Zhang Z, Li X, Peng Z, Yan X, Liu S, Hong Y, Shan Y, Xu X, Jin L, Liu B, Zhang X, Chai Y, Zhang S, Jen AK, Yang Z. Active self-assembly of piezoelectric biomolecular films via synergistic nanoconfinement and in-situ poling.Nature Communications · 2023 · 14(1):4094doi:10.1038/s41467-023-39692-y · PMID 37433769

     Beta-glycine films grown in nanoconfinement under an electric field: piezoelectric strain coefficient 11.2 pm/V, voltage coefficient 252 × 10^-3 V·m/N, stable to 192 °C. Materials chemistry.

144. 144
     Tao K, O'Donnell J, Yuan H, Haq EU, Guerin S, Shimon LJW, Xue B, Silien C, Cao Y, Thompson D, Yang R, Tofail SAM, Gazit E. Accelerated charge transfer in water-layered peptide assemblies.Energy & Environmental Science · 2019 · 13(1):96-101doi:10.1039/c9ee02875g · PMID 31976008

     Assemblies of L-tryptophan-D-tryptophan with alternating water and peptide layers show a piezoelectric response that can be tuned by iodine or isotope substitution. Laboratory materials.

145. 145
     Lee BY, Zhang J, Zueger C, Chung WJ, Yoo SY, Wang E, Meyer J, Ramesh R, Lee SW. Virus-based piezoelectric energy generation.Nature Nanotechnology · 2012 · 7(6):351-6doi:10.1038/nnano.2012.69 · PMID 22581406

     Films of M13 bacteriophage show piezoelectric strengths up to 7.8 pm/V, tunable by engineering the coat protein; a phage generator produced up to 6 nA and 400 mV and ran a liquid-crystal display. The virus is a material here, not an infection.

146. 146
     Cao L, Qiu X, Jiao Q, Zhao P, Li J, Wei Y. Polysaccharides and proteins-based nanogenerator for energy harvesting and sensing: A review.International Journal of Biological Macromolecules · 2021 · 173:225-243doi:10.1016/j.ijbiomac.2021.01.109 · PMID 33484800

     Review of nanogenerators built from natural polymers including cellulose, chitosan, silk, collagen, keratin, peptides and M13 phage, with the output and humidity problems that limit them. Engineering review.

147. 147
     Bai JP, Zhang C, Bahader I, Strenzke N, Renigunta V, Oliver D, Navaratnam D, Beckstein O, Santos-Sacchi J. Chloride binding does not influence prestin motor speed at very high frequencies in the mouse outer hair cell.Structure · 2025 · 33(8):1417-1424.e3doi:10.1016/j.str.2025.04.019 · PMID 40403717

     Mouse outer hair cell membrane patches: prestin's charge movement has a frequency cut-off of 27 kHz, unaltered in chloride-binding mutants; the authors describe prestin's tension sensitivity as piezoelectric-like behavior not explained by chloride. Mouse cells and molecular simulations.

148. 148
     Bistolfi F. The bioelectronic connectional system (BCS): a therapeutic target for non ionizing radiation.Panminerva Medica · 1990 · 32(1):10-8PMID 2263396

     A hypothesis paper proposing that collagen, keratin and the cytoskeleton, all piezoelectric, form a unitary system for 'coherent communication among cells' by piezoelectric and photon/phonon transduction, consistent with 'bioplasma'. No data; cited as the clearest published example of the leap from a material property to a communication system. No DOI in the record.

149. 149
     Jain S, Mills PJ. Biofield therapies: helpful or full of hype? A best evidence synthesis.International Journal of Behavioral Medicine · 2010 · 17(1):1-16doi:10.1007/s12529-009-9062-4 · PMID 19856109

     66 clinical studies of Reiki, therapeutic touch and healing touch, of medium quality overall: strong evidence for reduced pain intensity in pain populations, moderate for hospitalized and cancer patients, equivocal for fatigue and quality of life. The outcomes are subjective and the controls rarely blind the practitioner.

150. 150
     Bonanno F, Cedro C, Alito A, Milardi D, Rizzo V, Mento C, Lombardo C. Touch-based interventions, biofield therapies, and hypnosis for pain management: a scoping review of complementary approaches in physiotherapy.Frontiers in Pain Research · 2026 · 7:1869699doi:10.3389/fpain.2026.1869699 · PMID 42625788

     Scoping review of 14 studies and 1,001 patients from 2004 to December 2025: hypnosis consistently reduced pain, while touch-based and biofield interventions showed 'potential' improvements; the authors call the safety and effectiveness evidence preliminary.

151. 151
     Hammerschlag R, Sprengel ML, Baldwin AL. Biofield therapies: Guidelines for reporting clinical trials.Explore (NY) · 2024 · 20(2):196-205doi:10.1016/j.explore.2023.08.001 · PMID 38307816

     A 15-item reporting checklist for biofield therapy trials, developed by Delphi among practitioners and journal editors, acknowledging that systematic reviews have called for better reporting. Cited to show the field's own admission of poor trial reporting; the first author directs a consciousness-and-healing institute.

152. 152
     Schöni MH, Nikolaizik WH, Schöni-Affolter F. Efficacy trial of bioresonance in children with atopic dermatitis.International Archives of Allergy and Immunology · 1997 · 112(3):238-46doi:10.1159/000237460 · PMID 9066509

     Double-blind trial in 32 children hospitalized for 4 to 6 weeks in Davos for atopic dermatitis, randomized to an active or a sham bioresonance (biophysical information therapy) device on top of conventional inpatient therapy: both groups improved, and the device had no significant additive effect on skin, sleep or itch scores, allergy markers or questionnaire; the authors conclude it has no place in treating these children.

153. 153
     Gornale SS, Patil SS, Deo AW, Athani A. Transfer Learning-driven Biofield Image Analysis for Predictive Modeling of Diabetes.Journal of Medical Physics · 2026 · 51(1):136-144doi:10.4103/jmp.jmp_245_25 · PMID 42039726

     Neural networks trained on biofield images, from gas discharge visualization and related methods, sorted diabetic from nondiabetic subjects with 99.12% accuracy (97.45% mean on five-fold cross-validation); the authors say larger data sets and expert validation are needed. One author is affiliated with the Institute of Biofield Evaluation and Research Centre; that the images record a biofield is assumed, not shown.

154. 154
     Trivedi MK, Parulkar VR, Trivedi D, Branton A, Mondal S, Jana S. Pilot-Scale Testing of Blessing/Biofield Energy Treatment (BET) for Improving Eggs and Meat Quality of Rhode Island Red Laying Hens.Veterinary Medicine and Science · 2026 · 12(1):e70798doi:10.1002/vms3.70798 · PMID 41553162

     Fifty hens in two groups of 25: the 'blessing/biofield energy treated' group reported a 28.38% higher laying rate, 40.95% more edible meat and 383.33% more linoleic acid in meat. Five of the six authors are from Trivedi Global, Inc. or Trivedi Science Research Laboratory, companies of the group whose 2024 trial was retracted; a commercial conflict visible on the paper.

155. 155
     Yang P, Wei D, Chakraborty S, Nguyen P, Cusimano A, Deng D, Iqbal S, Nelson M, Cui M, Dai J, Gagea M, Wagner R, Li Y, Cohen L. The Preclinical Effects and Mechanisms of Biofield Therapy on Pancreatic Cancer Cell Growth and Metastasis.Cancer Medicine · 2026 · 15(4):e71726doi:10.1002/cam4.71726 · PMID 41968966

     From the University of Texas MD Anderson Cancer Center: mouse and human pancreatic cancer cell lines exposed to biofield therapy by three therapists using a standardized procedure grew less than sham-control and incubator-control cells, with reduced cell voltage potential, FOXM1 expression and invasiveness; in orthotopic mouse models the therapy inhibited primary tumor growth and liver metastasis (p < 0.05). Cells and mice, one center, no identified physical agent.

156. 156
     Chevalier G, Sinatra ST, Oschman JL, Sokal K, Sokal P. Earthing: health implications of reconnecting the human body to the Earth's surface electrons.Journal of Environmental and Public Health · 2012 · 2012:291541doi:10.1155/2012/291541 · PMID 22291721

     Narrative review by the practice's principal proponents, claiming better sleep and less pain from conductive contact with the ground and proposing the disconnection as a major contributor to unwellness. No systematic method; the authors' commercial ties are declared in later papers.

157. 157
     Sinatra ST, Oschman JL, Chevalier G, Sinatra D. Electric Nutrition: The Surprising Health and Healing Benefits of Biological Grounding (Earthing).Alternative Therapies in Health and Medicine · 2017 · 23(5):8-16PMID 28987038

     Summary of more than twelve of the authors' own reports, concluding that all studies discussed showed significant outcomes. A proponents' summary, not a systematic review. No DOI in the record.

158. 158
     Koniver L. Practical applications of grounding to support health.Biomedical Journal · 2023 · 46(1):41-47doi:10.1016/j.bj.2022.12.001 · PMID 36481428

     Asserts that touching the earth puts the body 'into a profound healing state' by joining a planetary direct-current circuit; the author's affiliation is a private company. No data presented.

159. 159
     Kattner AA. Down to earth - A new type of hygiene.Biomedical Journal · 2023 · 46(1):1-7doi:10.1016/j.bj.2023.02.003 · PMID 36773844

     Editorial by a freelance journalist introducing the journal's special section on earthing, including an article linking sunspots to pandemics. Cited to show how the grounding literature reached a journal, not for any finding.

160. 160
     Elkin HK, Winter A. Grounding Patients With Hypertension Improves Blood Pressure: A Case History Series Study.Alternative Therapies in Health and Medicine · 2018 · 24(6):46-50PMID 30982019

     Ten hypertensive patients in one cardiology practice grounded at home at least 10 hours a day for months: systolic pressure fell 8.6% to 22.7%, average 14.3%. No control group, no blinding, so regression to the mean and attention cannot be excluded. No DOI in the record.

161. 161
     Chevalier G, Patel S, Weiss L, Chopra D, Mills PJ. The Effects of Grounding (Earthing) on Bodyworkers' Pain and Overall Quality of Life: A Randomized Controlled Trial.Explore (NY) · 2019 · 15(3):181-190doi:10.1016/j.explore.2018.10.001 · PMID 30448083

     Sixteen massage therapists at the Chopra Center in a six-week stepped-wedge design reported better physical function, energy, fatigue, mood and pain while grounded. Sixteen participants, self-report outcomes, run by proponents at a wellness business.

162. 162
     Chevalier G. The effect of grounding the human body on mood.Psychological Reports · 2015 · 116(2):534-42doi:10.2466/06.PR0.116k21w5 · PMID 25748085

     Pilot study: 40 adults grounded or sham-grounded for one hour in a recliner fitted with a conductive pillow, mat and patches, double-blinded; pleasant and positive moods improved on the Brief Mood Introspection Scale in grounded but not sham-grounded participants. Single author, a coauthor of the founding grounding review; self-reported mood after one hour.

163. 163
     Brown R, Chevalier G, Hill M. Grounding after moderate eccentric contractions reduces muscle damage.Open Access Journal of Sports Medicine · 2015 · 6:305-17doi:10.2147/OAJSM.S87970 · PMID 26443876

     Thirty-two healthy young men randomly divided into grounded and sham-grounded groups after 200 half-knee bends, grounded for 4 hours on days 1 and 2: creatine kinase rose significantly on day 2 in the sham group but not in the grounded group (between-group P = 0.04); both groups had pain on all post-test days. Small, short, a surrogate blood marker; Chevalier is a coauthor.

164. 164
     Lin CH, Tseng ST, Chuang YC, Kuo CE, Chen NC. Grounding the Body Improves Sleep Quality in Patients with Mild Alzheimer's Disease: A Pilot Study.Healthcare (Basel) · 2022 · 10(3):581doi:10.3390/healthcare10030581 · PMID 35327058

     Twelve-week placebo (sham)-controlled pilot in mild Alzheimer's disease at Kaohsiung Chang Gung Memorial Hospital, Taiwan: 22 enrolled, 15 completed; the Pittsburgh Sleep Quality Index improved more with grounding than with sham (P = 0.006), while anxiety and depression scores did not differ. Tiny sample with heavy dropout; authors not from the grounding-products literature.

165. 165
     Muniz-Pardos B, Zelenkova I, Gonzalez-Aguero A, Knopp M, Boitz T, Graham M, Ruiz D, Casajus JA, Pitsiladis YP. The Impact of Grounding in Running Shoes on Indices of Performance in Elite Competitive Athletes.International Journal of Environmental Research and Public Health · 2022 · 19(3):1317doi:10.3390/ijerph19031317 · PMID 35162340

     Ten elite runners ran 20 minutes at 80% of anaerobic threshold in traditional training shoes and in grounding shoes with a conductor under the insole, in randomized order a week apart: no difference in oxygen uptake, heart rate, lactate or perceived fatigue (running economy 51.1 ± 4.2 against 50.9 ± 5.1 mL per kg per minute). Four of the nine authors are from adidas Innovation, the shoe company's research arm; the result was negative.

166. 166
     Kshirsagar S, Deshmukh H, Reddy AP, Reddy AP, Reddy PH. Grounding as a complementary intervention for Alzheimer's disease: Mechanisms, evidence, and potential therapeutic applications.Journal of Alzheimer's Disease · 2025 · 105(4):1239-1251doi:10.1177/13872877251334666 · PMID 40262107

     Narrative review proposing grounding for Alzheimer's disease through antioxidant and anti-inflammatory mechanisms; the authors describe the evidence as preliminary, call for robust trials in Alzheimer's populations, and still suggest integrating grounding into standard care protocols. A small sham-controlled pilot in mild Alzheimer's disease had already been published in 2022 (Lin and colleagues, on this page).

167. 167
     Giulivi C, Kotz R. Earthing effects on mitochondrial function: ATP production and ROS generation.FEBS Open Bio · 2025 · 15(9):1459-1470doi:10.1002/2211-5463.70062 · PMID 40512656

     Fluorescence assays of mitochondria under wired (grounded), sham and naive conditions: grounded mitochondria made 5% to 11% more ATP, 22% to 33% less reactive oxygen species and had a 5% to 6% lower membrane potential. Laboratory preparation only; the second author is affiliated with North American Science Associates (NAMSA), a private company.

168. 168
     Kalhour M, Zeinivand M, Kavyannejad R. Effects of prolonged grounding-based transcranial coupling to earth potential on learning, memory, and hippocampal biochemical status in male Wistar rats.Neuroscience · 2026 · 616:31-45doi:10.1016/j.neuroscience.2026.08.051 · PMID 42692391

     Forty-eight rats randomized to control, sham and continuous grounding through a cranial electrode for 7 to 28 days: at 21 to 28 days, better spatial, recognition and avoidance memory with lower hippocampal inflammatory and oxidative markers; the authors call it preliminary evidence of an association and say it should not be read as evidence of a direct electrical mechanism. Rats.