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In 1957, Fukada and Yasuda published the results of their systematic investigation on dry specimens cut from human and bovine long bones, in an article titled “On the piezoelectric effect of bone,” which credited them with the discovery of the existence of piezoelectricity in bone. They demonstrated that dry bone under proper load application generates surface charges, called piezoelectric currents. They established that the piezoelectric effect appears only when shearing force is applied to the collagen fibers in the bone, which are highly oriented, to make them slip past each other. There exist two types of piezoelectric effects – positive and negative. The former is due to strains generated within the crystal lattice of a material, leading to the production of a potential difference across the faces of that crystal and the latter, when an electric charge is passed across a molecule or crystal and leads to an inherent strain within that molecule (Isaacs, 1987). Both effects involve the organic molecules of collagen and the inorganic crystals of hydroxyapatite (McDonald, 1993). Bassett and Becker (1962) extended that research and discovered that the charges emanating from the bone surface at the time of bending are proportional to the internal strains engendered by the bending. They also showed that the polarization sign always depended upon the type of stress – there was a positive sign where there is tension and a negative sign where there is compression. These experiments were further developed by Shamos et al. (1963) and Shamos and Lavine (1964), who reported finding this phenomenon in a number of different bones, in different anatomical sites and species. They suggested that local electric fields resulting from these surface changes influence the deposition of ions and polarizable molecules.

The first observations of the piezoelectric phenomenon in wet and living bone was made by Bassett (1968), and this finding has contributed to the working hypothesis that piezoelectricity leads to a physical explanation of Wolff ’s law. Following this discovery, the universal existence of piezoelectricity in biological tissues was demonstrated by Fukada and Hara (1969) through their experiments on trachea, aorta, intestines, ligaments, and venous vessels. Marino and Becker (1975) reported on the piezoelectric characteristics of collagen, and concluded that these effects originate in tropocollagen molecules, or in molecules no larger than 50 Å in diameter. However, the hypothesis claiming that piezoelectricity is a major determinant of bone remodeling is weakened by the following:

 The generated electric potential is dependent on a strain gradient, and this was not taken into account when the hypothesis was proposed. Bone always experiences nonhomogenous deformation because of its centro‐symmetric nature, and because it can produce electrical polarization proportional to the strain gradient.

 The modulus of elasticity (E) of cortical bone under physiologic conditions is frequency dependent. Hence, bone cannot be considered as an elastic‐plastic material.

 End‐for‐end rotation of the sample in cantilever bending mode does not change the sign of generated potential as would be expected from classical piezoelectric material.

Proffit (2013) outlined two unusual properties of piezoelectricity, which do not seem to correlate well with OTM:

 A quick decay rate, where the electron transfer from one area to another following force application reverts back when the force is removed, which does not or should not happen once orthodontic treatment is over.

 Production of an equivalent signal in the opposite direction upon force removal.

Anderson and Erikkson (1968) challenged the piezoelectric hypothesis and reported that although dry collagen is strongly piezoelectric, full hydrated collagen is not, because of the structured water it contains. They argued that bone is a tissue with high symmetry, as the hydroxyapatite it contains is centrosymmetric in nature, and not piezoelectric. Follow‐up experiments conducted by these investigators (1970), using a similar apparatus to the one used by Fukada and Yasuda in 1957, proved that the piezoelectric coefficients varied with the state of hydration of bone, and that the variation decreased as the specimens were dried by evaporation. The loss of piezoelectricity in fully hydrated tendon collagen was explained as attainment of more symmetrical, nonpiezoelectric structure by absorption of water. Instead, the electrical signals generated when stress is applied to fully wet collagen are actually streaming potentials.

The electrokinetic phenomenon known as streaming potential or streaming current was described by many authors, like Glasstone, Overbeek, and Kortum (Gross and Williams, 1982). Anderson and Eriksson (1968) reintroduced the concept against the theoretical faults of the piezoelectric effect, and reported it to be present in bone as it is a porous tissue containing a fluid phase and calcified matrix (which is composed of inorganic (mainly hydroxyapatite) and organic (collagen) contents). Further, the porosity of bone contains membrane‐lined capillary vessels helping in the transportation of nutrition to the inside of bone. There exists a compartmental model for the bone fluid system whereby extracellular fluid in the calcified matrix is separated from membrane‐lined vascular channels. When the bone is mechanically stressed, as part of different loading conditions, or therapeutically induced as in orthodontic treatment, remodeling changes are initiated by the bioelectric potentials generated from inside of the bone. The presence of bioelectric potentials in bone matrix, which also contains extracellular ionic fluid, will generate a charge separation at the matrix–fluid interface. There will be attraction of opposite‐charged molecules at the matrix–fluid interface and repelling of similar charged molecules away from this interface. When the fluid is forced through a bone plug, the ionic charges in the fluid phase near the fluid–matrix interface are carried towards the low pressure end, which is otherwise known as Poiseuille flow. This flow constitutes the streaming current and accumulation of charges set up as an electrical field. This field will result in generation of conduction currents which flow in opposite directions through the bulk of liquid in the porous structure of bone. In steady state the conduction current is equal to the streaming current. The resulting electrostatic potential difference between these two sides of bone plug is known as streaming potential (Figure 2.20) (Walsh and Guzelsu, 1993). Briefly, streaming potential is the electric potential developed between two components by an electrolyte flowing between the solid surfaces. The movement of the electrostatic double layer at the fluid bone interface, created through the net surface charge gained by the bone surface in contact with an ionic fluid, generates this effect (Anderson and Eriksson, 1968). In bone, streaming potentials can be observed in vascular channels, Haversian systems, canaliculi, and microporosities of the structure due to blood flow and interstitial fluid movement. Neutrality is restored following equilibration of ion distribution.

Zeta potential, the common link among different electrokinetic potentials and the one used to allow comparison of different measuring techniques, is defined as average potential difference between the bulk and surface of shear. Surface of shear is an imaginary surface present in the area adjacent to electrically charged bone matrix, where the ions and fluid molecules remain stationary. The role of zeta potential is to separate the movement of ions bound to the solid surface from other ions that show normal viscous behavior under mechanical force application (Lech and Iwaniec, 2010). Zeta potential can be calculated from streaming potential experiments by knowing the applied pressure difference across the sample and generated streaming potentials (Hunter, 1981). Fluid conductivity and fluid viscosity determines the stress‐generated potentials in fluid‐filled bone, and it is possible to calculate the potential generated by the distortion of a fluid by the formula (McDonald, 1993):

Figure 2.20 Results of a typical intact bone‐streaming potential (mV) in pH 7.3, 0.145 M ionic strength buffer (physiologic conditions) versus time at various pressures (kPa). The arrows indicate when an increase in pressure (nitrogen gas) was placed on the sample. Streaming potential magnitude increased with an increase in pressure and a stable streaming potential was obtained. A positive streaming potential versus pressure response corresponds to a negative zeta potential and an exposed organic interface. Streaming potentials were consistently positive throughout all pressure levels in 0.145–0.6 M NaCl.

(Source: Walsh and Guzelsu, 1993. Reproduced with permission of Elsevier.)

where z is the zeta potential; V is the magnitude of the potential; δP is the pressure difference that forces the liquid through the channel; ε is the dielectric constant of the liquid; n is the viscosity of the liquid; σ is the specific conductance.

Scientists working in this field have concluded that piezoelectricity and streaming potentials are two coexisting phenomena and both play an important role in stress information transmission. They combined both phenomena as a bioelectric hypothesis, which states that structural alterations throughout the bone are conducted and/or triggered by ionic charge differences (Masella and Chung, 2008). Stress‐generated electric potentials were first reported in dog mandibles and teeth by Cochran, Pawluk and Bassett (1968). They postulated that these stress‐induced bioelectric potentials play a major role in regulating the orientation and functional demands of bone per se. Zengo et al. (1973) measured the electric potential in mechanically stressed dog alveolar bone during in vivo and in vitro experiments. They have demonstrated that the concave side of orthodontically treated bone is electronegative and favors osteoblastic activity, whereas the areas of positivity or electrical neutrality, i.e., convex surfaces, showed elevated osteoclastic activity (Figure 2.19). Shapiro, Roeber, and Klempner (1979) suggested that application of piezoelectric charges as pulses of force to the teeth can accelerate the osteogenic response. Based on their experiment in one patient, with application of 8 ounces of force, they reported increase in the rate of movement of maxillary second molar with less pain perception than that of the control teeth.

Figure 2.21 Transverse section, 6 μm thick, of a 1‐year‐old female cat’s mandible, after a 7‐day exposure to sham electrodes (control). Shown is the buccal periosteum of the second premolar opposite the sham cathode, stained immunohistochemically for cAMP. B, Alveolar bone. The bone surface lining cells are flat, and most stain lightly for cAMP.

It has been proposed by Davidovitch et al. (1980a, b) that a physical relationship exists between mechanical and electrical perturbation of bone. Their experiments in female cats with administration of exogenous electrical currents in conjunction with orthodontic forces demonstrated enhanced cellular activities in the PDL and alveolar bone, as well as rapid tooth movement (Figures ). Taken together, these findings led to the suggestion that bioelectric responses (piezoelectricity and streaming potentials) propagated by bone bending incident to orthodontic force application, might act as pivotal cellular first messengers.

Borgens (1984) investigated this phenomenon in bone fracture sites by inducing electric current for healing purposes. His experiments did not disclose any correlation with what had been proposed as piezoelectric effects and showed that the dispersion of current as it enters the lesion is unpredictable. He attributed this finding to the complexity of distribution of mineralized and nonmineralized matrices. However, he observed generation of endogenous ionic currents evoked in intact and damaged mouse bones, and classified these currents as stress‐generated potentials or streaming potentials, rather than piezoelectric currents. In contrast to piezoelectric spikes, the streaming potentials were having long decay periods. This finding led him to hypothesize that the mechanically stressed bone cells themselves, not the matrix, are the source of the electric current. His hypothesis received support from Pollack et al. (1984), who proposed a mechanism by which force‐evoked electric potentials may reach the surface of bone cells. Accordingly, an electric double layer surrounds bone, where electric charges flow in coordination with stress‐related fluid flow. These stress‐generated potentials may affect the charge of cell membranes, and of macromolecules present in the neighborhood. Davidovitch et al. (1980a, b) suggested that piezoelectric potentials result from distortion of fixed structures of the periodontium, such as collagen, hydroxyapatite, or bone cells’ surface. In hydrated tissues, however, streaming potentials (the electrokinetic effects that arise when an electrical double layer overlying a charged surface is displaced) predominate as the interstitial fluid moves. They further reported that mechanical perturbations of the order of about 1 min/day are apparently sufficient to cause an osteogenic response (Figure 2.24), perhaps due to matrix proteoglycan related strain memory.

Figure 2.22 Transverse section, 6 μm thick, of a 1‐year‐old female cat’s mandible (the same animal as shown in Figure 2.21), after exposure for 7 days to a constant application of a 20 μA direct current to the gingival mucosa, noninvasively. Shown are the tissues near the stainless‐steel cathode, stained immunohistochemically for cAMP. B, Alveolar bone. Compared with the cells shown in Figure 2.21, the bone surface lining cells near the cathode are larger and more darkly stained for cAMP.

Figure 2.23 Constant direct current, 20 μA, noninvasively, to the gingival and oral mucosa labial to the left maxillary canine in a cat. The right canine (control) received the same electrodes, but without electrical current. Both canines were moved distally by an 80 g tipping force. The right canine, which had been subjected only to mechanical force, moved distally a smaller distance than the left canine, which had been administered a combination of mechanical force and electrical current.

Figure 2.24 The number of alveolar bone osteoblasts bordering the PDL (±SEM) near cat maxillary canines, intensely stained for cAMP or cGMP following an electric stimulation. Cells were counted along a 0.1 mm surface opposite each electrode. Open circles, Control sites. Solid circles, Electrically treated sites. (a) Osteoblasts near cathode stained for cAMP. (b) Osteoblasts near anode, stained for cAMP. (c) Osteoblasts near cathode, stained for cGMP. (d) Osteoblasts near anode, stained for cGMP. Time periods when differences in number of cells intensely stained for cAMP and cGMP between electrically treated and control sites were not significant: cAMP near the cathode at day 3; cGMP at days 3 and 7 near the cathode. At the other time periods near the cathode and at all time periods near the anode, the differences between the treated and control sites were statistically significant (P < 0.01). It should be noted that all the bone surface cells are labeled as “osteoblasts,” although it is quite possible that some cells near the anode are stimulated by the electric currents to resorb bone rather than to participate in the synthesis and mineralization of new bone matrix. However, the authors did not detect typical osteoclastic lacunae at the alveolar socket wall near the anode and thus defined all bone surface cells as osteoblasts.

(Source: Davidovitch, 1980a. Reproduced with permission of Elsevier.)

The major criticism faced by both the piezoelectric as well as the streaming potentials theories was due to the highly conductive nature of the vascular system, periosteum, and tissue fluids. They often tend to drain away the change in potential difference. Researchers failed to establish whether the generated strain‐induced potentials were actual players in cellular remodelling or irrelevant by‐products of bone deformation. McDonald (1993) argued against the role of electrical signals in bone remodeling by stating that “surface potential differences are very small compared to the potential differences generated with muscle activity.” He concluded that the knowledge of action of electrical signaling inside the cells is inadequate and warrants further research into cellular behavior in response to applied mechanical forces.

It is evident from the ongoing discussion that neither of these hypotheses could provide conclusive evidence on the detailed nature of the biological mechanism of OTM. Histological, histochemical, and immunohistochemical studies performed in the twentieth century, as well as early in the twenty‐first century, have demonstrated that multiple phenomena, both physical and chemical, are involved in the process of tooth movement. When mechanical forces are applied, cells, as well as the ECM of the PDL and alveolar bone, respond concomitantly, resulting in tissue remodeling activities. During early phases of tooth movement, PDL fluids are shifted, producing cell and matrix distortions as well as interactions between these tissue elements. In response to these physicochemical events and interactions, cytokines, growth factors, colony stimulating factors, and vasoactive neurotransmitters are released, initiating and sustaining the remodeling activity, which facilitates the movement of teeth. A detailed discussion on these molecules along with the mechanisms of their operation is provided in Chapter 3.