SPECIAL ARTICLE Orthodontic materials research and applications: Part 2. Current status and projected future developments in materials and biocompatibility Theodore Eliades Thessaloniki, Greece The purpose of this 2-part opinion article was to project the developments expected to occur in the next few years in orthodontic materials research and applications. Part 1 reviewed developments in bonding to enamel. Part 2 looks at other orthodontic materials applications and explores emerging research strategies for probing the biological properties of materials. In the field of metallic brackets, expansion of the use of titanium alloys with improved hardness and nickel-free steels with better corrosion resistance and increased hardness is expected. Manufacturing techniques might be modified to include laser-welding methods and metal injection molding. Esthetic bracket research will involve the synthesis of high-crystallinity biomedical polymers with increased hardness and stiffness, decreased water sorption, and improved resistance to degradation. New plastic brackets might incorportate ceramic wings. Fiber-reinforced composite archwires, currently experimental, could soon be commercially available, and long-term applications of shape-memory plastics might become viable. Advancements in elastomeric materials will result in polymers with reduced relaxation, broader use of fluoride-releasing elastomers with decreased relaxation, and large-scale film coating of elastomers to decrease reactivity, water sorption, and degradation. Finally, biocompatibility assessments will incorporate testing of potential endocrinological action. New polymer formulations might be tested in adhesive and plastic bracket manufacturing, based on benzoic ring-free monomers to avoid the adverse effects of the estrogenic molecule bisphenol-A. (Am J Orthod Dentofacial Orthop 2007;131:253-62) he second part of this article includes a review of the current status of brackets, elastomerics, and archwires along with a projection of future developments in materials technology and clinical applications. It also gives a brief description of the novel assessment of the biological properties of polymers, which have already been implemented in associated biomedical disciplines. T BRACKETS The evolution of a bondable appliance equipped with an insert to facilitate engagement of the wire onto it has a remarkable growth curve. Less than half a century ago, in 1962, Robert Ricketts demonstrated the use of prefabricated bands for full banding at the American Association of Orthodontists conference in Los Angeles.1 In a televised demonstration, he manAssociate Professor, Department of Orthodontics, School of Dentistry, Aristotle University, Thessaloniki, Greece. Part of this article was presented as a keynote lecture at the 6th International Orthodontic Congress, Paris, France, September, 2005. Reprint requests to: Dr Theodore Eliades, 57 Agnoston Hiroon St, Nea Ionia 14231, Greece; e-mail, teliades@ath.forthnet.gr. Submitted, October 2005; revised and accepted, December 2005. 0889-5406/$32.00 Copyright © 2007 by the American Association of Orthodontists. doi:10.1016/j.ajodo.2005.12.029 aged to band all 4 quadrants of a patient with prefabricated bands made by Rocky Mountain Orthodontics (Denver, Colo) in less than 20 minutes. This was a breakthrough development at that time, because banding requires lengthy appointments because of the time needed to weld the attachments onto the bands. After that, appliance development expanded greatly to include all aspects of brackets; changes in size, design, composition, manufacturing process, and engagement scheme with the archwire occurred, and new wire engagement features were introduced—ie, active and passive self-ligation. In addition, a totally new concept, engineered removable appliances (Invisalign, Align Technology Inc, Santa Clara, Calif), programmed to move teeth to a predetermined position, was developed. Composition of metallic brackets: stainless steel, nonnickel steel, or titanium? Apart from standard stainless steel, concerns on the allergenicity of nickel have provoked the introduction of various nonnickel, or very low-nickel content, stainless-steel types that supposedly have little allergenic potential. However, the allergenic action of orthodontic alloys might have been overestimated because studies 253 254 Eliades showed that the percentage of orthodontic patients who react to nickel-containing orthodontic alloys is only a fraction of the general population.2,3 Some authors have gone a step farther by suggesting that orthodontics probably desensitizes those who receive therapy.4 Nonetheless, recent studies have shown that nickel has genotoxic effects, and thus care should be taken to minimize potential exposure to this element and its compounds.5 Nonnickel and low-nickel stainless steels were introduced in orthodontics as alternatives to conventional 316 and 318 types. These steels contain substantially less nickel relative to conventional types and the same or even higher hardness relative to the types of steel used for bracket manufacturing. Moreover, some types such as the 2205 alloy demonstrated substantially less crevice corrosion than the 316L alloy when coupled with nickel-titanium, beta-titanium,6 or stainless steel archwires in vitro. Another steel type, the precipitation-hardening 17-4 steel, exhibited higher hardness than the 316L steel bracket alloy, although the latter had significantly higher corrosion resistance.7 In general, this field shows extensive activity, with novel experimental steel compositions being introduced in the literature,8,9 and further research is needed to find the stainless steel alloy with an optimum combination of strength and corrosion resistance for orthodontic brackets. Titanium brackets consist of titanium or a titanium alloy (Ti-6Al-4V) and are currently available in 2 types: one with Vickers hardness (HV) close to grade II commercially pure titanium and a wing component of Ti-6Al-4V alloy, and another type made entirely of grade IV commercially pure titanium.10 The difference in hardness between the brackets tested might have significant effects on the wear phenomena when an archwire is engaged into the preadjusted bracket slot. Nickel-titanium archwires have a hardness of 300 to 430 HV, which is close to that of titanium bracket wings, whereas stainless steel archwires have a hardness of 600 HV. In contrast, the hardness of titanium brackets has been found to be about 270 HV for the 1-piece bracket and from 160 to 350 HV for the base and wing of the 2-piece appliance, respectively— values much lower than those of nickel-titanium and steel archwires. The clinical significance of this effect relates to the formation of obstacles in transferring torque because low hardness induces wear, which precludes full engagement of the wire to the slot walls and possibly causes plastic deformation of the wing.11 Also, the Ti-6Al-4V alloy with a friction coefficient of 0.28 might have different frictional variants from the commercially pure titanium with a coefficient of 0.34, American Journal of Orthodontics and Dentofacial Orthopedics February 2007 Fig 1. Three-dimensional x-ray microtomographic image of stainless steel bracket shows soldering alloy (middle phase). whereas, from a corrosion perspective, brackets formed from 2 components might be more susceptible to galvanic corrosion.12 Projected short-term future developments in metallic bracket composition ● ● Expansion of the use of titanium alloys with improved alloys of increased hardness. Introduction and greater use of nickel-free stainless steels for bracket manufacturing with corrosion resistance and hardness comparable to conventional types. Manufacturing of metallic brackets: 2 piece with alloy brazing, laser welded, or metal injection molded? As a standard manufacturing process, the industry uses brazing alloys to join the base and wing components of brackets (Fig 1). These alloys also contain traces of the cytotoxic cadmium, which is added to lower the melting temperature and improve wetting.13 Moreover, silver-based brazing alloys form a galvanic couple that can lead to ionic release, mainly copper and zinc. Corrosion, which has been substantially minimized in current materials, is the main reason for the progressive dissolution of brazing filler metal, leading to detachment of the wing from the bracket base during orthodontic therapy or at the debonding stage. To overcome this problem, several manufacturers have introduced gold-based brazing materials that might lead Eliades 255 American Journal of Orthodontics and Dentofacial Orthopedics Volume 131, Number 2 to the dissolution of stainless steel, because of the formation of the galvanic couple.14 Thus, although brazing alloys can facilitate the manufacturing of brackets with alloys of certain properties— eg, a stiffer alloy for the wing to withstand the loads from activated wires and a softer alloy for the base to facilitate a peel-off effect during debonding—they have several problems. The selection of an optimum brazing alloy presents some difficulties, because the ideal soldering medium should fulfill a wide range of criteria relevant to metallurgical structure, corrosion resistance, and biologic properties of materials.15 Laser welding was relatively recently introduced in bracket manufacturing as an alternative to alloy soldering. With this method, welding of the wing to the base does not extend to the bulk material, and thus a “surface seal” is formed that is confined to the periphery of the joint (Fig 2). This technique eliminates the intermediate phases such as soldering alloys and shows acceptable mechanical performance with a low risk of joint failure. The metal injection molding (MIM) process, which has significantly expanded during the past few years, involves mixing metal powders with particle sizes of a few microns with organic binders, lubricants, and dispersants to obtain a homogeneous mixture. Injection of the feedstock is performed by using an injection molding machine similar to that used in the plastic industry (Fig 3).16 MIM-manufactured products are 1-piece appliances with tolerances of the desired dimensions of approximately 0.3% and density values more than 97% of the theoretical density of the material. A recent study showed that MIM brackets had excessive porosity, which could be caused by the shrinkage of manufacturing components during sintering.17 Porosity is a known defect of MIM parts, with adverse effects on the mechanical and corrosion resistance of most MIM-manufactured products.18 The hardness of the MIM-made brackets tested varied from 154 to 287 HV, a value much lower than the hardness of wing components of conventional stainless steel brackets, introducing the problems associated with soft and compliant wing components, as noted previously. Currently, laser welding seems to have the most advantages, with reduced risks for corrosion or effect on the bulk material. Projected short-term future developments in the manufacturing process of metallic brackets ● ● ● Laser-welding will probably become routine. MIM manufacturing will increase rapidly. Alloy soldering will become obsolete. Fig 2. Three-dimensional x-ray microtomographic image of laser-welded bracket shows gap in bulk material of base-wing joint. Fig 3. Three-dimensional x-ray microtomographic image of stainless steel bracket manufactured with MIM process shows continuous phase. Esthetic brackets: plastic or ceramic? Esthetic bracket manufacturing involves a wide array of raw materials including zirconia, polycrystalline or single-crystal alumina, and plastics, most often polycarbonate-based appliances. Although transparent brackets are more attractive than their metallic counterparts, they have several undesirable effects such as higher incidence of bracket fracture attributed to the lack of grain boundaries for the inhibition of crack growth in single-crystal alumina, excessive wear because of decreased hardness as in polycarbonates, and 256 Eliades failure to deliver sufficient torque because of their low modulus.19 The first generation of plastic brackets had excessive creep deformation when subjected to torsional loads generated by activated archwires to the teeth and discoloration during clinical use.20 Ceramic- and fiberglass-reinforced and metallic insert-polycarbonate brackets were subsequently introduced to alleviate this deficiency, and novel syntheses were tested to overcome the esthetically unpleasing discoloration. Currently available plastic brackets still have some problems pertinent to their decreased hardness and wear resistance, as well as intraoral plasticization and softening.21-24 In general, the key properties to assess in examining esthetic brackets include (1) optical clarity (transparency or light transmittance), which is the main advantage of the single-crystal ceramic appliances because of the lack of grain boundaries as in the polycrystalline brackets or the presence of fillers, which cause light scattering and refraction, as used in polymeric brackets (Fig 4); (2) hardness, and consequently wear resistance, deals with the capacity of the appliance to maintain surface structural integrity with loads from mechanics such as archwire sliding, formation of high torquing moments, or masticatory forces; current ceramic brackets have greater hardness, although they might be brittle and have higher wear resistance and low degradation (hydrolytic or enzymatic); and (3) roughness, which is critical for the avoidance of high friction variants and associated obstacles in tooth movement. The use of low elastic moduli raw materials for manufacturing the wing and base components of plastic brackets inevitably imposes several limitations on the performance of the appliances. A recent study showed that poly(oxy)methylene bracket raw materials consistently had the lowest roughness and a higher hardness of plastic brackets25; however, this product might be less appealing because of its milky color and opacity. Also, a recent investigation caused some alarming concerns about possible formaldehyde release from poly(oxy)methylene brackets subjected to in vitro aging.26 However, laboratory aging media and various treatments of samples including exposure to excessive heat cannot simulate the oral environment reliably; also, the effect of biofilm formation of appliances, which can reduce their reactivity with the environment, has not been assessed. On the other hand, formaldehyde has also been shown to be eluted in vitro at minute concentrations from composite resins.27,28 Therefore, further research is required with samples aged in vivo before a definitive conclusion can be drawn on this subject. American Journal of Orthodontics and Dentofacial Orthopedics February 2007 Fig 4. Photograph showing difference in optical clarity between plastic bracket and ceramic bracket assigned to decreased light transmittance of polymeric appliance. Ceramic brackets—the esthetic alternative to plastic brackets—provide significantly better hardness and stiffness relative to polymeric appliances. Also, new generations of ceramic brackets have improved debonding characteristics, and, therefore, enamel damage risk during this stage is eliminated.29,30 These appliances have some problems because of their brittle nature. Particularly the single-crystal ceramics, which are the most transparent and consequently the most esthetic, have low fracture toughness because of their inability to absorb energy during loading, leading to failure.31 Because the critical stress for the start of a crack in brittle solids depends on the elastic modulus and the critical surface tension of the material, intraoral aging predisposes to fracture.32 This effect arises from the exposure to moisture and the resultant decrease in the critical surface tension of the material, which reduces the critical stress value.32,33 In support of the foregoing effect, a study reported that alumina ceramics had significantly reduced 3-point bending strength after exposure to water.34 Currently, ceramic brackets have superior mechanical properties, increased transparency, decreased reactivity with the oral environment, and an inert biological character. The latter, to be analyzed later here, is a matter of dispute for plastic brackets because of the potential action of various polymers at subtoxic levels. Projected short-term future developments in esthetic brackets ● Introduction of high-crystallinity biomedical polymers with increased hardness and stiffness, decreased water sorption, and high resistance to degra- American Journal of Orthodontics and Dentofacial Orthopedics Volume 131, Number 2 ● ● dation for use as the raw material in plastic bracket manufacturing. No significant advances are expected for ceramic brackets. Plastic combined with ceramic wings might become more commom, and the availability of esthetic selfligating brackets (currently limited to 3 brands) will be expanded. ARCHWIRES After the introduction of thermoelastic and niobium nickel-titanium archwires, a breakthrough in archwires, no major development has emerged in the past decade. Since the mid-1990s, 2 research teams working independently in the United States and Japan presented extensive evidence on the feasibility of esthetic polymeric wires.35-41 This new product consists of a composite polymer matrix reinforced with fibers. By varying the reinforcing fiber content of the composite matrix, the elastic modulus of these wires can be adjusted to the preferred range. Work by Zufall and Kusy37 characterized fundamental properties of the experimental material such as water sorption; they concluded that this experimental product seems promising. Recent research efforts in the broader polymer science field produced shape-memory plastics, which find many biomedical applications.42 The first plastics that can be reformed into temporary, preprogrammed shapes by illumination with ultraviolet light were developed in a joint project between German and US researchers. When exposed to ultraviolet light of a different wavelength, the bent plastic wires return to their original shapes. The mechanism involved relates to the grafting of photosensitive groups into the polymer network; this acts as a molecular switch. Projected short-term future developments in archwires ● ● Composite wires will be commercially available during the next several years if the industry finds that introducing them to the market will be profitable. Shape-memory plastics for orthodontic use might be a viable alternative in the future. ELASTOMERIC MODULES AND CHAINS Although self-ligating brackets can eliminate the need for elastomer modules by engaging the wire with a passive or an active mechanism, and nickel-titanium coil springs can replace elastomeric chains in retracting teeth, chain and elastic thread are the only options to close small diastemas in the anterior regions of arches. Eliades 257 The issue of force relaxation of elastomeric chains has attracted the interest of most investigators in the field because of the apparent clinical significance of the material’s performance.43-54 In spite of extensive evidence on this subject, there is a lack of information on the structural changes during stretching and unloading, including molecular conformation of the material. In general, a stretched elastomer must possess high tensile strength to avoid premature rupture; this, in turn, introduced the requirement for high crystallinity.54 High molecular weight polymers can serve this purpose; however, exaggerated molecular chain length might adversely affect the ability of the module to extend. Polymers consisting of molecular chains with polymerization greater than 1000 have little extensibility.33 When very long chains are deformed beyond a critical amount, the applied load must be carried by the primary bonds of the polymer chain, and, since there is no slippage that will allow dissipation of stress, the probability for breakage of those bonds is higher than that of unraveling the chains.55 This effect is termed “noodle analog” because it resembles the complexity of removing a very long noodle from a large pile without breaking it, because of the entanglement of the chains. On the other hand, fillers in the elastomers in the forms of color pigments, fluoride releasing beads, and substances to increase the strength of the materials might have a pronounced effect on the behavior of elastomers during stretching. As a rule, filler particles in the polymer structure have a larger modulus than the surrounding structure, and, consequently, they fail to extend to the same amount as the remaining material. That means that the ends of the fibrils in contact with the filler must be stretched more than the adjacent nonfiller-connected polymer fibrils to counteract the fillers’ inability to stretch. Filler content might thus be critical for the chain strain at the microscopic level, because closely packed fillers induce greater stretching of the intervening polymer chains, which ultimately fail earlier than their unbonded counterparts, reducing the capacity of the material to withstand loads (Fig 5).52 Evidence supporting this mechanism showed greater relaxation rates for colored specimens, whereas fluoride-releasing elastomerics could not deliver force levels comparable with those of conventional elastomerics after a week of fixed strain.53,54 In the future, polymers with less reactivity will become necessary to minimize water sorption, solubility, and associated degradation sequelae, which affect the mechanical properties of the material. Researchers reported that polymers treated with compounds have decreased water solubility and are not prone to hydrolytic degradation when tested in vitro.54 Although this 258 Eliades American Journal of Orthodontics and Dentofacial Orthopedics February 2007 Fig 5. Schematic of effect of fillers (cubes) on tensile strength of filled and stretched elastomer in which fibril has been outlined. Shorter fibrils, bonded to fillers (lower drawing), cannot extend to same length as long ones because fillers are stiffer than matrix, and therefore adjacent fibrils fracture. Unbonded ones (upper drawing) will probably survive longer, but tensile load is distributed to fewer fibrils, and some cannot withstand load and ultimately break. This might have softening effect on stretched material. innovative process might be a viable future application, further evidence must be available from in vivo-aged samples to validate its effectiveness. In the oral cavity, absorption of lipids was shown to cause potent structural alterations on polyurethanes because these complexes act as nuclei for calcification, lower the glass transition temperature of the polymer inducing a plasticizing effect, and decrease the free energy for crack propagation.56 Projected short-term future developments in orthodontic elastomers ● ● ● Introduction of new polymers with reduced and predetermined relaxation. Development and large-scale use of fluoride-releasing elastomers with decreased force decay. Application of films that can decrease reactivity of elastomers with water, resulting in less swelling and degradation. FUTURE ASSESSMENT OF BIOLOGICAL PROPERTIES OF POLYMERIC BIOMATERIALS: BEYOND CONVENTIONAL CYTOTOXICITY In recent years, the investigation of the biological properties of materials has departed from various routine cytotoxicity assays, ie, MTT and DNA synthesis. The wide application of new polymers has provoked investigation of their long-term effects at subtoxic levels—an array of effects with little relevance to common research approaches exploring biocompatibility. Fig 6. Chemical structures: A, BPA and B, hormone 17-␤ estradiol. Resemblance leads to BPA’s estrogenic action. A concern associated with polymeric adhesives and plastic brackets relates to the possibility of bisphenol-A (BPA) release.57,58 BPA is used in the production of epoxy resins and polycarbonate plastics for food-contact surface coatings in cans, metal jar lids, and adhesives, and as a coating for polyvinyl chloride water pipes.57-59 Most governmental standards do not consider BPA a pollutant of concern, although recent research indicates that it can act as an estrogen in biological systems. Estrogen analogs have the effect of feminizing the male fetus in animals, as well as interfering with normal estrogen production in females.60-64 This effect arises from its composition and structure, which demonstrate a remarkable resemblance to the female hormone estradiol (Fig 6). As a result, the body recognizes BPA as a female hormone and adapts its function accordingly, leading to a series of effects that include premature puberty and ovarian cancer in females, and disruption of the maturation of male reproductive organs. This mimicking effect occurs at Eliades 259 American Journal of Orthodontics and Dentofacial Orthopedics Volume 131, Number 2 levels far below the recommended safe concentrations listed by various organizations such as the US Environmental Protection Agency.57 The turmoil in the dental literature was initially provoked by a study published by a Spanish group of researchers, Olea et al,65 who reported elevated salivary levels of BPA in patients with dental sealants. Their results confirmed the leaching of estrogenic monomers into the environment by Bis-GMAbased composites and sealants in concentrations at which biologic effects had been previously demonstrated in in-vivo experimental models. However, the significance of the amount of BPA eluted from materials depends on the actual biological effects induced in humans and not the elution per se.66 The orthodontic concerns derive from the fact that monomers identical to those used for sealants are used in orthodontic polymeric adhesives, and plastic brackets and other polycarbonate-made appliances might also be sources of BPA.67-69 These studies demonstrated increases in BPA elution from polycarbonate brackets and adhesives with time in vitro. The literature cited by Olea et al65 in support of their statement indicated that 3 days of exposure to levels of BPA (60-100 ␮g per day) promoted cellular proliferation in rat uterus and vagina, yielding molecular and morphologic alterations nearly identical to those induced by estradiol. In addition, the authors claimed that some people might be sensitive to BPA, and thus the effects of low doses might not hold true for them, and other plastics might also expose humans to additive risks.70 It is surprising that the results from this research team were not confirmed by other independent laboratories. On the contrary, many others arrived at opposite conclusions.71-74 The latter group of studies suggested that the results of Olea et al65 were due to the use of bulky sealants that were not polymerized properly.73,74 In addition, investigations showed that BPA release from sealants was very low even when compared with the threshold for long-term exposure, which is 0.05 mg per kilogram of body weight daily. Nathanson et al74 measured BPA released from sealants in vitro and reported that this did not exceed 0.0001 ␮g of BPA per gram of sealant. Although this seems extremely small, BPA has estrogenic activity in vitro at concentrations as low as 10⫺6 mol/L.75,76 The intense interest in the literature on this subject has provoked the publication of guidelines by various organizations and legislative bodies. The American Dental Association (ADA) released a statement, referring to relevant experiments, that assessed the potential of BPA release by 12 brands of dental sealants that currently carry the ADA Seal of Acceptance. This research showed that 11 of the 12 sealants included in the study leached no detectable BPA, but 1 brand leached BPA within the range of detection threshold of the experimental method (5 ppb). The relevant ADA committee also examined blood samples from 40 dentists, 30 patients who had received sealants, and 10 controls. BPA was not found in any of those blood samples, suggesting that, if BPA is leached from dental sealants, it is not detectable in blood tests.77-79 In Europe, the Scientific Committee on Toxicity, Ecotoxicity, and the Environment of the European Union’s directorate of Human Health and Consumer Protection also produced relevant documents. This committee concluded that, although no carcinogenic, mutagenic, or genotoxic effects have been documented for BPA, its potential reproductive toxicity requires further investigation.58 The industry has been responsive to these concerns, and at least 2 manufacturers are currently developing sealants without BPA-forming byproducts based on alternative monomers without benzoic aromatic rings. These aromatic rings are part of the monomer systems of adhesives and plastics. In adhesive technology, monomers with those rings are usually of high molecular weight and thereby provide stability and the necessary consistency of the paste for handling purposes. Nevertheless, these materials have lower degrees of cure because of the stiffness of the molecule. To alleviate this effect, high molecular weight monomers are mixed with low molecular weight ones, which are capable of polymerizing at much higher percentages. The latter monomers, however, are very reactive and usually are found at higher proportions in immersion media.80 Thus, exclusion of the aromatic ring-containing monomer would result in some undesirable effects in product handling and potentially in the amount of unpolymerized monomer released. Therefore, there is a need for replacing the backbone monomer with an alternative high-molecular weight one that does not contain benzoic rings and will be free of other adverse effects. Projected short-term future developments in orthodontic polymeric materials ● ● Introduction of new monomers without the undesirable potential effects of benzoic rings; modification of manufacturing methods or synthesis of adhesives and plastic brackets to ensure that no BPA is released during use, including aging. Large-scale in-vitro and animal studies focusing on the effects of BPA released from dental and orth- 260 Eliades odontic materials on developmental and reproductive toxicity. CONCLUSIONS Advancements in orthodontic materials have had an impact in orthodontic practice, with prominent effects in mechanotherapy and biomechanics research.81,82 The search for efficient materials and convenient techniques to shorten treatment times has made significant progress, and the future outlook of orthodontic practice will change notably. However, the assessment of biocompatibility of materials must also evolve to incorporate aspects of the biologic properties of materials, which will not be confined to in-vitro cytotoxicity assays. The author thanks William A. Brantley, Ohio State University, Columbus, Ohio; Claude Matasa, Orthocycle; Spiros Zinelis, University of Athens, Athens, Greece, for discussions on the metallurgy of orthodontic alloys; and Petros Tsakiridis, University of Athens, for the reconstruction of the 3D x-ray microtomography images of brackets. REFERENCES 1. Ricketts RM. The reappearing American. 1993. Wright: Scottsdale, Ariz: p. 176. 2. Menezes LM, Campos LC, Quintao CC, Bolognese AM. Hypersensitivity to metals in orthodontics. Am J Orthod Dentofacial Orthop 2004;126:58-64. 3. Kusy RP. Clinical response to allergies in patients. Am J Orthod Dentofacial Orthop 2004;125:544-7. 4. Kerosuo H, Kullaa A, Kerosuo E, Kanerva L, Hensten-Pettersen A. 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Editors of the International Journal of Orthodontia (1915-1918), International Journal of Orthodontia & Oral Surgery (1919-1921), International Journal of Orthodontia, Oral Surgery and Radiography (1922-1932), International Journal of Orthodontia and Dentistry of Children (1933-1935), International Journal of Orthodontics and Oral Surgery (1936-1937), American Journal of Orthodontics and Oral Surgery (1938-1947), American Journal of Orthodontics (1948-1986), and American Journal of Orthodontics and Dentofacial Orthopedics (1986-present) 1915 1931 1968 1978 1985 2000 to to to to to to 1932 Martin Dewey 1968 H. C. Pollock 1978 B. F. Dewel 1985 Wayne G. Watson 2000 Thomas M. Graber present David L. Turpin