CLINICAL AND SCIENTIFIC DOSSIER › wp... · Laser Med Sci., 2012 Nov 9. ... Presented in Annual...

CLINICAL AND SCIENTIFIC DOSSIER

OrthoPulse™LIGHT ACCELERATED ORTHODONTICS

September 2015

orthopulse.com 3

LIGHT ACCELERATED ORTHODONCTICS CLINICAL AND SCIENTIC DOSSIER

TOC

Light Accelerated Orthodontics™ Clinical and Scientific Dossier

TOC

1. Executive Summary

2. Introduction

3. Photobiomodulation

4. Photobiomodulation Background

5. OrthoPulse™ Clinical Evidence

6. OrthoPulse™ in vitro and in vivo Evidence

7. Selected Photobiomodulation Abstracts

8. References

4

6

8

12

14

22

30

36

4 OrthoPulse™ Clinical and Scientific Dossier - September 2015

Clinical Research Fixed Appliances

• No clinically significant root resorption1

• 46% increase in rate of space closure in adults; 28% increase in rate of space closure in adolescents compared to control2

• 54% reduction in time to achieve anterior alignment3

• 2.3x faster mean alignment rate4

1 Nimeri et al, The effect of photobiomodulation on root resorption during orthodontic treatment. Clin Cosmet Investig Dent 6:1-8.

2 Samara et al. Velocity of en-masse space closure with and without Photobiomodulation: a prospective RCT. In review.

3 Shaughnessy et al. Intra-oral Photobiomodulation induced orthodontic tooth alignment: pilot feasibility study. Forthcoming 2015.

4 Kau et al. Photobiomodulation accelerates orthodontic alignment in the early phase of treatment. Prog in Ortho., 14:30. 2013

Aligners

• 66% reduction in the average duration per aligner during OrthoPulse™ treatment as compared to the conventionally recommended aligner wear duration1

• No measurable root resorption in 6 months2

1 Dickerson, T. The effect of OrthoPulse™ on the rate of progression through Invisalign® aligners: a pilot study. To be submited for publication.

2 Dickerson, T. A randomized controlled crossover trial on the effect of OrthoPulse™ on the rate of orthodontic tooth movement during alignment with Invisalign® aligners. To be submited for publication.

Refer to Section 5

Photomodulation

The application of therapeutic light in the near infrared wavelength (800 - 1000nm) has been shown to produce beneficial biological effects in stressed and ischemic tissue (3000+ published peer-reviewed articles). Mitochondrial enzymes can absorb these photons and increase the production of ATP (energy) allowing enhanced tissue metabolizism.

Light Accelerated Orthodontics

OrthoPulse™ photobiomodulation enhances and accelerates bone and soft tissue remodeling leading to faster tooth movement and decreased orthodontic treatment time.

Biolux sponsors and supports research at these leading research institutions:

• Forsyth Institute, USA

• University of Alabama at Birmingham, USA

• University of Southern California, USA

• Kyung Hee University, Korea

• European University College, UAE

• University of Sydney, Australia

• Tufts University, USA

Since 2003, Biolux has sponsored over 20 university- and clinician-based in vitro, in vivo studies and clinical trials.

400+ patients treated in clinical trials worldwide.

OrthoPulse Clinical and Scientific Evidence Executive Summary

SECTION 1

orthopulse.com 5

Animal (in vivo) Research

• 46% acceleration of tooth movement in 620nm treated animals & 80% less root resorption1

• Significantly more mature bone in expanded sutures2

• Significantly lower failure rate of immediately loaded TADs3

• 2.8 – 3.7x faster rate of tooth movement4

1 Ekizer A et al. Effect of LED-mediated photobiomodulation therapy on orthodontic tooth movement and root resorption in rats. Laser Med Sci., 2012 Aug 29.

2 Ekizer A et al. Light-emitting diode photobiomodulation: effect on bone formation in orthopedically expanded suture in rats-early bone changes. Laser Med Sci., 2012 Nov 9.

3 Uysal T et al. Resonance frequency analysis of orthodontic miniscrews subjected to light-emitting diode photobiomodulation therapy. Eur J Orthod., 2012 Feb; 34(1):44-51.

4 Chiari S et al. Photobiomodulation-induced tooth movement using extra-oral transcutaneous phototherapy on the rat periodontium. To be submitted for publication.

Refer to Section 6

Cellular (in vitro) Research

• Modulated gene expression in human MSF cells1

• Increased proliferation of gingival fibroblasts and endothelial cells2

• Stimulated proliferation and mineralization of human osteoblasts3

• Inflamed PDL cell response modulated4

1 Yen et al. Visible red and infrared light stimulates differential gene expression in human MSF cells. Orthod Craniofac Res. 2015 Apr;18 Suppl 1:50-61

2 Iscan et al. Photobiostimulation of gingival fibroblast and vascular endothelial cell proliferation. Presented in Annual Meeting of Turkish Society of Orthodontics, October 26-30, 2014 Ankara, Turkey.

3 Le et al. Human osteoblast response to LED photobiomodulation. Presented at IADR 2015 General Session. Boston, MA. March 14, 2015.

4 Konerman et al. Impact of LED photobiomodulation on the gene expression profile of PDL cells under simulated inflammation. To be submitted for publication.

Refer to Section 6

OrthoPulse Clinical and Scientific Evidence Executive Summary

SECTION 1


LIGHT ACCELERATED ORTHODONCTICSCLINICAL AND SCIENTIC DOSSIER

SECTION 2

Introduction

Introduction

Orthodontic therapy is predictable1 where conventional methods result in the completion of treatment in 12 to 24 months and a variable follow-up period for retention. One of the common deterrents to orthodontic treatment is the length of time in which a patient needs to commit. Thus, there has been a continuous search for methods to enhance the rate and efficacy of orthodontic tooth movement2,3. At present, there are three main strategies to improve treatment efficiency.

The first approach is to create an accurate road map of the end point of orthodontic treatment and utilize sophisticated three-dimensional virtual plans to simulate and predict the possible pitfalls in a case4. Often, these provide the shortest pathway between the initial, malaligned tooth position and its final, corrected position, providing an excellent visualization for the delivery of the best biomechanical plan and serving for patient education.

A second approach aims to increase the rate of orthodontic tooth movement through biologically-based techniques6,7. One of the best-characterized methods is surgical corticotomy-accelerated orthodontics8-11. Clinicians raise surgical flaps around the dentoalveolar complex and create selective buccal and lingual decortications of the alveolar bone using rotary and hand instruments or piezoelectricity12. Active orthodontic treatment is applied almost immediately. While results from available data have been variable13-16, the most important finding was that there is a window of intervention for accelerated tooth movement following surgical procedures. Once the wound resolution of the corticotomy sites is completed, the ‘accelerated’ tooth movement returns to the rates of the control sites17-19. Surgery, even if it is highly effective and predictable, potentially carries the risk for morbidity and needs to be carefully planned with the orthodontic protocol and precisely timed for maximum effect during the course of treatment. In addition, beyond the clinical case series and anecdotal evidence, randomized clinical trials are required for

orthopulse.com 7


Introduction SECTION 2

an accurate assessment of the outcomes of surgical corticotomies in humans. Nonsurgical alternatives to the highly invasive surgical methods have been explored. Endothelial growth factors20, osteoclast precursors like osteocalcin, prostaglandins21, bone resorptive factors like RANKL22, leukotrienes23, and macrophage colony-stimulating factors have been tested. Studies in these areas are limited, which makes understanding these mechanisms difficult.

A third approach involves the enhancement of mechanical aspects of tooth movement26. Conventional efforts to this end have been focused on enhancing the biomaterial properties and biomechanical interactions of orthodontic brackets and wires based on innovations regarding orthodontic wires and self-ligating systems5. Collectively, the progress has reduced the binding interactions of brackets and established constant force systems. Arguably, these enhancements have reached their peak, and any further advancement would result in a minimal impact on the length of orthodontic treatment.

Another recently explored area involves device-assisted therapy to biologically enhance the orthodontic tooth movement. To this end, a number of systems such as light, electrical currents24, cyclic forces25, and resonance vibration26 have been introduced. This area is emerging while the majority of these methods have been limited to case reports.

Light Accelerated Orthodontics™ (LAO) is a technique within the scope of photobiomodulation or low-level laser therapy (LLLT). LAO shows promise in producing a noninvasive stimulation of the dentoalveolar complex with a potential impact on ATP production by mitochondrial cells. The assumption is that an increase in ATP at a localized site will induce cells to undergo remodeling. Cytochrome C oxidase mediates ATP production, which is upregulated two-fold by infrared light.27 During the tooth movement phase, higher ATP availability helps cells ‘turnover’ more efficiently leading to an increased remodeling process and accelerated tooth

movement. LAO may also be functioning through increased vascular activity28, which would also contribute to the rapid turnover of the bone. A number of clinical case series have suggested an enhanced impact by LAO29,30, increased velocity of canine movement, decreased pain31, and a significantly higher acceleration of retraction of treated canines32. However, there are also some studies that show questionable efficacy33,34.

Excerpted from: Kau CH, Kantarci A, Shaughnessy T, Vachiramon A, Santiwong P, De la Fuente A, Skrenes D, Ma D, Brawn P. Photobiomodulation accelerates orthodontic alignment in the early phase of treatment. Progress in Orthodontics 2013, 14:30

Refer to Section 5.1



SECTION 3

Photobiomodulation

3.1. Physiology

• “Light in the red to near infrared (NIR) range (600–1000 nm) generated by using low energy laser or light-emitting diode (LED) arrays has been reported to have beneficial biological effects in many injury models. Such photobiomodulation has been observed to increase mitochondrial metabolism, facilitate wound healing and promote angiogenesis in skin, bone, nerve and skeletal muscle in primary neurons.” 35

• US National Library of Medicine National Institutes of Health, pubmed.gov, lists 3,369 peer-reviewed published articles on Photobiomodulation / Low level light therapy (as of January 2013).

There exists an “optical window” between 600 – 1200nm in biologic tissues. This allows for maximum tissue penetration of photons.36

• Ex-vivo biopsy tissue study shows higher wavelengths penetrate tissue deeper, Stolik et al, Ex-vivo biopsy tissue study evaluated tissue penetration depths of 632, 675,780 and 835nm light measurement of the penetration depths of red and near infrared light in human ex-vivo tissues.

orthopulse.com 9


Photobiomodulation SECTION 3

Activation of cytochrome c cxidase by light initiates intracellular signaling cascades, resulting in various cellular responses including ATP production in the mitochondria.

Action spectra of DNA & RNA synthesis rate matches CCO absorption spectra.

• Karu and Kolyakov38 performed experiments to find action spectra based on DNA and RNA synthesis rate. HeLa cell mono-layers irradiated with monochromatic light of 580-860 nm.38

Exact action spectra for cellular responses relevant to phototherapy.

3.2. Mechanism of Action

Mechanisms thought to be involved in photobiomodulation biological response:

• Mitochondrial chromophores (inc. cytochrome C oxidase) absorb photons, which leads to h proton pumping and h ATP production g increased energy available to the cell g increased / normalized metabolism

• Reactive Oxygen Species (ROS) production and mitochondrial signaling stimulates/suppresses transcription factors, DNA/RNA synthesis g plethora of tissue/cellular activity

• Inducible Nitric Oxide (NO) production through absorption of photons by Nitric Oxide Synthase g increased micro and regional blood flow and osteoclastic activity

Otto Warburg discovered cytochrome c oxidase (CCO), the terminal enzyme in the mitochondrial oxidative respiration chain. He demonstrated that carbon monoxide inhibited CCO function and could be displaced by a flash of light. Displacing carbon monoxide, allows oxygen to bind again and resume CCO function and respiration

Photobiomodulation activates cytochrome c oxidase and increases mitochondrial electron transport which leads to increased ATP production.

• Eells et al37 showed that cytochrome c oxidase is the photoacceptor in the red to near-infrared spectral range.


LIGHT ACCELERATED ORTHODONCTICSCLINICAL AND SCIENTIC DOSSIER PhotobiomodulationSECTION

3

Oron et al39 showed twofold increase in ATP production with one LLLT treatment

• Method: NHNP were grown in tissue culture and were treated by Ga-As laser (808 nm, 50 mW/cm2, 0.05 J/cm2), and ATP was determined at 10 min after laser application

• Result: LLLT treatment Group shows a twofold ATP production

3.3. Genome Activation

Multiple genetic pathways are stimulated by 850nm IR light

• Deregulation of specific sets of genes detected by microarray analysis of marrow stromal fibroblast cells

Yen S, Guo J, Wang Q, Le A, Shi S. Center for Craniofacial Molecular Biology, USC. Orthod Craniofac Res. 2015 Apr;18 Suppl 1:50-61

Refer to Section 6.1

orthopulse.com 11


SECTION 3

Photobiomodulation

MECHANISM OFACTION

SCHEMA

ATP production is driven by a high proton concentration in the inner mitochondrial

membrane

Stressed cells have decreased metabolism, thus lower proton concentration and lower ATP

production

Photobiomodulation increases ATP production by stimulating CCO to absorb photons and

pump protons

As a result of increased energy ATP, mitochondrial signaling, and up/down regulation

of genes. A plethora of tissue/cellular activity begins.


LIGHT ACCELERATED ORTHODONCTICSCLINICAL AND SCIENTIC DOSSIER PhotobiomodulationSECTION

4

4.1. Summary of Key in vitro Bone Metabolism Findings

• Increases osteocyte numbers40 ,41

• Increases DNA synthesis42,43

• Increases collagen production 44

• Increases ALP activity and number of mineral nodules45

• Increases differentiation and proliferation of human osteoblasts46

• Increases bone nodule formation, ALP activity and gene expression47

• Increases osteoblastic activity48

• Increases ostoclastic activity49

• Increases the velocity of tooth movement through the stimulation of the osteoclasts and osteoblasts50

orthopulse.com 13


SECTION 4

Photobiomodulation

4.2. Summary of Key in vivo Orthodontic Findings

• Low-level laser (LLL) therapy accelerates bone regeneration in the midpalatal suture following palatal expansion in the rat model51

• Kawasaki and Shimizu52 concluded that low energy laser irradiation can accelerate tooth movement accompanied with alveolar bone remodeling in the rat model

• The same effects were observed when the LLL therapy was applied to the rabbit model53

Fujita et al54 demonstrated that laser irradiation stimulates the velocity of tooth movement via induction of RANK and RANKL in rats.

• Increased expression of fibronectin and Type I collagen in LLL tooth movement in rats55.

• Goulart et al56 showed lower dosage (5J/cm2) of LLL accelerates dog premolar tooth movement; higher dosage (35J/cm2) may retard it.

• LLLT accelerates the velocity of tooth movement via stimulation of the alveolar bone remodeling in rats57.

• LLLT facilitates the velocity of tooth movement and MMP-9, cathepsin K, and integrin subunits of alpha(v)beta3 expression in rats58.

LLLT significantly increased PDL cell proliferation, decreased PDL cell inflammation, and increased PDL OC activity.59


LIGHT ACCELERATED ORTHODONCTICSCLINICAL AND SCIENTIC DOSSIER OrthoPulse™ Clinical EvidenceSECTION

5

5.1. Photobiomodulation accelerates orthodontic alignment in the early phase of treatment Kau CH1, Kantarci A2, Shaughnessy T3, Vachiramon A, Santiwong P, De la Fuente A, Skrenes D, Ma D, Brawn P. Progress in Orthodontics 2013, 14:301Department of Orthodontics, School of Dentistry, University of Alabama, Birmingham, AL 35233, USA2Forsyth Institute, Cambridge, MA, USA3Shaughnessy Orthodontics, Private Practice, Suwanee, GA

Background: Numerous strategies have been proposed to decrease the treatment time a pa-tient requires in orthodontic treatment. Recently, a number of device-accelerated therapies have emerged in orthodontics. Photobiomodulation is an emerging area of science that has clinical ap-plications in a number of human biological pro-cesses. The aim of this study was to determine if photobiomodulation reduces the treatment time in the alignment phase of orthodontic treatment.

Methods: This multicenter clinical trial was per-formed on 90 subjects (73 test subjects and 17 controls), and Little’s Index of Irregularity (LII) was used as a measure of the rate of change of tooth movement. Subjects requiring orthodontic treat-ment were recruited into the study, and the LII was measured at regular time intervals. Test sub-jects used a device which produced near-infrared light with a continuous 850-nm wavelength. The surface of the cheek was irradiated with a power density of 60 mW/cm2 for 20 or 30 min/day or 60 min/week to achieve total energy densities of 72, 108, or 216 J/cm2, respectively. All subjects were fitted with traditional orthodontic brackets and wires. The wire sequences for each site were standardized to an initial round alignment wire (014 NiTi or 016 NiTi) and then advanced through a progression of stiffer arch wires unit alignment occurred (LII < 1 mm).

Results: The mean LII scores at the start of the clinical trial for the test and control groups were 6.35 and 5.04 mm, respectively. Multi-level mixed effect regression analysis was

orthopulse.com 15


OrthoPulse™ Clinical Evidence SECTION 5

5.2. The effect of photobiomodulation on root resorption during orthodontic treatment Nimeri G1, Kau CH1, Corona R1, Shelly J1 Clin Cosmet Investig Dent. 2014:6

1Department of Orthodontics, University of Alabama, Birmingham, AL, USA.

Abstract: Photobiomodulation is used to accel-erate tooth movement during orthodontic treat-ments. The changes in root morphology in a group of orthodontic patients who received pho-tobiomodulation were evaluated using the cone beam computed tomography technique. The de-vice used is called OrthoPulse, which produces low levels of light with a near infrared wavelength of 850 nm and an intensity of 60 mW/cm2 con-tinuous wave. Twenty orthodontic patients were recruited for these experiments, all with class 1 malocclusion and with Little’s Irregularity Index (2 mm) in either of the arches. Root resorption was detected by measuring changes in tooth length using cone beam computed tomography. These changes were measured before the orthodontic treatment and use of low-level laser therapy and after finishing the alignment level. Little’s Irregu-larity Index for all the patients was calculated in both the maxilla and mandible and patients were divided into three groups for further analysis, which were then compared to the root resorption measurements. Our results showed that photobi-omodulation did not cause root resorption great-er than the normal range that is commonly de-tected in orthodontic treatments. Furthermore, no correlation between Little’s Irregularity Index and root resorption was detected.

This study was supported in part by Biolux Research.

performed on the data, and the mean rate of change in LII was 0.49 and 1.12 mm/week for the control and test groups, respectively.

Conclusions: Photobiomodulation produced clinically significant changes in the rates of tooth movement as compared to the control group during the alignment phase of orthodontic treatment.

Figure 4: Boxplots showing differences in alignment rates (mm/week) between control and test (LAO) patients. The box-plots were created using arch level data to provide a more accurate weighting of alignment rates over total treatment time. Arch level summaries and Wilcoxon rank-sum tests revealed that the combined LAO arches started at a higher average LII (8.39mm versus 6.67mm). There were no statisti-cally significant difference between the two groups in terms of destination LII. Outliers (rates greater than 3mm/week) were removed from the test group to make these figures more con-servative. The test group’s mean alignment rates were 0.99 compared to a control rate of 0.44, with a comparison group of 23 control arches and 111 treatment arches.



incisor type. No statistically significant changes in root lengths were noted above 0.32 mm.

5.3. Intraoral photobiomodulation and orthodontic treatment-induced root resorption: A preliminary study.Shaughnessy T1, Kantarci A2, Kau CH3, Skrenes D, Skrenes S, Ma D. In review.1Shaughnessy Orthodontics, Private Practice, Suwanee, GA2Forsyth Institute, Cambridge, MA, USA 3Department of Orthodontics, School of Dentistry, University of Alabama, Birmingham, AL 35233, USA

Introduction: External apical root resorption (EARR) is a common side effect of orthodontic treatment. The aim of our study was to deter-mine the degree of EARR in patients treated with intraoral photobiomodulation (PBM) in conjunc-tion with orthodontic treatment. Furthermore, the correlation between EARR and several po-tentially contributing factors was investigated.

Materials and Methods: Ten patients, aged 12 to 16 years were included in a study to accelerate tooth movement using PBM. The group received daily PBM treatment with an Orthopulse intra-oral LED device in combination with orthodontic treat-ment. The device produced near infrared light with a continuous 850-nm peak wavelength providing a mean daily energy density of approximately 9.5 J/cm² at the surface of the LED array. Panoramic radiographs were taken before orthodontic treat-ment (T0) and at the completion of the alignment phase of treatment (T1). EARR of the 4 maxillary incisors was determined by measuring the dif-ference in tooth length between the two images. Length measurements were made from the me-sial buccal roots to the distal extent of the crown.

Results: The overall mean EARR was found to be 0.74 mm (5th-95th percentile: -1.31-2.96). EARR was only significant at values be-low 0.32 mm. A multivariate regression analy-sis was used to determine the relation of EARR with several potentially influential variables.

Conclusion: EARR is correlated with Orthopulse PBM dosage, and the duration of treatment. However, it is not linked to ethnicity, sex, degree of initial crowding, or

OrthoPulse™ Clinical EvidenceSECTION 5

orthopulse.com 17

Conclusions: Our findings suggest that intra-oral PBM could be used to decrease an terior alignment treatment time, which could consequently decrease full orthodontic treatment time.

5.4. Intra-oral photobiomodulation-induced orthodontic tooth alignment: A pilot feasibility studyShaughnessy T1, Kantarci A2, Kau CH3, Skrenes D, Skrenes S, Ma D. Forthcoming 2015.1Shaughnessy Orthodontics, Private Practice, Suwanee, GA2Forsyth Institute, Cambridge, MA, USA 3Department of Orthodontics, School of Dentistry, University of Alabama, Birmingham, AL 35233, USA

Background: Numerous strategies have been pro-posed to decrease orthodontic treatment time. Photobiomodulation (PBM) has previously been demonstrated to assist in this objective. The aim of this pilot study was to test if intra-oral PBM increas-es the rate of tooth alignment and reduces the time required to resolve anterior dental crowding.

Methods: Nineteen orthodontic subjects with Class I or Class II malocclusion and Little’s Irregu-larity Index (LII) greater or equal to 3 mm were selected from a pool of applicants. The test group (N=11) received daily PBM treatment with an intra-oral LED device in combination with orth-odontic treatment, and the control group (N=8) received only orthodontic treatment. The PBM device produced near-infrared light with a con-tinuous 850-nm wavelength, generating an av-erage daily energy density of 9.5 J/cm². LII was measured at the start (T0) of orthodontic treat-ment until alignment was reached (T1, where LII < 1 mm). The rate of anterior alignment and treatment time was determined for both groups.

Results: The mean alignment rate for the PBM group was significantly faster than that of the control group, with rates of 1.27 and 0.44 mm/week, respectively (p=0.0002). Furthermore, the alignment treatment time was significantly faster for the PBM group, which was achieved in 48 days, as compared to the control group, which was achieved in 104 days (p=0.0049). These results demonstrated that intra-oral PBM increased the rate of tooth movement by 2.9-fold, which resulted in a 54% decrease in alignment duration compared to control.



OrthoPulse™ OPx1 and OPx2 treatments result in a significant reduction in the number of days required per aligner as com-pared to what is prescribed for conventional Invisalign treat-ment: 65% reduction for OPx1 and 69% reduction for OPx2.

5.5. The effect of OrthoPulse™ on the rate of progression through Invisalign®

aligners: a pilot studyDickerson T1. To be submitted for publication.1Dickerson Orthodontics, Private Practice, Phoenix, AZ

Introduction: Photobiomodulation (PBM) has previously been demonstrated to accelerate tooth movement in traditional orthodontic treatment. However, it has not yet been tested in conjunction with Invisalign aligners. The aim of this pilot study was to asses if PBM treatment can reduce the average wearing duration required for 7 and 14 day recommended aligners.

Materials and Methods: Nine patients aged 16-67 who presented for Invisalign treatment were recruited in the study. Implementing a crossover design, each patient established their control aligner wearing duration using a method of self-assessment. Following this control period, patients received daily PBM treatment with an OrthoPulse intra-oral LED device in combination with Invisalign treatment. The device produced near infrared light with a continuous 850-nm peak wavelength. Treatment was divided into two different regimens: 10 minutes of daily treatment (5 minutes per arch), or 20 minutes of daily treatment (10 minutes per arch). The average duration of aligner wearing during treatment was then compared to each patient’s control, and to the conventionally recommended wearing duration.

Results: Patients experienced a 66% reduction in the average duration per aligner during OPx1 treatment, and a 70% reduction during OPx2 treatment as compared to the conventionally recommended aligner wearing duration. Compared to the control period, patients showed a 51% and 56% decrease in aligner wearing duration for OPx1 and OPx2 treatments, respectively.

Conclusions: OrthoPulse treatment results in a significant reduction in the number of days required per aligner as compared to control, and to what is conventionally prescribed for Invisalign treatment.


orthopulse.com 19

periods, respectively. This indicates that the rate of tooth movement for the OrthoPulse™ period was 1.8-fold faster than that of the baseline period, with significance (p-value = 0.02). The presence of period effects were not supported. Carryover effects were also undetected, likely due to the adequate washout period utilized in our study.

The overall mean EARR was -0.673 mm, indicating marginal root elongation rather than resorption. Thus, no mean root resorption was detected after 6 months of OrthoPulse™ treatment. There was no gingival recession, pathological tooth mobility and post-orthodontic relapse reported by the PI at any point during the course of the study.

There were no patients discontinued from the study due to negative adverse events. There were no adverse events or side effects reported in this study, and none of the patients reported using anything beyond OTC medication to alleviate tooth and mouth discomfort.

In summary, OrthoPulse™ may be used to increase the rate of orthodontic tooth movement and decrease treatment time with aligner treatment.

5.6. A randomized controlled crossover trial on the effect of OrthoPulse™ on the rate of orthodontic tooth movement during alignment with Invisalign® aligners.Dickerson T1. To be submitted for publication.1Dickerson Orthodontics, Private Practice, Chandler, AZ

Study Purpose: The primary aim of this crossover study is to determine if daily OrthoPulse™ use affects the rate of orthodontic tooth movement during alignment with Invisalign® aligners in the mandibular arch.

The secondary aim of this study is to determine whether patients treated with OrthoPulse™ demonstrate root resorption beyond what is usually expected during orthodontic treatment.

The study also aims to collect confirmatory evidence on the safety of the device for which no serious adverse events are expected.

Effectiveness Objective: To compare the amount of tooth movement in millimeters per week according to the arch perimeter analysis between the baseline and OrthoPulse™ periods during aligner orthodontic treatment.

Safety Objective: To observe the safety of the device by observing the degree of root resorption as well as by freedom from any significant adverse events during the course of OrthoPulse™ treatment.

Study Population: A total of 21 patients from 14 to 53 years old received Invisalign® treatment in conjunction with 5-minute daily OrthoPulse™ treatments (OP), per arch.

Results: A total of 17 patients reached the primary outcome of the study, providing complete baseline and OrthoPulse™ tooth movement data. The average tooth movement rates were 0.126 and 0.231 mm/wk for the baseline and OrthoPulse™



Canada) during the en-masse retraction phase. Patients were required to maintain over 80% compliance with daily device use. Compliance was monitored by an inbuilt micro-processor embedded within the device controller.

Results: Sixty patients were randomized between the two groups of which 15 patients dropped out during the study period. A total of 45 patients with 123 extraction spaces were included in the primary analysis of the PBM group (n=23; mean age: 20.7 years) and the control group (n=22; mean age: 18.3 years). Patients treated with PBM exhibited a statistically significant faster velocity of space closure by 0.276 mm/month, {p<0.01, 95% Cl (0.082- 0.471)} over that of the control group. The mean velocity of space closure in the PBM group was (1.07 mm/month; SD 0.49) compared with the control group, which had an average velocity of (0.85 mm/month; SD 0.37).

Harms: No serious harms due to treatments were encountered during the study period. Conclusion: The results of this study suggest that PBM therapy may accelerate the rate of orthodontic space closure during en-masse retraction.

Trial registration: This trial and its protocol were not registered on a publicly accessible registry. Funding: Biolux Research (Vancouver, Canada) provided the PBM devices used in this study.

5.7. Velocity of en-masse space closure with and without photobiomodulation on root resorption during orthodontic treatment.Samara et al. In review.

Introduction: The objective of this two-arm parallel-randomized clinical trial was to assess the effectiveness of low-level light therapy (photobiomodulation) using an intra-oral light emitting diode (LED) device with respect to accelerating the rate of premolar extraction space closure during en-masse retraction. This trial was conducted between January 2013 and February 2014 in the orthodontic department of orthodontics at European University College.

Methods: The study included 60 orthodontic patients (age range, 11.3 to 47.1 years; mean age, 20.4 years) with premolar extractions. Patients (n=60) were randomized into the photobiomodulation (PBM) group (n=30) and a control group (n=30). Eligibility criteria included no active caries, good oral hygiene and an extraction orthodontic treatment plan. Extraction spaces were closed using NiTi closed springs utilizing (150 g) force. Extraction spaces were measured on study models and the date was recorded at the beginning of en-masse retraction (T1) and at space closure completion (T2).

Blinding: All of the measurements were obtained by a single investigator who was blinded to the allocation of study models to either group.

Outcome: The primary outcome was the velocity of extraction space closure (mm/month) during the period of en-masse retraction. Randomization: Treatment allocation was implemented using simple randomization by asking each patient to draw from a sealed envelope (n=60) indicating allocation to the PBM or control group. The allocation ratio was 1:1. Intervention: PBM group of patients (n=30) were treated with intra-oral infrared light therapy for 3 min per arch per day using OrthoPulse™ (Biolux Research, Vancouver,


orthopulse.com 21



LIGHT ACCELERATED ORTHODONCTICSCLINICAL AND SCIENTIC DOSSIER OrthoPulse™ in vitro and in vivo EvidenceSECTION

6

6.1. Visible red and infrared light alters gene expression in human marrow stromal fibroblast cells.Guo J1, Wang Q, Wai D, Zhang QZ, Shi SH, Le AD, Shi ST, Yen SL.1Center for Craniofacial Molecular Biology, Ostrow School of Dentistry, Univer-sity of Southern California, Los Angeles, CA, USA; Department of Orthodontics, School of Stomatology, Shandong University, Jinan, China.

Objectives: This study tested whether or not gene expression in human marrow stromal fibro-blast (MSF) cells depends on light wavelength and energy density.

Materials and Methods: Primary cultures of iso-lated human bone marrow stem cells (hBMSC) were exposed to visible red (VR, 633 nm) and in-frared (IR, 830 nm) radiation wavelengths from a light emitting diode (LED) over a range of energy densities (0.5, 1.0, 1.5, and 2.0 Joules/cm2) Cul-tured cells were assayed for cell proliferation, os-teogenic potential, adipogenesis, mRNA and pro-tein content. mRNA was analyzed by microarray and compared among different wavelengths and energy densities. Mesenchymal and epithelial cell responses were compared to determine whether responses were cell type specific. Protein array analysis was used to further analyze key path-ways identified by microarrays.

Result: Different wavelengths and energy densi-ties produced unique sets of genes identified by microarray analysis. Pathway analysis pointed to TGF-beta 1 in the visible red and Akt 1 in the infrared wavelengths as key pathways to study. TGF-beta protein arrays suggested switching from canonical to non-canonical TGF-beta path-ways with increases to longer IR wavelengths. Mi-croarrays suggest RANKL and MMP 10 followed IR energy density dose-response curves. Epithe-lial and mesenchymal cells respond differently to stimulation by light suggesting cell type-specific response is possible.

Conclusions: These studies demonstrate dif-ferential gene expression with different wave-

orthopulse.com 23


SECTION 6

OrthoPulse™ in vitro and in vivo Evidence

6.2. Light-emitting diode photobiomodulation: effect on bone formation in orthopedically expanded suture in rats-early bone changes. Ekizer A1, Uysal T, Güray E, Yüksel Y. Lasers Med Sci. 2012 Nov 9.

1 Faculty of Dentistry, Department of Orthodontics, Erciyes University, Kayseri, Turkey.

Abstract: The aim of this experimental study was to evaluate histomorphometrically the effects of light-emitting diode (LED) photobiomodulation therapy (LPT) on bone formation in response to expansion of the interpremaxillary suture in rats. Twenty male, 50- to 60-day-old Wistar rats were divided into two equal groups (control and exper-imental). Both groups were subjected to expan-sion for 5 days, and 50 cN of force was applied to the maxillary incisors with helical spring. An Os-seoPulse® LED device, 618-nm wavelength and 20-mW/cm(2) output power irradiation, was ap-plied to the interpremaxillary suture for 10 days. Bone formation in the sutural area was histomor-phometrically evaluated, including the amount of new bone formation (in square micrometers), number of osteoblasts, number of osteoclasts, and number of vessels. Mann-Whitney U test was used for statistical evaluation at p < 0.025 level. Significant differences were found between groups for all investigated histomorphometric parameters. New bone formation area (p = 0.024, 1.48-fold), number of osteoblasts (p < 0.001, 1.59-fold), number of osteoclasts (p = 0.004, 1.43-fold), and number of vessels (p = 0.007, 1.67-fold) showed higher values in the experimental group than the control. Bone histomorphometric mea-surements revealed that bone architecture in the LPT group was improved. The application of LPT can stimulate bone formation in the orthopedi-cally expanded interpremaxillary suture during expansion and the early phase of the retention periods.

lengths, energy densities and cell types. These differences in gene expression have the potential to be exploited for therapeutic purposes and can help explain contradictory results in the litera-ture when wavelengths, energy densities and cell types differ.


LIGHT ACCELERATED ORTHODONCTICSCLINICAL AND SCIENTIC DOSSIER OrthoPulse™ in vitro and in vivo EvidenceSECTION

6

6.4. Effect of LED-mediated-photobiomodulation therapy on orthodontic tooth movement and root resorption in rats.Ekizer A1, Uysal T, Guray E. Lasers Med Sci. 2013 July 17.

1 Faculty of Dentistry, Department of Orthodontics, Erciyes University, Kayseri, Turkey.

Abstract: The aim of this experimental study was to evaluate the effects of light-emitting diode-mediated-photobiomodulation therapy (LPT), on the rate of orthodontic tooth movement (TM) and orthodontically induced root resorption, in rats. Twenty male 12-week-old Wistar rats were separated into two groups (control and LPT) and 50 cN of force was applied between maxillary left molar and incisor with a coil spring. In the treat-ment group, LPT was applied with an energy density of 20 mW/cm2 over a period of 10 con-secutive days directly over the movement of the first molar teeth area. The distance between the teeth was measured with a digital caliper on days 0 (T0), 10 (T1), and 21 (T2) on dental cast models. The surface area of root resorption lacunae was measured histomorphometrically using digital photomicro- graphs. Mann–Whitney U and Wil-coxon tests were used for statistical evaluation at p < 0.05 level. TM during two different time inter-vals (T1–T0 and T2–T1) were compared for both groups and a statistically significant difference was found in the LPT group (p = 0.016). The TM amount at the first time period (1.31±0.36 mm) was significantly higher than the second time pe-riod (0.24 ± 0.23 mm) in the LPT group. Statistical analysis showed significant differences between two groups after treatment/observation period (p = 0.017). The magnitude of movement in the treatment group was higher (1.55 ± 0.33 mm) compared to the control group (1.06±0.35 mm). Histomorphometric analysis of root resorption, expressed as a percentage, showed that the aver-age relative root resorption affecting the maxil-lary molars on the TM side was 0.098 ± 0.066 in the LPT group and 0.494 ± 0.224 in the control

6.3. Resonance frequency analysis of orthodontic miniscrews subjected to light-emitting diode photobiomodulation therapy.Uysal T1, Ekizer A, Akcay H, Etoz O, Guray E. Eur J Orthod. 2012 Feb;34(1):44-51.

1Department of Orthodontics, Faculty of Dentistry, Erciyes University, Kayseri, Turkey

Abstract: The aim of this prospective experimen-tal study was to evaluate the effect of light-emit-ting diode (LED) photobiomodulation therapy (LPT) on the stability of immediately loaded mini-screws under different force levels, as assessed by resonance frequency analysis (RFA). Sixty tita-nium orthodontic miniscrews with a length of 8 mm and a diameter of 1.4 mm were implanted into cortical bone by closed flap technique in each proximal tibia of 15 New Zealand white adult male rabbits (n = 30). The animals were randomly divided into irradiated and control groups under different force levels (0, 150, and 300 cN). Osseo-Pulse® LED device (Biolux Research Ltd.) 618 nm wavelength and 20 mW/cm(2) output power irra-diation (20 minutes/day) was applied to the mini-screws for 10 days. The RFA records were per-formed at miniscrew insertion session (T1) and 21 days after surgery (T2). Wilcoxon and Mann-Whit-ney U-tests were used for statistical evaluation at P < 0.005 level. It was found that initial primer stability of all miniscrews was similar in all groups at the start of the experimental procedure. Sta-tistically significant differences were found for changes in implant stability quotient (ISQ) values between LED-photobiomodulated group and the control (0 cN, P = 0.001; 150 cN, P < 0.001; and 300 cN, P < 0.001). Significant increase was found in ISQ values of LPT applied miniscrews under 0 cN (+11.63 ISQ), 150 cN (+10.50 ISQ), and 300 cN (+7.00 ISQ) force during observation period. By the increase of force levels, it was determined that ISQ values decreased in non-irradiated con-trol miniscrews. Within the limits of this in vivo study, the present RFA findings suggest that LPT might have a favourable effect on healing and attachment of titanium orthodontic miniscrews.

orthopulse.com 25


OrthoPulse™ in vitro and in vivo Evidence SECTION 6

6.5. Photobiomodulation-induced orthodontic tooth movement.Chiari S1,2, Baloul S1,3, Goguet-Surmenian E1, Dyke T1, Kantarci A1. To be submitted for publication.

1Boston University Goldman School of Dental Medicine, Department of Peri-odontology and OralBiology, Boston MA USA2 University of Vienna, Department of Orthodontics, Vienna, Austria3 Boston University Goldman School of Dental Medicine, Department of Orthodontics, Boston MA USA

Objective: The study has been designed to assess the effect of LED radiation versus NIR-Laser radia-tion phototherapy on the rate of the orthodontic tooth movement and the biological impact in the rat model.

Materials/Methods: Nineteen healthy adult CRL-CD male rats with a body weight of 350-400 g were used as experimental animals. The orth-odontic appliances were placed to mesially move the left maxillary 1st molar. The test animals in phototherapy groups daily received LED or Laser applications while the stability of the orthodontic appliances were constantly checked under iso-flurane anesthesia. All animals were constantly monitored for 21 days. Two different application times were selected to deliver the two different doses: 333 seconds (5 minutes and 33 seconds) or 1000 seconds (16 minutes and 40 seconds) and the photobiomodulation test groups were designated as LED-Short, Laser-Short, LED-Long, or Laser-Long accordingly. Animals in the LED-Short group, the device was applied for a cumu-lative energy dose of 10J/cm2; for the LED-Long group for 30J/cm2; for animals in the Laser-Short group for 10J/cm2; and for the Laser-Long group for 30J/cm2.

Results: The Faxitron analyses demonstrated that mesial movement of the first molar in three (LED-Long, Laser- Short, Laser-Long: 1.46 to 1.88 mm) of the four test groups with light application compared was significantly enhanced compared to the tooth movement (0.51±0.05 mm) alone (p<0.05). The magnitude of movement in the fourth group (LED-Short) was also higher

group. Statistically significant inhibition of rootresorption with LPT was determined (p < 0.001) on the TM side. The LPT method has the potential of accelerating orthodontic tooth movement and inhibitory effects on orthodontically induced re-sorptive activity.


6.6. The effect of light-emitting diode and laser on mandibular growth in rats.El-Bialy T1, Alhadlaq A, Felemban N, Yeung J, Ebrahim A, H Hassan A. Angle Orthod. 2014 Jul 14.

1 Associate Professor, Department of Orthodontics, School of Dentistry, Facul-ty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada.

Objective: To evaluate the effect of a light-emit-ting diode (LED) and/or low-level laser (LLL) with or without the use of anterior bite jumping appli-ances (also known as functional appliances [FAs]) on mandibular growth in rats.

Materials and Methods: Thirty-six 8-week-old male Sprague-Dawley rats weighing 200 g were obtained from Charles River Canada (St. Constant, QC, Canada) and were divided into six groups of six animals each. Groups were as follows: group 1: LLL; group 2: LLL + FA; group 3: LED; group 4: LED + FA; group 5: FA; and group 6: control (no treatment). Mandibular growth was evaluated by histomorphometric and micro computed tomo-graphic (microCT) analyses.

Results: The LED and LED + FA groups showed an increase in all condylar tissue parameters com-pared with other groups.

Conclusions: The LED-treated groups showed more mandibular growth stimulation compared with the laser groups.

OrthoPulse™ in vitro and in vivo EvidenceSECTION 6

(1.17±0.70 mm) compared to the TM group but the difference was not statistically significant. Collectively, all light application groups resulted in significantly more tooth movement compared to the TM group (p<0.05). When NIR (LASER) groups were compared to LED-treated groups, there was no statistically significant difference.

Conclusions: Both phototherapy methods have the potential of accelerating orthodontic tooth movement with an increase of bone remodeling in the interradicuar area. NIR-Laser irradiation and an increased application time per day lead to a more predictable tooth movement. LED applica-tion however provides a lower velocity compared to Laser application but the tooth movement can be considered of a higher quality, as indicated by the high bone regeneration and the bodily move-ment of the mesialized tooth and the less resorp-tive activity in the distance, in the third molar re-gion. No negative effects due to light penetration could be found in any group.

orthopulse.com 27

3 weeks. At week 5, however, 1 min radiation resulted in the highest ALP activity (1.8-fold higher than Group 2 and 4.4-fold higher than the control; p<0.05).

Conclusion: The data suggests that photobiomodulation stimulates the proliferation and mineralization of human osteoblasts by modulating their activity.

Support Funding Agency/Grant Number: Supported by NIH/NIDCR grant DE020906, Biolux Research and CAPES/BRAZIL grant.

6.7. Human osteoblast response to photobiomodulationLe A2, Mendes RT1,2, Iscan D2, Pamuk F2, Hasturk H2, A. Kantarci A2. Presented at IADR 2015 General Ses-sion. Boston, MA. March 14, 2015.1UEPG - Universidade Estadual de Ponta Grossa, Ponta Grossa, Paraná, Brazil2Applied Oral Sciences, The Forsyth Institute, Cambridge, Massachusetts, United States.

Objectives: Photobiomodulation is a non-inva-sive method for accelerated orthodontic tooth movement. Photobiomodulation is known to in-crease the rate of tooth movement by more than 2-fold compared to conventional techniques. The mechanism of action at the cellular level how-ever, remains unclear. The aim of this study was to investigate the effect of photobiomodulation on the proliferation and mineralization of human osteoblasts in vitro.

Methods: Human osteoblasts were seeded and cultured in a concentration of 104 cells per well. A near infrared light source with a continuous wavelength of 850 nm and a power density of 60 mW/cm2 was used to irradiate the cell lay-er directly, with a distance of 2.5 cm below the plate. The samples were divided into 3 groups per plate: Group 1– 1 minute daily radiation for 9 days; Group 2– 10-minute radiation only at Days 1 and 5 and Group 3– control (no radiation). MTT assay was used to study the proliferation and vi-ability of cells for 9 days over the course of the experiment (5 weeks). Alkaline phosphatase (ALP) activity was measured once a week.

Results: Photobiomodulation increased osteoblast proliferation in a dose-dependent manner. 10 minutes radiation resulted in a significantly higher proliferation compared to control and 1 minute radiation (p<0.05). At day 5, proliferation in Group 1 was 1.8-fold higher than the control and remained higher up to day 8 (p<0.05). After day 8, all groups showed a decrease in proliferation. Photobiomodulation also dose-dependently increased the ALP activity, which was higher for Group 2 during the first



growth and the impact of LEDT is dose-dependent.


6.8. Photobiostimulation of gingival fibroblast and vascular endothelial cell proliferationIscan D1,2, Mendes R1, Kantarci A1. Presented in Annual Meeting of Turkish Society of Orthodontics, October 26-30, 2014 Ankara, Turkey.1 Forsyth Institute, Cambridge, MA, USA2 Marmara University, Istanbul, Turkey

Background and Objective: Photobiomodulation is a non-invasive method for accelerated orthodontic tooth movement. LED treatment (LEDT) increases the rate of tooth movement by more than 2-fold compared to the conventional techniques. The mechanism of action at the cellular level however, is unclear. The aim of this study was to investigate the impact of LED on the proliferation of human gingival fibroblasts (HGF) and vascular endothelial cells (HUVEC) in vitro.

Materials and Methods: HGF and HUVEC’s were plated in 96-well-plates with a concentration of 104 cells per well. The setup was designed to irradiate the cell layer directly, with a distance of 2.5 cm below the plate. The near infrared light source was with a continuous wavelength of 850nm and a power density of 60mW/cm2. Group1 samples were irradiated every day for 1 minute while group2 samples were irradiated for 10 minutes during 8 days of experiment. Proliferation and viability of the cells were evaluated by the MTT assay.

Results: The impact was mostly similar for both cell lines. Viable number of HGF cells increased for irradiated groups in 24hours, while HUVEC cells were not affected for the first 72hours. There was an increase in cell proliferation in response to 1-minute irradiation and a decrease in the 10-minute irradiation group in comparison with control groups.

Conclusion: This data suggests that while a low dose exposure to LEDT stimulates the proliferation of gingival fibroblasts and endothelial cells, higher exposure inhibits their

OrthoPulse™ in vitro and in vivo EvidenceSECTION 6

orthopulse.com 29

6.9. Impact of LED photobiomodulation on the gene expression profile of PDL cells under simulated inflammationKonermann A 1, Jäger A1, Nguyen D2, Kantarci A2. To be submitted for publication.1 Department of Orthodontics, Medical Faculty, University of Bonn, Bonn, Germany2 Forsyth Institute, Cambridge, MA, USA

Background and objective: This study was de-signed to investigate the impact of LED treatment (LEDT) on the expression of osteogenic differen-tiation markers, inflammatory cytokines and mol-ecules involved in tissue metabolism in periodon-tal ligament (PDL) cells subjected to inflammatory challenge. The hypothesis was that inflammatory processes occurring during orthodontic tooth movement regulate PDL cell responses, which in turn might determine bone turnover.

Material and Methods: Human PDL cells were challenged with Interleukin (IL-) 1ß, Tumor Necro-sis Factor (TNF) α, or Transforming Growth Factor (TGF) β1. Cells were irradiated with a LEDT device at a wavelength of 850 nm and a power density of 60 mW/cm2 for 10 minutes either directly before application of the cytokine stimuli to mimic pro-phylactic irradiation, or 18 hours after the chal-lenge to simulate therapeutic irradiation in an inflammatory milieu. Quantitative real-time poly-merase chain reaction (Q-PCR) was performed for family with sequence similarity 5, member C (FAM5C), osteocalcin, S100A4, IL-1ß, TGFß1, tis-sue inhibitor of metalloproteinase-1 (TIMP1) and TIMP2. Statistical analysis was performed using one-way ANOVA and Bonferroni post-hoc test (p<0.05).

Results: FAM5C, undetected in resting cells, was induced 4.2-fold by TGFß1. LEDT increased FAM5C expression by 6.5-fold when applied simultaneously with TGFß1. Osteocalcin was significantly downregulated by IL-1ß+LEDT. When PDL cells were first challenged with TNFα and exposed to LEDT after 18 hours, osteocalcin was significantly reduced. LEDT did not have any


significant impact on the expression of S100A4 or TGFß1 alone while it decreased the baseline expression of IL-1ß. LEDT further prevented and reduced the upregulation of IL-1ß when cells were challenged with IL-1ß. IL-1ß upregulation by TNF-α (28.6-fold) was enhanced when LEDT was simultaneously applied (40.7-fold) or when the cells were first challenged with TNF-α and exposed to the LEDT after 18 hours (31-fold). TIMP1 and TIMP2 were significantly reduced by inflammatory cytokines. LEDT further decreased the inflammatory cytokine-suppressed TIMP1 and TIMP2 expression.

Conclusions: These data suggest that LEDT modulates the PDL cell response under resting and inflammatory conditions, which could determine the local tissue homeostasis and remodeling processes in the periodontium during orthodontic tooth movement.



LIGHT ACCELERATED ORTHODONCTICSCLINICAL AND SCIENTIC DOSSIER Selected Photobiomodulation AbstractsSECTION

7

7.1. Mechanism of Action

7.1.1. The nuts and bolts of low-level la-ser (light) therapy. Chung H1, Dai T, Sharma SK, Huang YY, Carroll JD, Hamblin MR. Ann Biomed Eng. 2012 Feb;40(2):516-33. 1Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA, USA

Abstract: Soon after the discovery of lasers in the 1960s it was realized that laser therapy had the potential to improve wound healing and reduce pain, inflammation and swelling. In recent years the field sometimes known as photobiomodula-tion has broadened to include light-emitting di-odes and other light sources, and the range of wavelengths used now includes many in the red and near infrared. The term “low level laser thera-py” or LLLThas become widely recognized and im-plies the existence of the biphasic dose response or the Arndt-Schulz curve. This review will cover the mechanisms of action of LLLT at a cellular and at a tissular level and will summarize the various light sources and principles of dosimetry that are employed in clinical practice. The range of diseas-es, injuries, and conditions that can be benefited by LLLT will be summarized with an emphasis on those that have reported randomized controlled clinical trials. Serious life-threatening diseases such as stroke, heart attack, spinal cord injury, and traumatic brain injury may soon be amena-ble to LLLT therapy.

orthopulse.com 31


Selected Photobiomodulation Abstracts SECTION 7

movement was significantly greater than that in the non-irradiated group at the end of the ex-periment (P < 0.05). Cells positively stained with TRAP, MMP-9, cathepsin K, and integrin subunits of alpha(v)beta3 were found to be significantly increased in the irradiated group on days 2-7 compared with those in the non-irradiated group (P < 0.05). These findings suggest that low-ener-gy laser irradiation facilitates the velocity of tooth movement and MMP-9, cathepsin K, and integ-rin subunits of alpha(v)beta3 expression in rats.

7.1.2. Low-energy laser irradiation facilitates the velocity of tooth movement and the expressions of matrix metalloproteinase-9, cathepsin K, and alpha(v) beta(3) integrin in rats. Yamaguchi M1, Hayashi M, Fujita S, Yoshida T, Utsunomiya T, Yamamoto H, Kasai K. Eur J Orthod. 2010 Apr;32(2):131-9. 1Department of Orthodontics, Nihon University School of Dentistry at Mat-sudo, Chiba, Japan

Abstract: It has previously been reported that low-energy laser irradiation stimulated the veloc-ity of tooth movement via the receptor activator of nuclear factor kappa B (RANK)/RANK ligand and the macrophage colony-stimulating factor/its receptor (c-Fms) systems. Matrix metallo-proteinase (MMP)-9, cathepsin K, and alpha(v) beta(3) [alpha(v)beta3] integrin are essential for osteoclastogenesis; therefore, the present study was designed to examine the effects of low-energy laser irradiation on the expression of MMP-9, cathepsin K, and alpha(v)beta3 inte-grin during experimental tooth movement. Fifty male, 6-week-old Wistar strain rats were used in the experiment. A total force of 10g was applied to the rat molars to induce tooth movement. A Ga-Al-As diode laser was used to irradiate the area around the moving tooth and, after 7 days, the amount of tooth movement was measured. To determine the amount of tooth movement, plaster models of the maxillae were made us-ing a silicone impression material before (day 0) and after tooth movement (days 1, 2, 3, 4, and 7). The models were scanned using a contact-type three-dimensional (3-D) measurement apparatus. Immunohistochemical staining for MMP-9, cathepsin K, and integrin subunits of alpha(v)beta3 was performed. Intergroup com-parisons of the average values were conducted with a Mann-Whitney U-test for tooth movement and the number of tartrate-resistant acid phos-phatase (TRAP), MMP-9, cathepsin K, and integ-rin subunits of alpha(v)beta3-positive cells. In the laser-irradiated group, the amount of tooth


LIGHT ACCELERATED ORTHODONCTICSCLINICAL AND SCIENTIC DOSSIER Selected Photobiomodulation AbstractsSECTION

7

teoblastic and osteoclastic cell proliferation and function during orthodontic tooth movement.

7.1.3. Metrical and histological investigation of the effects of low-level laser therapy on orthodontic tooth movement. Altan BA1, Sokucu O, Ozkut MM, Inan S. Lasers Med Sci. 2012 Jan;27(1):131-40. 1Department of Orthodontics, Faculty of Dentistry, Cumhuriyet University, Sivas, Turkey

Abstract: The aim of this study was to evaluate the effects of 820-nm diode laser on osteoclas-tic and osteoblastic cell proliferation-activity and RANKL/OPG release during orthodontic tooth movement. Thirty-eight albino Wistar rats were used for this experiment. Maxillary incisors of the subjects were moved orthodontically by a helical spring with force of 20 g. An 820-nm Ga-Al-As di-ode laser with an output power of 100 mW and a fiber probe with spot size of 2 mm in diameter were used for laser treatment and irradiations were performed on 5 points at the distal side of the tooth root on the first, second, and 3rd days of the experiment. Total laser energy of 54 J (100 mW, 3.18 W/cm(2), 1717.2 J/cm(2)) was applied to group II and a total of 15 J (100 mW, 3.18 W/cm(2), 477 J/cm(2)) to group III. The experiment lasted for 8 days. The number of osteoclasts, osteoblasts, inflammatory cells and capillaries, and new bone formation were evaluated histologically. Besides immunohistochemical staining of PCNA, RANKL and OPG were also performed. No statistical dif-ference was found for the amount of tooth move-ment in between the control and study groups (p > 0.05). The number of osteoclasts, osteoblasts, inflammatory cells, capillary vascularization, and new bone formation were found to be in-creased significantly in group II (p < 0.05). Immu-nohistochemical staining findings showed that RANKL immunoreactivity was stronger in group II than in the other groups. As to OPG immuno-reactivity, no difference was found between the groups. Immunohistochemical parameters were higher in group III than in group I, while both were lower than group II. On the basis of these findings, low-level laser irradiation accelerates the bone remodeling process by stimulating os-

orthopulse.com 33


Selected Photobiomodulation Abstracts SECTION 7

sonable dose in the target zone leads to obtain-ing the desired biological effect and achievinga reduction of the orthodontic treatment time, although there are studies that do not demon-strate any benefit according to their values.

7.2. Systematic Review 7.2.1. Tooth movement in orthodontic treatment with low-level laser therapy: A systematic review of human and animal studies. Carvalho-Lobato P1, Garcia VJ, Kasem K, Ustrell-Torrent JM, Tallón-Walton V, Manzanares-Céspedes MC. Photomed Laser Surg. 2014 Mar 14.1Human Anatomy and Embryology Unit, HUBc, University of Barcelona , Barcelona, Spain.

Objective: This review attempts to organize the existing published literature regarding tooth movement in orthodontic treatment when low-level laser therapy (LLLT) is applied.

Background Data: The literature discusses differ-ent methods that have been developed to moti-vate the remodeling and decrease the duration of orthodontic treatment. The application of LLLT has been introduced to favor the biomechanics of tooth movements. However there is disagree-ment between authors as to whether LLLT reduc-es orthodontic treatment time, and the param-eters that are used vary.

Materials and methods: Studies in humans and animals in which LLLT was applied to increase the dental movement were reviewed. Three review-ers selected the articles. The resulting studies were analyzed according to the parameters used in the application of laser and existing changes clinically and histopathologically.

Results: Out of 84 studies, 5 human studies were selected in which canine traction had been per-formed after removing a premolar, and 11 stud-ies in rats were selected in which first premolar traction was realized. There were statistically sig-nificant changes in four human studies and eight animal studies.

Conclusions: Varying the wavelength with a rea-


LIGHT ACCELERATED ORTHODONCTICSCLINICAL AND SCIENTIC DOSSIER Selected Photobiomodulation Abstracts SECTION

7

at the optimal dose (which induces photobios-timulation of stem cells in the BM), or at a higherdose (such as five times the optimal dose), does not cause histopathological changes or neoplas-mic response in various organs in mice, as exam-ined over a period of 8 months.

7.3. Safety Assessment

7.3.1. Long-term safety of low-level laser therapy at different power densities and single or multiple applications to the bone marrow in mice.Tuby H1, Hertzberg E, Maltz L, Oron U. Photomed Laser Surg. 2013 Jun;31(6):269-73. 1Department of Zoology, The George S. Wise Faculty of Life Sciences, Tel-Aviv University Tel-Aviv, Israel.

Objective: The purpose of this study was to de-termine the long-term safety effect of low-level laser therapy (LLLT) to the bone marrow (BM) in mice.

Background Data: LLLT has been shown to have a photobiostimulatory effect on various cellu-lar processes and on stem cells. It was recently shown that applying LLLT to BM in rats post-myo-cardial infarction caused a marked reduction of scar tissue formation in the heart.

Methods: Eighty-three mice were divided into five groups: control sham-treated and laser-treated at measured density of either 4, 10, 18, or 40 mW/cm(2) at the BM level. The laser was applied to the exposed flat medial part of the tibia 8 mm from the knee joint for 100 sec. Mice were monitored for 8 months and then killed, and histopathology was performed on various organs.

Results: No histological differences were ob-served in the liver, kidneys, brain or BM of the laser-treated mice as compared with the sham-treated, control mice. Moreover, no neoplasmic response in the tissues was observed in the la-ser-treated groups as compared with the control, sham-treated mice. There were no significant histopathological differences among the same organs under different laser treatment regimes in response to the BM-derived mesenchymal stem cell proliferation following LLLT to the BM.Conclusions: LLLT applied multiple times either

orthopulse.com 35


SECTION 7

Selected Photobiomodulation Abstracts


LIGHT ACCELERATED ORTHODONCTICSCLINICAL AND SCIENTIC DOSSIER References SECTION

8

12. Murphy KG, Wilcko MT, Wilcko WM, Ferguson DJ. Periodontal accelerated osteogenic orthodon-tics: a description of the surgical technique. J Oral Maxillofac Surg. 2009; 67(10):2160–6.

13. Ren A, Lv T, Kang N, Zhao B, Chen Y, Bai D. Rapid orthodontic tooth movement aided by alveo-lar surgery in beagles. Am J Orthod Dentofacial Orthop. 2007; 2(160):1–10.

14. Kang N, Lu T, Ren AS, Huang L, Bai D. Effect of alveolar surgery-aided rapid orthodontic tooth movement on bone formation. Sichuan Da Xue Xue Bao Yi Xue Ban. 2006; 2:254–7.

15. Lv T, Kang N, Wang C, Han X, Chen Y, Bai D. Bio-logic response of rapid tooth movement with periodontal ligament distraction. Am J Orthod Dentofacial Orthop. 2009; 136(3):401–11.

16. Sebaoun JD, Kantarci A, Turner JW, Carvalho RS, Van Dyke TE, Ferguson DJ. Modeling of trabec-ular bone and lamina dura following selec-tive alveolar decortication in rats. J Periodontol. 2008; 79(9):1679–88.

17. Baloul SS, Gerstenfeld LC, Morgan EF, Carvalho RS, Van Dyke TE, Kantarci A. Mechanism of action and morphologic changes in the alveolar bone in response to selective alveolar decortica-tion-facilitated tooth movement. Am J Orthod Dentofacial Orthop. 2011; 139(4 Suppl):S83–101.

18. Aboul-Ela SM, El-Beialy AR, El-Sayed KM, Selim

EM, El-Mangoury NH, Mostafa YA. Miniscrew im-plant-supported maxillary canine retraction with and without corticotomy-facilitated or-thodontics. Am J Orthod Dentofacial Orthop. 2011; 139(2):252–9.

19. Han XL, Meng Y, Kang N, Lv T, Bai D. Expression of osteocalcin during surgically assisted rapid orthodontic tooth movement in beagle dogs. J Oral Maxillofac Surg. 2008; 66(12):2467–75.

20. Alves JB, Ferreira CL, Martins AF, Silva GA, Alves GD, Paulino TP, Ciancaglini P, Thedei G Jr, Napimo-ga MH. Local delivery of EGF-liposome mediat-ed bone modeling in orthodontic tooth move-ment by increasing RANKL expression. Life Sci. 2009; 85(19–20):693–9.

21. Leiker BJ, Nanda RS, Currier GF, Howes RI, Sinha PK. The effects of exogenous prostaglandins on orthodontic tooth movement in rats. Am J Or-thod Dentofacial Orthop. 1995; 108(4):380–8.

8.1. References1. Proffit WR, Fields HW, Sarver DM. Contemporary

Orthodontics. 5th ed. St Louis: Elsevier; 2012.

2. Kau CH. Biotechnology in Orthodontics. Dentistry. 2012; 2:e108.

3. Scott P, DiBiase AT, Sherriff M, Cobourne MT. Alignment efficiency of Damon self-ligating and conventional orthodontic bracket sys-tems: a randomized clinical trial. Am J Orthod Dentofacial Orthop. 2008; 134(4):470.e1–8.

4. Kau CH. Creation of the virtual patient for the study of facial morphology. Facial Plast Surg Clin North Am. 2011; 4:615–22.

5. Fleming PS, DiBiase AT, Lee RT. Self-ligating ap-pliances: evolution or revolution? J Clin Orthod. 2008; 42(11):641–51.

6. Krishnan V, Davidovitch Z. Cellular, molecular, and tissue-level reactions to orthodontic force. Am J Orthod Dentofacial Orthop. 2006; 129(4):469.e1–32.

7. Krishnan V, Davidovitch Z. On a path to unfold-ing the biological mechanisms of orthodontic tooth movement. J Dent Res. 2009; 88(7):597–608.

8. Iglesias-Linares A, Yanez-Vico RM, Moreno-Fer-nandez AM, Mendoza- Mendoza A, Solano-Reina E. Corticotomy-assisted orthodontic enhance-ment by bone morphogenetic protein-2 admin-istration. J Oral Maxillofac Surg. 2012; 70(2):e124–32.

9. Iseri H, Kisnisci R, Bzizi N, Tuz H. Rapid canine retraction and orthodontic treatment with dentoalveolar distraction osteogenesis. Am J Orthod Dentofacial Orthop. 2005; 127(5):533–41. quiz 625.

10. Wilcko MT, Wilcko WM, Murphy KG, Carroll WJ, Ferguson DJ, Miley DD, Bouquot JE. Full-thickness flap/subepithelial connective tissue grafting with intramarrow penetrations: three case re-ports of lingual root coverage. Int J Periodontics Restorative Dent. 2005; 25(6):561–9.

11. Wilcko WM, Wilcko T, Bouquot JE, Ferguson DJ. Rapid orthodontics with alveolar reshaping: two case reports of decrowding. Int J Periodontics Re-storative Dent. 2001; 21(1):9–19.

orthopulse.com 37


References SECTION 8

33. Youssef M, Ashkar S, Hamade E, Gutknecht N, Lampert F, Mir M. The effect of low-level laser therapy during orthodontic movement: a pre-liminary study. Lasers Med Sci. 2008; 23:27–33.

34. Kim SJ, Moon SU, Kang SG, Park YG. Effects of low-level laser therapy after corticision on tooth movement and paradental remodeling. Lasers Surg Med. 2009; 41:524–33.

35. Zhang R, et al. Near infrared light protects car-diomyocytes from hypoxia and reoxygenation injury by a nitric oxide dependant mechanism. J Mol & Cell Card. 2009; 46:4-14

36. Hamblin MR, Waynant RW, Anders J. Mechanisms for Low-Light Therapy, Proc. of SPIE Vol. 6140, 614001, (2006)

37. Eells JT, Henry MM, Summerfelt P, Wong-Riley MT, Buchmann EV, Kane M, Whelan NT, Whelan HT. Therapeutic photobiomodulation for metha-nol-induced retinal toxicity. Proc Natl Acad Sci USA. 2003; Mar 18; 100(6):3439-44

38. Karu TI, Kolyakov SF. Exact action spectra for cellular responses relevant to phototherapy. Photome Laser Surg. 2005; 23(4)

39. Ad N, Oron U. Impact of low level laser irradia-tion on infarct size in the rat following myocar-dial infarction. Int J Cardiol. 2001; 80:109-116.

40. 41. 42. 43. 44.

45. Ozawa Y, Shimizu N, Kariya G, Abiko Y. Formation at early stages of cell culture in rat calvarial cells. Bone 1998, 22:347-354.

46. Stein A, Benayahu D, Maltz M, Oron U. Low-Level daser irradiation promotes proliferation and differentiation of human osteoblasts in vitro. Photome Laser Surg. 2005, 23:161-166

47. Barushka O, Yaakobi T, Oron U. Effect of low-en-ergy laser (He-Ne) irradiation on the process of bone repair in the rat tibia. Bone 1995, 16:47-55.

48. Yaakobi T, Maltz L, Oron U. Promotion of bone repair in the cortical bone of the tibia in rats by low energy laser (He-Ne) irradiation. Calcif Tissue Int 1996, 59:297-300.

22. Kanzaki H, Chiba M, Arai K, Takahashi I, Haruyama N, Nishimura M, Mitani H. Local RANKL gene transfer to the periodontal tissue acceler-ates orthodontic tooth movement. Gene Ther. 2006; 13(8):678–85.

23. Hou Y, Liang T, Luo C. Effects of IL-1 on experi-mental tooth movement in rabbits. Zhonghua Kou Qiang Yi Xue Za Zhi. 1997; 1:46–8.

24. Hashimoto H. Effect of micro-pulsed electricity on experimental tooth movement. Nihon Kyo-sei Shika Gakkai Zasshi. 1990; 49(4):352–61.

25. Kau CH. A radiographic analysis of tooth mor-phology following the use of a novel cyclical force device in orthodontics. Head Face Med. 2011; 7:14.

26. Nishimura M, Chiba M, Ohashi T, Sato M, Shimizu Y, Igarashi K, Mitani H. Periodontal tissue acti-vation by vibration: intermittent stimulation by resonance vibration accelerates experi-mental tooth movement in rats. Am J Orthod Dentofacial Orthop. 2008; 133(4):572–83.

27. Oron U, Ilic S, De Taboada L, Streeter J. Ga-As (808 nm) laser irradiation enhances ATP production in human neuronal cells in culture. Photomed Laser Surg. 2007; 25(3):180–2.

28. Tuby H, Maltz L, Oron U. Low-level laser irradia-tion (LLLI) promotes proliferation of mesen-chymal and cardiac stem cells in culture. Lasers Surg Med. 2007; 39(4):373–8.

29. Eells JT, Henry MM, Summerfelt P, Wong-Riley MT, Buchmann EV, Kane M, Whelan NT, Whelan HT. Therapeutic photobiomodulation for metha-nol- induced retinal toxicity. Proc Natl Acad Sci USA. 2003; 100(6):3439–44.

30. Kau CH. Orthodontics in the 21st century: a view from across the pond. J Orthod. 2012; 39(2):75–6.

31. Sousa MV, Scanavini MA, Sannomiya EK, Velasco LG, Angelieri F. Influence of low-level laser on the speed of orthodontic movement. Photomed Laser Surg. 2011; 29(3):191–6.

32. Cruz DR, Kohara EK, Ribeiro MS, Wetter NU. Ef-fects of low-intensity laser therapy on the orthodontic movement velocity of human teeth: a preliminary study. Lasers Surg Med. 2004; 35(2):117–20.



59. Huang TH, Liu SL, Chen CL, Shie MY, Kao CT. Low-level laser effects on simulated orth-odontic tension side periodontal liga-ment cells. Photome Laser Surg. 2013; 31:1-6

60. Stolik S, Delgado JA, Pérez A, Anasagasti L,J Mea-surement of the penetration depths of red and near infrared light in human “ex vivo” tissues. Photochem Photobiol B. 2000 Sep;57(2-3):90-3

ReferencesSECTION 8

49. Kim HJ, Zhang K, Zhang L, Ross FP, Teitelbaum SL, Faccio R. The Src family kinase, Lyn, suppresses osteoclastogenesis in vitro and in vivo. Proc Natl Acad Sci USA. 2009 Feb 17;106(7):2325-30

50. 51. Saito S, Shimizu N. Stimulatory effects of low

power laser irradiation on bone regeneration in midpalatal suture during expansion in the rat. Am J Orthod Dentofac Orthop 1997;111:525-32

52. Kawasaki K, Shimizu N. Effects of low-energy la-ser irradiation on bone remodeling during ex-perimental tooth movement in rats. Lasers Surg Med. 2000;26(3):282-91.

53. Lu H, Zhu T. Effect of sensitized lymphocytes on rabbit calvarial osteoblasts. Zhonghua Yi Xue Za Zhi. 2001 Apr 10;81(7):429-31.

54. Fujita S, Yamaguchi M, Utsunomiya T, Yamamoto H, Kasai K. Low-energy laser stimulates tooth movement velocity via expression of RANK and RANKL. Orthod Craniofac Res. 2008 Aug;11(3):143-155.

55. Kim YD, Kim SS, Kim SJ, Kwon DW, Jeon ES, Son WS. Low-level laser irradiation facilitates fi-bronectin and collagen type I turnover during tooth movement in rats. Lasers Med Sci. 2010 Jan;25(1):25-31.

56. Goulart CS, Nouer PR, Mouramartins L, Garbin IU, de Fátima Zanirato Lizarelli R. Photoradiation and orthodontic movement: experimental study with canines. Photomed Laser Surg. 2006 Apr;24(2):192-6.

57. Yoshida T, Yamaguchi M, Utsunomiya T, Kato M, Arai Y, Kaneda T, Yamamoto H, Kasai K. Low-en-ergy laser irradiation accelerates the velocity of tooth movement via stimulation of the al-veolar bone remodeling. Orthod Craniofac Res 2009;12:289–298

58. Yamaguchi M et al. Low-energy laser irradia-tion facilitates the velocity of tooth movement and the expressions of matrix metalloprotein-ase-9, cathepsin K, and alpha(v) beta(3) integ-rin in rats. Eur J Orthod. 2010 Apr;32(2):131-9.

orthopulse.com 39




SECTION 8

References

Lane N. Power games. Nature, 2006 443: 901-903

Takeda Y . Irradiation effect of low-energy laser on alveolar bone after tooth extraction: Experimental study in rats. Int J Oral Maxillofac Surg 1988, 17:388-391.

Clokie C, Bentley KC, Head TW. The effects of the he-lium-neon laser on postsurgical discomfort: a pilot study. J Can Dent Assoc 1991, 57:584-586.

Bibikova A, Belkin V, Oron U. Enhancement of angio-genesis in regenerating gastrocnemius muscle of the toad (Bufo viridis) by low-energy laser irradia-tion. Anat Embyrol (Berl) 1994, 190: 597-602.

Barushka O, Yaakobi T, Oron U. Effect of low-energy laser (He-Ne) irradiation on the process of bone re-pair in the rat tibia.Bone 1995, 16:47-55.

Yaakobi T, Maltz L, Oron U. Promotion of bone repair in the cortical bone of the tibia in rats by low en-ergy laser (He-Ne) irradiation. Calcif Tissue Int 1996, 59:297-300.

Agaiby AD, Ghali LR, Wilson R, Dyson M. Laser modula-tion of angiogenic factor production by T-lympho-cytes. Lasers Surg Med 2000, 26:357-363.

Ozawa Y, Shimizu N, Kariya G, Abiko Y. Low-energy la-ser irradiation stimulates bone nodule formation at early stages of cell culture in rat calvarial cells. Bone 1998, 22:347-354.

Maegawa Y, Itoh T, Hosokawa T, Yaegashi K, et al. Ef-fects of near-infrared low-level laser irradiation on microcirculation. Lasers Surg Med 2000, 27:427-437.

Stadler I, Evans R, Kolb B, Naim JO, et al. In vitro ef-fects of low-level laser irradiation at 660 nm on pe-ripheral blood lymphocytes. Lasers Surg Med 2000, 27:255-261.

Ad N, Oron U. Impact of low level laser irradiation on infarct size in the rat following myocardial in-farction. Int J Cardiol 2001, 80:109-116.

Guzzardella GA, Fini M, Torricelli P, Giavaresi G, et al. Laser stimulation on bone defect healing: an in vi-tro study. Lasers Med Surg 2002, 17:216-230.

7.2. Additional Citations

Coombe AR, Ho CT, Darendeliler MA, Hunter N, Philips JR, Chapple CC, Yum LW. The effects of low level la-ser irradiation on osteoblastic cells. Clin Orthod Res. 2001 Feb;4(1):3-14.

Zhang H, Hou, JF, Wang W, Wei YJ, Hu SJ. Low Level Laser Irradiation Precondition to Create Friendly Milieu of Infracted Myocardium and Enhance Early Survival of Transplanted Bone Marrow Cells. of Cell and Mol Med 2009 Sep 1.

Kim, S-J, Moon S-U, Kang S-G, Park Y-G. Effects of Low-Level Laser Therapy After Corticision on Tooth Movement and Paradental Remodeling. Laser Surg Med 41:524–533 (2009

Karu T, Pyatibrat L, Kolyakov SF, Afanasyeva NI. Ab-sorption measurements of cell monolayers rele-vant to mechanisms of laser phototherapy: reduc-tion or oxidation of cytochrome c oxidase under laser radiation at 632.8nm. Photomed Laser Surg. 2008 26:593-599

Pretel H, Lizarelli RFZ, and Ramalho LTO. Effect of low-level laser therapy on bone repair: Histological study in rats. Lasers Surg. Med., 2007 39:788-796

Eells JT, Wong-Riley MTT, VerHoeve J, Henry M, Buch-man EV, Kane MP, Gould LJ, Das R, Jett M, Hodson BD, Margolis D, Whelan HT . Mitochondrial signal trans-duction in accelerated wound and retinal healing by near-infrared light therapy. Mitochondrion, 2006 4:559-567

Zhang R, et al. Near infrared light protects cardio-myocytes from hypoxia and reoxygenation injury by a nitric oxide dependant mechanism. J Mol & Cell Card., 2009 46:4-14

Ying R, Kiang HL, Whelan HT, Ealls JT, Wing-Riley MTT. Pretreatment with near-infrared light via light-emitting diode provides added benefit against ro-tenone- and MPP+ -induced neutrotoxicity. Brain Reseach, 2008 1243:167-173

Takeda Y . Irradiation effect of low-energy laser on alveolar bone after tooth extraction: Experimental study in rats. Int J Oral Maxillofac Surg 1988, 17:388-391.

orthopulse.com 41


Schindl A, Merwald H, Schindl L, Kaun C, Wojta J. Direct stimulatory effect of low-intensity 670 nm laser ir-radiation on human endothelial cell proliferation. Br. J Dermatol 2003, 148:224-336.

Eells JT, Henry MM, Summerfelt P, Wong-Riley MT, Bu-chmann EV, Kane M, Whelan NT, Whelan HT. Thera-peutic photobiomodulation for methanol-induced retinal toxicity. Proc Natl Acad Sci USA. 2003 Mar 18;100 (6):3439-44

Vinck EM, Cagnie BJ, Cornelissen MJ, Declercq HA, Cam-bier DC. Increased fibroblast proliferation induced by light emitting diode and low power laser irradia-tion. Lasers Med Sci. 2003; 18(2):95-9.

Wong-Riley MT, Bai X, Buchmann E, Whelan HT. Light-emitting diode treatment reverses the effect of TTX on cytochrome oxidase in neurons. Neuroreport. 2001 Oct 8; 12 (14):3033-7.

Whelan HT, Buchmann EV, Dhokalia A, Kane MP, Whel-an NT, Wong-Riley MT, Eells JT, Gould LJ, Hammamieh R, Das R, Jett M. Effect of NASA light-emitting diode irradiation on molecular changes for wound heal-ing in diabetic mice. J Clin Laser Med Surg. 2003 Apr; 21 (2):67-74.

Almeida-Lopes L, Rigau J, Zangaro RA, Guidugli-Neto J, et al. Comparison of the low level laser therapy effects on cultured human gingival fibroblast pro-liferation using different irradiance and same flu-ence. Lasers Surg Med 2001, 29:179-184.

Okajima M, Kobayashi H, Tokismitsu I, et al. Improve-ment of macromolecular clearance via lymph flow in hamster gingiva by low-power carbon dioxide laser-irradiation. Shimotoyodome. Lasers Surg Med 2001, 29:442-447

Whelan HT, Smits RL Jr, Buchman EV, Whelan NT, et al. Effect of NASA light-emitting diode irradiation on wound healing. J Clin Laser Med Surg 2001, 19:305-314.

Blaya DS, Guimaraes MB, Pozza DH, Weber JBB, do Oliviera MG. Histology study of the Effect of Laser Therapy on Bone Repair. J Cont. Dent. Pract. 2008 Sept.1, 9(6):1-8.

Kreisler M, Christoffers AB, Al-Haj H, Willershausen B, et al. Low level 809-nm diode laser-induced in vitro stimulation of the proliferation of human gingival fibroblasts. Lasers Surg Med 2002, 30:365-369.

Pereira AN, Eduardo Cde P, Matson E, Marques MM. Effect of low-power laser irradiation on cell growth and procollagen synthesis of cultured fibroblasts. Lasers Surg Med 2002, 31:263-267.

Silva Junior AN, Pinheiro AL, Oliveira MG, Weismann R, et al. Computerized morphometric assessment of the effect of low-level laser therapy on bone repair: an experimental animal study. J Clin Laser Med Surg 2002, 20:83-87.

Nicola RA, Jorgetti V, Rigau J, Pacheco MT, et al. Effect of low-power GaAlAs laser (660 nm) on bone structure and cell activity: an experimental animal study. La-sers Med Sci 2003, 18:89-94.

Ninomiya T, Miyamoto Y, Ito T, Yamashita A, et al. High-intensity pulsed laser irradiation accelerates bone formation in metaphyseal trabecular bone in rat femur. Bone Miner Metab 2003, 21:67-73.

Pinheiro AL, Limeira Junior Fde A, Gerbi ME, Ramalho LM, et al. Effect of 830-nm laser light on the repair of bone defects grafted with inorganic bovine bone and decalcified cortical osseous membrane. J Clin Laser Med Surg 2003, 21:301-306.

© Biolux Research Ltd. All rights reserved. Orthopulse is a registered trademark of Biolux Research. OPi-AC235 Rev 1506

Biolux Research is a world leader in the development of innovative Light Accelerated OrthodonticsTM technology and products for use in orthodontics, implantology, and other dentistry markets. Biolux focuses on product development and clinical research, and its proprietary, patent-pending technologies have been developed to enhance clinical outcomes and dramatically reduce treatment timelines in orthodontics and dentistry in a safe, effective and non-invasive approach.

Biolux Research230-825 Powell StreetVancouver BC V6A 1H7

bioluxresearch.comorthopulse.com

Date post:	05-Jul-2020
Category:	Documents
Upload:	others
View:	0 times
Download:	0 times

CLINICAL AND SCIENTIFIC DOSSIER › wp... · Laser Med Sci., 2012 Nov 9. ... Presented in Annual...

Documents