clinical and scientific dossier

Transcription

CLINICAL AND SCIENTIFIC DOSSIER
LIGHTLight
ACCELERATED
ORTHODONCTICS
Accelerated
Orthodontics™
CLINICAL
AND
SCIENTIC
Clinical and ScientificDOSSIER
Dossier
Table of Contents
1. Executive Summary
4
2. Introduction
8
3. What is Photobiomodulation?
10
4. Photobiomodulation Scientific Evidence in Orthodontics
14
5. OrthoPulse® Clinical Evidence
16
6. OrthoPulse® in vitro and in vivo Evidence
22
7. Selected Photobiomodulation Abstracts
32
8. References
38
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OrthoPulse® Clinical and Scientific
Evidence Executive Summary
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1
Photobiomodulation
The application of therapeutic light in the near
infrared wavelength (800 - 1000 nm) 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 Research has and continues to sponsor
and support 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, there have been over 30 OrthoPulse®
published clinical trials, as well as in vivo and in
vitro studies.
Published Clinical Research
Fixed Appliances
•
No clinically significant root resorption1,2
•
54% reduction in time to achieve anterior
alignment compared to control2
•
46% increase in rate of space closure in adults
compared to control3
1
Nimeri et al. The effect of photobiomodulation on root resorption
during orthodontic treatment. Clin Cosmet Investig Dent, 2014. 6:1-8.
2
Shaughnessy et al.
Intraoral photobiomodulation-induced
orthodontic tooth alignment: a preliminary study. BMC Oral Health,
2016. 16:3.
3
Samara et al. Velocity of orthodontic active space closure with
and without photobiomodulation therapy: A single-center,
cluster-randomized clinical trial. In review.
Aligners
•
63% reduction in the average time per aligner
during OrthoPulse® treatment as compared
to conventionally recommended aligner wear
time1
•
No measurable root resorption in 6 months1
1
Dickerson, T. A randomized controlled crossover trial on the
effect of OrthoPulse® photobiomodulation on the rate of aligner
progression during alignment with Invisalign® aligners. To be
submitted for publishing.
Case Reports
•
More than 10 OrthoPulse® studies have been
published in the scientific literature.
Two long-distance patients, unable to attend
frequent and regular appointments, achieved
excellent results at a reduced overall
treatment time when using OrthoPulse®1.
•
More than 400 patients have been treated in
clinical trials world-wide.
A patient using OrthoPulse® changed aligners
every 3 days throughout treatment and
achieved successful results2
1
Shaughnessy, T. Long distance orthodontic treatment with
adjunctive light therapy . J Clin Orthod, 2015. 12:757-69.
2
Ojima, K. Photobiomodulation accelerates orthodontics with the
Invisalign System. J Clin Orthod. In review.
Refer to Section 5
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OrthoPulse® Clinical and Scientific Dossier
OrthoPulse® Clinical and Scientific
Evidence Executive Summary
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1
Published in vitro Research
•
Stimulation of gene expression in human
cells1
•
Increased proliferation of gingival fibroblasts
and endothelial cells2
•
Stimulated proliferation and mineralization
of human osteoblasts3
•
Modulated PDL cell response, which could
regulate bone turnover during orthodontic
tooth movement4
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. In
review.
Refer to Section 6
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OrthoPulse
Clinical and
Scientific
LIGHT ACCELERATED
ORTHODONCTICS
Evidence
Executive
Summary
CLINICAL AND
SCIENTIC
DOSSIER
Published in vivo Research
•
3.3-fold faster rate of tooth movement1
•
80% less root resorption in animals treated
with 620 nm light.2
•
Significantly more mature bone in expanded
sutures3
•
Significantly lower failure rate of immediately
loaded TADs4
1
Chiari S et al. Photobiomodulation-induced tooth movement
using extra-oral transcutaneous phototherapy on the rat
periodontium. In review.
2
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.
3
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.
4
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.
Refer to Section 6
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LIGHT ACCELERATED ORTHODONCTICS
CLINICAL AND SCIENTIC DOSSIER
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ACCELERATED ORTHODONCTICS
Introduction
Introduction
Orthodontic therapy is predictable1,8 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 for which a patient needs to commit. Thus,
there has been a continuous search for methods
to enhance the rate and efficacy of orthodontic
tooth movement9,10. 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 case11. 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 involves the enhancement
of mechanical aspects of tooth movement10.
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
systems12. 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.
A third approach aims to increase the rate
of orthodontic tooth movement through
biologically-based
techniques13,14.
One
of
the best-characterized methods is surgical
corticotomy-accelerated
orthodontics15-18.
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
8
Introduction
piezoelectricity19. Active orthodontic treatment is
applied almost immediately. While results from
available data have been variable20-23, 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 sites24-26. 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
an accurate assessment of the outcomes of
surgical corticotomies in humans. Nonsurgical
alternatives to the highly invasive surgical
methods have been explored. Endothelial growth
factors27, osteoclast precursors like osteocalcin,
prostaglandins28, bone resorptive factors like
RANKL29, leukotrienes30, and macrophage
colony-stimulating factors have been tested.
Studies in these areas are limited, which makes
understanding these mechanisms difficult.
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to undergo remodeling. cytochrome c oxidase
mediates ATP production, which is upregulated
two-fold by infrared light34. 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 activity35, which
would also contribute to the rapid turnover of
the bone and is amenable to light36. A number of
clinical case series have suggested an enhanced
impact by LAO9,37, increased velocity of canine
movement, decreased pain38, and a significantly
higher acceleration of retraction of treated
canines39. However, there are also some studies
that show questionable efficacy40,41.
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
Another recently explored area involves deviceassisted therapy to biologically enhance the
orthodontic tooth movement. To this end, a
number of systems such as light, electrical
currents31, cyclic forces32, and resonance
vibration33 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). The terms photobiomodulation and LAO
can be interchangeably used to define the specific
wavelength range, intensity, and light penetration
and to differentiate from other methods utilizing
light for treatment elsewhere in dentistry. 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
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ORTHODONCTICS
What isACCELERATED
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.” 42
• pubmed.gov (US National Library of
Medicine | National Institutes of Health)
lists over 3,000 peer-reviewed published
articles on Photobiomodulation (PBM) or
Low Level Light (Laser) Therapy (LLLT).
There exists an “optical window” between 600
– 1200 nm in biologic tissues. This allows for
maximum tissue penetration of photons.43
• Ex-vivo biopsy tissue study shows higher
wavelengths penetrate tissue deeper44.
Ex-vivo biopsy tissue study evaluated tissue
penetration depths of 632, 675,780 and 835
nm light measurement of the penetration
depths of red and near infrared light in
human ex-vivo tissues.
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ORTHODONCTICS
What is Photobiomodulation?
3.2. Mechanism of Action
Mechanisms thought to be involved
photobiomodulation biological response 42:
in
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Activation of cytochrome c cxidase by light
initiates intracellular signaling cascades, resulting
in various cellular responses including ATP
production in the mitochondria.
• Mitochondrial
chromophores
(inc.
cytochrome c oxidase) absorb photons,
pump protons and increase ATP production
thereby increasing energy available to the
cell, which increases/normalizes metabolism.
• Reactive Oxygen Species (ROS) production
and mitochondrial signaling
stimulate/
suppress transcription factors and DNA/RNA
synthesis.
• produce inducible nitric oxide (NO) through
absorption of photons by nitric oxide
synthase increases 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.
Action spectra of DNA & RNA synthesis rate
matches CCO absorption spectra.
• Karu and Kolyakov46 performed experiments
to find action spectra based on DNA and
RNA synthesis rate. HeLa cell mono-layers
were irradiated with monochromatic light of
580-860 nm.
Exact action spectra for cellular responses
relevant to phototherapy.
• Eells et al45 showed that cytochrome c
oxidase is the photoacceptor in the red to
near-infrared spectral range.
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ORTHODONCTICS
What isACCELERATED
Photobiomodulation?
Oron et al47 showed twofold increase in ATP
production with one LLLT treatment
• Method: Human neuronal progenitor cells
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 850
nm IR light
• Deregulation of specific sets of genes
detected by microarray analysis of marrow
stromal fibroblast cells48
Refer to Section 6.1
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ORTHODONCTICS
What is Photobiomodulation?
MECHANISM OF
ACTION
SCHEMA
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3
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
OrthoPulse® Photon
As a result of increased energy ATP,
mitochondrial signaling, and up/down regulation
of genes.
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LIGHT
Photobiomodulation
Scientific Evidence in
Orthodontics
4.1. Summary of Key in vitro Bone
Metabolism Findings
•
•
•
•
•
•
•
•
•
14
Increased osteocyte numbers49, 50
Increased DNA synthesis51
Increased collagen production 52
Increased ALP activity and number of mineral
nodules53
Increased differentiation and proliferation of
human osteoblasts54
Increased bone nodule formation, ALP
activity and gene expression55
Increased osteoblastic activity56
Increased ostoclastic activity57
Increased the velocity of tooth movement
through the stimulation of the osteoclasts
and osteoblasts58
LIGHT ACCELERATED
ORTHODONCTICS
Photobiomodulation
Scientific
Evidence in
CLINICAL AND SCIENTIC
DOSSIER
Orthodontics
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4.2. Summary of Key in vivo
Orthodontic Findings
• Low-level laser therapy (LLLT) accelerates
bone regeneration in the midpalatal suture
following palatal expansion in the rat model59
• Kawasaki and Shimizu60 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
LLLT was applied to the rabbit model61
Fujita et al62 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 LLLT tooth movement in rats63.
• Goulart et al64 showed lower dosage (5 J/
cm2) of LLLT accelerates dog premolar tooth
movement; higher dosage (35 J/cm2) may
retard it.
• LLLT accelerates the velocity of tooth
movement via stimulation of the alveolar
bone remodeling in rats65.
• LLLT facilitates the velocity of tooth
movement and MMP-9, cathepsin K, and
integrin subunits of alpha(v)beta3 expression
in rats66.
LLLT
significantly
increases
PDL
cell
proliferation, decreases PDL cell inflammation,
and increased PDL OC activity.67
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ACCELERATED
ORTHODONCTICS
OrthoPulse
Clinical Evidence
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, 14:30
1
Department of Orthodontics, School of Dentistry, University of Alabama,
Birmingham, AL, USA
2
Forsyth Institute, Cambridge, MA, USA
3
Shaughnessy Orthodontics, Private Practice, Suwanee, GA
Introduction: Numerous strategies have been
proposed to decrease the treatment time a patient
requires for orthodontic treatment. Recently, a
number of device-accelerated therapies have
emerged in orthodontics. Photobiomodulation
is an emerging area of science that has clinical
applications in a number of human biological
processes.
Objective: The aim of this study was to determine
if photobiomodulation reduces the treatment
time in the alignment phase of orthodontic
treatment.
Materials and Methods: This multicenter clinical
trial was performed 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 treatment were recruited into the
study, and the LII was measured at regular time
intervals. Test subjects 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
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LIGHT ACCELERATED
OrthoPulse®ORTHODONCTICS
Clinical Evidence
clinical trial for the test and control groups
were 6.35 and 5.04 mm, respectively. Multilevel mixed effect regression analysis was
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 boxplots
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 (8.39
mm versus 6.67 mm). There were no statistically significant
difference between the two groups in terms of destination
LII. Outliers (rates greater than 3 mm/week) were removed
from the test group to make these figures more conservative.
The test group’s mean alignment rates were 0.99 mm/week
compared to a control rate of 0.44 mm/week, with a comparison
group of 23 control arches and 111 treatment arches.
This study was supported in part by Biolux Research.
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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
Department of Orthodontics, University of Alabama, Birmingham, AL, USA.
1
Introduction: Photobiomodulation is used to
accelerate tooth movement during orthodontic
treatments.
Materials and Methods: The changes in root
morphology in a group of orthodontic patients
who
received
photobiomodulation
were
evaluated using the cone beam computed
tomography (CBCT) technique. The device 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 continuous wave.
Twenty orthodontic patients were recruited for
these experiments, all with Class 1 malocclusion
and with Little’s Irregularity Index of 2 mm in
either of the arches.
Results: Root resorption was detected by
measuring changes in tooth length using CBCT.
These changes were measured before the
orthodontic treatment and use of low-level laser
therapy and after finishing the alignment level.
Little’s Irregularity Index for all the patients was
calculated in both the maxilla and mandible
arches, and patients were divided into three
groups for further analysis, which were then
compared to the root resorption measurements.
Our results showed that photobiomodulation did
not cause root resorption greater than the normal
range that is commonly detected in orthodontic
treatments. Furthermore, no correlation between
Little’s Irregularity Index and root resorption was
detected.
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OrthoPulse® Clinical Evidence
5.3. Intraoral photobiomodulationinduced orthodontic treatmentinduced root resorption: A preliminary
study.
Shaughnessy T1, Kantarci A2, Kau CH3, Skrenes D,
Skrenes S, Ma D. In review.
Birmingham, AL, USA
1
2
3
Objective: External apical root resorption (EARR)
is a common side effect of orthodontic treatment.
The aim of our study was to determine the
degree of EARR in patients treated with intraoral
photobiomodulation (PBM) in conjunction
with orthodontic treatment. Furthermore,
the correlation between EARR and several
potentially 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 treatment. 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 on the surface
of the LED array. Panoramic radiographs were
taken before orthodontic treatment (T0) and
at the completion of the alignment phase of
treatment (T1). EARR of the 4 maxillary incisors
was determined by measuring the difference in
tooth length between the two images. Length
measurements were made from the mesial
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 below
0.32 mm. A multivariate regression analysis
was used to determine the relation of EARR
with several potentially influential variables.
Conclusion:
18
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
incisor type. No statistically significant changes
in root lengths were noted above 0.32 mm.
OrthoPulse® Clinical Evidence
5.4. Intra-oral photobiomodulationinduced orthodontic tooth alignment:
A preliminary study
Shaughnessy T1, Kantarci A2, Kau CH3, Skrenes D,
Skrenes S, Ma D. BMC Oral Health 2016, 16:3
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Conclusions: Our findings suggest that intra-oral
PBM could be used to decrease anterior alignment
treatment time, which could consequently
decrease full orthodontic treatment time.
3
Birmingham, AL, USA
1
2
Objective:
Numerous
strategies
have
been proposed 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 increases the
rate of tooth alignment and reduces the time
required to resolve anterior dental crowding.
Materials and Methods: Nineteen orthodontic
subjects with Class I or Class II malocclusion and
Little’s Irregularity 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
orthodontic treatment, and the control group (N
= 8) received only orthodontic treatment. The
PBM device produced near-infrared light with
a continuous 850 nm wavelength, generating
an average daily energy density of 9.5 J/cm². LII
was measured at the start (T0) of orthodontic
treatment until alignment was reached (T1, where
LII < 1 mm). The rate of anterior alignment and
treatment time was determined for both groups.
OrthoPulse® OPx1 and OPx2 treatments result in a significant
reduction in the number of days required per aligner as
compared to what is prescribed for conventional Invisalign
treatment: 65% reduction for OPx1 and 69% reduction for
OPx2.
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
mean alignment treatment time was significantly
shorter 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.
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OrthoPulse
Clinical Evidence
LIGHT ACCELERATED
ORTHODONCTICS
5.5. A randomized controlled crossover
trial on the effect of OrthoPulse® on
the rate of aligner progression during
alignment with Invisalign® aligners.
Dickerson T1. To be submitted for publishing.
Dickerson Orthodontics, Private Practice, Chandler, AZ
1
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 study was to assess if PBM treatment
can reduce the average wearing duration
required for 14-day recommended aligners.
Effectiveness Objective: To compare progression
rate in days/aligner during baseline and
OrthoPulse® periods during aligner orthodontic
treatment.
Safety Objective: To assess 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 32 patients
from 14 to 59 years old received Invisalign®
treatment in conjunction with 5-minute
daily OrthoPulse® treatments (OP), per arch.
Results: The aligner progression rates of the 32
patients were 7.7 and 5.2 days/aligner for the
baseline and OrthoPulse® periods, respectively.
This indicates that the rate of aligner switching
during the OrthoPulse® period was 1.5-fold
faster than that of the baseline period, with
significance (p-value < 0.0001). 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.
20
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 aligner progression and
decrease treatment time with aligner treatment.
LIGHT ACCELERATED
ORTHODONCTICS
OrthoPulse® Clinical
Evidence
5.6. Velocity of orthodontic active
space closure with and without
photobiomodulation therapy: A singlecenter, cluster-randomized clinical
trial.
Samara1 et al. In review.
European University College, UAE
1
Objective: 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.
Materials and 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.
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5
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, 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.
Funding: Biolux Research (Vancouver, Canada)
provided the PBM devices used in this study.
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.
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6
®
LIGHT
ACCELERATED
ORTHODONCTICS
OrthoPulse
in vitro and
in vivo Evidence
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. Orthod. Craniofac. Res. 2015, Suppl
1:50-61
1
Center for Craniofacial Molecular Biology, Ostrow School of Dentistry, University 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 fibroblast
(MSF) cells depends on light wavelength and
energy density.
Materials and Methods: Primary cultures of
isolated human bone marrow stem cells (hBMSC)
were exposed to visible red (VR, 633 nm) and
infrared (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 J/cm2). Cultured cells
were assayed for cell proliferation, osteogenic
potential, adipogenesis, mRNA and protein
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 pathways
identified by microarrays.
Result: Different wavelengths and energy
densities 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
pathways with increases to longer IR wavelengths.
Microarrays suggest RANKL and MMP 10 followed
IR energy density dose-response curves. Epithelial
and mesenchymal cells respond differently to
stimulation by light suggesting cell type-specific
response is possible.
22
®
LIGHT ACCELERATED
OrthoPulse
in vitro and inORTHODONCTICS
vivo Evidence
Conclusions:
These
studies
demonstrate
differential gene expression with different
wavelengths, 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
literature when wavelengths, energy densities
and cell types differ.
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6
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.
Objectives: 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.
Materials and Methods: Twenty male, 50- to
60-day-old Wistar rats were divided into two equal
groups (control and experimental). Both groups
were subjected to expansion for 5 days, and 50 cN
of force was applied to the maxillary incisors with
helical spring. An OsseoPulse® LED device, 618
nm wavelength and 20 mW/cm2 output power
irradiation, was applied to the interpremaxillary
suture for 10 days. Bone formation in the sutural
area was histomorphometrically 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 measurements
revealed that bone architecture in the LPT
group was improved. The application of LPT can
stimulate bone formation in the orthopedically
expanded interpremaxillary suture during
expansion and the early phase of the retention
periods.
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6
®
LIGHT
ACCELERATED
ORTHODONCTICS
OrthoPulse
in vitro and
in vivo Evidence
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.
1
Department of Orthodontics, Faculty of Dentistry, Erciyes University, Kayseri,
Turkey
Objective: The aim of this prospective
experimental study was to evaluate the effect of
light-emitting diode (LED) photobiomodulation
therapy (LPT) on the stability of immediately
loaded miniscrews under different force levels, as
assessed by resonance frequency analysis (RFA).
Materials and Methods: Sixty titanium 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). OsseoPulse® LED device (Biolux
Research Ltd.) of 618 nm wavelength and 20
mW/cm2 power output irradiation (20 minutes/
day) was applied to the miniscrews for 10 days.
The RFA records were performed at miniscrew
insertion session (T1) and 21 days after surgery
(T2). Wilcoxon and Mann-Whitney U-tests were
used for statistical evaluation at P < 0.005 level.
Results: It was found that initial primer stability
of all miniscrews was similar in all groups at the
start of the experimental procedure. Statistically
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
control miniscrews. Within the limits of this in
24
vivo study, the present RFA findings suggest that
LPT might have a favourable effect on healing and
attachment of titanium orthodontic miniscrews.
LIGHT ACCELERATED
ORTHODONCTICS
®
OrthoPulse
in vitro and
in vivo Evidence
6.4. Effect of LED-mediatedphotobiomodulation 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.
SECTION
6
average relative root resorption affecting the
maxillary molars on the TM side was 0.098 ± 0.066
in the LPT group and 0.494 ± 0.224 in the control
group. Statistically significant inhibition of root
resorption 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
resorptive activity.
Objective: The aim of this experimental study
was to evaluate the effects of light-emitting diodemediated-photobiomodulation therapy (LPT), on
the rate of orthodontic tooth movement (TM) and
orthodontically induced root resorption, in rats.
Materials and Methods: Twenty male 12-weekold 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 treatment group, LPT was
applied with an energy density of 20 mW/cm2
over a period of 10 consecutive 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 photomicrographs. Mann–Whitney U and Wilcoxon tests were
used for statistical evaluation at p < 0.05 level.
Results: TM during two different time intervals
(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 period (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
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6
OrthoPulse® in vitro and in vivo Evidence
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.
1
Boston University Goldman School of Dental Medicine, Department of Periodontology and Oral Biology, Boston MA USA
2
University of Vienna, Department of Orthodontics, Vienna, Austria
3
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 NIRLaser radiation phototherapy on the rate of the
orthodontic tooth movement and the biological
impact in the rat model.
Materials and Methods: Nineteen healthy
adult CRL-CD male rats with a body weight of
350-400 g were used as experimental animals.
The orthodontic appliances were placed to
mesially move the left maxillary first molar. The
test animals in phototherapy groups received LED
or laser applications daily while the stability of the
orthodontic appliances were constantly checked
under isoflurane 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, LaserShort, LED-Long, or Laser-Long accordingly. For
animals in the LED-Short group, the device was
applied for a cumulative energy dose of 10 J/cm2;
for the LED-Long group for 30 J/cm2; for animals
in the Laser-Short group for 10 J/cm2; and for the
Laser-Long group for 30 J/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 (1.17
± 0.70 mm) compared to the TM group but
26
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 interradicular area. NIR-Laser irradiation
and an increased application time per day lead
to a more predictable tooth movement. LED
application 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 movement of the mesialized tooth and
the less resorptive activity in the distance, in the
third molar region. No negative effects due to
light penetration could be found in any group.
6.6. The effect of light-emitting diode
and laser on mandibular growth in
rats.
SECTION
6
6.7. Human osteoblast response to
photobiomodulation
El-Bialy T , Alhadlaq A, Felemban N, Yeung J,
Ebrahim A, H Hassan A. Angle Orthod. 2014 Jul 14.
Le A2, Mendes RT1,2, Iscan D2, Pamuk F2, Hasturk H2,
A. Kantarci A2. Presented at IADR 2015 General Session. Boston, MA. March 14, 2015.
Associate Professor, Department of Orthodontics, School of Dentistry, Faculty
of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada.
UEPG - Universidade Estadual de Ponta Grossa, Ponta Grossa, Paraná, Brazil
Applied Oral Sciences, The Forsyth Institute, Cambridge, Massachusetts,
United States.
1
1
1
Objective: To evaluate the effect of a lightemitting diode (LED) and/or low-level laser (LLL)
with or without the use of anterior bite jumping
appliances (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
tomographic (microCT) analyses.
Results: The LED and LED + FA groups showed
an increase in all condylar tissue parameters
compared with other groups.
Conclusions: The LED-treated groups showed
more mandibular growth stimulation compared
with the laser groups.
2
Objectives: Photobiomodulation is a noninvasive method for accelerated orthodontic
tooth movement. Photobiomodulation is known
to increase the rate of tooth movement by
more than 2-fold compared to conventional
techniques. The mechanism of action at the
cellular level however, 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 layer
directly, with a distance of 2.5 cm below the plate.
The samples were divided into 3 groups per plate:
Group 1 – one-minute daily radiation for nine
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
viability 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-minute radiation resulted in a
significantly higher proliferation compared to
control and one-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 3
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6
weeks. At Week 5, however, one-minute 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.
6.8. Photobiostimulation of gingival
fibroblast and vascular endothelial cell
proliferation
Iscan D1,2, Mendes R1, Kantarci A1. Presented at
Annual Meeting of Turkish Society of Orthodontics,
October 26-30, 2014 Ankara, Turkey.
1
2
Marmara University, Istanbul, Turkey
Objective: Photobiomodulation is a non-invasive
method for accelerated orthodontic tooth
movement. LED treatment (LEDT) increases the
rate of tooth movement by more than twofold
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
had a continuous wavelength of 850 nm and a
power density of 60 mW/cm2. Group 1 samples
were irradiated every day for one minute while
Group 2 samples were irradiated for 10 minutes
during eight 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 24 hours, while HUVEC cells
were not affected for the first 72 hours. There
was an increase in cell proliferation in response
to one-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
28
growth and the impact of LEDT is dose-dependent.
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6
6.9. Impact of LED photobiomodulation
on the gene expression profile of PDL
cells under simulated inflammation
Konermann A 1, Jäger A1, Nguyen D2, Kantarci A2.
In review.
Department of Orthodontics, Medical Faculty, University of Bonn, Bonn,
Germany
2
1
Objective: This study was designed to investigate
the impact of LED treatment (LEDT) on the
expression of osteogenic differentiation markers,
inflammatory cytokines and molecules involved
in tissue metabolism in periodontal 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
Necrosis Factor (TNF) α, or Transforming Growth
Factor (TGF) ß1. 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 prophylactic irradiation, or 18 hours after
the challenge to simulate therapeutic irradiation
in an inflammatory milieu. Quantitative realtime polymerase chain reaction (Q-PCR) was
performed for family with sequence similarity 5,
member C (FAM5C), osteocalcin, S100A4, IL-1ß,
TGFß1, tissue 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
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6
®
OrthoPulse
in vitro and
in vivo Evidence
LIGHT
ACCELERATED
ORTHODONCTICS
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.
30
orthopulse.com
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SECTION
7
Selected
Photobiomodulation
Abstracts
LIGHT ACCELERATED
ORTHODONCTICS
7.1. Mechanism of Action
7.1.1. The nuts and bolts of lowlevel laser (light) therapy.
Chung H1, Dai T, Sharma SK, Huang YY, Carroll JD,
Hamblin MR. Ann Biomed Eng. 2012 Feb;40(2):51633.
1
Wellman 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
photobiomodulation has broadened to include
light-emitting diodes and other light sources,
and the range of wavelengths used now includes
many in the red and near infrared. The term
“low level laser therapy” or LLLT has become
widely recognized and implies the existence of
the biphasic dose response or the Arndt-Schulz
curve. This review will cover the mechanisms of
action of LLLT at cellular and tissular levels and
will summarize the various light sources and
principles of dosimetry that are employed in
clinical practice. The range of diseases, 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 amenable
to LLLT therapy.
32
LIGHT ACCELERATED
ORTHODONCTICS
Selected
Photobiomodulation
Abstracts
7.1.2. Low-energy laser irradiation
facilitates the velocity of tooth
movement and the expressions of
matrix metalloproteinase-9, cathepsin
K, and α(v)β(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.
1
Department of Orthodontics, Nihon University School of Dentistry at
Matsudo, Chiba, Japan
SECTION
7
of tooth movement was significantly greater than
that in the non-irradiated group at the end of the
experiment (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 lowenergy laser irradiation facilitates the velocity of
tooth movement and MMP-9, cathepsin K, and
integrin subunits of α(v)β(3) expression in rats.
Abstract: It has previously been reported that lowenergy laser irradiation stimulated the velocity
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
metalloproteinase (MMP)-9, cathepsin K, and α(v)
β(3) 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
α(v)β(3) integrin during experimental tooth
movement. Fifty male, 6-week-old Wistar strain
rats were used in the experiment. A total force of
10 g 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 seven days, the amount of tooth movement
was measured. To determine the amount of
tooth movement, plaster models of the maxillae
were made using 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 α(v)β(3) was performed. Intergroup
comparisons of the average values were
conducted with a Mann-Whitney U-test for tooth
movement and the number of tartrate-resistant
acid phosphatase (TRAP), MMP-9, cathepsin K,
and integrin subunits of alpha(v)beta3-positive
cells. In the laser-irradiated group, the amount
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Selected
Photobiomodulation
Abstracts
LIGHT ACCELERATED
ORTHODONCTICS
7.1.3. Metrical and histological
investigation of the effects of lowlevel laser therapy on orthodontic
tooth movement.
Altan BA1, Sokucu O, Ozkut MM, Inan S. Lasers Med
Sci. 2012 Jan;27(1):131-40.
1
Department 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 osteoclastic
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
diode 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 five points at the distal side
of the tooth root on the first, second, and third
days of the experiment. Group I received no
laser energy. Total laser energy of 54 J (100 mW,
3.18 W/cm2, 1717.2 J/cm2) was applied to Group
II and a total of 15 J (100 mW, 3.18 W/cm2, 477
J/cm2) 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
difference was found for the amount of tooth
movement 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 increased significantly in Group
II (p < 0.05). Immunohistochemical staining
findings showed that RANKL immunoreactivity
was stronger in Group II than in the other
groups. As to OPG immunoreactivity, 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
34
findings, low-level laser irradiation accelerates
the bone remodeling process by stimulating
osteoblastic and osteoclastic cell proliferation and
function during orthodontic tooth movement.
LIGHT ACCELERATED
ORTHODONCTICS
Selected
Photobiomodulation
Abstracts
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.
SECTION
7
Conclusions: Varying the wavelength with a
reasonable dose in the target zone leads to
obtaining the desired biological effect and achieving
a reduction of the orthodontic treatment
time, although there are studies that do not
demonstrate any benefit according to their
values.
Carvalho-Lobato P1, Garcia VJ, Kasem K, UstrellTorrent JM, Tallón-Walton V, ManzanaresCéspedes MC. Photomed Laser Surg. 2014 Mar 14.
1
Human 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 lowlevel laser therapy (LLLT) is applied.
Background Data: The literature discusses
different methods that have been developed
to motivate 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 disagreement between authors as to
whether LLLT reduces orthodontic treatment
time, and the parameters 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 reviewers
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 performed after removing a premolar,
and 11 studies in rats were selected in which
first premolar traction was realized. There were
statistically significant changes in four human
studies and eight animal studies.
orthopulse.com
35
SECTION
7
Selected
Photobiomodulation
Abstracts
LIGHT ACCELERATED
ORTHODONCTICS
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.
1
Department of Zoology, The George S. Wise Faculty of Life Sciences, Tel-Aviv
University Tel-Aviv, Israel.
Objective: The purpose of this study was to
determine 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 cellular
processes and on stem cells. It was recently
shown that applying LLLT to BM in rats postmyocardial 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/
cm2 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
observed in the liver, kidneys, brain or BM of the
laser-treated mice as compared with the shamtreated, control mice. Moreover, no neoplasmic
response in the tissues was observed in the lasertreated 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.
36
Conclusions: LLLT applied multiple times
either at the optimal dose (which induces
photobiostimulation of stem cells in the BM), or
at a higher dose (such as five times the optimal
dose), does not cause histopathological changes
or neoplasmic response in various organs in
mice, as examined over a period of 8 months.
orthopulse.com
37
SECTION
8
LIGHT
References
8.1. References
8.1.1. Studies Using OrthoPulse®
1. Kau CH, Kantarci A, Shaughnessy T, Vachimaron
A, Santiwong P, De le Fuente A, Skrenes D, Ma
D, Brawn P. Photobiomodulation accelerates
orthodontic alignment in the early phase of
treatment. Progress in Orthodontics. 2013; 14:30.
2. Nimeri G, Kau CH, Corona R, Shelly J. The effect of
photobiomodulation on root resorption during
orthodontic treatment. Clin Cosmet Investig Dent.
2014; 6;1-8.
3. Shaughnessy T, Kantarci A, Kau CH, Skrenes D,
Skrenes S, Ma D. Intra-oral photobiomodulationinduced orthodontic tooth movement: A
preliminary study. BMC Oral Health. 2016; 16(1):3.
4. Dickerson T. A randomized controlled crossover
trial on the effect of OrthoPulse® on the rate of
orthodontic tooth movement during aligment
with Invisalign® aligners. To be submitted.
5. Samara S, Velocity of orthodontic active space
closure with and without photobiomodulation
therapy: A single-center, cluster-randomized
clinical trial. To be submitted.
6. Shaughnessy, T. Long distance orthodontic
treatment with adjunctive light therapy. J Clin
Orthod. 2015; 49(12):757-69.
7. Ojima, K. Photobiomodulation accelerates
orthodontics with Invisalign® system. In review.
38
References
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Orthodontics. 5th ed. St Louis: Elsevier; 2012.
9. Kau CH. Biotechnology in Orthodontics. Dentistry.
2012; 2:e108. 10.Scott P, DiBiase AT, Sherriff M, Cobourne MT.
Alignment efficiency of Damon self-ligating and
conventional orthodontic bracket systems: a
randomized clinical trial. Am J Orthod Dentofacial
Orthop. 2008; 134(4):470.e1–8.
11.Kau CH. Creation of the virtual patient for the
study of facial morphology. Facial Plast Surg Clin
North Am. 2011; 4:615–22.
12.Fleming PS, DiBiase AT, Lee RT. Self-ligating
appliances: evolution or revolution? J Clin
Orthod. 2008; 42(11):641–51.
13.Krishnan V, Davidovitch Z. Cellular, molecular,
and tissue-level reactions to orthodontic force.
Am J Orthod Dentofacial Orthop. 2006; 129(4):469.
e1–32.
14.Krishnan V, Davidovitch Z. On a path to unfolding
the biological mechanisms of orthodontic
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15.Iglesias-Linares A, Yanez-Vico RM, MorenoFernandez AM, Mendoza- Mendoza A, SolanoReina E. Corticotomy-assisted orthodontic
enhancement
by
bone
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protein-2 administration. J Oral Maxillofac Surg.
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16.Iseri H, Kisnisci R, Bzizi N, Tuz H. Rapid canine
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8
19.Murphy KG, Wilcko MT, Wilcko WM, Ferguson
DJ.
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accelerated
osteogenic
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technique. J
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67(10):2160–6.
20.Ren A, Lv T, Kang N, Zhao B, Chen Y, Bai D. Rapid
orthodontic tooth movement aided by alveolar
surgery in beagles. Am J Orthod Dentofacial
Orthop. 2007; 2(160):1–10.
21.Kang N, Lu T, Ren AS, Huang L, Bai D. Effect of
alveolar surgery-aided rapid orthodontic tooth
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Biologic response of rapid tooth movement
with periodontal ligament distraction. Am J
23.Sebaoun JD, Kantarci A, Turner JW, Carvalho
RS, Van Dyke TE, Ferguson DJ. Modeling of
trabecular bone and lamina dura following
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24.Baloul SS, Gerstenfeld LC, Morgan EF, Carvalho RS,
Van Dyke TE, Kantarci A. Mechanism of action
and morphologic changes in the alveolar bone
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Dentofacial Orthop. 2011; 139(4 Suppl):S83–101.
25.Aboul-Ela SM, El-Beialy AR, El-Sayed KM, Selim
EM, El-Mangoury NH, Mostafa YA. Miniscrew
implant-supported maxillary canine retraction
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26.Han XL, Meng Y, Kang N, Lv T, Bai D. Expression
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27.Alves JB, Ferreira CL, Martins AF, Silva GA,
Alves GD, Paulino TP, Ciancaglini P, Thedei G Jr,
Napimoga MH. Local delivery of EGF-liposome
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orthopulse.com
39
SECTION
8
LIGHT
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30.Hou Y, Liang T, Luo C. Effects of IL-1 on
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31.Hashimoto H. Effect of micro-pulsed electricity
on experimental tooth movement. Nihon
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32.Kau CH. A radiographic analysis of tooth
morphology following the use of a novel
cyclical force device in orthodontics. Head Face
Med. 2011; 7:14.
33.Nishimura M, Chiba M, Ohashi T, Sato M,
Shimizu Y, Igarashi K, Mitani H. Periodontal
tissue activation by vibration: intermittent
stimulation by resonance vibration accelerates
experimental tooth movement in rats. Am J
34.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.
40.Youssef M, Ashkar S, Hamade E, Gutknecht N,
Lampert F, Mir M. The effect of low-level laser
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41.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.
42.Zhang R, Mio Y, Pratt PR, Lohr N, Warltier DC, et
al. Near infrared light protects cardiomyocytes
from hypoxia and reoxygenation injury by a
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Cardiol. 2009; 46:4-14.
43.Hamblin MR, Waynant RW, Anders J. Mechanisms
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44.Stolik S, Delgado JA, Pérez A, Anasagasti L,J
Measurement of the penetration depths of
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35.Tuby H, Maltz L, Oron U. Low-level laser
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mesenchymal and cardiac stem cells in culture.
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45.Eells JT, Henry MM, Summerfelt P, Wong-Riley
MT, Buchmann EV, Kane M, Whelan NT, Whelan
HT. Therapeutic photobiomodulation for
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36.Eells JT, Henry MM, Summerfelt P, Wong-Riley
MT, Buchmann EV, Kane M, Whelan NT, Whelan
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46.Karu TI, Kolyakov SF. Exact action spectra for
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37.Kau CH. Orthodontics in the 21st century: a
view from across the pond. J Orthod. 2012;
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47.Ad N, Oron U. Impact of low level laser
irradiation on infarct size in the rat following
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38.Sousa MV, Scanavini MA, Sannomiya EK, Velasco
LG, Angelieri F. Influence of low-level laser
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40
39.Cruz DR, Kohara EK, Ribeiro MS, Wetter NU.
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2004; 35(2):117–20.
48.Guo J, Wang Q, Wai D, Zhang QZ, Shi SH, Le AD, Shi
ST, Yen SL. Visible red and infrared light alters
gene expression in human marrow stromal
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49.Kreisler M, Christoffers AB, Al-Haj H, Willershausen
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60.Kawasaki K, Shimizu N. Effects of low-energy
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51.Mognato M, Squizzato F, Facchin F, Zaghetto L,
Corti L. Cell growth modulation of human cells
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52.Wataha JC, Lewis JB, Lockwood PE, Hsu S, Messer
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at early stages of cell culture in rat calvarial
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54.Stein A, Benayahu D, Maltz M, Oron U. Low-Level
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laser irradiation on the release of bFGF from
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56.Takeda Y . Irradiation effect of low-energy
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JR, Chapple CC, Yum LW. The effects of low level laser
irradiation on osteoblastic cells. Clin Orthod Res.
2001 Feb;4(1):3-14.
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low-level laser therapy on bone repair: Histological
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Buchman EV, Kane MP, Gould LJ, Das R, Jett M,
Hodson BD, Margolis D, Whelan HT . Mitochondrial
signal transduction in accelerated wound and
retinal healing by near-infrared light therapy.
Mitochondrion, 2006 4:559-567
Ozawa Y, Shimizu N, Kariya G, Abiko Y. Low-energy
laser 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.
Effects of near-infrared low-level laser irradiation
on microcirculation. Lasers Surg Med 2000, 27:427437.
Stadler I, Evans R, Kolb B, Naim JO, et al. In vitro
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Almeida-Lopes L, Rigau J, Zangaro RA, Guidugli-Neto
J, et al. Comparison of the low level laser therapy
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Pretreatment with near-infrared light via lightemitting diode provides added benefit against
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Agaiby AD, Ghali LR, Wilson R, Dyson M. Laser
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Wong-Riley MT, Bai X, Buchmann E, Whelan HT. Lightemitting diode treatment reverses the effect of
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Whelan HT, Buchmann EV, Dhokalia A, Kane MP, Whelan
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
healing in diabetic mice. J Clin Laser Med Surg. 2003
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44
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 Research
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