LASER : PHOTO - BIOMODULATION
Acta Chir Acad Sci Hung. 1976;17(1):49-55
Laser stimulation of wound healing
Mester E, Nagylucskay S, Doklen A, Tisza S
Serum complement activity, immunoglobulin levels and the circulatin auto-antibodies
were studied in the course of laser treatment of 20 cases of crural ulcer. After temporary
changes a normalization of the humoral immune response was observed in the healing
cases, while in the stagnating ones opposite trend was manifest. In none of the groups
were detected circulating auto-antibodies against the investigated antigens.
Vestn Khir Im I I Grek. 1982 Dec;129(12):64-6
Use of laser irradiation in the treatment of trophic ulcers of the lower limbs
Iupatov SI, Smotrin SM, Anufrik SS
Results of the complex treatment of 65 patients with trophic ulcers of lower extremities
resulting from chronic venous insufficiency with the use of laser irradiation of the
ultraviolet range are reported. The laser irradiation was shown to exert a stimulating
effect upon the regeneration of trophic ulcers. Its use was found to give considerably
better results of the complex treatment.
Vestn Khir Im I I Grek. 1984 Jan;132(1):69-71
Use of the helium-neon laser in the treatment of crural varicose ulcers
Usik VS
Results of the laser therapy of varicose ulcers of the crus in 45 patients were analyzed.
The laser therapy is considered by the author to favourably influence the healing of the
ulcers, to reduce pain, edema and skin hyperemia.
Dermatologica. 1984;168(4):157-62
In vitro fibroblast and dermis fibroblast activation by laser irradiation at low
energy. An electron microscopic study
Bosatra M, Jucci A, Olliaro P, Quacci D, Sacchi S
The effects of laser irradiations have been estimated both from the clinical point of view
(rate of reduction of the ulcerated area) and in ultrastructural terms. The modification
produced by laser in human fibroblasts in culture have also been investigated. Under our
clinical and experimental conditions, laser stimulates the secretion of fibroblasts, both in
vivo and in vitro, for reasons that are still the object of research. After irradiation the
formation of periodic collagen fibrils is not observed, so that complete ' restitutio ad
integrum' of the dermal matrix does not occur.
Photodermatol. 1984 Oct;1(5):245-9
Inadequate effect of helium-neon laser on venous leg ulcers
Santoianni P, Monfrecola G, Martellotta D, Ayala F
A study to determine whether laser radiation of low-power photon density would really
affect the healing of venous leg ulcers in man was performed. The ulcers were irradiated
6 d per wk with a helium-neon laser (wavelength 632.8 nm). Energy densities of 1 J/cm2
(16 patients) and 4 J/cm2 (17 patients) were administered daily. The control group (28
patients) received only antiseptic local compresses as treatment. No statistically
significant difference between the laser-treated group and the control group was found.
It was concluded that helium-neon laser radiation has no advantages over standard local
treatments, at least with the dosage schedules and protocols employed.
Vestn Khir Im I I Grek. 1985 Feb;134(2):55-8
Treatment of trophic ulcers and non-healing wounds with CO2 laser
Koshelev VN, Glukhov EI, Barkhatov LN
The authors used high and low intensity CO2 lasers for the treatment of 140 patients
with trophic ulcers and continuously non-healing wounds. Choice of the method of
treatment, parameters of laser radiation are based on concrete values of indices of the
regeneration processes in the wounds and ulcers. In 83,6% of patients there was a
complete recovery of the wounds, in 16,4% the recovery was partial.
Health Phys 1989 May;56(5):691-704
Photobiology of low-power laser effects
Karu T
Quantitative studies have been performed to determine the action of low-intensity visible
monochromatic light on various cells (E. coli, yeasts, HeLa, Chinese hamster fibroblasts
and human lymphocytes); also irradiation conditions (wavelength, dose and intensity)
conducive to vital activity stimulation have been examined. Respiratory chain
components are discussed as primary photoacceptors. The possible ways for photosignal
transduction and amplification are discussed. It is proposed that enhanced wound healing
due to irradiation with low-intensity visible laser light (He-Cd, He-Ne and semiconductor
lasers) is due to the increasing proliferation of cells.
G Ital Dermatol Venereol. 1989 Jun;124(6):317-9
Defocused CO2 laser in the treatment of leg ulcers. Preliminary results
Campolmi P, Lotti T, Bonan P, Tsampau D, Palleschi GM, Andreassi L
We studied the therapeutic action of CO2 Laser on leg ulcers due to chronic venous
hypertension in 30 subjects. Our findings show good results in reducing pain and leg
oedema and wound healing.
Ortop Travmatol Protez. 1989 Oct;(10):66-70
Experimental and clinical substantiation of laser therapy of wounds and trophic
ulcers
Rakcheev AP, Kiprenskii IuV
The authors have studied the results of 120 experiments on 60 guinea-pigs and 110
rabbits who received the treatment of modelled fenestrated musculocutaneous wounds
and trophic ulcers respectively on the replanted extremity and on the back with helium
and neon laser until they healed completely. The authors have demonstrated that the
laser therapy accelerates the process of reparative regeneration. In 50 intact rabbits who
received local irradiation with helium and neon laser there was an increase in the activity
of lysosome enzymes and in the protein metabolism values in the blood serum. The use
of the helium and neon laser with the specific density of the irradiation rate of 2.5
mWt/cm2 and the exposition during 5 minutes in the treatment of trophic ulcers and
persistent wounds in 56 patients as well as in 38 patients with consequences of injuries
to the main blood vessels, the nerve trunks, the muscles and the tendons of the
extremities before and after the reconstructive operations testifies to its high efficacy.
Khirurgiia (Mosk). 1989 Sep;(9):97-9.
Treatment of acute thrombophlebitis of the lower limbs with laser irradiation
Dudenko GI, Zaliubovskii VI
Low-intensity helium-neon laser (LG-75) radiation produces a marked analgesic,
desensitizing, hypocoagulative, and immunostimulating effect, which can be used in the
treatment of acute thrombophlebitis of the lower limbs. Laser therapy alters the phase
course of the wound process and in this way improves microcirculation and oxygenation
of the tissues, shortens the terms of wound healing, and may be used as the method of
choice in the treatment of trophic ulcers of the lower limbs.
Ann Vasc Surg 1990 Mar;4(2):179-81
The use of infrared laser therapy in the treatment of venous ulceration
Sugrue ME, Carolan J, Leen EJ, Feeley TM, Moore DJ, Shanik GD
Management of intractable venous ulceration remains an unrewarding task which is
increasingly delegated to the realm of the vascular surgeon. The purpose of this pilot
study was to assess the ulcer-healing effects of the newest form of biostimulation--the
low power laser. Twelve patients with chronic venous ulcers unresponsive to conservative
measures were treated with infrared laser irradiation for twelve weeks. Two ulcers healed
completely and there was a 27% (p less than 0.01) reduction in size of the remaining
ulcers. Treatment resulted in a 44% (p less than 0.01) increase in ulcer floor area
occupied by healthy granulation tissue. The most dramatic effect of laser treatment was
the reduction in ulcer pain, from 7.5 to 3.5 (linear analogue scale) (p less than 0.001).
Laser irradiation had no effect on TcPO2, number of skin capillaries or pericapillary fibrin
deposition in the lipodermatosclerotic area around the ulcer. The results of this pilot
study are encouraging and a carefully controlled randomized study is indicated to
compare low power laser irradiation to conventional treatment in the management of
venous ulcers.
Khirurgiia (Mosk) 1990 May;(5):105-8
Treatment of trophic ulcers of the lower extremities in elderly patients
Iupatov SI, Smotrin SM, Gavcrilik BL, Sten'ko VG
The article analyses the results of treatment of trophic ulcers of the lower extremities
consequent upon chronic venous insufficiency in 199 elderly patients. Concomitant
diseases were encountered in 82% of patients, which called for a differential approach to
the choice of the method of treatment. Combined laser therapy in the system of complex
treatment in 83 patients proved to be highly effective.
Khirurgiia (Mosk) 1990 Dec;(12):93-6
Treatment of non-healing wounds and trophic ulcers by low- intensity laser
irradiation in an outpatient clinic
Georgadze AK, Karpov VI, Kuznetsov EV, Soldatov AV, Rukosuev VP
Experience in treating 351 patients with persistent wounds and trophic ulcers by lowintensity laser radiation in out-patient clinics is generalized. Complete epithelialization of
the wound or ulcer surface occurred in 236 patients. There were 246 patients aged 60,
all were treated without leave from work. Thus, the inclusion of laser therapy in the
complex of measures for persistent wounds and trophic ulcers is a highly effective
method which may be applied in preoperative management and which will reduce
considerably the term of in-patient treatment.
Scand J Plast Reconstr Surg Hand Surg. 1991;25(3):249-51
Effect of low power gallium arsenide laser on healing of venous ulcers
Malm M, Lundeberg T
The healing of venous ulcers of the leg with and without gallium arsenide laser treatment
was studied in 42 patients randomly divided into two groups. One group received
standard conservative treatment and gallium arsenide laser, and the other received the
same standard treatment and placebo laser treatment. There were no differences in
results between the two groups.
Ann Plast Surg. 1991 Dec;27(6):537-9
Low-power HeNe laser treatment of venous leg ulcers
Lundeberg T, Malm M
Clinical observations have suggested that low-energy lasers, mainly helium-neon (HeNe)
lasers, might stimulate wound healing. A controlled study of the effects of low-power
HeNe laser was performed in conjunction with a standard treatment for healing chronic
venous leg ulcers on 46 patients divided randomly into two groups. All patients received
standard treatment (paste-impregnated bandage and a self-adhesive elastic bandage)
plus either HeNe laser (wave-length, 632.8 nm; beam power, 6 mW; continuous
emission, energy density, 4 J/cm2) or placebo HeNe laser twice weekly for 12 weeks. The
areas of healing were examined and compared percentage-wise after 2, 4, 6, 8, and 12
weeks. There were no significant differences in the proportion of healed ulcers or ulcer
area in the HeNe group compared with the placebo group.
Klin Khir. 1992;(3):47-9
The use of helium-neon laser radiation in the treatment of trophic disorders in
patients with diabetes mellitus
Zubkova ST
The effectiveness of laser therapy in trophic skin disorders (ulcer, diabetic bulla,
hematoma, skin chap) in patients with diabetes mellitus was studied. The foci of trophic
disorders and biologically active points were irradiated by means of heliumneon laser
installations. The technique was employed in a hospital and in out-patient treatment in
the complex with medicamentous therapy and without that in patients resistant to
medicamentous therapy. A high effectiveness of laser therapy has been established.
Clin Podiatr Med Surg. 1992 Jul;9(3):709-19
The efficacy of carbon dioxide laser surgery for adjunct ulcer therapy
Chromey PA
This article focuses on the application of the carbon dioxide (CO2) laser at various levels
of power density to achieve a level of efficacy in tissue ablation for cutaneous and deep
indolent ulcerations that afflict the lower extremities. This article also supports theories of
the CO2 laser generating a sterile nonpathogenic environment within ulcers. A cross
section of various ulcer types are used to determine duration of healing.
Khirurgiia (Mosk). 1992 Jul-Aug;(7-8):30-3
Treatment of suppurative wounds in patients with diabetes mellitus by
magnetic field and laser irradiation
Kuliev RA, Babaev RF, Akhmedova LM, Ragimova AI
The efficacy of including a magnetic field, low-intensity laser beam, and their
combination in the complex of therapeutic measures was studied in 119 patients with
suppurative wounds and diabetes mellitus. With the use of magnetic field or laser beam
intoxication diminished, the organism's immunological status was stabilized within a
shorter time, the wound process followed a quicker course, and treatment took less time.
The magnetic-laser effect has advantages over separate use of these factors.
Biomed Tech (Berl) 1993 Jul-Aug;38(7-8):168-71
LILAB, a new system for superficial application of low intensity laser beams in
medicine
Sommer A, Franke RP
Laser energy densities between 1 and 4 J/cm2 evoked a significant biostimulation in
human tissues. Lower energy densities had no apparent effect, but higher energy
densities resulted in cell damage. In principle, low energy densities can be applied with
high-energy lasers in combination with laser beam diverging lenses, or with low-power
lasers in combination with scanning devices. High-energy lasers are undesirable because
of their high cost. Low-energy lasers in combination with conventional scanners also
suffer from high cost, and these scanners have another major disadvantage: the energy
density at the edge of the application field may be up to five times as great as in the
center. A new laser beam distribution system for medical applications is introduced here.
Because of its moderate price it is well-suited for use with low-energy lasers. Any desired
geometrical shape of the application field is easily created, and with a homogeneous
energy density.
Phys Ther. 1994 Sep;74(9):812-23; discussion 824-5
Comparison of ultrasound/ultraviolet-C and laser for treatment of pressure
ulcersin patients with spinal cord injury
Nussbaum EL, Biemann I, Mustard B
Background And Purpose: The purpose of this study was to compare in patients
withspinal cord injury the effect on wound healing of nursing care alone with the
effect on wound healing of nursing care combined with either laser treatment or a
regimen of ultrasound and ultraviolet-C (US/UVC).
Subjects: Twenty patients (22 wounds) were randomly assigned to the treatment
groups.
Methods: All patients received standard wound care consisting of wound cleaning
twice daily, application of moist dressings, and continuous relief of pressure
until the wounds were healed. The laser protocol consisted of three treatments
weekly using a cluster probe with an 820-nm laser diode and 30 superluminous
diodes (10 each at 660, 880, and 950 nm), and energy density of 4J/cm2, and a
pulse repetition rate of 5,000 pulses per second. The US/UVC regimen consisted of
five treatments weekly, alternating the treatment modality daily. The pulsed US
was applied at a frequency of 3 MHz and a spatial average-temporal average
intensity of 0.2 W/cm2 (1:4 pulse ratio) for 5 minutes per 5 cm2 of wound area.
The UVC dosage (95% emission at 250 nm) was calculated each session according to
wound appearance. The dosage level was E1 for clean/granulating areas, E3 for
purulent/slow-granulating areas, E4 for heavily infected areas, and 2E4 for wound
debridement. Wounds were traced every 14 days, and surface areas were calculated
using the Sigma-Scan Measurement System. Weekly percentage changes in wound area
were compared.
Results: Results showed that US/UVC treatment had a greater effect on wound
healing than did nursing care, either alone or combined with laser.
Conclusion And Discussion: Ultrasound/ultraviolet-C may decrease healing time and
may allow faster return to rehabilitation programs, work, and leisure activities
for patients with spinal cord injury who have pressure ulcers.
Am J Phys Med Rehabil. 1997 Jul-Aug;76(4):288-96.
Combined ultrasound, electrical stimulation, and laser promote collagen
synthesis with moderate changes in tendon biomechanics
Gum SL, Reddy GK, Stehno-Bittel L, Enwemeka CS
The biomechanical, biochemical, and ultrastructural effects of a multitherapeutic protocol
were studied using regenerating rabbit Achilles tendons. The multitherapeutic protocol
was composed of low-intensity Ga:As laser photostimulation, low intensity ultrasound,
and electrical stimulation. Achilles tendons of 63 male New Zealand rabbits were
tenotomized, sutured, immobilized, and subjected to the multitherapeutic protocol for
five days, after which casts were removed and the therapy was continued for nine more
days without electrical stimulation. The tendons were excised and compared with control
tendons. Multitherapy treatment produced a 14% increase in maximal strength, a 42%
increase in load-at-break, a 20% increase in maximal stress, a 45% increase in stressat-break, a 21% increase in maximal strain, and a 14% increase in strain-at-break.
Similarly, multitherapy treatment was associated with an increase in Young's modulus of
elasticity of 31%, an increase in energy absorption at maximum load of 9%, and an
increase in energy absorption at load-at-break of 11%. Biochemical analysis of the
tendons showed an increase of 23% in the total amount of collagen in the multitherapytreated tendons, with fewer mature crosslinks (decrease of 6%). Electron micrographs
revealed no ultrastructural or morphologic changes in the tendon fibroblasts or in the
extracellular matrix. The improvements measured in tendons receiving multitherapy were
consistent but less remarkable compared with our earlier works with single modality
protocols. The results warrant the hypothesis that the beneficial effects of ultrasound and
laser photostimulation on tendon healing may counteract one another when applied
simultaneously.
Lasers Surg Med. 1998;22(5):281-7.
Laser photostimulation of collagen production in healing rabbit Achilles
tendons
Reddy GK, Stehno-Bittel L, Enwemeka CS
Background And Objective: Low energy laser photostimulation at certain wavelengths
can enhance tissue repair by releasing growth factors from fibroblasts and stimulate the
healing process. This study was designed to evaluate the influence of laser
photostimulation on collagen production in experimentally tenotomized and repaired
rabbit Achilles tendons.
Study Design/Materials And Methods: A total of 24 male New Zealand rabbits, ages
10-12weeks, were used. Following tenotomy and repair, the surgical hind limbs of
therabbits were immobilized in customized polyurethane casts. The experimental animals
were treated with a 632.8 nm He:Ne laser daily at 1.0 J cm(-2) for 14 days. Control
animals were sham treated with the laser head. On the fifth day after repair, the casts
were removed to allow the animals to bear weight on the lower extremity. The animals
were euthanized on the 15th postoperative day, then, the Achilles tendons were excised,
processed and analyzed. RESULTS: Biochemical analyses of the tendons revealed a 26%
increase in collagen concentration with laser photostimulation indicating a more rapid
healing process in treated tendons compared to controls. Sequential extractions of
collagen from regenerating tissues revealed that the laser photostimulated tendons had
32% and 33% greater concentrations of neutral salt soluble collagen and insoluble
collagen, respectively, than control tendons suggesting an accelerated production of
collagen with laser photostimulation. A significant decrease (9%) in pepsin soluble
collagen was observed in laser-treated tendons compared to controls. There were no
statistically significant differences recorded in the concentrations of hydroxypyridinium
crosslinks and acid soluble collagen between treated and control tendons.
Conclusion: This study of laser photostimulation on tendon healing in rabbits suggests
that such therapy facilitates collagen production in a manner that enhances tendon
healing.
Diabetes Care. 1998 Apr;21(4):580-4
Low-intensity laser irradiation improves skin circulation in patients with
diabetic microangiopathy
Schindl A, Schindl M, Schon H, Knobler R, Havelec L, Schindl L
Objective: Diabetic foot problems due to angiopathy and neuropathy account for 50% of
all nontraumatic amputations and constitute a significant economic burden to society.
Low-intensity laser irradiation has been shown to induce wound healing in conditions of
reduced microcirculation. We investigated the influence of low-intensity laser irradiation
by means of infrared thermography on skin blood circulation in diabetic patients with
diabetic microangiopathy.
Research design And Methods: Thirty consecutive patients with diabetic ulcers or
gangrenes and elevated levels of glycosylated hemoglobin were randomized by blocks of
two to receive either a single low-intensity laser irradiation with an energy density of 30
J/cm2 or a sham irradiation over both forefoot regions in a double-blind placebocontrolled clinical study. Skin blood circulation as indicated by temperature recordings
over the forefoot region was detected by infrared thermography.
Results: After a single transcutaneous low-intensity laser irradiation, a statistically
significant rise in skin temperature was noted (P < 0.001 by ANOVA for repeated
measurements), whereas in the sham-irradiated control group, a slight but significant
drop in temperature (P < 0.001) was found. Subsequently performed contrasts for
comparison of measurements before and after irradiation revealed significant
temperature increases at 20 min of irradiation time (P < 0.001), at the end of the
irradiation (P < 0.001), and 15 min after stopping the irradiation (P < 0.001). In the
sham-irradiated feet, the drop in local skin temperature was not significant at 20 min (P
= 0.1), but reached significance at the end of the sham-irradiation procedure (P < 0.001)
and 15 min after the end of sham irradiation (P < 0.001).
Conclusions: The data from this first randomized double-blind placebo-controlled clinical
trial demonstrate an increase in skin microcirculation due to athermic laser irradiation in
patients with diabetic microangiopathy.
Lasers Surg Med 1998;22(5):294-301
Stimulatory effect of 660 nm low level laser energy on hypertrophic scarderived fibroblasts: possible mechanisms for increase in cell counts
Webb C, Dyson M, Lewis WH
Background And Objective: Varying effects of red light wavelengths on in vitro cells
have been reported. Low level lasers (LLL) are employed to assist wound healing
especially for indolent ulcers. On healing, burn wounds may become hypertrophic,
resulting in excessive wound contraction, poor cosmesis, and functional impairment. This
study enquired whether 660 nm LLL affected hypertrophic scar-derived fibroblasts.
Study Design/Materials And Methods: The experiments investigated the effect of a
660 nm, 17 mW laser diode at dosages of 2.4 J/cm2 and 4 J/cm2 on cell counts of two
human fibroblast cell lines, derived from hypertrophic scar tissue (HSF) and normal
dermal (NDF) tissue explants, respectively. The protocol avoided transfer of
postirradiated cells. Estimation of fibroblasts utilized the methylene blue bioassay.
Results/Conclusion: Thepost-660 nm-irradiated HSFs exhibited very significantly
higher cell counts thancontrols P < 0.01 on days 1-4 (Mann-Whitney U-test), and P <
0.01 on days 1-3 for similarly irradiated NDFs.
Khirurgiia (Mosk) 1998;(4):42-5
Combined therapy of trophic ulcers with protracted healing
Babadzhanov BR, Sultanov IA
The results of treatment of 126 patients with trophic ulcers of the low extremities were
analyzed. Trophic ulcers in 74 patients (58.7%) appeared due to postthrombophlebitic
disease, in 25 patients (19.8%) due to primary varicose veins of lower limbs, in 15
(11.9%) patients due to obliterative diseases of peripheral vessels and in 12 (9.5%)-other diseases. The duration of the illness made up from 1 to 50 years. In 26 patients
(group 1) low-intensity laser irradiation (LLI) was used together with combined
conservative therapy; in 32 patients (group 2) hyperbaric oxygenation (HBO), in 21 (3
group)—combined application of LLI and HBO was used. The examination of regional
macrohemodynamics and microcirculation in 39 patients showed decrease of rheographic
index (RI) in the shin, increase of the arterioles tone and venous outflow disturbance.
The use of LLI and HBO resulted in undoubtful increase of RI and improvement of
microcirculatory indexes. As a result of combined application of LLI and HBO microflora of
the ulcers lowered from 10 and 10 per 1 gr in patients of group 1 and 2, respectively, in
patients of group 3 there was no growth of pathogenic microflora. The investigation of
humoral and cellular immunity after the application of LLI and HBO demonstrated strong
immunocorrective action.
Arch Orthop Trauma Surg. 1998;117(3):156-8
Topical hyperbaric oxygen and low energy laser for the treatment of diabetic
foot ulcers
Landau Z
Fifty patients with chronic diabetic foot ulcers in whom conventional therapy had failed
were treated with topical hyperbaric oxygen alone (15 patients) or in combination with a
low energy laser (35 patients). Eleven of these patients were treated on an ambulatory
basis with topical hyperbaric oxygen. The mean time the ulcer was present before
therapy was 9+/-6.6 months. The mean number of treatments was 25+/-13, and the
mean duration of therapy was 3+/-1.8 months. Forty-three of the 50 patients were
cured. No adverse reactions were noted. Our impression is that topical hyperbaric oxygen
alone or in combination with a low power laser are valuable adjuvants to conventional
therapy for diabetic foot ulcers.
J Clin Laser Med Surg 1999 Feb;17(1):29-33
Low power laser therapy and analgesic action
Tam G
Objective: The semiconductor or laser diode (GaAs, 904 nm) is the most appropriate
choice in pain reduction therapy.
Summary Background Data: Low-powerdensity laser acts on the prostaglandin (PG)
synthesis, increasing the change ofn PGG2 and PGH2 into PG12 (also called prostacyclin,
or epoprostenol). The last is the main product of the arachidonic acid into the endothelial
cells and into the smooth muscular cells of vessel walls, that have a vasodilating and
anti-inflammatory action.
Methods: Treatment was performed on 372 patients (206 women and 166 men) during
the period between May 1987 and January 1997. The patients, whose ages ranged from
25 to 70 years, with a mean age of 45 years, suffered from rheumatic, degenerative, and
traumatic pathologies as well as cutaneous ulcers. The majority of patients had been
seen by orthopedists and rheumatologists and had undergone x-ray examination. All
patients had received drug-based treatment and/or physiotherapy with poor results; 5
patients had also been irradiated with He:Ne and CO2 lasers. Two-thirds were
experiencing acute symptomatic pain, while the others suffered long-term pathology with
recurrent crises. We used a pulsed diode laser, GaAs 904 nm wavelength once per day
for 5 consecutive days, followed by a 2-day interval. The average number of applications
was 12. We irradiated the trigger points, access points to the joint, and striated muscles
adjacent to relevant nerve roots. RESULTS: We achieved very good results, especially in
cases of symptomatic osteoarthritis of the cervical vertebrae, sport-related injuries,
epicondylitis, and cutaneous ulcers, and with cases of osteoarthritis of the coxa.
Conclusions: Treatment with 904-nm diode laser has substantially reduced the
symptoms as well as improved the quality of life of these patient, ultimately postponing
the need for surgery.
J Wound Care 1999 Mar;8(3):111-4
A systematic review of laser therapy for venous leg ulcers
Flemming KA, Cullum NA, Nelson EA
A systematic review of randomised controlled trials (RCTs) was conducted to establish
the effectiveness of low-level laser therapy as a treatment for venous leg ulcers. Woundcare journals, conference proceedings and electronic databases (including Medline and
Cinahl) were searched up to October 1997 for RCTs comparing low-level laser therapy
with sham laser, no laser, or non-coherent light of other wavelengths. In addition,
companies who manufacture or distribute therapeutic lasers were contacted for any
unpublished or ongoing studies. Results from searches were scrutinised by one reviewer
to identify possible RCTs and full reports of these were obtained. Details of eligible
studies were extracted and summarised using a data extraction sheet. Data extraction
was checked by a second reviewer. Meta-analysis was used to combine the results of
trials where the interventions and outcome measures were sufficiently similar. A total of
four eligible RCTs were identified. Two compared treatment with laser therapy to sham or
placebo laser treatment. One study compared laser therapy with ultraviolet therapy. The
fourth was a three-armed study which compared the effects of laser therapy alone, laser
therapy plus infrared light, and non-coherent unpolarised red light. The comparisons of
laser therapy with
placebo, and laser therapy with ultraviolet therapy, showed no significant difference
between treatments with regard to ulcer healing rates. The comparison of laser with red
light showed a significant increase in complete healing at nine months for the
combination of laser and infrared light compared to non-coherent unpolarised red light.
We have not found any evidence of the benefit of low-level laser therapy per se on
venous leg ulcer healing. It appears that a combination of HeNe laser and infrared light
may promote the healing of venous ulcers, however more research is needed.
Nurs Stand 1999 Oct 6-12;14(3):66-70, 72
Low intensity laser therapy for chronic venous leg ulcers
Ashford R, Lagan K, Brown N, Howell C, Nolan C, Brady D, Walsh M
Ulceration of the lower extremities is one of the most important medicosocial problems
(Skobelkin et al 1990). In this article, two case studies show that it is the length of time
that laser therapy is used that can have a significant impact on ulcer size.
Dermatology. 1999;198(3):314-6
Diabetic neuropathic foot ulcer: successful treatment by low-intensity laser
therapy
Schindl A, Schindl M, Pernerstorfer-Schon H, Kerschan K, Knobler R, Schindl L
Objective: To evaluate the efficacy of low-intensity laser irradiation for the induction of
wound healing of a diabetic neuropathic foot ulcer.
Case: We report a case of a man with insulin-dependent diabetes mellitus, sensory
neuropathy, macroangiopathy and microangiopathy who had been suffering from an
ulcer of his first left toe accompanied by osteomyelitis for 6 weeks.
Results: After a total of 16 sessions of low-intensity laser therapy using a 670-nm diode
laser administered within a 4-week period the ulcer healed completely. During a followup period of 9 months, there was no recurrence of the ulcer even though the patient's
metabolic condition remained unstable.
Conclusions: Although laser therapy was not applied as a monotherapy, the present
observation suggests that it might constitute a useful side-effect-free alternative
treatment modality for the induction of wound healing of neuropathic ulcers in diabetic
patients. Therefore large properly controlled randomized studies seem justified.
J Photochem Photobiol B 2000 Jan;54(1):55-60
Effects of 780 nm diode laser irradiation on blood microcirculation: preliminary
findings on time-dependent T1-weighted contrast-enhanced magnetic
resonance imaging (MRI)
Schaffer M, Bonel H, Sroka R, Schaffer PM, Busch M, Reiser M, Duhmke E
Laser therapy by low light doses shows promising results in the modulation of some cell
functions. Various clinical studies indicate that laser therapy is a valuable method for pain
treatment and the acceleration of wound healing. However, the mechanism behind it is
still not completely understood. To explore the effect of a low-power diode laser (lambda
= 780 nm) on normal skin tissue, time-dependent contrast enhancement has been
determined by magnetic resonance imaging (MRI). In the examinations, six healthy
volunteers (four male and two female) have been irradiated on their right planta pedis
(sole of foot) with 5 J/cm2 at a fluence rate of 100 mW/cm2. T1-weighted magnetic
resonance imaging is used to quantify the time-dependent local accumulation of
Gadolinium-DPTA, its actual content in the local current blood volume as well as its
distribution to the extracellular space. Images are obtained before and after the
application of laser light. When laser light is applied the signal to noise ratio increases by
more than 0.35 +/- 0.15 (range 0.23-0.63) after irradiation according to contrastenhanced MRI. It can be observed that, after biomodulation with light of low energy and
low power, wound healing improves and pain is reduced. This effect might be explained
by an increased blood flow in this area. Therefore, the use of this kind of laser treatment
might improve the outcome of other therapeutic modalities such as tumour ionizing
radiation therapy and local chemotherapy.
J Clin Laser Med Surg 2000 Feb;18(1):15-22
A case report of low intensity laser therapy (LILT) in the management of venous
ulceration: potential effects of wound debridement upon efficacy
Lagan KM, Mc Donough SM, Clements BA, Baxter GD
Objective: This single case report (ABA design) was undertaken as a preliminary
investigation into the clinical effects of low intensity laser upon venous ulceration, applied
to wound margins only, and the potential relevance of wound debridement and wound
measurement techniques to any effects observed.
Methods: Ethical approval was granted by the University of Ulster's Research Ethical
Committee and the patient recruited was required to attend 3 times per week for a total
of 8 weeks. Treatments were carried out using single source irradiation (830 nm; 9
J/cm2, CB Medico, Copenhagen, Denmark) in conjunction with dry dressings during each
visit. Assessment of wound surface area, wound appearance, and current pain were
completed by an independent investigator. Planimetry and digitizing were completed for
wound tracings and for photographs to quantify surface areas. Video image analysis was
also performed on photographs of wounds.
Results: The primary findings were changes in wound appearance, and a decrease in
wound surface area (range 33.3-46.3%), dependent on the choice of measurement
method. Video image analysis was used, but rejected as an accurate method of wound
measurement. Treatment intervention produced a statistically significant reduction in
wound area using the C statistic on digitizing data for photographs (at Phase one only; Z
= 2.412; p < 0.05). Wound debridement emerged as an important procedure to be
carried out prior to measuring wounds. Despite fluctuating pain levels recorded
throughout the duration of the study, VAS scores showed a decrease of 15% at the end
of the study. This hypoalgesic effect was, however, statistically significant (using the C
statistic) at Phase one only (Z = 2.554; p < 0.05).
Conclusions: Low intensity laser therapy at this dosage, and using single source
irradiation would seem to be an effective treatment for patients suffering venous
ulceration. Further group studies are indicated to establish the most effective therapeutic
dosage for this and other types of ulceration.
Cochrane Database Syst Rev. 2000;(2):CD001182
Laser therapy for venous leg ulcers
Flemming K, Cullum N
Objectives: To assess the effectiveness of low level laser therapy in the treatment of
venous leg ulcers.
Search Strategy: Searches of 19 databases, hand searching of journals and conference
proceedings from 1948 onwards, and examination of bibliographies.
Selection Criteria: Randomised controlled trials comparing low level laser therapy with:
sham laser; no laser; non-coherent light. There was no restriction on date or language.
The main outcome measure used was complete healing of the ulcers.
Data Collection And Analysis: Dataextraction was done by one reviewer and checked
by a second. Meta analysis wasused to combine the results of trials where the
interventions and outcomemeasures were sufficiently similar. MAIN RESULTS: There
were 4 eligible trials.Two RCTs compared laser therapy with sham, 1 with ultraviolet
therapy and 1 withnon-coherent, unpolarised red light. Neither of the two RCTs
comparing laserwith sham found a significant difference in healing rates; there was no
significant of laser evident when the trials were pooled. A three-arm study compared: laser therapy alone - laser therapy plus infrared light - non-coherent, unpolarised red
light. Significantly more ulcers completely healed in the group receiving a combination of
laser and infrared light compared with non-coherent, unpolarised red light. A fourth trial
compared laser and ultraviolet light and found no difference.
Reviewer's Conclusions: We have found no evidence of any benefit associated with
low level laser therapy on venous leg ulcer healing. One small study suggests that a
combination of laser and infrared light may promote the healing of venous ulcers,
however more research is needed.
J Clin Laser Med Surg 2000 Oct;18(5):235-40
Low-level laser therapy for wound healing: feasibility of wound dressing
transillumination
Lilge L, Tierney K, Nussbaum E
Objective: The purpose of this study was to assess the feasibility of exposing wounds
during low-level laser therapy (LLLT) by transillumination of the wound dressings.
Background Data: LLLT has been associated with accelerated wound healing in chronic
ulcers. The usual approach is to remove wound dressings prior to exposure and to treat
three to five times weekly. Frequent change of wound dressings is time consuming and
costly; it disrupts the healing process, increases the risk of wound infection, and may be
traumatic for the patient.
Methods: A double integrating sphere setup was employed to quantify the diffuse
transmittance and reflectance of various wound dressings. Differences in transmittance
for large area sources and point sources were demonstrated through the use of a diode
laser and an incoherent light source. RESULTS: There were a number of gels and
membrane style wound dressings with diffuse transmittance of more than 50%. Hence,
for these dressings the prescribed radiant exposure to the wound surface could be
achieved by increasing the exposure duration, while maintaining reasonable overall
treatment times.
Conclusions: Although LLLT by transillumination of wound dressings is feasible for a
variety of wound dressings without significant commitments in additional treatment time,
the specific transmission of products not included in this study needs to be determined at
the intended treatment wavelength. A transillumination approach may facilitate a faster
rate of wound healing than LLLT applied to exposed wounds by reducing trauma and the
risk of infection.
J Photochem Photobiol B 2000 Dec;59(1-3):1-8
Magnetic resonance imaging (MRI) controlled outcome of side effects caused by
ionizing radiation, treated with 780 nm-diode laser -- preliminary results
Schaffer M, Bonel H, Sroka R, Schaffer PM, Busch M, Sittek H, Reiser M,
Duhmke E
Background And Objective: Ionizing radiation therapy by way of various beams such
as electron, photon and neutron is an established method in tumor treatment. The side
effects caused by this treatment such as ulcer, painful mastitis and delay of wound
healing are well known, too. Biomodulation by low level laser therapy (LLLT) has become
popular as a therapeutic modality for the acceleration of wound healing and the
treatment of inflammation. Evidence for this kind of application, however, is not fully
understood yet. This study intends to demonstrate the response of biomodulative laser
treatment on the side effects caused by ionizing radiation by means of magnetic
resonance imaging (MRI).
Study Design/Patients And Methods: Six female patients suffering from painful
mastitis after breast ionizing irradiation and one man suffering from radiogenic ulcer
were treated with lambda=780 nm diode laser irradiation at a fluence rate of 5 J/cm2.
LLLT was performed for a period of 4-6 weeks (mean sessions: 25 per patient, range 19
35). The tissue response was determined by means of MRI after laser treatment in
comparison to MRI prior to the beginning of the LLLT.
Results: All patients showed complete clinical remission. The time-dependent contrast
enhancement curve obtained by the evaluation of MR images demonstrated a significant
decrease of enhancement features typical for inflammation in the affected area.
Conclusion: Biomodulation by LLLT seems to be a promising treatment modality for side
effects induced by ionizing radiation.
J Clin Laser Med Surg 2000 Apr;18(2):67-73
Wound healing of animal and human body sport and traffic accident injuries
using low-level laser therapy treatment: a randomized clinical study of seventyfour patients with control group
Simunovic Z, Ivankovich AD, Depolo A
Background And Objective: The main objective of current animal and clinical studies
was to assess the efficacy of low level laser therapy (LLLT) on wound healing in rabbits
and humans.
Study Design/Materials And Methods: In the initial part of our research we
conducted a randomized controlled animal study, where we evaluated the effects of laser
irradiation on the healing of surgical wounds on rabbits. The manner of the application of
LLLT on the human body are analogous to those of similar physiologic structure in animal
tissue, therefore, this study was continued on humans. Clinical study was performed on
74 patients with injuries to the following anatomic locations: ankle and knee, bilaterally,
Achilles tendon; epicondylus; shoulder; wrist; interphalangeal joints of hands,
unilaterally. All patients had had surgical procedure prior to LLLT. Two types of laser
devices were used: infrared diode laser (GaAlAs) 830 nm continuous wave for treatment
of trigger points (TPs) and HeNe 632.8 nm combined with diode laser 904-nm pulsed
wave for scanning procedure. Both were applied as monotherapy during current clinical
study. The results were observed and measured according to the following clinical
parameters: redness, heat, pain, swelling and loss of function, and finally postponed to
statistical analysis via chi2 test.
Results: After comparing the healing process between two groups of patients, we
obtained the following results: wound healing was significantly accelerated (25%-35%) in
the group of patients treated with LLLT. Pain relief and functional recovery of patients
treated with LLLT were significantly improved comparing to untreated patients.
Conclusion: In addition to accelerated wound healing, the main advantages of LLLT for
postoperative sport- and traffic-related injuries include prevention of side effects of
drugs, significantly accelerated functional recovery, earlier return to work, training and
sport competition compared to the control group of patients, and cost benefit.
Yale J Biol Med. 2001 Mar-Apr;74(2):95-100
Topical hyperbaric oxygen and low energy laser therapy for chronic diabetic
foot ulcers resistant to conventional treatment
Landau Z, Schattner A
Chronic foot ulcers are common in long-standing diabetes, may herald severe
complications and are often resistant to therapy. To evaluate the effects of adjunctive
topical hyperbaric oxygen treatment (THBO) and low energy laser (LEL) irradiation on
ulcer healing, a 100 consecutive patients with chronic diabetic foot ulcers (DFU)
refractory to 4.5 +/- 1.2 months of comprehensive treatment, were enrolled in a
prospective open study. While conventional treatment was continued as necessary, THBO
was administered by pumping 100 percent oxygen into a disposable sealed polythylene
hyperbaric chamber (150 min x 2 to 3/wk at up to 1.04 atm). Helium-neon LEL
irradiation was given concurrently using a Unilaser Scan Unit at 4 J/cm2 for 20 min.
Some patients continued THBO at home or their treatment was confined to THBO at
home. Patients were monitored every two weeks revealing 81 percent cure after 25 +/13 treatments over 3.2 +/- 1.7 months. On follow-up (median 18 months), only 3/81 (4
percent) had reulceration, which responded to THBO/LEL retreatment. Nonresponders
had significantly lower ankle brachial indices (ABI) than patients whose ulcers were
healed (0.55 vs. 0.78, p < 0.01) and ultimately required amputation. Patient compliance
was full and no adverse events occurred. In conclusion, although the study was open and
uncontrolled, an 81 percent healing of DFU in patients who previously did not respond to
a comprehensive treatment program, constitutes an intriguing preliminary result. Thus,
THBO/LEL therapy may be a safe, simple, and inexpensive early adjunctive treatment for
patients with chronic diabetic foot ulcers. Our findings should prompt its evaluation by
large randomized controlled trials.
Health Technol Assess. 2001;5(9):1-221
Systematic reviews of wound care management: (5) beds; (6) compression; (7)
laser therapy, therapeutic ultrasound, electrotherapy and electromagnetic
therapy
Cullum N, Nelson EA, Flemming K, Sheldon T
Background: Chronic wounds such as leg ulcers, diabetic foot ulcers and pressure sores
are common in both acute and community healthcare settings. The prevention and
treatment of these wounds involves many strategies: pressure-relieving beds, mattresses
and cushions are universally used as measures for the prevention and treatment of
pressure sores; compression therapy in a variety of forms is widely used for venous leg
ulcer prevention and treatment; and a whole range of therapies involving laser,
ultrasound and electricity is also applied to chronic wounds. This report covers the final
three reviews from a series of seven. AIMS: To assess the clinical effectiveness and costeffectiveness of: (1) pressure-relieving beds, mattresses and cushions for pressure sore
prevention and treatment; (2) compression therapy for the prevention and treatment of
leg ulcers; (3) low-level laser therapy, therapeutic ultrasound, electrotherapy and
electromagnetic therapy for the treatment of chronic wounds.
Methods - Data Sources: Nineteen electronic databases, including MEDLINE, CINAHL,
EMBASE and the Cochrane Controlled Trials Register (CENTRAL), were searched.
Relevant journals, conference proceedings and bibliographies of retrieved papers were
handsearched. An expert panel was also consulted. METHODS - STUDY SELECTION:
Randomised controlled trials (RCTs) which evaluated these interventions were eligible for
inclusion in this review if they used objective measures of outcome such as wound
incidence or healing rates.
Results - Beds, Mattresses And Cushions For Pressure Sore Prevention And
Treatment: A total of 45 RCTs were identified, of which 40 compared different
mattresses, mattress overlays and beds. Only two trials evaluated cushions, one
evaluated the use of sheepskins, and two looked at turning beds/kinetic therapy.
Results - Compression For Leg
Ulcers: A total of 24 trials reporting 26 comparisons were included (two of prevention
and 24 of treatment strategies).
Results - Low-Level Laser Therapy, Therapeutic Ultrasound, Electrotherapy And
Electromagnetic Therapy: Four RCTs of laser (for venous leg ulcers), 10 of
therapeutic ultrasound (for pressure sores and venous leg ulcers), 12 of electrotherapy
(for ischaemic and diabetic ulcers, and chronic wounds generally) and five of
electromagnetic therapy (for venous leg ulcers and pressure sores) were included.
Studies were generally small, and of poor methodological quality. CONCLUSIONS (1)
Foam alternatives to the standard hospital foam mattress can reduce the incidence of
pressure sores in people at risk, as can pressure-relieving overlays on the operating
table. One study suggests that air-fluidised therapy may increase pressure sore healing
rates. (2) Compression is more effective in healing venous leg ulcers than is no
compression, and multi-layered high compression is more effective than single-layer
compression. High-compression hosiery was more effective than moderate compression
in preventing ulcer recurrence. (3) There is generally insufficient reliable evidence to
draw conclusions about the contribution of laser therapy, therapeutic ultrasound,
electrotherapy and electromagnetic therapy to chronic wound healing.
Wound Repair Regen. 2001 May-Jun;9(3):248-55.
Laser photostimulation accelerates wound healing in diabetic rats
Reddy GK, Stehno-Bittel L, Enwemeka CS
In this study, we examined the hypothesis that laser photostimulation can
facilitate healing of impaired wounds in experimental diabetes using a rat
model. Diabetes was induced in male rats by streptozotocin injection and two 6
mm diameter circular wounds were created on either side of the spine. The left
wound of each animal was treated with a 632.8 nm He:Ne laser at a dose of 1.0
J/cm2 for five days a week until the wounds closed (three weeks). Measurements
of the biomechanical properties of the laser-treated wounds indicated there was
a marginal increase in maximum load (16%), stress (16%), strain (27%), energy
absorption (47%) and toughness (84%) compared to control wounds of diabetic
rats. Biochemical assays revealed that the amount of total collagen was
significantly increased in laser treated wounds (274 +/- 8.7 microg) over the
control wounds (230 +/- 8.4 microg). Sequential extractions of collagen from
healing wounds showed that laser treated wounds had significantly greater
concentrations of neutral salt soluble (15%) and insoluble collagen (16%) than
control wounds, suggesting accelerated collagen production in laser treated
wounds. There was an appreciable decrease in pepsin soluble collagen (19%) in
laser treated wounds over control wounds, indicating higher resistance to
proteolytic digestion. In conclusion, the biomechanical and biochemical results
collectively suggest that laser photostimulation promotes the tissue repair
process by accelerating collagen production and promoting overall connective
tissue stability in healing wounds of diabetic rats.
Lasers Surg Med. 2001;29(2):105-6.
780 nm low power diode laser irradiation stimulates proliferation of
keratinocyte cultures: involvement of reactive oxygen species
Grossman N, Schneid N, Reuveni H, Halevy S, Lubart R
Background And Objective: The purpose of this study was to determine irradiation
parameters of a 780 nm low power CW diode laser (6.5 mW) leading to enhanced
proliferation of cultured normal human keratinocytes (NHK). The possible role of
reactive oxygen species (ROS) in this response was evaluated.
Study Design/Materials And Methods: NHK were exposed to a single dose of 0 to 3.6
J/cm2 (0-180 sec) of irradiation. Proliferation parameters studied were: incorporation of
3H-thymidine during 6-24 hr following irradiation; percentage of dividing cells and
number of cells, 24 hr and 48 hr following irradiation, respectively.
Results: Proliferation of NHK exposed to 0.45-0.95 J/cm2 was significantly enhanced by
1.3-1.9-folds relative to sham-irradiated controls, as inferred from parameters studied.
Exposure to other energy densities was considerably less effective in enhancing
proliferation parameters. Added enzymatic antioxidants, superoxide dismutase or
catalase, scavenging superoxide anions and H2O2, suppressed this enhanced
proliferation. Added scavengers (alpha-tocopherol acetate, scavenging lipid peroxidation,
or sodium azide, histidine, mannitol, scavenging singlet oxygen, superoxide anions, and
hydroxyl radicals, respectively), or N-acetyl cysteine, the thiol-reducing agent,
suppressed the response, but to different extents.
Conclusions: The results indicate that 780 nm low power diode laser irradiation
enhanced keratinocytes proliferation in vitro, with an apparent involvement of ROS in this
response, and comparably, might be used to promote their proliferation in vivo to
enhance wound healing.
Lasers Surg Med 2001;28(1):27-32
Low intensity laser therapy (830nm) in the management of minor postsurgical
wounds: a controlled clinical study
Lagan KM, Clements BA, McDonough S, Baxter GD
Background And Objective: The stimulatory effects of low intensity laser therapy
(LILT) have been widely published for the treatment of chronic ulceration. In contrast to
this previous work, the current study investigated its potential efficacy (by using a
dosage of 9 J/cm2) in the management of acute wounds. For this purpose,
uncomplicated postoperative wounds after minor podiatric surgery were examined.
Study Design/Materials And Methods: The study was designed as a controlled group
study. Ethical approval was granted by the University of Ulster's Research Ethics
Committee. Patients (n = 9) presenting with a total of 12 wounds after minor surgical
procedures (partial/total nail avulsions/electrosurgery) were recruited from the Podiatry
Teaching Clinic, Northern Ireland. Patients attended the clinic once per week for
assessment and treatment. Weekly irradiation was performed by using a CBM Master 3
(CB Medico, Copenhagen, Denmark) diode laser (GaAlAs). The physical parameters of the
output of this unit were as follows: wavelength, 830 nm; average power output, 30 mW;
spot size, 0.1 cm2; irradiance, 300 mW/cm2; continuous wave output. Wound
assessment and recording of pain levels were conducted weekly. Wound measurement
was completed by using planimetry and digitising methods. RESULTS: Current findings
indicated no statistically significant differences between Laser and Control groups for
wound closure (P = 0.28 digitising; P = 0.49 planimetry) nor for pain levels reported (P
= 0.88). CONCLUSION: It would seem that LILT provides no advantages in the
management of minor postoperative wounds over current practice. Despite no apparent
benefit of infrared laser at this dosage in the management of acute stage wounds, further
research is required to determine its potential efficacy in the management of other
wound types.
14 Th World Congress of International Union of Phlebology
Rome 9-14 Sept 2001, Abstract P 243
Low lever laser therapy (LLL) in chronic venous insufficiency
V.I.Kozlov, K.T.Zaitzev, O.A.Terman
Aims: To estimate a range of changeability in rnicrocirculation (MC) under LLL-therapy,
as well as to determine a pathogenic role of microcirculation activation in complex
treatment of chronic venous insufficiency (CVI) in low limbs.
Material and methods: We have investigated 91 patients with CVI and trophic
impairments (ulcers). LLL-energy (wavelength 0.83 pin) application to the surface of a
trophic ulcer and also laser reflexotherapy (wavelength 1.3 pin) at the body acupuncture
points and the points of the ear lobe were used. The treatment session involved 15 , =
20 procedures every day. The rnicrocirculation was studied with conjunctival and skin
biomicroscopy and the Laser Doppler Fluxmetry (LDF).
Results: The comparison of biomicroscopy and LDF results indicates a high correlation
between these two methods. Disturbances of blood inflow and outflow, decrease of
capillary blood flow, rheological disorders, leukocyte adhesion and derangements of
permeability were identified as the pathogenic signs of CVI. The amplitude-frequency
analysis of flux motions ascertained the disorder of correlation between the low-frequent
rhythms, which characterize vasomotions, and the high-frequent rhythms, connected
with respiration and cardiac pulsation. After LLL-therapy ulcer healing took place in 71%
of patients; noticeable improvement in 12% and a recurrence rate within 1 year was 6%.
Clinical effect of LLL-therapy has been accompanied by disappearance of microcirculation
disorders.
Conclusion: LLL-therapy in combined treatment of CVI patients has been successful.
The essence of its pathogenic effect is based on the photostimulation of microcirculation
and reparative processes.
Pol Merkuriusz Lek 2001 Nov;11(65):418-21
Laser's biostimulation in healing or crural ulcerations
Krol P, Franek A, Hunka-Zurawinska W, Bil J, Swist D, Polak A, Bendkowski W
Katedra i Zaklad Biofizyki Lekarskiej Slaskiej Akademii Medycznej w Katowicach
The objective of this paper was to evaluate effect of laser's biostimulation on the process
of healing of crural ulcerations. Three comparative groups of patients, A, B and C, were
made at random from the patients with venous crural ulcerations. The group A consisted
of 17, the group B 15, the group C 17 patients. The patients in all comparative groups
were treated pharmacologically and got compress therapy. Ulcerations at patients in
group A were additionally irradiated by light of biostimulation's laser (810 nm) in this
way that every time ulcerations got dose of energy 4 J/cm2. The patient's in-group B
additionally got blind trial (with placebo in the form of quasi-laserotherapy). The
evaluated factors were to estimate how laser's biostimulation causes any changes of the
size of the ulcers and of the volume of tissue defect. The speed of changes of size and
volume of tissue defect per week was calculated. After the treatment there was
statistically significant decrease of size of ulcers in all comparative groups while there
was no statistically significant difference between the groups observed. After the
treatment there was statistically significant decrease of volume of ulcers only in groups A
and C but there was no statistically significant difference between the groups observed.
Lasers Surg Med. 1997;20(1):56-63.
Comment in: Lasers Surg Med. 2001;29(2):105-6.
Effects of photostimulation on wound healing in diabetic mice
Yu W, Naim JO, Lanzafame RJ
Background And Objective: Low-level laser irradiation at certain fluences and
wavelengths can enhance the release of growth factors from fibroblasts and
stimulate cell proliferation in vitro. We evaluated whether low-level laser
irradiation can improve wound healing in diabetes mellitus.
Study Design/Materials And Methods: Genetically diabetic mice (C57BL/Ksj/db/db)
were used as the animal model for this wound healing study. The experimental animals
were divided among four groups: negative control, positive control (topical basic
fibroblast growth factor [bFGF] on wound), laser therapy group; and a combination group
of laser therapy and topical bFGF. An argon dye laser (Lexel Auora Model 600) at a
wavelength of 630 nm and an output of 20 m W/cm2 was used as the light source. The
speed of wound closure and histological evaluation were used to analyze the
experimental results.
Results: Laser irradiation enhanced the percentage of wound closure over time as
compared to the negative control group (58.4 +/- 2.6 vs. 40.8 +/- 3.4 at day 10 and
95.7 +/- 2 vs. 82.3 +/- 3.6 at day 20, P < .01). Histological evaluation showed that laser
irradiation improved wound epithelialization, cellular content, granulation tissue
formation, and collagen deposition in laser-treated wounds as compared to the negative
control group (6.4 +/- 0.16 vs. 3.8 +/- 0.13 at day 10 and 12 +/- 0.21 vs. 8.2 +/- 0.31,
P < .01).
Conclusion: This study of laser biostimulation on wound healing in diabetic mice
suggests that such therapy may be of great benefit in the treatment of chronic wounds
that occur as a complication of diabetes mellitus.
Lasers Med Sci 2002, 17:110-134
Review article Wound healing in cell studies and animal model experiments by
low level laser therapy; were clinical studies justified ? A systematic Review
C. Lucas, L.J. Criens-Poublon, C.T. Cockrell and R.J. de Hann
Based on results of cell studies and animal experiments, clinical trials with Low Level
Laser Therapy (LLLT) were performed, which finally did not demonstrate a beneficial
effect on outcome of wound healing. The aim of this study was to investigate whether the
evidence from cell studies and animal experiments with respect tu wound healing was
unequivocally in favour of LLLT, which would imply that these models might be adequate
to predict treatment response in patients, or that the data of cell studies and animal
experiments were inconclusive, which would mean that the clinical trials were based on
insuftcient evidence. We performed a systematic review of cell studies and animal
experiment with LLLT on wound healing. Manuscripts were identified by searching
Medline, Embase, and SPIE (the International Society for Optical Engineering). We
assessed whether studies showed a beneficial effect of active treatment or not. The effect
size was expressed in standardised mean difference [(SMD) the mean outcome measure
of the treatment group minus the mean outcome measure of the control group, divided
by the pooled standard deviation of these measurements]. In-depth analyses were
perfomed on (1) studies in which infiicted wounds on animals were irradiated and
evaluated; (2) studies with primary outcome measures on dimensions with direct
reference to wound healing (ranging from acceleration of wound closure to
epithelialisation, but excluding surrogate dimensions with regard to wound healing; in
this case: tensile strength); (3) animal studies with `true controls'; (4) studies in which
animals functioned as their `own controls' and (5) studies with the highest
methodological quality score. The 36 included studies contained 49 outcome parameters
of which 30 reported a positive effect of laser irradiation and 19 did not. Eleven studies
presented exact data about the effect of active treatment and controls. The pooled effect
size (SMD) over 22 outcome measures of these studies was - 1.05 (95% CI: -1.67 to 0.43) in favour of LLLT. Methodological quality of the studies was poor. In-depth analysis
of studies showed no significant pooled effect size in studies with highest methodological
quality scores [0.06 (95% CI: - 0.42 Io 0.53)]. Summarising the data of cell studies and
animal experiments, reviewed in this manuscript, these studies failed to show
unequivocal evidence Io substantiate the decision for trials with LLLT in a large number
of patients. In tact, there were no diflerences between the results of these experiments
and clinical studies. Remarkably, we found that (almost from the introduction on) animal
experiments and clinical studies that adress the biological eflects of LLLT on wound
healing, ran simultaneously, rather than in sequence. We conclude that this type of
phototherapy should not be considered a valuable (adjuvant) treatment for this selected,
generally therapy-refractory condition in humans.
J Clin Laser Med Surg 2002 Jun;20(3):109-16
Low-intensity laser therapy/combined phototherapy in the management of
chronic venous ulceration: a placebo-controlled study
Lagan KM, McKenna T, Witherow A, Johns J, McDonough SM, Baxter GD
Objective: The current placebo-controlled study was undertaken to investigate the
efficacy of combined phototherapy and low-intensity laser therapy (LILT) in the
management of chronic venous ulceration when used in conjunction wit standardized
nursing intervention.
Materials And Methods: Approval was granted by Research Ethical Committees at the
University of Ulster and Altnagelvin Hospitals Health and Social Services Trust. Patients
(n = 15; 10 female/5 male; age +/- SD = 69.9 +/- 13.8 years) were recruited from an
outpatient "leg ulcer clinic," where they attended once per week for irradiation/sham
treatments for 4 weeks. Treatment was withheld for a total of 8 weeks, and patients
were reviewed during this time (weeks 8 and 12) for ulcer and pain assessment only. A
multisource diode array (660-950 nm) was used for irradiation; parameters were kept
constant for the duration of the study (532 mW; 5 kHz; 12 J/cm(2)). Wound and pain
assessment were carried out by an independent investigator. Digitizing was used to
quantify surface areas from wound tracings.
Results: Although there was no statistically significant difference between Treatment
and Placebo groups, an apparent clinical difference in wound healing rate was noted; at
postirradiation, a continued reduction in wound size was evident for the treatment group.
These effects were believed to be due to an apparent delayed effect. There was no
statistically significant difference between groups for pain.
Conclusion: These findings provide only limited evidence for the use of this modality as
an adjunctive therapy with current nursing intervention. Further group studies are
indicated to investigate the apparent delayed effect reported here for various etiologies
of ulceration.
Microvasc Res 2002 Sep;64(2):240-6
Systemic effects of low-intensity laser irradiation on skin microcirculation in
patients with diabetic microangiopathy
Schindl A, Heinze G, Schindl M, Pernerstorfer-Schon H, Schindl L
Low-intensity laser irradiation has been shown to induce wound healing in conditions of
reduced microcirculation, which is in part explained by systemic effects. We therefore
investigated such a potential systemic effect of low-intensity laser irradiation on skin
blood circulation in patients with diabetic microangiopathy. Patients with diabetic
microangiopathy were randomized to receive either a single helium-neon (HeNe, 632.8
nm) low-intensity laser irradiation with a dose of 30 J/cm(2) or a sham irradiation over
the forefoot region in a double-blind, placebo-controlled clinical study. Skin blood
circulation by means of temperature recordings over forefoot regions was detected by
infrared thermography. Following a single transcutaneous low-intensity laser irradiation,
a rise in skin temperature in both feet of the subjects in the laser group was noted,
whereas in both feet of the subjects in the placebo group a drop in skin temperature
occurred. The baseline-adjusted skin temperature 15 min after the end of the irradiation
was significantly higher in the laser-treated forefeet compared to the placebo-"treated"
forefeet (p < 0.0001); the baseline-adjusted difference in the temperature was 1.94 +/0.35 degrees C. Simultaneously, the baseline-adjusted skin temperature was significantly
higher in the laser-untreated forefeet compared to the placebo-"untreated" forefeet (P <
0.0001); the baseline-adjusted difference was 1.70 +/- 0.33 degrees C. Our data show a
significant increase in skin circulation due to athermic laser irradiation in patients with
diabetic microangiopathy and point to the possibility of inducing systemic effects.
Lasers Surg Med 2002;31(5):343-51
Effects of 810 nm laser irradiation on in vitro growth of bacteria: Comparison
of continuous wave and frequency modulated light
Nussbaum EL, Lilge L, Mazzulli T
Background And Objectives: Low intensity laser therapy may modify growth of wound
bacteria, which could affect wound healing. This study compares the effects on bacteria
of 810 nm laser using various delivery modes (continuous wave or frequency modulated
light at 26, 292, 1,000, or 3,800 Hz).
Study Design/Materials And Methods: Staphylococcus (S.) aureus, Escherichia (E.)
coli,and Pseudomonas (P.) aeruginosa were plated on agar and then irradiated
(0.015W/cm(2); 1-50 J/cm(2)) or used as controls (sham irradiated); growth
wasexamined after 20 hours of incubation post exposure.
Results: There wereinteractions of species and modulation frequency in the overall
effects ofirradiation (P = 0.0001), and in the radiant exposure mediated effects (P
=0.0001); thus individual frequencies and each bacterium were analysedseparately.
Bacteria increased following 3,800 Hz (P = 0.0001) and 1,000 Hz (P =0.0001) pulsed
irradiation; at particular radiant exposures P. aeruginosaproliferated significantly more
than other bacteria. Pulsed laser at 292 and 26Hz also produced species-dependent
effects (P = 0.0001; P = 0.0005); however,the effects for different radiant exposures
were not significant. Bacterialgrowth increased overall, independent of species, using
continuous mode laser,significantly so at 1 J/cm(2) (P = 0.02). Analysis of individual
speciesdemonstrated that laser-mediated growth of S. aureus and E. coli was
dependenton pulse frequency; for S. aureus, however, there was no effect for
differentradiant exposures. Further tests to examine the radiant exposure effects on
E.coli showed that growth increased at a frequency of 1,000 Hz (2 J/cm(2); P =0.03). P.
aeruginosa growth increased up to 192% using pulsed irradiation at1,000-3,800 Hz;
whereas 26-292 Hz laser produced only a growth trend.
Conclusions: The findings of this study point to the need for wound culturesprior to
laser irradiation of infected wounds. Similar investigations usingother common
therapeutic wavelengths are recommended.
Ned Tijdschr Tandheelkd 2002 Sep;109(9):334-8
Lasers in dentistry 6. The soft laser
ten Bosch JJ
A soft laser is a low-power laser emitting in the red and near-infrared part of the
spectrum. Studies with cell cultures have shown that radiation from a soft laser, when
used under proper conditions, promotes cell function and cell proliferation. However,
wavelength and dose should be carefully adjusted to an optimum value: too low a dose
does not work and neither does a high dose. The dose should be adjusted within an
interval of about 10%. In a few animal studies a positive effect on wound healing has
been demonstrated, although other studies did not show such an effect. Of the human
studies done in the dental field, many do not meet scientific standards because there was
no control group or the study was not double-blind. A few studies showed a positive
effect but most did not. Perhaps the large variation in results may be explained by the
required accuracy of adjustment of the dose, combined with the complicated processes
that relate the incident dose to the dose to cells lying on or in tissue. More research, in
particular studies in which the dose and wave length are varied systematically, are
needed before responsible clinical use can be recommended.
Lasers Surg Med 2002;31(4):263-7
Effect of low-power laser irradiation on cell growth and procollagen synthesis
of cultured fibroblasts
Pereira AN, Eduardo Cde P, Matson E, Marques MM
Background And Objectives: In dentistry, low-power lasers have been used in the
treatment of dentin hypersensitivity, gingivitis, periodontitis, and different forms of oral
ulcers. This in vitro study focuses on the biostimulation of NIH-3T3 fibroblasts by a lowpower Ga-As-pulsed laser.
Study Design/Materials And Methods: We have studied cell growth and procollagen
synthesis of cultured fibroblasts submitted to low-power laser irradiation with energy
densities varying from 3 to 5 J/cm(2) over a period of 1-6 days. The light source was a
120 mW Ga-As diode laser (lambda = 904 nm). Growth curves and procollagen
immunoprecipitation were obtained.
Results: Irradiation of 3 and 4 J/cm(2) increased the cell numbers about threefold to
sixfold comparing to control cultures. However, this effect was restricted to a small range
of energy densities since 5 J/cm(2) had no effect on cell growth. The energy density of 3
J/cm(2) remarkably increased cell growth, with no effect on procollagen synthesis, as
demonstrated by the immunoprecipitation analysis.
Conclusions: Our results showed that a particular laser irradiation stimulates fibroblast
proliferation, without impairing procollagen synthesis.
J Clin Laser Med Surg 2002 Feb;20(1):37-40
Effects of 1047-nm neodymium laser radiation on skin wound healing
Simoes RM, Teixeira D, Maldonado EP, de RW, Zezell DM
Previous research in our laboratory has shown that the polarization component of the
electrical field plays an important role on the healing process of inflammatory lesions
created in the end of the spinal column of Lewis rats, using a He-Ne laser at lambda =
632.8 nm. It is well known that polarization is lost in a turbid medium, such as living
tissue. However, the Nd:YLF wavelength (lambda = 1,047 nm) allows more polarization
preservation than lambda = 632.8 nm, and the Nd:YLF laser beam has been used in
clinical trials as a biostimulating agent. In this work, we investigated the influence of a
low-intensity, linearly polarized Nd:YLF laser beam on skin wound healing, considering
two orthogonal directions of polarization. We have considered a preferential axis as the
animals' spinal column, and we aligned the linear laser polarization first parallel, then
perpendicular to this direction. Burns of about 6 mm in diameter were created with liquid
N2 on the back of the animals, and the lesions were irradiated on days 3, 7, 10, and 14
postwounding, D = 1.0 J/cm2. Lesions 1 and 2 were illuminated using Nd:YLF pulsed
laser radiation. Lesion 1 was irradiated with linear polarization parallel with the rat spinal
column. Lesion 2 was irradiated using the same protocol, but the light polarization was
aligned with the perpendicular relative orientation. Control lesions were not irradiated.
We have taken photographs from the wound areas on the 3rd, 7th, 10th, 14th, and 17th
postoperative day for a biometrical analysis. The results have shown that lesion 1 healed
faster than the control lesions (p < 0,05), which presented a smaller degree of healing
after 14 days postwounding.
Med Eng Phys. 2002 Nov;24(9):607-15
Does low output laser stimulation enhance the healing of crural ulceration?
Some critical remarks
Franek A, Krol P, Kucharzewski M
The objective of the experiment was to evaluate the impact of laser stimulation on crural
ulceration healing.Three groups were established at random from patients with crural
ulceration: A, B and C. Group A included 21 patients, group B included 22 patients and
group C, 22 patients. Patients in all groups were treated with pharmaceuticals and with
compressive therapy. The ulcers in group A were additionally irradiated with laser light of
wavelength 810 nm, so that a dose of 4 J/cm2 was applied in each procedure. Patients in
group B were additionally subjected to a blind test (with placebo in the form of quasi
laser therapy).At the end of the treatment a statistically significant reduction of the area
and volume of the ulcers was found in all groups. No statistically significant difference
was found between the groups in terms of average rate of change per week of the
relative area of ulceration and average rate of change per week of the relative volume of
ulceration. Reduction of infected area was observed in all groups, but a significant
change was only observed in group C.No significant impact of laser light (lambda=810
nm, P=65 mW, p=4 J/cm2) on any of the stages of ulceration healing was observed.
Am J Clin Dermatol 2003;4(1):1-12
Can thermal lasers promote skin wound healing?
Capon A, Mordon S
Lasers are now widely used for treating numerous cutaneous lesions, for scar revision
(hypertrophic and keloid scars), for tissue welding, and for skin resurfacing and
remodeling (wrinkle removal). In these procedures lasers are used to generate heat. The
modulation of the effect (volatilization, coagulation, hyperthermia) of the laser is
obtained by using different wavelengths and laser parameters. The heat source obtained
by conversion of light into heat can be very superficial, yet intense, if the laser light is
well absorbed (far-infrared:CO(2) or Erbium:Yttrium Aluminum Garnet [Er:YAG] lasers),
or it can be much deeper and less intense if the laser light is less absorbed by the skin
(visible or near-infrared). Lasers transfer energy, in the form of heat, to surrounding
tissues and, regardless of the laser used, a 45-50 degrees C temperature gradient will be
obtained in the surrounding skin. If a wound healing process exists, it is a result of live
cells reacting to this low temperature increase. The generated supraphysiologic level of
heat is able to induce a heat shock response (HSR), which can be defined as the
temporary changes in cellular metabolism. These changes are rapid and transient, and
are characterized by the production of a small family of proteins termed the heat shock
proteins (HSP). Recent experimental studies have clearly demonstrated that HSP 70,
which is over-expressed following laser irradiation, could play a role with a coordinated
expression of other growth factors such as transforming growth factor (TGF)-beta. TGFbeta is known to be a key element in the inflammatory response and the fibrogenic
process. In this process, the fibroblasts are the key cells since they produce collagen and
extracellular matrix. In conclusion, the analysis of the literature, and the fundamental
considerations concerning the healing process when using thermal lasers, are in favor of
a modification of the growth factors synthesis after laser irradiation, induced by an HSR.
An extensive review of the different techniques and several clinical studies confirm that
thermal lasers could effectively promote skin wound healing, if they are used in a
controlled manner.
Br J Dermatol. 2003 Feb;148(2):334-6
Direct stimulatory effect of low-intensity 670 nm laser irradiation on human
endothelial cell proliferation
Schindl A, Merwald H, Schindl L, Kaun C, Wojta J
Background: Endothelial cell (EC) proliferation plays a key role in the process of tissue
repair. Low-intensity laser irradiation has been demonstrated to accelerate wound
healing and to improve microvascularization. OBJECTIVES: The present study evaluated
a possible stimulatory influence of low-intensity laser irradiation on human umbilical vein
endothelial cell (HUVEC) proliferation in a systematic manner.
Methods: Subconfluent cultures of HUVEC were irradiated every other day with a 670nm diode laser (intensity: 10-65 mW cm(-2), dose: 2-8 J cm(-2)) during a period of 6
days. Cell proliferation was evaluated quantitatively by counting in a haemocytometer.
Results: Our data demonstrate a dose-dependent and intensity-dependent stimulatory
effect of laser irradiation on HUVEC cell proliferation. Doses of between 2 and 8 J cm(-2)
induced statistically significant cell proliferation. Testing different intensities at a constant
dose of 8 J cm(-2), 20 and 65 mW cm(-2) induced most pronounced cell proliferation.
Conclusions: Low-intensity laser irradiation influences EC proliferation and might
thereby contribute to the increase in angiogenesis and the acceleration of wound healing
in vivo.
J Clin Laser Med Surg. 2003 Jun;21(3):165-70
Low-level laser irradiation attenuates production of reactive oxygen species by
human neutrophils
Fujimaki Y, Shimoyama T, Liu Q, Umeda T, Nakaji S, Sugawara K
Objective: The aim of this study was to examine the effects of low-level laser therapy
(LLLT) on production of reactive oxygen (ROS) species by human neutrophils.
Background Data: LLLT is an effective therapeutic modality for inflammatory
conditions.
Materials And Methods: The laser device used was the infrared diode laser (GaAlAs),
830-nm continuous wave (150 mW/cm² ). After irradiation, ROS production by
neutrophils was measured using luminol-dependent chemiluminescence (LmCL) and
expression of CD11b and CD16 on neutrophil surface was measured by flow cytometry.
Results: The LmCL response of neutrophils was reduced by laser irradiation at 60 min
prior to the stimulation with opsonized zymosan and calcium ionophore. The attenuating
effect of LLLT was larger in neutrophils of smokers than non-smokers, while the amount
of produced ROS was larger in neutrophils of smokers. Expression of CD11b and CD16 on
neutrophil surface was not affected by LLLT. CONCLUSION: Attenuation of ROS
production by neutrophils may play a role in the effects of LLLT in the treatment of
inflammatory tissues. There is a possible usage of LLLT to improve wound healing
in smokers.
Lasers Med Sci. 2003;18(2):72-7
Efficacy of low-level laser therapy in the management of stage III decubitus
ulcers: a prospective, observer-blinded multicentre randomised clinical trial
Lucas C, van Gemert MJ, de Haan RJ
Low-level laser therapy (LLLT) has been suggested as a promising treatment option for
open wounds. In view of the absence of randomised studies with sufficiently large sample
sizes, we assessed the efficacy of LLLT in the treatment of stage III decubitus ulcers. We
performed a prospective, observer-blinded multicentre randomised clinical trial to assess
the effect of LLLT as adjuvant to standard decubitus care. A total of 86 patients were
enrolled into the study. Treatment was the prevailing consensus decubitus treatment
(n=47); one group (n=39) had LLLT in addition, five times a week over a period of 6
weeks. The primary outcome measure was the absolute (mm2) and relative (%) wound
size reduction at 6 weeks compared to baseline. Secondary outcome measures were the
number of patients developing a stage IV ulcer during the study period, and the median
change in Norton scores at 6 weeks compared to baseline. Based on the intention-totreat principle, using last-observation-carried-forward analyses, Mann-Whitney U tests
showed that the differences between the two groups in terms of absolute improvement
(p=0.23) and relative improvement (p=0.42) were not significant. Because the wound
size areas were non-normally distributed, we also analysed the data after logarithmic
transformation of the wound size measurements. No significant difference in log(e)
improvement scores between groups could be demonstrated (unpaired t-test: p=0.59).
During the treatment period 11% of the patients in the control group and 8% of the
patients in the LLLT group developed a stage IV decubitus ulcer (Fisher's exact test:
p=0.72). The patients' Norton scores did not change during the treatment period. In this
trial we found no evidence that justifies using low-level laser therapy as an adjuvant to
the consensus decubitus ulcer treatment.
J Biol Chem. 2005 Feb 11;280(6):4761-71. Epub 2004 Nov 22
Photobiomodulation directly benefits primary neurons functionally inactivated
by toxins: role of cytochrome c oxidase
Wong-Riley MT, Liang HL, Eells JT, Chance B, Henry MM, Buchmann E, Kane M,
Whelan HT
Far red and near infrared (NIR) light promotes wound healing, but the mechanism is
poorly understood. Our previous studies using 670 nm light-emitting diode (LED) arrays
suggest that cytochrome c oxidase, a photoacceptor in the NIR range, plays an important
role in therapeutic photobiomodulation. If this is true, then an irreversible inhibitor of
cytochrome c oxidase, potassium cyanide (KCN), should compete with LED and reduce its
beneficial effects. This hypothesis was tested on primary cultured neurons. LED
treatment partially restored enzyme activity blocked by 10-100 microm KCN. It
significantly reduced neuronal cell death induced by 300 microm KCN from 83.6 to
43.5%. However, at 1-100 mm KCN, the protective effects of LED decreased, and
neuronal deaths increased. LED significantly restored neuronal ATP content only at 10
microm KCN but not at higher concentrations of KCN tested. Pretreatment with LED
enhanced efficacy of LED during exposure to 10 or 100 microm KCN but did not restore
enzyme activity to control levels. In contrast, LED was able to completely reverse the
detrimental effect of tetrodotoxin, which only indirectly down-regulated enzyme levels.
Among the wavelengths tested (670, 728, 770, 830, and 880 nm), the most effective
ones (830 nm, 670 nm) paralleled the NIR absorption spectrum of oxidized cytochrome c
oxidase, whereas the least effective wavelength, 728 nm, did not. The results are
consistent with our hypothesis that the mechanism of photobiomodulation involves the
up-regulation of cytochrome c oxidase, leading to increased energy metabolism in
neurons functionally inactivated by toxins.
Photomed Laser Surg. 2004 Aug;22(4):281-90
Photobiomodulation improves cutaneous wound healing in an animal model of
type II diabetes Byrnes KR, Barna L, Chenault VM, Waynant RW, Ilev IK, Longo
L, Miracco C, Johnson B, Anders JJ
OBJECTIVE: We investigated the effects of photobiomodulation (PBM) on cutaneous
wound healing in an animal model of type II diabetes, Psammomys obesus (Sand Rats).
Background Data: 632-nm light has been established as the most effective wavelength
for treatment of cutaneous wounds; however, the inconsistent efficacy of PBM may be
due to inadequate treatment parameter selection.
Methods: Using 632-nm light, an initial series of experiments were done to establish
optimal treatment parameters for this model. Following creation of bilateral full-thickness
skin wounds, non-diabetic Sand Rats were treated with PBM of differing dosages. Wound
healing was assessed according to wound closure and histological characteristics of
healing. Optimal treatment parameters were then used to treat type II diabetic Sand
Rats while a diabetic control group received no irradiation. In order to elucidate the
mechanism behind an improvement in wound healing, expression of basic fibroblast
growth factor (bFGF) was assessed.
Results: Significant improvement in wound healing histology and wound closure were
found following treatment with 4 J/cm(2) (16 mW, 250-sec treatments for 4 consecutive
days; p < 0.05). The 4 J/cm(2) dosage significantly improved histology and closure of
wounds in the diabetic group in comparison to the non-irradiated diabetic group.
Quantitative analysis of bFGF expression at 36 h post-injury revealed a threefold increase
in the diabetic and non-diabetic Sand Rats after PBM.
Conclusions: The results demonstrate that PBM at an energy density of 4 J/cm(2) is
effective in improving the healing of cutaneous wounds in an animal model of type II
diabetes, suggesting that PBM (632 nm, 4 J/cm(2)) would be effective in treating chronic
cutaneous wounds in diabetic patients.
Mitochondrion. 2004 Sep;4(5-6):559-67
Mitochondrial signal transduction in accelerated wound and retinal healing by
near-infrared light therapy
Eells JT, Wong-Riley MT, VerHoeve J, Henry M, Buchman EV, Kane MP, Gould LJ,
Das R, Jett M, Hodgson BD, Margolis D, Whelan HT
Photobiomodulation by light in the red to near infrared range (630-1000 nm) using low
energy lasers or light-emitting diode (LED) arrays has been shown to accelerate wound
healing, improve recovery from ischemic injury in the heart and attenuate degeneration
in the injured optic nerve. Recent evidence indicates that the therapeutic effects of red to
near infrared light result, in part, from intracellular signaling mechanisms triggered by
the interaction of NIR light with the mitochondrial photoacceptor molecule cytochrome c
oxidase. We have demonstrated that NIR-LED photo-irradiation increases the production
of cytochrome oxidase in cultured primary neurons and reverses the reduction of
cytochrome oxidase activity produced by metabolic inhibitors. We have also shown that
NIR-LED treatment prevents the development of oral mucositis in pediatric bone marrow
transplant patients. Photobiomodulation improves wound healing in genetically diabetic
mice by upregulating genes important in the promotion of wound healing. More recent
studies have provided evidence for the therapeutic benefit of NIR-LED treatment in the
survival and functional recovery of the retina and optic nerve in vivo after acute injury by
the mitochondrial toxin, formic acid generated in the course of methanol intoxication.
Gene discovery studies conducted using microarray technology documented a significant
upregulation of gene expression in pathways involved in mitochondrial energy production
and antioxidant cellular protection. These findings provide a link between the actions of
red to near infrared light on mitochondrial oxidative metabolism in vitro and cell injury in
vivo. Based on these findings and the strong evidence that mitochondrial dysfunction is
involved in the pathogenesis of numerous diseases processes, we propose that NIR-LED
photobiomodulation represents an innovative and non-invasive therapeutic approach for
the treatment of tissue injury and disease processes in which mitochondrial dysfunction
is postulated to play a role including diabetic retinopathy, age-related macular
degeneration, Leber's hereditary optic neuropathy and Parkinson's disease.
Photomed Laser Surg. 2005 Jun;23(3):268-72
Effects of 670-nm phototherapy on development.
Yeager RL, Franzosa JA, Millsap DS, Angell-Yeager JL, Heise SS, Wakhungu P,
LimJ, Whelan HT, Eells JT, Henshel DS
Objective: The objective of the present study was to assess the survival and hatching
success of chickens (Gallus gallus) exposed in ovo to far-red (670-nm) LED therapy.
Background Data: Photobiomodulation by light in the red to near-infrared range (6301000 nm) using low-energy lasers or light-emitting diode (LED) arrays has been shown
to accelerate wound healing and improve recovery from ischemic injury. The mechanism
of photobiomodulation at the cellular level has been ascribed to the activation of
mitochondrial respiratory chain components resulting in initiation of a signaling cascade
that promotes cellular proliferation and cytoprotecton.
Materials And Methods: Fertile chicken eggs were treated once per day from
embryonic days 0-20 with 670-nm LED light at a fluence of 4 J/cm2. In ovo survival and
death were monitored by daily candling (after Day 4).
Results: We observed a substantial decrease in overall and third-week mortality rates in
the light-treated chickens. Overall, there was approximately a 41.5% decrease in
mortality rate in the light-treated chickens (NL: 20%; L: 11.8%). During the third week
of development, there was a 68.8% decrease in the mortality rate in light-treated
chickens (NL: 20%; L: 6.25%). In addition, body weight, crown-rump length, and liver
weight increased as a result of the 670-nm phototherapy. Light-treated chickens pipped
(broke shell) earlier and had a shorter duration between pip and hatch.
Conclusion: These results indicate that 670-nm phototherapy by itself does not
adversely affect developing embryos and may improve the hatching survival rate.
Rozhl Chir. 2005 Aug;84(8):417-21
Effect of laser irradiation of diode laser on healing of surgical wounds in rats
Vidinsky B, Gal P, Toporcer T, Balogacova M, Hutnanova Z, Kilik R, Bober J, Sabo
J, Longauer F
The aim of this work was to continue in previous study, which concerns biostimulation of
skin wound healing evaluated after 24, 48, 120, 168 hours and so complete the
chronological continuance of the process during the first seven days. Male, Sprague
Dawley rats (n=21) were used for the experiment. The rats were divided into 3 groups of
7 animals. In general anaesthesia (combination of xylazine, ketamine and tramadol)
under aseptic condition two 3,5 cm long parallel skin incisions were performed on the left
and right side of the rats spine and immediately sutured. The left wounds were daily
stimulated with the diode laser (670 nm). The right wounds were not stimulated and
served as control. The specimens of skin wounds were removed for histological
evaluation 72, 96 and 144 hours after surgery. The biological specimens were stained
with hematoxylin and eosin and histopathologically evaluated. In summary, in our
histomorphological study of the influence of laser irradiation on primary wound healing
evaluated after 72, 96 and 144 hours was concluded, that the healing of stimulated
wounds was accelerated in comparison with controls. The histological evaluation showed
earlier regress of inflammatory phase, faster finishing of reepithelization and acceleration
in maturation phase. Presented experimental study completes the previous study and
achieves the positive effect of biostimulation on all phases of skin wound healing in vivo.
J Wound Care. 2005 Sep;14(8):391-4
Comment in: J Wound Care. 2005 Nov;14(10):478-9; author reply 478
Does the use of low-level laser influence wound healing in chronic venous leg
ulcers?
Kopera D, Kokol R, Berger C, Haas J
Objective: Venous leg ulcer treatment often requires months or years of regular
wound care by trained staff. It has been suggested that low-level laser
irradiation has a biostimulative and wound healing effect, but this has not been
clinically verified by controlled studies. This study aimed to compare the
effectiveness of low-level laser irradiation with that of a placebo 'light
source'.
Method: Forty-four patients were assigned to two treatment groups
(laser and placebo) or a third group (standardised treatment only) to quantify
the effect of the laser therapy. Patients in all three groups received
standardised wound care (disinfection, a hydrofibre dressing and compression
bandaging). Ulcer size was measured at baseline (day 1), at the end of therapy
(day 28) and then two months later (day 90). The relative difference in wound
size was evaluated.
Results: The difference in the reduction in wound size was
not statistically significant in all three groups. A positive effect of using
the non-laser device (placebo effect) was demonstrated in some patients.
Conclusion: These study results suggest that low-level laser does not stimulate
wound healing in venous leg ulcers. Further controlled studies are needed to
clarify the efficacy of low-level laser treatment as a wound-healing stimulant.
Photomed Laser Surg. 2005 Oct;23(5):485-92
Polarized light (400-2000 nm) and non-ablative laser (685 nm): a description of
the wound healing process using immunohistochemical analysis
Pinheiro AL, Pozza DH, Oliveira MG, Weissmann R, Ramalho LM
Objective: This study aimed to describe, through morphologic and cytochemical
analysis, the healing process of wounds submitted (or not) to laser therapy
(lambda 685 nm) or polarized light (lambda 400-2000 nm).
Background Data: There are many reports on different effects of several types of
phototherapies on the treatment of distinct conditions, amongst them, on wound healing.
Laser therapy and the use of polarized light are still controversial despite successive
reports on their positive effects on several biological processes.
Methods: Thirty male Wistar rats, approximately 4 months old, were used, and
standardized excisional wounds were created on their dorsum. The wounds were
irradiated in four equidistant points with laser light or illuminated with polarized light,
both with doses of 20 or 40 J/cm2. Group 1 acted as untreated controls. Animals were
irradiated every 48 h during 7 days, starting immediately after surgery, and were
humanely killed on the 8th post-operative day. Specimens were taken and routinely
processed and stained with H&E, and for descriptive analysis of myofibroblasts and
collagen fibers, the specimens were imunnomarked by smooth muscle alpha-actin and
picrosirius stain.
Results: Control specimens showed the presence of ulceration, hyperemia, discrete
edema, intense, and diffuse inflammation, collagen deposition was irregular, and
myofibroblasts were seen parallel to the wound margins. Wounds treated by laser
therapy with a dose of 20 J/cm2 showed mild hyperemia, inflammation varied from
moderate to intense, the number of fibroblasts was large, and the distribution of collagen
fibers was more regular. Increasing the dose to 40 J/cm2 evidenced exuberant
neovascularization, severe hyperemia, moderate to severe inflammation, large collagen
deposition, and fewer myofibroblasts. On subjects illuminated with polarized light with a
dose of 20 J/cm2, mild to moderate hyperemia was detectable, and collagen matrix was
expressive and unevenly distributed; a larger number of myofibroblasts was present and
no re-epithelialization was seen. Increasing the dose resulted in mild to moderate
hyperemia, no re-epithelialization was seen, edema was discrete, and inflammation was
moderate.
Conclusion: The use of 685-nm laser light or polarized light with a dose of 20 J/cm2
resulted in increased collagen deposition and better organization on healing wounds, and
the number of myofibroblast was increased when polarized light is used.
Biofizika. 2005 Nov-Dec;50(6):1137-44
A comparative study of the effects of laser and light-emitting diode
irradiation on the wound healing and functional activity of wound exudate
leukocytes
Klebanov GI, Shuraeva NIu, Chichuk TV, Osipov AN, Rudenko TG, Shekhter AB,
Vladimirov IuA
The effects of coherent He-Ne laser and non-coherent light-emitting diode radiation on
rat skin wound healing and functional activity of wound excudate leukocytes were
compared. A comparative pathomorphological analysis showed that the He-Ne laser and
light-emitting diode irradiation stimulated the transition of the inflammatory phase of the
wound healing into the reparative (proliferative) and scarring phases sequentially. It was
also detected that the functional activity of leucocytes changed in a dose-dependent
manner. The leukocyte activity was found to be similar in the groups with laser and lightemitting diode irradiation. Thus, we can conclude that coherent laser and non-coherent
light-emitting diode radiation have very close effects on wound healing and activity of
wound exudate leukocytes, and coherence is not required for this activity.
Khirurgiia (Mosk). 2005;(4):37-41
Surgical technologies in the treatment of varicose veins of the lower
extremities complicated with trophic ulcer
Kuznetsov NA, Barinov VE, Teleshov BV, Trepilets VE, Zheltikov AN
Results of an open randomized study of staged treatment of 94 patients suffering from
varicose veins of the lower extremities with open infected trophic ulcers of the shank
were analyzed. All the patients were divided into 3 groups depending on the treatment
variant. Based on this study, clinical efficacy of early correction of upper vertical venousvenous reflux is substantiated. Efficacy of CO(2) laser application for sanation of trophic
venous ulcers and practical importance of their auto-venous plastic reconstruction are
demonstrated. Thus, up-to-date technologies provide differential treatment in patients
with trophic venous ulcers.
Dermatol Surg. 2006 Jan;32(1):21-5
Clinical effect of a single pulsed dye laser treatment of fresh surgical scars:
randomized controlled trial
Alam M, Pon K, Van Laborde S, Kaminer MS, Arndt KA, Dover JS
Background: Pulsed dye laser has been used to decrease erythema and telangiectasia
associated with scars, including surgical scars. There is limited evidence indicating
improved surgical scar appearance if pulsed dye laser treatments are commenced
immediately at the time of suture removal.
Objective: To determine whether a single one-pass pulsed dye laser treatment at the
time of suture removal can improve the appearance of surgical scars.
Methods: Randomized controlled trial enrolling 20 patients (complete data for 17
patients) at two geographic sites, with blinded ratings of pre- and post-treatment
photographs obtained at various time points. Included patients underwent elliptical
excision for atypical nevi of the trunk and/or extremities, with at least one resulting scar
of at least 5 cm in length or two scars of at least 2.5 cm in length. For each patient, each
scar or half-scar (if a larger scar was used) was randomized to treatment or control
groups. Treatment scars received a single one-pass treatment with a 595 nm pulsed dye
laser (Vbeam, Candela Corporation, Wayland, MA, USA) at the time of suture removal
(ie, 2 weeks after excision) at the following parameters: 7 J/cm2 fluence, 7 mm spot
size, 1.5-millisecond pulse duration, and 30-millisecond spray, 20-millisecond delay of
dynamic cooling. The treatment area included 1 cm on either side of the scar, and the
round laser spots were overlapped 10%. Control scars were not treated with laser.
Results: Immediate purpura was induced from the laser treatment Six weeks after laser
treatment, no significant difference was found in the clinical appearance of surgical scars
treated with a single pulsed dye laser treatment on suture removal day versus those
surgical scars not treated with laser. Parameters on which no significant difference was
found included visibility of incision, erythema, hyperpigmentation, hypopigmentation,
induration, and atrophy. Both sets of scars improved over time.
Conclusions: A single pulsed dye laser treatment at the time of suture removal does not
appear to have a beneficial effect on clinical scar appearance. The point of minimal
benefit for such laser treatments may lie somewhere between one and three treatments.
Lasers Surg Med. 2006 Jan;38(1):74-83
The role of laser fluence in cell viability, proliferation, and membrane integrity
of wounded human skin fibroblasts following helium-neon laser irradiation
Hawkins DH, Abrahamse H
Background: In medicine, lasers have been used predominantly for applications, which
are broadly termed low level laser therapy (LLLT), phototherapy or photobiomodulation.
This study aimed to establish cellular responses to Helium-Neon (632.8 nm) laser
irradiation using different laser fluences (0.5, 2.5, 5, 10, and 16 J/cm(2)) with a single
exposure on 2 consecutive days on normal and wounded human skin fibroblasts.
Materials And Methods: Changes in normal and wounded fibroblast cell morphology
were evaluated by light microscopy. Changes following laser irradiation were evaluated
by assessing the mitochondrial activity using adenosine triphosphate (ATP) luminescence,
cell proliferation using neutral red and an alkaline phosphatase (ALP) activity assay,
membrane integrity using lactate dehydrogenase (LDH), and percentage cytotoxicity and
DNA damage using the Comet assay.
Results: Morphologically, wounded cells exposed to 5 J/cm(2) migrate rapidly across the
wound margin indicating a stimulatory or positive influence of phototherapy. A dose of 5
J/cm(2) has a stimulatory influence on wounded fibroblasts with an increase in cell
proliferation and cell viability without adversely increasing the amount of cellular and
molecular damage. Higher doses (10 and 16 J/cm(2)) were characterized by a decrease
in cell viability and cell proliferation with a significant amount of damage to the cell
membrane and DNA.
Conclusions: Results show that 5 J/cm(2) stimulates mitochondrial activity, which leads
to normalization of cell function and ultimately stimulates cell proliferation and migration
of wounded fibroblasts to accelerate wound closure. Laser irradiation can modify cellular
processes in a dose or fluence (J/cm(2)) dependent manner.
Biofizika. 2006 Jan-Feb;51(1):116-22
A comparison of the effects of laser and light-emitting diodes on superoxide
dismutase activity and nitric oxide production in rat wound fluid
Klebanov GI, Shuraeva NIu, Chichuk TV, Osipov AN, Vladimirov IuA
The action of laser and light-emitting diode radiation in the visible region on the content
of reactive nitrogen species and activity of superoxide dismutase in rat wound fluid was
studied, and efficiency of action of coherent laser and incoherent light emitting diode
radiations in the red region of the spectrum on the parameters under study was
compared. A model of incised aseptic wounds in rats proposed by L.I. Slutskiy was used.
A He-Ne laser (632 nm) and a Y-332B light emitting diode served as radiation sources. It
was shown that (1) exposure of wounds to the visible light of both laser and lightemitting diodes causes dose-dependent changes in superoxide dismutase activity and
production of nitrites and (2) the radiation coherence does not play any significant role in
the changes of superoxide dismutase activity or nitrogen oxide formation by wound fluid
phagocytes.
Lasers Med Sci. 2006 Apr;21(1):5-10. Epub 2006 Mar 17
Closure of skin incisions by 980-nm diode laser welding
Gulsoy M, Dereli Z, Tabakoglu HO, Bozkulak O
A 980-nm diode laser is proposed to be an alternative welding laser in dermatology due
to its optimal penetration in tissue. An in vivo predosimetry study was done to estimate
the optimal laser energy delivery conditions (6 W, 400 ms). Next, in vivo experiments
were comparatively performed to examine healing of wounds closed either with suture or
laser welding. One-centimeter-long, full-thickness incisions were done on the dorsal side
of Wistar rats. Wounds were surgically removed at 1, 4, 7, 14, and 21 days
postoperatively. Macroscopic examinations showed that welding had minimal scarring
and a fine quality healing. According to histological (hematoxylin and eosin staining)
results, change of epidermal thickness and granulation tissue formation through 21 days
of healing period showed similarities in both methods. Epidermal thickness of welded
wounds decreased from 62.46+/-6.87 microm (first day) to 36.49+/-0.92 microm (21st
day) and that of sutured wounds decreased from 62.94+/-13.53 microm (first day) to
37.88+/-7.41 microm (21st day). At day 14, epidermal thickness of sutured wounds
(61.20+/-6.60 microm) were higher than welded wounds (49.69+/-6.31 microm)
(p<0.05). Besides, granulation values were greater for the sutured wounds but the
difference was statistically significant (p<0.05) only for the seventh day (197,190.29+/.89,554.96 microm(2) for sutured wounds, 138,433.1+/-51,077.17 microm(2) for
welded wounds). Those differences indicate a faster recovery with laser welding. It is
concluded that tissue welding with a 980-nm diode laser can be a good candidate for
tissue welding applications with accelerated and improved healing, but further
investigations are in progress for clinical use.
Photomed Laser Surg. 2006 Apr;24(2):121-8
Clinical and experimental applications of NIR-LED photobiomodulation
Desmet KD, Paz DA, Corry JJ, Eells JT, Wong-Riley MT, Henry MM, Buchmann EV,
Connelly MP, Dovi JV, Liang HL, Henshel DS, Yeager RL, Millsap DS, Lim J, Gould
LJ, Das R, Jett M, Hodgson BD, Margolis D, Whelan HT
This review presents current research on the use of far-red to near-infrared (NIR) light
treatment in various in vitro and in vivo models. Low-intensity light therapy, commonly
referred to as "photobiomodulation," uses light in the far-red to near-infrared region of
the spectrum (630-1000 nm) and modulates numerous cellular functions. Positive effects
of NIR-light-emitting diode (LED) light treatment include acceleration of wound healing,
improved recovery from ischemic injury of the heart, and attenuated degeneration of
injured optic nerves by improving mitochondrial energy metabolism and production.
Various in vitro and in vivo models of mitochondrial dysfunction were treated with a
variety of wavelengths of NIR-LED light. These studies were performed to determine the
effect of NIR-LED light treatment on physiologic and pathologic processes. NIRLED light
treatment stimulates the photoacceptor cytochrome c oxidase, resulting in increased
energy metabolism and production. NIR-LED light treatment accelerates wound healing
in ischemic rat and murine diabetic wound healing models, attenuates the retinotoxic
effects of methanol-derived formic acid in rat models, and attenuates the developmental
toxicity of dioxin in chicken embryos. Furthermore, NIR-LED light treatment prevents the
development of oral mucositis in pediatric bone marrow transplant patients. The
experimental results demonstrate that NIR-LED light treatment stimulates mitochondrial
oxidative metabolism in vitro, and accelerates cell and tissue repair in vivo. NIR-LED light
represents a novel, noninvasive, therapeutic intervention for the treatment of numerous
diseases linked to mitochondrial dysfunction.
J Photochem Photobiol B. 2006 May 1;83(2):87-93. Epub 2006 Feb 7
Effect of low-level helium-neon laser therapy on the healing of third-degree
burns in rats
Bayat M, Vasheghani MM, Razavi N
This paper presents the results of a study on the effects of low-level helium-neon laser
therapy (LL He-Ne LT) on the healing of burns. Seventy-eight adult male rats, having
been subjected to third-degree burns, were randomly divided into four groups: two laser
treated groups (n=20, each), one control group (n=19) and one nitrofurazone treated
group (n=19). In the two laser treated groups, the burns were treated on a daily basis
with LL He-Ne LT with an energy density of 1.2 and 2.4 J/cm(2), respectively. The
response to treatment was assessed histologically at 7, 16 and 30 days after burning,
and microbiologically at day 15. Analysis of variance showed that the mean of blood
vessel sections in the 1.2J/cm(2) laser group was significantly higher than those in the
other groups and the mean of the depth of new epidermis in the 2.4 J/cm(2) laser group
on day 16 was significantly lower than in the nitrofurazone treated group (P=0.025,
P=0.047, respectively). When Staphylococcus aureus and Pseudomonas aeruginosa grew
in more than 50% of samples obtained from control group, there were no S. aureus and
P. aeruginosa in the samples of 2.4 J/cm(2) laser group. It is concluded that LL He-Ne LT
induced the destruction of S. aureus and P. aeruginosa in third-degree burns of rats, yet
at the same time our histological findings showed that LL He-Ne LT caused a significant
increase in the mean of blood vessel sections on day 7 after third degree burns and a
decrease in the mean of the depth of new epidermis on day 16 after the same burns in
rats.
Photomed Laser Surg. 2006 Jun;24(3):389-96
Effects of laser therapy in CO2 laser wounds in rats
Grbavac RA, Veeck EB, Bernard JP, Ramalho LM, Pinheiro AL
Objective: The aim of this study was to assess the effects of laser therapy and its
possible dose dependency on the healing of CO2 laser surgical wounds.
Background Data: Several reports from our group and others have indicated that light
therapies may improve healing, depending on wavelength, dose, intensity of the light,
and both local and systemic conditions. METHODS: Circular surgical wounds were created
on the dorsum of Wistar rats, which were separated into three groups (A, B, and C).
Group A acted as control and had no additional treatment. Groups B and C were
irradiated with GaAlAs lambda685-nm laser light, either with 20 J/cm2 (Group B) or 40
J/cm2 (Group C). The animals were humanely killed at the end of the experimental
period; specimens were taken and routinely processed to wax and stained with
Hematoxylin and Eosin, Sirius Red, and alpha-Smooth Muscle Actin (alphaSMA).
Results: Laser-irradiated groups showed a healing process characterized by a more
prominent fibroblastic proliferation, with young fibroblasts actively producing collagen; no
myofibroblasts were found. No statistically significant differences were observed when
the different doses were compared.
Conclusion: It may be concluded that, using this methodology, laser therapy has a
positive effect in wound healing produced by CO2 laser, and the dose has no influence on
the treatment.
Photomed Laser Surg. 2006 Aug;24(4):474-9
Comparison between wound healing in induced diabetic and nondiabetic rats
after low-level laser therapy
Rabelo SB, Villaverde AB, Nicolau R, Salgado MC, Melo Mda S, Pacheco MT
Objective: The aim of this work was to compare the effect of low-level laser therapy
(LLLT) on the wound healing process in nondiabetic and diabetic rats.
Background Data: Among the clinical symptoms caused by diabetes mellitus, a delay in
wound healing is a potential risk for patients. It is suggested that LLLT can improve
wound healing.
Methods: The tissue used for this study was extracted from animals suffering from
diabetes, which was induced by Streptozotocin, and from nondiabetic rats. Animals were
assembled into two groups of 25 rats each (treated and control) and further subdivided
into two groups: diabetic (n = 15) and nondiabetic (n = 10). A full-thickness skin wound
was made on the dorsum area, with a round 8-mm holepunch. The treated group was
irradiated by a HeNe laser at 632.8 nm, with the following parameters: 15 mW,
exposition time of 17 sec, 0.025 cm2 irradiated area, and energy density of 10 J/cm2.
Square full-thickness skin samples (18 mm each side, including both injured and
noninjured tissues) were obtained at 4, 7, and 15 days after surgery and analyzed by
qualitative and quantitative histological methods. RESULTS: Quantitative
histopathological analysis confirmed the results of the qualitative analysis through
histological microscope slides. When comparing tissue components (inflammatory cells,
vessels and fibroblast/area), we found that treated animals had a less intense
inflammatory process than controls.
Conclusion: Results obtained by both qualitative and quantitative analyses suggested
that irradiation of rats with HeNe (632.8 nm), at the tested dose, promoted efficient
wound healing in both nondiabetic and diabetic rats as, compared to the control group.
Photomed Laser Surg. 2006 Aug;24(4):480-8
Histological assessment of the effect of laser irradiation on skin wound healing
in rats
Gal P, Vidinsky B, Toporcer T, Mokry M, Mozes S, Longauer F, Sabo J
Objective: The purpose of this study was to evaluate, from the histological point of
view, the effect of diode laser irradiation on skin wound healing in Sprague-Dawley rats.
Background Data: Various biological effects have been described in different studies
after low-level laser therapy (LLLT). METHODS: Two parallel full-thickness skin incisions
were performed on the back of each rat (n = 49) and immediately sutured. After surgery,
one wound of each rat was exposed to laser irradiation (continuous mode, 670 nm, daily
dose 30 J/cm2), whereas the parallel wound was not irradiated and served as control.
Both wounds were removed 24, 48, 72, 96, 120, 144, and 168 h after surgery and
routinely fixed and embedded in paraffin sections, stained with hematoxylin and eosin,
van Gieson, periodic acid Schiff + periodic acid Schiff diastase, Mallory's phosphotungstic
hematoxylin, and azur and eosin, and histopathologically evaluated. RESULTS: As
compared to non irradiated control wounds, laser stimulation shortened the inflammatory
phase as well as accelerated the proliferative and maturation phase, and positively
stimulated the regeneration of injured epidermis and the reparation of injured striated
muscle.
Conclusion: LLLT at 670 nm positively influences all phases of rat skin wound healing.
Lasers Surg Med. 2006 Sep;38(8):779-86
Low-level laser irradiation modulates matrix metalloproteinase activity and
gene expression in porcine aortic smooth muscle cells
Gavish L, Perez L, Gertz SD
Background And Objectives: The vascular extracellular matrix is maintained by a
dynamic balance between matrix synthesis and degradation. This equilibrium is disrupted
in arterial pathologies such as abdominal aortic aneurysm. Low-level laser irradiation
(LLLI) promotes wound healing. However, its effect on smooth muscle cells (SMCs), a
central player in these responses, has not been established. The current study was
designed to determine the effects of LLLI on arterial SMC proliferation, inflammatory
markers, and matrix proteins.
Study Design/Materials And MethODS: Porcine primary aortic SMCs were irradiated
with a 780 nm laser diode (1 and 2 J/cm(2)). Trypan blue exclusion assay,
immunofluorescent staining for collagen I and III, Sircol assay, gelatin zymography, and
RT-PCR were used to monitor proliferation; collagen trihelix formation; collagen
synthesis; matrix metalloproteinase-2 (MMP-2) activity, and gene expression of MMP-1,
MMP-2, tissue inhibitor of MMP-1 (TIMP-1), TIMP-2, and IL-1-beta, respectively.
Results: LLLI-increased SMC proliferation by 16 and 22% (1 and 2 J/cm(2),
respectively) compared to non-irradiated cells (P<0.01 and P<0.0005). Immediately
after LLLI, trihelices of collagen I and III appeared as perinuclear fluorescent rings.
Collagen synthesis was increased twofold (2 days after LLLI: 14.3+/-3.5 microg, nonirradiated control: 6.6+/-0.7 microg, and TGF-beta stimulated control: 7.1+/-1.2 microg,
P<0.05), MMP-2 activity after LLLI was augmented (over non-irradiated control) by
66+/-18% (2 J/cm(2); P<0.05), and MMP-1 gene expression upregulated. However,
TIMP-2 was upregulated, and MMP-2 gene expression downregulated. IL-1-beta gene
expression was reduced.
Conclusions: LLLI stimulates SMC proliferation, stimulates collagen synthesis,
modulates the equilibrium between regulatory matrix remodeling enzymes, and inhibits
pro-inflammatory IL-1-beta gene expression. These findings may be of therapeutic
relevance for arterial diseases such as aneurysm where SMC depletion, weakened
extracellular matrix, and an increase in pro-inflammatory markers are major pathologic
components.
J Photochem Photobiol B. 2006 Nov 17; [Epub ahead of print]
Evaluation of mitochondrial respiratory chain activity in wound healing by
low-level laser therapy
Silveira PC, Streck EL, Pinho RA
Laser therapy is used in many biomedical sciences to promote tissue regeneration. Many
studies involving low-level laser therapy have shown that the healing process is
enhanced by such therapy. In this work, we evaluated mitochondrial respiratory chain
complexes II and IV and succinate dehydrogenase activities in wounds after irradiation
with low-level laser. The animals were divided into two groups: group 1, the animals had
no local nor systemic treatment and were considered as control wounds; group 2, the
wounds were treated immediately after they were made and every day after with a low
level laser (AsGa, wavelength of 904nm) for 10 days. The results showed that low-level
laser therapy improved wound healing. Besides, our results showed that low-level laser
therapy significantly increased the activities of complexes II and IV but did not affect
succinate dehydrogenase activity. These findings are in accordance to other works,
where cytochrome c oxidase (complex IV) seems to be activated by low-level laser
therapy. Besides, we showed, for the first time, that complex II activity was also
activated. More studies are being carried out in order to evaluate other mitochondrial
enzymes activities after different doses and irradiation time of low-level laser.
Photomed Laser Surg. 2006 Dec;24(6):705-14
Effect of multiple exposures of low-level laser therapy on the cellular
responses of wounded human skin fibroblasts
Hawkins D, Abrahamse H
Objective: This study aimed to establish the behavior of wounded human skin
fibroblasts (HSF) after heliumneon (HeNe) (632.8 nm) laser irradiation using one, two, or
three exposures of different doses, namely, 2.5, 5.0, or 16.0 J/cm(2) on each day for 2
consecutive days.
Background Data: Low-level laser therapy (LLLT) is a form of phototherapy used to
promote wound healing in different clinical conditions. LLLT at than adequate wavelength,
intensity, and dose can accelerate tissue repair. However, there is still conflicting
information about the effect of multiple irradiations on the cellular responses of wounded
cells.
Methods: Cellular responses to HeNe laser irradiation were evaluated by measuring
changes in cell morphology, cell viability, cell proliferation, and damage caused by
multiple irradiations.
Results: A single dose of 5.0 J/cm(2), and two or three doses of 2.5 J/cm(2) had a
stimulatory or positive effect on wounded fibroblasts with an increase in cell migration
and cell proliferation while maintaining cell viability, but without causing additional stress
or damage to the cells. Multiple exposures at higher doses (16 J/cm(2)) caused
additional stress, which reduces cell migration, cell viability, and ATP activity, and inhibits
cell proliferation.
Conclusion: The results show that the correct energy density or fluence (J/cm(2)) and
number of exposures can stimulate cellular responses of wounded fibroblasts and
promote cell migration and cell proliferation by stimulating mitochondrial activity and
maintaining viability without causing additional stress or damage to the wounded cells.
Results indicate that the cumulative effect of lower doses (2.5 or 5 J/cm(2)) determines
the stimulatory effect, while multiple exposures at higher doses (16 J/cm(2)) result in an
inhibitory effect with more damage.
J Photochem Photobiol B. 2007 Feb 1;86(2):87-96. Epub 2006 Oct 9
Ultrastructural and autoradiographical analysis show a faster skin repair in
He-Ne laser-treated wounds
de Araujo CE, Ribeiro MS, Favaro R, Zezell DM, Zorn TM
There are evidences that low-intensity red laser radiation is capable to accelerate wound
healing. Nowadays, this therapy has been gradually introduced in clinical practice
although mechanisms underlying laser effects are poorly understood. To better
understand the photobiological effects of laser radiation, this study investigated by
electron microscopy, immunohistochemistry and autoradiography the morphological and
functional features of irradiated and none irradiated injured mice skin. Full-thickness skin
lesions were created on the back of mice and irradiated on days 1, 5, 8, 12, and 15 postwounding with a He-Ne laser (lambda=632.8nm), dose 1J/cm(2), exposure time 3min.
Non-irradiated lesions were used as a control. The mice were inoculated with (3)Hproline and sacrificed one hour after on the 8th, 15th and 22nd days to histological and
radioautographical analysis. The irradiated-lesions showed a faster reepithelization
compared with control lesions. The irradiated dermis contained a higher number of
activated fibroblasts compared to control group and, most of them showed several
cytoplasmic collagen-containing phagosomes. In irradiated-lesions, smooth muscle
alpha-actin positive cells predominated, which correspond to a higher number of
myofibroblasts observed in the electron microscope. Moreover, laser radiation reduced
the local inflammation and appears to influence the organization of collagen fibrils in the
repairing areas. Quantitative autoradiography showed that the incorporation of (3)H
proline was significantly higher in irradiated-dermis on the 15th day post-wounding
(p<0.05). These results suggest that laser radiation may accelerate cutaneous
wound healing in a murine model.
Photomed Laser Surg. 2007 Apr;25(2):102-6
Photobiomodulation on the angiogenesis of skin wounds in rats using different
light sources
Corazza AV, Jorge J, Kurachi C, Bagnato VS
Objective: The aim of this study was to compare the angiogenic effects of laser and
light-emitting diode (LED) illumination on wounds induced in rats, with
varied fluence.
Background Data: The LED is an alternative light source that accelerates wound
healing, and its efficiency concerning the angiogenic effect was compared to low-level
laser therapy (LLLT).
Methods: The experimental model consisted of a circular wound inflicted on the
quadriceps of 120 rats, using a 15-mm-diameter "punch." Animals were divided
randomly into five groups: two groups of laser, with dosages of 5 and 20 J/cm(2),
respectively, two groups of LED, also with dosages of 5 and 20 J/cm(2), and a control
group. Six hours after wound infliction, the treated groups received the diverse
applications accordingly and were irradiated every 24 h. Angiogenesis was studied
through histomorphometry on days 3, 7, 14, and 21 after the wounds were inflicted.
Results: On days 3, 7, and 14, the proliferation of blood vessels in all irradiated groups
was superior in comparison to those of the control group (p < 0.05). Treatment with
fluence of 5 J/cm(2) was better than the laser group with 20 J/cm(2) on day 21.
Conclusion: Red LLLT and LED demonstrated expressive results in angiogenesis. Light
coherence was shown not to be essential to angiogenesis. However, further studies are
needed in order to investigate the photobiomodulatory effects of LED in relation to LLLT
in various biological tissues.
Wound Repair Regen. 2007 Nov-Dec;15(6):866-74
Activation of latent TGF-beta1 by low-power laser in vitro correlates with
increased TGF-beta1 levels in laser-enhanced oral wound healing
Arany PR, Nayak RS, Hallikerimath S, Limaye AM, Kale AD, Kondaiah P
The term Laser "Photobiomodulation" was coined to encompass the pleiotropic effects of
low-power lasers on biological processes. The purpose of this study was to investigate
whether transforming growth factor (TGF)-beta had a role in mediating the biological
effects of low-power far-infrared laser irradiation. We assayed for in vitro activation
using various biological forms of cell-secreted, recombinant, and serum latent TGF-beta
using the p3TP reporter and enzyme-linked immunosorbent assays. We demonstrate
here that low-power lasers are capable of activating latent TGF-beta1 and -beta3 in vitro
and, further, that it is capable of "priming" these complexes, making them more
amenable to physiological activation present in the healing milieu. Using an in vivo oral
tooth extraction-healing model, we observed an increased TGF-beta1, but not beta3,
expression by immunohistochemistry immediately following laser irradiation while TGFbeta3 expression was increased after 14 days, concomitant with an increased
inflammatory infiltrate. All comparisons were performed between laser-irradiated
wounds and nonirradiated wounds in each subject essentially using them as their own
control (paired T-test p<0.05). Low-power laser irradiation is capable of activating the
latent TGF-beta1 complex in vitro and its expression pattern in vivo suggests that TGFbeta play a central role in mediating the accelerated healing response.
J Wound Ostomy Continence Nurs. 2008 Jan-Feb;35(1):113-5; discussion 116-7
Light therapy and advanced wound care for a neuropathic plantar ulcer on a
Charcot foot
Sutterfield R
Light therapy is a relatively novel modality in wound care. I used a light-emitting diode
(LED) and superluminous diode (SLD) to deliver low-intensity laser light as an adjunctive
treatment to a patient with a chronic diabetic foot ulcer. Standard treatment of
conservative sharp debridement, off-loading, bioburden management, and advanced
dressings was delivered in a WOC clinic setting. This combination of therapies resulted in
closure of the neuropathic plantar ulcer within 8 weeks.
Photomed Laser Surg. 2008 Feb;26(1):47-54
Effectiveness of laser photobiomodulation at 660 or 780 nanometers on the
repair of third-degree burns in diabetic rats
Meireles GC, Santos JN, Chagas PO, Moura AP, Pinheiro AL
Objective: The aim of this investigation was to compare by light microscopy the effects
of laser photobiomodulation (LPBM) at lambda = 660 nm and lambda = 780 nm on thirddegree burns in diabetic Wistar rats.
Background Data: Burns are severe injuries that result in fluid loss, tissue destruction,
infection, and shock, that may result in death. Diabetes is a disease that reduces the
body's ability to heal properly. LPBM has been suggested as an effective method of
improving wound healing.
Materials And Methods: A third-degree burn measuring 1.5 x 1.5 cm was created in
the dorsum of each of 55 animals, and they were divided into three groups that were or
were not treated with LPBM (lambda = 660 nm or lambda = 780 nm, 35 mW, varphi = 2
mm, 20 J/cm(2)). The treatments were started immediately post-burn at four points
within the burned area (5 J/cm(2)) and were repeated at 24-hour intervals over 21 d.
The animals were humanely killed after 3, 5, 7, 14, and 21 d by an overdose of
intraperitoneal general anesthetic. The specimens were routinely cut and stained and
analyzed by light microscopy.
Results: We found that healing in the animals receiving 660-nm laser energy was more
apparent at early stages, with positive effects on inflammation, the amount and quality
of granulation tissue, fibroblast proliferation, and on collagen deposition and
organization. Epithelialization and local microcirculation were also positively affected by
the treatment.
Conclusion: The use of 780-nm laser energy was not as effective as 660-nm energy,
but it had positive effects at early stages on the onset and development of inflammation.
At the end of the experimental period the primary effect seen was on the amount and
quality of the granulation tissue. The 660-nm laser at 20 J/cm(2), when used on a daily
basis, was more effective than the 780-nm laser for improving the healing of thirddegree burns in the diabetic rats beginning at the early stages post-burn.
Photomed Laser Surg. 2008 Apr;26(2):159-66
A comparative study of the effects of laser photobiomodulation on the healing
of third-degree burns: a histological study in rats
Meirelles GC, Santos JN, Chagas PO, Moura AP, Pinheiro AL
Objective: The aim of this investigation was to compare by light microscopy the effects
of laser photobiomodulation at wavelengths of 660 and 780 nm on third-degree burns in
Wistar rats.
Background Data: Burns are severe injuries that result in the loss of fluid and
destruction of tissue, infection, and shock that may result in death. Laser energy has
been suggested as an effective method to improve wound healing.
Materials And Methods: Fifty-five animals were used in this study. A third-degree burn
measuring 1.5 x 1.5 cm was created on the dorsum of each animal. The animals were
divided into three subgroups according the type of laser photobiomodulation they
received (wavelength of 660 or 780 nm, 35 mW, theta = 2 mm, and 20 J/cm2). In the
animals receiving treatment, it was begun immediately post-burn at four points around
the burn (5 J/cm2) and repeated at 24-h intervals for 21 d. The animals were humanely
killed after 3, 5, 7, 14, and 21 d by an intraperitoneal overdose of general anesthetic.
The specimens were routinely cut and stained, and then were analyzed by light
microscopy.
Results: The results showed more deposition of collagen fibers, larger amounts of
granulation tissue, less edema, a more vigorous inflammatory reaction, and increased
revascularization on all laser-treated animals. These features were more evident at early
stages when the 660-nm laser was used, and were more evident throughout the
experimental period for the animals receiving 780-nm laser therapy.
Conclusion: We concluded that laser photobiomodulation using both wavelengths
improved healing of third-degree burns on Wistar rats.
Photomed Laser Surg. 2008 Aug;26(4):289-99
The use of light photobiomodulation on the treatment of second-degree burns: a
histological study of a rodent model
Oliveira PC, Meireles GC, dos Santos NR, de Carvalho CM, de Souza AP, dos
Santos
JN, Pinheiro AL
Objective: The aim of this investigation was to compare, by light microscopy, the effects
of the use of laser photobiomodulation (LPBM) and polarized light (PL) on second-degree
burns on rodents.
Background Data: Burns are severe injuries that result in the loss of tissue fluids,
destruction of tissues, infection, and shock. With severe and widespread third-degree
burns death may occur. Several light sources have been suggested as being effective for
improving wound healing.
Materials And Methods: Forty five rats were used in this study. A second-degree burn
was created on the dorsum of each animal, and the animals were divided into four
groups: PL (400-2000 nm, 40 mW, 2.4 J/cm(2)/min); LPBM-1 (780 nm, 35/40 mW,
theta approximately 2 mm, 4 x 5 J/cm(2)); LPBM-2 (660 nm, 35/40 mW, theta
approximately 2 mm, 4 x 5 J/cm(2)); and untreated animals acted as controls. The
treatment was started immediately post-burn at four points around the burned area
(laser: 5 J/cm(2) per site). The illumination with PL was performed according to the
manufacturer's instructions. Treatments were repeated at 24-h intervals for 7 d. The
animals were sacrifice at 3, 5, and 7 d post-burn. The specimens were routinely cut and
stained and analyzed by light microscopy using hematoxylin and eosin and Sirius red.
Results: The analysis of the results demonstrated that the damaged tissue was able to
efficiently absorb and process the light at all tested wavelengths. LPBM at 660 nm
showed better results at early stages of wound healing. However, the use of 780-nm
laser light had beneficial effects throughout the experimental period, with the animals
growing newly-formed tissue similar to normal dermis.
Conclusion: Despite our findings that the use of both types of light energy improved the
healing of second-degree burns at the early stages, long-term assessment is needed to
verify if this improvement will influence the final results of treatment.
J Photochem Photobiol B. 2008 Sep 18;92(3):144-52. Epub 2008 Jul 7
Influence of laser photobiomodulation upon connective tissue remodeling
during wound healing
Medrado AP, Soares AP, Santos ET, Reis SR, Andrade ZA
The modulation of collagen fibers during experimental skin wound healing was studied in
112 Wistar rats submitted to laser photobiomodulation treatment. A standardized 8mmdiameter wound was made on the dorsal skin of all animals. In half of them, 0.2ml of a
silica suspension was injected along the border of the wound in order to enhance collagen
deposition and facilitate observation. The others received saline as vehicle. The
treatment was carried out by means of laser rays from an aluminum-gallium arsenide
diode semiconductor with 9mW applied every other day (total dose=4J/cm2) on the
borders of the wound. Tissue sections obtained from four experimental groups
representing sham-irradiated animals, laser, silica and the association of both, were
studied after 3, 7, 10, 15, 20, 30 and 60 days from the laser application. The wounded
skin area was surgically removed and submitted to histological, immunohistochemical,
ultrastructural, and immunofluorescent studies. Besides the degree and arrangement of
collagen fibers and of their isotypes, the degree of edema, the presence of several cell
types especially pericytes and myofibroblasts, were described and measured. The
observation of Sirius-red stained slides under polarized microscopy revealed to be of
great help during the morphological analysis of the collagen tissue dynamic changes. It
was demonstrated that laser application was responsible for edema regression and a
diminution in the number of inflammatory cells (p<0.05). An evident increase in the
number of actin-positive cells was observed in the laser-treated wounds. Collagen
deposition was less than expected in silica-treated wounds, and laser treatment
contributed to its better differentiation and modulation in all irradiated groups. Thus,
laser photobiomodulation was able to induce several modifications during the cutaneous
healing process, especially in favoring newly-formed collagen fibers to be better
organized and compactedly disposed.
Lasers Surg Med. 2008 Sep;40(7):509-14
A possible mechanism for visible light-induced wound healing
Lipovsky A, Nitzan Y, Lubart R
Background And Objectives: Chronic wounds resistant to conventional therapy have
been treated successfully with low energy lasers and light emitting diodes (LEDs) in the
visible and near IR region. It has been proposed that production of low level reactive
oxygen species (ROS) following illumination is the first step of photobiomodulation. It
was also shown that white light (400-800 nm) has similar stimulatory effects as lasers
and LEDs. ROS at higher levels are toxic to cells and bacteria.
Study Design/Materials And Methods: In the present study, we examined the
phototoxicity of broadband (400-800 nm, 120 J/cm(2)) visible light on the survival of
several pathogenic bacteria: Staphylococcus aureus 195, Pseudomonas aeruginosa 1316,
Escherichia coli 1313, and Serratia marcescens. These bacteria were chosen due to their
high prevalence in infected wounds. The survival of bacterial cells following illumination
was monitored by counting the number of colony forming units before and after exposure
to light.
Results: Illumination with white light, 120 J/cm(2), caused a reduction of 62%, 83%,
and 56% in the colony count of E. coli 1313, S. aureus 195 and S. marcescens,
respectively, though no reduction in the viability of P. aeruginosa 1316 was
demonstrated. The phototoxic effect was found to involve induction of ROS production by
the bacteria. It was also found that illumination of S. aureus 195 and E. coli 1313 in the
presence of pyocyanin, known to be secreted by P. aeruginosa, had a stronger
bactericidal effect compared to illumination alone.
Conclusion: Visible light at high intensity can kill bacteria in infected wounds. Thus,
illumination of infected wounds with intense visible light, prior to low intensity
illumination for stimulating wound closure, may reduce infection and promote healing.
J Biochem Mol Toxicol. 2009 Jan-Feb;23(1):1-8
Effects of low-level light therapy on hepatic antioxidant defense in acute and
chronic diabetic rats
Lim J, Ali ZM, Sanders RA, Snyder AC, Eells JT, Henshel DS, Watkins JB 3rd
Diabetes causes oxidative stress in the liver and other tissues prone to complications.
Photobiomodulation by near infrared light (670 nm) has been shown to accelerate
diabetic wound healing, improve recovery from oxidative injury in the kidney, and
attenuate degeneration in retina and optic nerve. The present study tested the
hypothesis that 670 nm photobiomodulation, a low-level light therapy, would attenuate
oxidative stress and enhance the antioxidant protection system in the liver of a model of
type I diabetes. Male Wistar rats were made diabetic with streptozotocin (50 mg/kg, ip)
then exposed to 670 nm light (9 J/cm(2)) once per day for 18 days (acute) or 14 weeks
(chronic). Livers were harvested, flash frozen, and then assayed for markers of oxidative
stress. Light treatment was ineffective as an antioxidant therapy in chronic diabetes, but
light treatment for 18 days in acutely diabetic rats resulted in the normalization of
hepatic glutathione reductase and superoxide dismutase activities and a significant
increase in glutathione peroxidase and glutathione-S transferase activities. The results of
this study suggest that 670 nm photobiomodulation may reduce, at least in part, acute
hepatic oxidative stress by enhancing the antioxidant defense system in the diabetic rat
model.
Photomed Laser Surg. 2009 Feb;27(1):49-55
Immunohistochemical assessment of myofibroblasts and lymphoid cells during
wound healing in rats subjected to laser photobiomodulation at 660 nm
Ribeiro MA, Albuquerque RL Jr, Ramalho LM, Pinheiro AL, Bonjardim LR, Da
Cunha SS
Objective: The goal of this study was to assess the biomodulatory effect of low-level
laser therapy (LLLT) on myofibroblasts and T and B cells during wound healing.
Background Data: Phtotobiomodulation using LLLT has been extensively applied to
improve wound healing.
Materials And Methods: Standardized artificial surgical wounds were made on the
backs of 24 male rats. Half of them underwent LLLT (20 J/cm(2) at 660 nm delivered for
7 d. At 8 and 14 d post-surgery the healing wounds were removed and
immunohistochemical analysis of myofibroblasts, T cells, and B cells was carried out. The
mean of each cell subset was calculated and compared to one another using two-way
analysis of variance (ANOVA) and Tukey's test.
Results: The average number of myofibroblasts was statistically significantly higher in
the irradiated group than in the non-irradiated group on the eighth (p = 0.001) but not
the 14th (p = 0.555) day. B and T cells were significantly more conspicuous in the
irradiated group on both the eighth (p = 0.004 and 0.02, respectively) and 14th days
(p = 0.04 and 0.03, respectively).
Conclusions: Our results suggest that LLLT facilitates myofibroblastic differentiation
during the early stages of the cicatricial repair process. Furthermore, LLLT also appears
to modulate the inflammatory response by downregulating lymphocytic proliferation
during the wound healing process.
Lasers Med Sci. 2009 Mar;24(2):234-40. Epub 2008 Apr 17
Bone repair following bone grafting hydroxyapatite guided bone regeneration
and infra-red laser photobiomodulation: a histological study in a rodent model.
Pinheiro AL, Martinez Gerbi ME, de Assis Limeira F Jr, Carneiro Ponzi EA,
Marques AM, Carvalho CM, de Carneiro Santos R, Oliveira PC, Nóia M,
Ramalho LM
The aim of the investigation was to assess histologically the effect of laser
photobiomodulation (LPBM) on a repair of defects surgically created in the femurs of rats.
Forty-five Wistar rats were divided into four groups: group I (control); group II (LPBM);
group III (hydroxyapatite guided bone regeneration; HA GBR); group IV (HA GBR LPBM).
The animals in the irradiated groups were subjected to the first irradiation immediately
after surgery, and it was repeated every day for 2 weeks. The animals were killed 15
days, 21 days and 30 days after surgery. When the groups irradiated with implant and
membrane were compared, it was observed that the repair of the defects submitted to
LPBM was also processed faster, starting from the 15th day. At the 30th day, the level of
repair of the defects was similar in the irradiated groups and those not irradiated. New
bone formation was seen inside the cavity, probably by the osteoconduction of the
implant, and, in the irradiated groups, this new bone formation was incremental. The
present preliminary data seem to suggest that LPMB therapy might have a positive effect
upon early wound healing of bone defects treated with a combination of HA and GBR.
Photochem Photobiol. 2009 Jul-Aug;85(4):987-96. Epub 2009 Feb 13
Mitochondrial responses of normal and injured human skin fibroblasts following
low level laser irradiation--an in vitro study
Zungu IL, Hawkins Evans D, Abrahamse H
Laser irradiation has proved to be very efficient in speeding and improving the quality of
healing in pathological conditions of diverse etiologies. However, the mechanisms by
which the beneficial effects are attained are not clear. Mitochondria are the primary
phototargets during irradiation. The study aimed to establish if laser irradiation had an
effect on hypoxic and acidotic cells. The study also aimed to use existing information
regarding the possible mechanism of action (established in wounded cells) and apply
these principles to acidic and hypoxic irradiated cells to determine whether laser has a
stimulatory or inhibitory effect. Cell cultures were modified to simulate conditions of
hypoxia (hypoxic gas mixture 95% N2 and 5% O2) and acidosis (pH 6.7) whereas the
central scratch model was used to simulate a wound. Cells were irradiated with a
helium-neon (632.8 nm, 3 mW cm(-2)) laser using 5 or 16 J cm(-2) on days 1 and 4.
Mitochondrial responses were measured 1 or 24 h after laser irradiation by assessing
changes in mitochondrial membrane potential (MMP), cyclic AMP, intracellular Ca2+ and
adenosine triphosphate (ATP) cell viability. Hypoxia and acidosis significantly reduced
MMP when compared with normal nonirradiated control cells. Wounded, hypoxic and
acidotic cells irradiated with 5 J cm(-2) showed an increase in mitochondrial responses
when compared with nonirradiated cells while 16 J cm(-2) showed a significant decrease.
The study confirmed that laser irradiation with 5 J cm(-2) stimulated an increase in
intracellular Ca2+ which resulted in an increase in MMP, ATP and cAMP, which ultimately
results in photobiomodulation to restore homeostasis of injured cells.
Indian J Dent Res. 2009 Jul-Sep;20(3):390
Morphological analysis of second-intention wound healing in rats submitted to
16 J/cm 2 lambda 660-nm laser irradiation
Gonzaga Ribeiro MA, Cavalcanti de Albuquerque RL, Santos Barreto AL, Moreno
de Oliveira VG, Santos TB, Freitas Dantas CD
Background And Objectives: Low-level laser therapy (LLLT) has been extensively
applied to improve wound healing due to some biostimulatory properties presented by
laser arrays apparently able to accelerate the cicatricial repair of soft tissue injuries.
However, many controversial results have been reported in the literature, probably as a
result of the wide sort of different protocols of photobiomodulation employed in those
experiments. The goal of this study was to investigate the effect of a low-dose protocol of
LLT on the intensity of the inflammatory response and the pattern of collagen fibers'
deposition during second-intention wound healing in rodents.
Materials And Methods: Standard-sized wounds were carried out in the back of 24
male rats. Half of them underwent LLLT treatment (16 J/cm 2 ) at 660 nm delivered for 7
days. Eight and 14 days after the wounds were performed, the repairing area was
removed and stained in HE and Masson's trichrome, and the inflammatory response,
epithelization, and collagen fiber depositions were evaluated.
Results: We found that LLLT was able to slightly reduce the intensity of the
inflammatory reaction as well as to enhance substantially the epithelization process at
both 8 th and 14 th days. In addition, it also appeared to stimulate the deposition of
collagen fibers at the final stages of wound healing.
Conclusions: The LLLT protocol tested in this study resulted in some improvements in
second-intention wound healing in rodents.
Indian J Dent Res. 2009 Jul-Sep;20(3):390
Morphological analysis of second-intention wound healing in rats submitted to
16 J/cm 2 lambda 660-nm laser irradiation
Gonzaga Ribeiro MA, Cavalcanti de Albuquerque RL, Santos Barreto AL, Moreno
de Oliveira VG, Santos TB, Freitas Dantas CD
Background And Objectives: Low-level laser therapy (LLLT) has been extensively
applied to improve wound healing due to some biostimulatory properties presented by
laser arrays apparently able to accelerate the cicatricial repair of soft tissue injuries.
However, many controversial results have been reported in the literature, probably as a
result of the wide sort of different protocols of photobiomodulation employed in those
experiments. The goal of this study was to investigate the effect of a low-dose protocol of
LLT on the intensity of the inflammatory response and the pattern of collagen fibers'
deposition during second-intention wound healing in rodents.
Materials And Methods: Standard-sized wounds were carried out in the back of 24
male rats. Half of them underwent LLLT treatment (16 J/cm 2 ) at 660 nm delivered for 7
days. Eight and 14 days after the wounds were performed, the repairing area was
removed and stained in HE and Masson's trichrome, and the inflammatory response,
epithelization, and collagen fiber depositions were evaluated.
Results: We found that LLLT was able to slightly reduce the intensity of the
inflammatory reaction as well as to enhance substantially the epithelization process at
both 8 th and 14 th days. In addition, it also appeared to stimulate the deposition of
collagen fibers at the final stages of wound healing.
Conclusions: The LLLT protocol tested in this study resulted in some improvements in
second-intention wound healing in rodents.
Dermatol Ther. 2009 Nov;22 Suppl 1:S8-15
Fractional CO2 laser: a novel therapeutic device upon photobiomodulation of
tissue remodeling and cytokine pathway of tissue repair
Prignano F, Campolmi P, Bonan P, Ricceri F, Cannarozzo G, Troiano M, Lotti T
Minimally ablative fractional laser devices have gained acceptance as a preferred method
for skin resurfacing. Notable improvements in facial rhytides, photodamage, acne
scarring, and skin laxity have been reported. The aim of the present work was to
compare how different CO(2) laser fluences, by modulating the secretory pathway of
cytokines, are able to influence the wound-healing process, and how these fluences are
associated with different clinical results. Eighteen patients, all with photodamaged skin,
were treated using a fractional CO(2) laser (SmartXide DOT, Deka M.E.L.A., Florence,
Italy) with varying laser fluencies (2.07, 2.77, and 4.15 J/cm(2)). An
immunocytochemical study was performed at defined end points in order to obtain
information about specific cytokines of the microenvironment before and after treatment.
The secretory pathway of cytokines changed depending on the re-epithelization and the
different laser fluences. Different but significant improvements in wrinkles, skin texture,
and hyperpigmentation were definitely obtained when using 2.07, 2.77, and 4.15
J/cm(2), indicating fractional CO(2) laser as a valuable tool in photorejuvenation with
good clinical results, rapid downtime, and an excellent safety profile.
J Plast Reconstr Aesthet Surg. 2009 Dec;62(12):1684-7. Epub 2008 Nov 1
The use of argon beam coagulation in pressure sore reconstruction
Buck DW 2nd, Lewis VL Jr
Purpose: Pressure sores are a significant source of physical and financial burden for
debilitated patients. When conservative measures fail, surgical reconstruction with
myocutaneous flaps may be the last hope for cure and/or improved quality of life in these
patients. Adequate haemostasis is an integral component of these reconstructive
procedures, as bleeding and haematoma formation can lead to increased morbidity. This
study was designed to investigate the use of argon beam coagulation in patients
undergoing bony debridement and subsequent pressure sore reconstruction with
myocutaneous flaps.
Methods: The clinical records of 34 patients undergoing pressure sore reconstruction
with the use of argon beam coagulation from 2004 to 2006 at an academic institution
were reviewed and outcomes were assessed.
Results: Reconstruction was performed by a single surgeon on 34 patients (31 men,
three women; mean age 41+/-15 years), with a total of 41 pressure sores. Thirteen
(32.5%) patients had evidence of osteomyelitis preoperatively and five (12.5%) had
previous coccygectomies secondary to infection. Twenty-six (65%) of the pressure sores
were treated with hamstring V-Y musculocutaneous flaps, 10 (25%) with gluteal flaps,
and four (10%) with tensor fascia lata flaps. Overall, suture line dehiscence occurred in
six (15%) cases, flap failure and pressure sore recurrence occurred in six (15%) cases,
an abscess developed in one (2.5%) case, and a sinus tract with a superficial wound
developed in one (2.5%) case. There were no complications related to haemostasis,
including excessive bleeding or haematoma formation.
Conclusions: Argon beam coagulation is an efficacious tool for achieving adequate
haemostasis during pressure sore reconstruction, particularly when significant bony
debridement is involved. The use of argon beam coagulation does not result in an
increased complication or recurrence rate when compared with conventional
electrocautery methods.
Photomed Laser Surg. 2010 Feb;28(1):81-90
Effects of laser photobiomodulation on cutaneous wounds treated with
mitomycin C: a histomorphometric and histological study in a rodent model
Santos NR, dos Santos JN, Sobrinho JB, Ramalho LM, Carvalho CM, Soares LG,
Pinheiro AL
Aim: The aim of the present study was to assess histologically the effect of Laser
Photobiomodulation (LPBM) on skin wounds treated with Mitomycin C (MMC).
Background Data: Wound healing occurs because of a competitive mechanism between
the synthesis and lyses of collagen. Therefore, any factor that increases the lyses or
reduces the synthesis of collagen may result in changes in the healing process. MMC is
an antineoplastic drug that inhibits fibroblast proliferation, collagen synthesis, and
neoangiogenesis. LPBM has been shown to stimulate wound healing, increasing the
production of collagen, fibroblastic proliferation, and angiogenesis.
Materials And Methods: Forty-eight Wistar rats were randomly distributed into 4 main
groups (n = 12): G1--control (G1a--7 d and G1b--14 d); G2--MMC (G2a--7 d and G2b-14 d); G3--MMC + lambda660 nm laser (G3a--7 d and G3b--14 d); and G4--MMC +
lambda790 nm laser (G4a--7 d and G4b--14 d). Under general anesthesia, one excisional
wound was created on the dorsum of each animal. Two ml of MMC solution was applied
to the wound 4 h after surgery for 5 min. LPBM was performed on groups G3 (lambda690
nm; 20 J/cm(2); 30 mW; Phi = 2 mm) and G4 (lambda790 nm; 20 J/cm(2); 40 mW; Phi
= 2 mm), starting immediately after the application of the MMC and repeated every other
day during the experimental period. Laser light was applied transcutaneously at 4
equidistant points on the wound margin (4 x 5 J/cm(2), 20 J/cm(2)/session). The
specimens were routinely cut and processed to wax. The slides were stained with HE and
Sirius red. Computerized hystomorphometry was performed.
Results: LPBM resulted in reduced inflammation and an increase in both fibroblast
proliferation and collagen deposition.
Conclusion: The use of LPBM improves wound healing in subjects treated with MMC.
Lasers Surg Med. 2010 Apr;42(4):348-52
Visible light induces nitric oxide (NO) formation in sperm and endothelial cells
Ankri R, Friedman H, Savion N, Kotev-Emeth S, Breitbart H, Lubart R
Background: Visible light-based stimulation using low-intensity lasers, LEDs, and
broadband visible light devices has been recently introduced for therapy of human tissues
in the absence of exogenous photosensitizers. Nitric oxide (NO) formation might be a
potential mechanism for photobiomodulation because it is synthesized in cells by nitric
oxide synthase (NOS), which contains both flavin and heme groups that absorb visible
light. NO synthesis may also result from increased reactive oxygen species (ROS), which
are found in various cell cultures following visible light illumination. NO is mainly known
for inducing blood vessel dilation by endothelial cells, and in sperm cells NO is considered
as an important agent in acrosome reaction and capacitation process, which are essential
for successful fertilization.
Purpose: To study NO formation in endothelial and sperm cells following visible light
irradiation.
Materials And Methods: Sperm and endothelial cells were illuminated with broadband
visible light, 400-800 nm, 130 mW/cm(2), for 5 minutes. During illumination, the
endothelial cells were incubated in PBS free of Ca(+2) and Mg(+2), and the sperm cells
were incubated in NKM buffer, to induce "stress conditions." NO production was
quantified by using the Griess reagent which reacts with nitrite in the medium to yield an
Azo compound which has an absorption band at 540 nm.
Results: Visible light illumination increased NO concentration both in sperm and
endothelial cells. Blue light was more effective than red. Light-induced NO occurred only
when endothelial cells were incubated in PBS free of Ca(+2) and Mg(+2), and in sperm
cells, only when incubated in NKM.
Conclusion: Light induces NO formation in endothelial and sperm cells. In endothelial
cells, NO formation may explain previous results demonstrating enhanced wound healing
and pain relief following illumination. In illuminated sperm cells, NO formation may
account for the enhanced fertilization rate.
Photomed Laser Surg. 2010 Apr;28(2):251-61
Laser photobiomodulation of wound healing in diabetic and non-diabetic mice:
effects in splinted and unsplinted wounds.
Chung TY, Peplow PV, Baxter GD
Objective: The aim of this investigation was to compare the healing of laser-irradiated
and non-irradiated wounds covered by an occlusive dressing in mice.
Background Data: Many previous studies of the effects of laser irradiation of
experimental wounds in mice and rats did not cover the wounds so that healing occurred
mainly by contraction. Healing of covered wounds is slower and mimics more closely
wound healing in humans.
Materials And Methods: Forty-seven diabetic and twenty non-diabetic mice were used.
A single wound (5 mm diameter) was created on the left flank of each animal and
covered by Tegaderm HP dressing (Day 1). Wounds were irradiated (660 nm) for 20 s
using a lower power (18 mW) or higher power (80 mW) laser starting immediately postwounding for seven consecutive days (0.36 or 1.6 J/day); untreated wounds served as
controls. Animals were euthanized on Day 8, 10, or 14. Wound specimens were cut and
stained using haematoxylin and eosin, and picrosirius red, and examined by microscopy.
Results: Results confirmed that wound healing was impaired in diabetic mice. Analysis of
the data demonstrated that Tegaderm HP dressing had retarded contraction (splinted the
wounds) in a large proportion of diabetic mice and, to a lesser extent, in non-diabetic
mice. Healing of splinted wounds was delayed compared to unsplinted wounds, but laser
irradiation (1.6 J/day, 7 days) stimulated healing by re-epithelization and granulation
tissue formation.
Conclusion: These are the first findings of laser-mediated stimulation of healing in
splinted wounds. Further studies are needed to assess the effects of different
constellation sets of laser parameters in this wound model.
Photomed Laser Surg. 2010 Jun;28(3):291-325
Laser photobiomodulation of wound healing: a review of experimental studies
in mouse and rat animal models
Peplow PV, Chung TY, Baxter GD
Objectives: This investigation reviewed experimental studies of laser irradiation of
wound healing in mice and rats published from 2003 to August 2008, respectively, to
assess putative stimulatory effects of this treatment.
Background: Animal models, including rodents, attempt to reflect human wound healing
and associated problems such as dehiscence, ischemia, ulceration, infection, and
scarring. They have played a key role in furthering understanding of underlying
mechanisms involved in impaired wound healing, and in testing new therapeutic
strategies including laser irradiation.
Method: Original research papers investigating effects of laser or monochromatic light
therapy on wound healing in mice and rats and published from January 2003 to August
2008 were retrieved from library sources, PubMed and Medline databases, reference lists
from retrieved papers, and hand searches of relevant journals. Papers were selected for
this review with regard to specific inclusion and exclusion criteria. Studies were critically
reviewed in terms of study design, methodology, and appropriateness of laser irradiation
parameters.
Results: The literature search identified eight studies in mice and 39 in rats. A variety of
wound models were investigated, including acute-wound, impaired-healing, and chronicwound models. Considerable variation was observed in research design, methodology,
and irradiation parameters employed, limiting comparison of research findings between
studies. Inadequate reporting of key experimental details, or errors in specification
and/or calculation of key irradiation parameters was also found. Evidence from the
studies reviewed suggested that use of red or infrared wavelength at a range of dosage
parameters (median 4.2 J cm(-2)) results in significant benefits in measured parameters
of wound healing. Interestingly, coherence does not seem essential to the
photobiomodulatory effects of 'laser' phototherapy.
Conclusion: Studies reviewed consistently demonstrated the ability of laser or
monochromatic light to photobiomodulate wound healing processes in experimental
wounds in rats and mice, and strongly support the case for further controlled research in
humans.
J Orthop Sci. 2010 Mar;15(2):233-9. Epub 2010 Apr 1
Effect of near-infrared light-emitting diodes on nerve regeneration
Ishiguro M, Ikeda K, Tomita K
Background: Photobiomodulation by red to near-infrared light-emitting diodes (LEDs)
has been reported to accelerate wound healing, attenuate degeneration of an injured
optic nerve, and promote tissue growth. The purpose of this study was to investigate the
effect of LEDs on nerve regeneration. A histological study as well as a measurement of
antioxidation levels in the nerve regeneration chamber fluid was performed.
Methods: For the histological study, the bilateral sciatic nerves were transected, and the
left proximal stump and the right distal stump were inserted into the opposite ends of a
silicone chamber, leaving a 10-mm gap. Light from an LED device (660 nm, 7.5
mW/cm(2) was irradiated for 1 h per day. At 3 weeks after surgery, regenerated tissue
was fixed and examined by light microscopy. For the antioxidation assay of chamber
fluid, the left sciatic nerve and a 2-mm piece of nerve from the proximal stump were
transected and inserted into opposite sides of a silicone chamber leaving a 10-mm gap.
LEDs were irradiated using the same parameters as those described in the histological
study. At 1, 3, and 7 days after surgery, antioxidation of the chamber fluid was
measured using an OXY absorbent test.
Results: Nerve regeneration was promoted in the LED group. Antioxidation of the
chamber fluid significantly decreased from 3 days to 7 days in the control group. In the
LED group, antioxidation levels did not decrease until 7 days.
Conclusions: Chamber fluid is produced from nerve stumps after nerve injury. This fluid
contains neurotrophic factors that may accelerate axonal growth. Red to near-infrared
LEDs have been shown to promote mitochondrial oxidative metabolism. In this study,
LED irradiation improved nerve regeneration and increased antioxidation levels in the
chamber fluid. Therefore, we propose that antioxidation induced by LEDs may be
conducive to nerve regeneration.
Photomed Laser Surg. 2010 Aug;28 Suppl 1:S3-40
Laser photobiomodulation of proliferation of cells in culture: a review of human
and animal studies
Peplow PV, Chung TY, Baxter GD
Aim: The aim of this article was to review experimental studies of la irradiation of human
and animal cells in culture to assess the photobiomodulatory effects of such irradiation.
Background: Previous studies have shown that various types of cells respond differently
to laser irradiation, depending on irradiation parameters. Cellular outcomes measured or
examined include cell numbers, cell viability, and ultrastructural features. A review of
these studies may provide a further insight into the clinical effects brought about by laser
light on cells and tissues, including laser effects in wound healing and repair of nerves
and skeletal muscle after injury.
Methods: A systematic review was completed of original research articles investigating
the effects of laser therapy on human and animal cells in culture (January 2002 to
September 2009). Relevant articles were primarily sourced from PubMed and Medline by
using EndNote X1, and from secondary searches. Search terms were "cell proliferation,"
"laser therapy," "laser irradiation," "laser phototherapy," and "phototherapy."
Results: In total, 46 relevant articles were included in the review, comprising work
completed on a variety of cell types. Although results consistently demonstrated the
potential of laser irradiation to affect cellular proliferation in a wavelength- and dosagedependent manner, the relevance of other key irradiation parameters, such as irradiance,
to such effects remained unclear.
Conclusions: Findings from studies of cells in culture clearly demonstrate the ability of
laser irradiation to modulate (typically stimulate) cellular proliferation. The relevance of
some irradiation parameters remains occult and represents an important area for further
research.
Photomed Laser Surg. 2011 Jan;29(1):11-7. Epub 2010 Aug 11
Influence of laser photobiomodulation on collagen IV during skeletal muscle
tissue remodeling after injury in rats
Baptista J, Martins MD, Pavesi VC, Bussadori SK, Fernandes KP, Pinto Júnior
Ddos S, Ferrari RA
Objective: The aim of the present study was to determine the effect of GaAlAs low-level
laser therapy (LLLT) on collagen IV remodeling of the tibialis anterior (TA) muscle in rats
after cryolesion.
Background: Considerable interest exists in skeletal muscle regeneration in situations
such as repair after exercise-induced muscle injury, after muscle transplantation, in
muscular dystrophy, exercise-induced muscle injury, and the recovery of strength after
atrophy due to disuse. A number of studies have demonstrated the potential of LLLT in
facilitating the muscle-healing process; however, no consensus is found in the literature
regarding the best laser-irradiation parameters.
Methods: Adult male Wistar rats (n = 45) were used and randomly divided into three
groups: control (n = 5); nontreated cryolesioned group (n = 20), and LLLT-cryolesioned
group (n = 20). The cryolesioned groups were analyzed at 1, 7, 14, and 21 days after
the injury procedure. Laser irradiation was performed 3 times per week on the injured
region by using the GaAlAs laser (660 nm; beam spot of 0.04 cm(2), output power of 20
mW, power density of 500 mW/cm(2), and energy density of 5 J/cm(2), for 10 sec). The
muscles were removed, frozen, cryosectioned, and then stained with hematoxylin-eosin
for the visualization of general morphology or used for immunohistochemical analysis of
collagen IV.
Results: It was demonstrated that LLLT promotes an increase in collagen IV
immunolabeling in skeletal muscle in the first 7 days after acute trauma caused by
cryoinjury, but does not modify the duration of the tissue-repair process. Even with LLLT,
the injured muscle tissue needs ∼21 days to achieve the same state of organization as
that in the noninjured muscle.
Conclusion: The collagen IV content is modulated in regenerating skeletal muscle under
LLLT, which might be associated with better tissue outcome, although the histologic
analysis did not detect tissue improvement in the LLLT group.
Photomed Laser Surg. 2010 Oct;28(5):639-46. Epub 2010 Oct 9
Influence of laser (λ670 nm) and dexamethasone on the chronology of
cutaneous repair
Marchionni AM, Medrado AP, Silva TM, Fracassi LD, Pinheiro AL, Reis SR
Objective: This study aimed to assess the effect of LLLT associated with and without
dexamethasone on inflammation and wound healing in cutaneous surgical wounds.
Background: Limited studies are directed at the possible interference of laser
photobiomodulation on the formation of myofibroblasts, associated with an
antiinflammatory drug.
Methods And Materials: Standard skin wounds were performed on 80 Wistar rats,
distributed into four groups: no treatment (sham group), laser only (λ670 nm, 9 mW,
0.031 W/cm(2), 4 J/cm(2), single dose after surgery), dexamethasone only (2 mg/kg 1 h
before surgery), and laser with dexamethasone. Tissue was examined histologically to
evaluate edema, presence of polymorphonuclear, mononuclear cells, and collagen. The
analysis of myofibroblasts was assessed by immunohistochemistry and transmission
electron microscopy. The intensity was rated semiquantitatively.
Results: The results showed that laser and dexamethasone acted in a similar pattern to
reduce acute inflammation. Collagen synthesis and myofibroblasts were more intense in
the laser group (p = 0.048), whereas animals treated with dexamethasone showed lower
results for these variables. In a combination of therapies, the synthesis of collagen and
actin and desmin-positive cells was less than laser group.
Conclusions: Laser was effective in reducing swelling and polymorphonuclear cells and
accelerated tissue repair, even in the presence of dexamethasone.
Photomed Laser Surg. 2010 Oct;28(5):597-602
Comparative study of the effects of gallium-aluminum-arsenide laser
photobiomodulation and healing oil on skin wounds in wistar rats: a
histomorphometric study
Gonçalves RV, Novaes RD, Matta SL, Benevides GP, Faria FR, Pinto MV
Objective: The present study compared the effects of gallium-aluminum-arsenide diode
laser and healing oil on fibroblasts, blood vessels, and collagen maturation of skin
wounds in Wistar rats.
Materials And Methods: Twenty-four male rats weighing 325 ± 27 g were used. Five
wounds, 12 mm in diameter, were made on the animals' backs. The rats were randomly
divided into four groups with six animals in each group. Control group: saline solution;
L30 group: 30 J/cm(2) laser; L60 group: 60 J/cm(2) laser; Oil group: healing oil.
Histomorphometric analysis was performed on the scar tissue removed from the different
wounds every 4 d for 20 d.
Results: On day 4, there were significantly more fibroblasts in the wounds treated with
the laser and the healing oil compared to the controls. On day 8, there were significantly
more fibroblasts in the oil group compared to the L30 and L60 groups. On the same day,
the quantity of vessels was significantly greater in the L60 group compared to the other
groups. On day 16, there was a significant increase in the number of blood vessels in the
wounds treated with the 60 J/cm(2) laser compared to the other groups. Analysis of the
collagen maturation index throughout the experiment showed significantly higher values
in the L60 group compared to the other groups at all time points.
Conclusion: The healing oil exerted a greater effect on fibroblast proliferation, whereas
the 60 J/cm(2) laser was more effective in stimulating angiogenesis and scar-tissue
maturation.
Photomed Laser Surg. 2011 Apr;29(4):233-7. Epub 2010 Dec 23
Effect of photobiomodulation on vinblastine-poisoned murine HERS cells
Hodgson BD, Pyszka B, Henry MM, Buchmann E, Whelan HT
Objective: The aim of this study was to investigate the effect of near-infrared (NIR)
photobiomodulation on the proliferation and glutathione levels in murine Hertwig's
epithelial root sheath (HERS) cells after poisoning with vinblastine.
Background: Photobiomodulation has been shown to improve wound healing in a
number of animal models. There have been no studies on the effect of
photobiomodulation on cancer-related chemotherapy injury to the cells that initiate tooth
root growth.
Materials And Methods: Control groups consisted of murine HERS cells without
vinblastine (VB-) and cells with vinblastine at 10, 20, and 30 ng/mL (VB10, VB20, and
VB30). Experimental groups consisted of these same groups with light therapy
(VB-L, VB10L, VB20L, and VB30L). The cells were exposed to vinblastine for 1 h.
Photobiomodulation consisted of a 75-cm(2) gallium-aluminum-arsenide light-emitting
diode (LED) array at an energy density of 12.8 J/cm(2), delivered with 50 mW/cm(2)
power over 256 s.
Results: Vinblastine alone significantly decreased HERS cell proliferation and glutathione
levels at all concentrations (VB10 [-55%, p < 1.0 × 10(-8)]; VB20 [-72%, p < 1.0 × 10(9)]; VB30 [-80%, p < 1.0 × 10(-10)]; and VB10 [-36%, p < 0.0001]; VB20 [-49%,
p < 1.0 × 10(-6)]; VB30 [-53%, p < 1.0 × 10(-7)] respectively). Photobiomodulation
significantly increased cell proliferation at all levels of vinblastine exposure (VB10L
[+50%, p < 0.0001]; VB20L [+45%, p < 0.05]; VB30 [+39%, p < 0.05]) but not of the
control (+22%, p = 0.063). The photobiomodulation significantly increased glutathione
production in all concentrations of vinblastine except 20 ng/mL (VB10L [+39%,
p = 0.007]; VB20L [+19%, p = 0.087]; VB30 [+14%, p = 0.025]) and the control (+12%,
p = 0.13).
Conclusions: Photobiomodulation demonstrated an improvement in proliferation and
glutathione levels in vinblastine-poisoned murine HERS cells.
PM R. 2010 Dec;2(12 Suppl 2):S292-305
Role of low-level laser therapy in neurorehabilitation
Hashmi JT, Huang YY, Osmani BZ, Sharma SK, Naeser MA, Hamblin MR
This year marks the 50th anniversary of the discovery of the laser. The development of
lasers for medical use, which became known as low-level laser therapy (LLLT) or
photobiomodulation, followed in 1967. In recent years, LLLT has become an increasingly
mainstream modality, especially in the areas of physical medicine and rehabilitation. At
first used mainly for wound healing and pain relief, the medical applications of LLLT have
broadened to include diseases such as stroke, myocardial infarction, and degenerative or
traumatic brain disorders. This review will cover the mechanisms of LLLT that operate
both on a cellular and a tissue level. Mitochondria are thought to be the principal
photoreceptors, and increased adenosine triphosphate, reactive oxygen species,
intracellular calcium, and release of nitric oxide are the initial events. Activation of
transcription factors then leads to expression of many protective, anti-apoptotic, antioxidant, and pro-proliferation gene products. Animal studies and human clinical trials of
LLLT for indications with relevance to neurology, such as stroke, traumatic brain injury,
degenerative brain disease, spinal cord injury, and peripheral nerve regeneration, will be
covered.
J Photochem Photobiol B. 2011 Dec 2;105(3):175-82. Epub 2011 Sep 6
Enhancement of cutaneous immune response to bacterial infection after lowlevel light therapy with 1072 nm infrared light: a preliminary study
Lee SY, Seong IW, Kim JS, Cheon KA, Gu SH, Kim HH, Park KH
We investigated the photobiomodulation effects of 1072 nm infrared light on the natural
immune response involved in anti-bacterial and wound healing processes. Thirty mice
infected with MRSA on the skin were divided into two groups. The experimental group
was treated with 1072 nm infrared light (irradiance: 20 mW/cm(2), fluence: 12 J/cm(2)
for 10 min) at 2, 4, 8, 12, 24 h, 3 and 5 days after inoculation and the control group with
sham light. Serial changes of the mRNA levels of TLR2, IL-1β, TNF-α, IL-6, iNOS, MCP-1,
TGF-β, bFGF and VEGF were studied by real time RT-PCR and those of the expression
level of VEGF, bFGF, TGF-β and NF-κB by immunohistochemistry. The mRNA levels of the
cytokines involved in the early phase of anti-bacterial immune response (IL-1β, TNF-α,
IL-6, MCP-1) increased significantly in the 1072 nm group, peaking between 12 and 24 h
post-inoculation. These levels normalized after 3-5 days. Immunohistochemistry revealed
a notably stronger expression of VEGF in the 1072 nm group from 8-h post-inoculation to
5-day post-inoculation. We concluded that
1072 nm infrared light had a photobiomodulation effect which resulted in an enhanced
biological immune response to the bacterial infection by MRSA and also increased the
expression of VEGF to a significant level.
Ann Biomed Eng. 2011 Nov 2. [Epub ahead of print]
The Nuts and Bolts of Low-level Laser (Light) Therapy
Chung H, Dai T, Sharma SK, Huang YY, Carroll JD, Hamblin MR
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 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 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.