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Tendon and Ligament Healing

A randomised, placebo controlled trial of low level laser therapy for activated Achilles tendinitis with microdialysis measurement of peritendinous prostaglandin E2 concentrations.

Bjordal JM, Lopes-Martins RA, Iversen VV.

Br J Sports Med. 2006 Jan;40(1):76-80; discussion 76-80.

Physiotherapy Science, University of Bergen, Bergen, Norway.

BACKGROUND: Low level laser therapy (LLLT) has gained increasing popularity in the management of tendinopathy and arthritis. Results from in vitro and in vivo studies have suggested that inflammatory modulation is one of several possible biological mechanisms of LLLT action.

OBJECTIVE: To investigate in situ if LLLT has an anti-inflammatory effect on activated tendinitis of the human Achilles tendon.

SUBJECTS: Seven patients with bilateral Achilles tendinitis (14 tendons) who had aggravated symptoms produced by pain inducing activity immediately before the study.

METHOD: Infrared (904 nm wavelength) LLLT (5.4 J per point, power density 20 mW/cm2) and placebo LLLT (0 J) were administered to both Achilles tendons in random blinded order.

RESULTS: Ultrasonography Doppler measurements at baseline showed minor inflammation through increased intratendinous blood flow in all 14 tendons and measurable resistive index in eight tendons of 0.91 (95% confidence interval 0.87 to 0.95). Prostaglandin E2 concentrations were significantly reduced 75, 90, and 105 minutes after active LLLT compared with concentrations before treatment (p = 0.026) and after placebo LLLT (p = 0.009). Pressure pain threshold had increased significantly (p = 0.012) after active LLLT compared with placebo LLLT: the mean difference in the change between the groups was 0.40 kg/cm2 (95% confidence interval 0.10 to 0.70).

CONCLUSION: LLLT at a dose of 5.4 J per point can reduce inflammation and pain in activated Achilles tendinitis. LLLT may therefore have potential in the management of diseases with an inflammatory component.

Low-level laser therapy improves early healing of medial collateral ligament injuries in rats.

Bayat M, Delbari A, Almaseyeh MA, Sadeghi Y, Bayat M, Reziae F.

Photomed Laser Surg. 2005 Dec;23(6):556-60.

Cell and Molecular Biology Research Center, Medical School, Shaheed Beheshti University of Medical Sciences, Tehran, Iran.

OBJECTIVE: This study sought to investigate whether or not low-level laser therapy (LLLT) with a helium-neon laser increased biomechanical parameters of transected medial collateral ligament (MCL) in rats.

BACKGROUND DATA: It has been reported that LLLT can enhance tendon healing.

METHODS: Thirty rats received surgical transection to their right MCL, and five were assigned as the control group. After surgery, the rats were divided into three groups: group 1 (n = 10) received LLLT with 0.01 J/cm(2) energy density per day, group 2 (n = 10) received LLLT with 1.2 J/cm(2) energy density per day, and group 3 (sham = exposed group; n = 10) received daily placebo laser with shut-down laser equipment, while the control group received neither surgery nor LLLT. Biomechanical tests were performed at 12 and 21 days after surgery. The data were analyzed by one-way analysis of variance.

RESULTS: The ultimate tensile strength (UTS) of group 2 on day 12 was significantly higher than that of groups 1 and 3. Furthermore, the UTS and energy absorption of the control (uninjured) group were significantly higher than those of the other groups.

CONCLUSIONS: LLLT with a helium-neon laser is effective for the early improvement of the ultimate tensile strength of medial collateral ligament injuries.

Effect of In-Ga-Al-P diode laser irradiation on angiogenesis in partial ruptures of Achilles tendon in rats.

Salate AC, Barbosa G, Gaspar P, Koeke PU, Parizotto NA, Benze BG, Foschiani D.

Photomed Laser Surg. 2005 Oct;23(5):470-5.

Department of Physiotherapy, Federal University of Sao Carlos, Sao Paulo, Brazil.

OBJECTIVE: This study was conducted to analyze the effect of different irradiances of low-level laser therapy (LLLT) on angiogenesis after partial rupture of Achilles tendon of rats.

BACKGROUND DATA:
METHODS: Ninety-six animals were divided into three groups subject to treatment during 3, 5, and 7 days post-lesion. Thirty-two animals were used in each group. The groups were further divided into four subgroups with eight animals in each, receiving In-Ga-Al-P laser (660 nm) treatment at (1) mean output of 10 mW, (2) 40 mW during 10 sec, (3) a sham subgroup, and (4) a non-treatment subgroup. Each animal was subjected to a lesion of the Achilles tendon by dropping a 186-g weight from a 20-cm height over the tendon. Treatment was initiated 6 h post-injury for all the groups. Blood vessels were colored with India ink injection and were examined in a video microscope.

RESULTS: Laser exposure promoted an increase in blood vessel count when compared to controls. The 40-mW group showed early neovascularization, with the greatest number of microvessels after three laser applications. The 10-mW subgroup showed angiogenesis activity around the same time as the sham laser group did, but the net number of vessels was significantly higher in the former than in the controls. After seven irradiations, the subgroup receiving 40 mW experienced a drop in microvessel number, but it was still higher than in the control groups.

CONCLUSIONS: LLLT of different intensities seems to promote neovascularization in damaged Achilles tendons of rats after partial rupture compared to controls.

Low-level laser therapy (LLLT) prevents oxidative stress and reduces fibrosis in rat traumatized Achilles tendon.

Fillipin LI, Mauriz JL, Vedovelli K, Moreira AJ, Zettler CG, Lech O, Marroni NP, Gonzalez-Gallego J.

Lasers Surg Med. 2005 Oct;37(4):293-300.

Department of Physiology, Universidade Federal de Rio Grande do Sul, Brazil.

BACKGROUND AND OBJECTIVES: The present study investigated the effects of low-level laser therapy (LLLT) on oxidative stress and fibrosis in an experimental model of Achilles tendon injury induced by a single impact trauma. STUDY

DESIGN/MATERIALS AND METHODS: Male Wistar rats were randomly divided into four groups (n = 8): control, trauma, trauma+LLLT for 14 days, and trauma+LLLT for 21 days. Achilles tendon traumatism was produced by dropping down a load with an impact kinetic energy of 0.544 J. A low level Ga-As laser was applied with a 904 nm wavelength, 45 mW average power, 5 J/cm(2) dosage, for 35 seconds duration, continuously. Studies were carried out at day 21.

RESULTS: Histology showed a loss of normal architecture, with inflammatory reaction, angiogenesis, vasodilatation, and extracellular matrix formation after trauma. This was accompanied by a significant increase in collagen concentration when compared the control group. Oxidative stress, measured by the concentration of thiobarbituric acid reactive substances and hydroperoxyde-initiated chemiluminiscence, was also significantly increased in the trauma group. Administration of LLLT for 14 or 21 days markedly alleviated histological abnormalities reduced collagen concentration and prevented oxidative stress. Superoxide dismutase activity was significantly increased by LLLT treatment over control values.

CONCLUSION: LLLT by Ga-As laser reduces histological abnormalities, collagen concentration, and oxidative stress in an experimental model of Achilles tendon injury. Reduction of fibrosis could be mediated by the beneficial effects on the oxidant/antioxidant balance.

Comparison of the effects of laser, ultrasound, and combined laser + ultrasound treatments in experimental tendon healing.

Demir H, Menku P, Kirnap M, Calis M, Ikizceli I.

Lasers Surg Med. 2004;35(1):84-9.

Erciyes University Medical Faculty, Department of Physical Medicine & Rehabilitation, Kayseri, Turkey.

BACKGROUND AND OBJECTIVE: Therapeutic ultrasound (US) and laser (L) treatments accelerate and facilitate wound healing, and also have beneficial effects on tendon healing. This randomized control study was designed to evaluate the effects of low-intensity US and low-level laser therapy (LLLT) on tendon healing in rats.

STUDY DESIGN/MATERIALS AND METHODS: Eighty-four healthy male Swiss-Albino rats were divided into three groups consisting of 28 rats, the left Achilles tendons were used as treatment and the right Achilles tendons as controls. The right and left Achilles tendons of rats were traumatized longitudinally. The treatment was started on postinjury day one. We applied the treatment protocols including low-intensity US treatment in Group I (US Group), Sham US in Group II (SUS Group), LLLT in Group III (L Group), Sham L in Group IV (SL Group), US and LLLT in Group V (US + L Group), and Sham US and Sham L in Group VI (SUS + SL Group). The US treatment was applied with a power of 0.5 W/cm2, a frequency of 1 MHz, continuously, 5 minutes daily. A low-level Ga-As laser was applied with a 904 nm wavelength, 6 mW average power, 1 J/ cm2 dosage, 16 Hz frequency, for 1 minute duration, continuously. In the control groups, the similar procedures as in the corresponding treatment groups were applied with no current (Sham method). The treatment duration was planned for 9 days (sessions) in all groups, except the rats used for biochemical evaluation on the 4th day of treatment, which were treated for 4 days. We measured the levels of the tissue hydroxyproline for biochemical evaluation on the 4th, 10th, and 21st days following the beginning of treatment and the tendon breaking strength on the 21st day following the beginning of treatment for biomechanical evaluation. Seven rats in each group were killed on the 4th, 10th, and 21st days for biochemical evaluation and on the 21st day for biomechanical evaluation.

RESULTS: The hydroxyproline levels were found to be significantly increased in the treatment groups on the 10th and 21st days compared to their control groups (P < 0.05). In comparison of the treatment groups on the 4th, 10th, and 21st days of the treatment, the levels of tissue hydroxyproline were found to be more increased in combined US+L Group compared with US Group and L Group, but the difference was not significant (P > 0.05). In comparison of the tendon breaking strengths, it was found as significantly increased in the treatment groups compared with their control groups (P < 0.05), although there was no significant difference between the treatment groups.

CONCLUSIONS: Although US, L, and combined US + L treatments increased tendon healing biochemically and biomechanically more than the control groups, no statistically significant difference was found between them. Also we did not find significantly more cumulative positive effects of combined treatment. As a result, both of these physical modalities can be used successfully in the treatment of tendon healing.

Investigation of the supplementary effect of GaAs laser therapy on the rehabilitation of human digital flexor tendons.

Ozkan N, Altan L, Bingol U, Akln S, Yurtkuran M.

J Clin Laser Med Surg. 2004 Apr;22(2):105-10.

Ataturk Rehabilitation Center, Rheumatic Disease and Hydrotherapy Section, Uludag University Medical Faculty, Bursa, Turkey.

OBJECTIVE: To investigate the effect of laser photostimulation in rehabilitation of human digital flexor tendons with a placebo-controlled double-blind prospective study model.

BACKGROUND DATA: Low-energy laser therapy has been applied in several rheumatoid and soft tissue disorders with a varying rate of success and it has also been shown to have a positive effect on tendon healing in animal experiments, but no clinical study on laser photostimulation in the treatment of human tendons has been reported to date.

MATERIALS AND METHODS: This study was performed in a total of 25 patients with 41 digital flexor tendon injuries in five anatomical zones. In Group I (21 digits in 13 patients), whirlpool and infrared GaAs diode laser with a frequency of 100 Hz. was applied between the 8th and 21st days postoperatively and all patients were given the Washington rehabilitation program until the end of the 12th week. In Group II (20 digits in 12 patients), the same treatment protocol was given but the laser instrument was switched off during applications.

RESULTS: The results of the study showed a significant improvement in the laser-treated group only for the parameter of edema reduction (p < 0.01) but the difference between the two groups was non-significant for pain reduction, hand grip strength, and functional evaluation performed according to Strickland and Buck-Gramcko systems using total active motion and fingertip-to distal palmar crease distance parameters (p > 0.05).

CONCLUSIONS: Significant improvement obtained in edema reduction both immediately and 12 weeks after supplementary GaAs laser application in our study has been interpreted as an important contribution to the rehabilitation of human flexor tendon injuries because edema is known to have a detrimental effect on functional recovery during both early and late stages of tendon healing. However, our study has failed to show a significant positive effect of supplementary GaAs laser application on the other functional recovery parameters of human flexor tendon injury rehabilitation and we suggest further clinical study in this topic be done using different laser types and dosages in order to delineate the role of this promising treatment modality.

Comparison of single and multiple applications of GaAlAs laser on rat medial collateral ligament repair.

Ng GY, Fung DT, Leung MC, Guo X.

Lasers Surg Med. 2004;34(3):285-9.

Department of Rehabilitation Sciences, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong. rsgng@polyu.edu.hk

BACKGROUND AND OBJECTIVES: To examine single versus multiple applications of the gallium aluminum arsenide (GaAlAs) laser on the healing of surgically injured medial collateral ligaments (MCLs) in rats.

STUDY DESIGN/MATERIALS AND METHODS: Sixteen rats were studied, with 12 receiving surgical transection to their right MCL and 4 receiving a sham injury. Group 1 (n = 4) received a single dose of GaAlAs laser therapy (wavelength 660 nm, average power 8.8 mW, pulse 10 kHz, dosage 31.6 J/cm(2)) directly to their MCL during surgery. Group 2 (n = 4) received 9 doses of GaAlAs laser therapy applied transcutaneously on alternate days (wavelength 660 nm, average power 8.8 mW, pulse 10 kHz, dosage 3.5 J/cm(2)). The controls (Group 3, n = 4) received one session of placebo laser at the time of surgery, with the laser equipment shut down, while the sham injured Group 4 (n = 4) received no treatment. Biomechanical tests for structural stiffness, ultimate tensile strength (UTS), and load-relaxation were done at 3 weeks after injury. The stiffness and UTS data were normalized by expressing as a percentage of the left side of each animal before statistical analysis.

RESULTS: The load-relaxation data did not show any differences between the groups (P = 0.18). The normalized stiffness levels of Groups 2 (81.08+/-11.28%) and 4 (92.66+/-13.19%) were significantly higher (P = 0.025) than that of the control Group 3 (58.99+/-15.91%). The normalized UTS of Groups 2 (81.38+/-5.68%) and 4 (90.18+/-8.82%) were also significantly higher (P = 0.012) than that of the control (64.49+/-9.26%). Although, Group 1 had higher mean stiffness and UTS values than the control, no statistically significant difference was found between these two groups.

CONCLUSIONS: Multiple laser therapy improves the normalized strength and stiffness of repairing rat MCLs at 3 weeks after injury. The multiple treatments seem to be superior to a single treatment when the cumulative dosages are comparable between the two modes of application.

Effects of a therapeutic laser on the ultrastructural morphology of repairing medial collateral ligament in a rat model.

Fung DT, Ng GY, Leung MC, Tay DK.

Lasers Surg Med. 2003;32(4):286-93.

Department of Rehabilitation Sciences, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong.

BACKGROUND AND OBJECTIVES: Low energy laser therapy has been shown to enhance mechanical strength of healing medial collateral ligament (MCL) in rats. The present study investigated its effects on the ultrastructural morphology and collagen fibril profile of healing MCL in rats.

STUDY DESIGN/MATERIALS AND METHODS: Thirty-two mature male Sprague-Dawley (SD) rats were used. Twenty-four underwent surgical transection to their right MCLs and eight received only skin wound. Immediately after surgery, eight of the MCL transected rats were treated with a single dose of laser therapy at 63.2 J cm(-2), eight were treated with a single dose of laser therapy at 31.6 J cm(-2), the rest had no treatment and served as control. At 3 and 6 weeks after surgery, the MCLs were harvested and examined with electron microscopy for collagen fibril size, distribution, and alignment.

RESULTS: Significant differences (P < 0.001) were found in fibril diameters from the same anatomical site and time period among different groups. The mass-averaged diameters of the laser-treated (64.99-186.29 nm) and sham (64.74-204.34 nm) groups were larger than the control group (58.66-85.89 nm). The collagen fibrils occupied 42.55-59.78, 42.63-53.94, and 36.92-71.64% of the total cross-sectional areas in the laser-treated, control and sham groups, respectively. Mode obliquity was 0.53-0.84 among the three groups.

CONCLUSIONS: Single application of low energy laser therapy increases the collagen fibril size of healing MCLs in rats.

Effect of low-level GaAlAs laser irradiation on the proliferation rate of human periodontal ligament fibroblasts: an in vitro study.

Kreisler M, Christoffers AB, Willershausen B, d'Hoedt B.

J Clin Periodontol. 2003 Apr;30(4):353-8.

Department of Oral Surgery, Johannes Gutenberg-University, Augustusplatz 2, 55131 Mainz, Germany. matthiaskreisler@web.de

AIM: The aim of this in vitro study was to evaluate a potential stimulatory effect of low-level laser irradiation on the proliferation of human periodontal ligament fibroblasts (PDLF).

MATERIALS AND METHODS: PDLF obtained from third molar periodontal ligaments were cultured under standard conditions and spread on 96-well tissue culture plates. Subconfluent monolayers were irradiated with an 809-nm diode laser operated at a power output of 10 mW in the continuous wave (cw) mode at energy fluences of 1.96-7.84 Jcm-2. The variable irradiation parameters were the time of exposure (75-300 s per well) and the number of irradiations (1-3). After laser treatment, the cultures were incubated for 24 h. The proliferation rate of the lased and control cultures was determined by means of fluorescence activity of a reduction-oxidation (REDOX) indicator (Alamar Blue Assay) added to the cell culture. Proliferation, expressed in relative fluorescence units (RFU), was determined 24, 48 and 72 h after irradiation.

RESULTS: The irradiated cells revealed a considerably higher proliferation activity than the controls. The differences were significant up to 72 h after irradiation (Mann-Whitney U-test, p<0.05).

CONCLUSION: A cellular effect of the soft laser application is clearly discernible. Clinical studies are needed to evaluate whether the application of low-level laser therapy might be beneficial in regenerative periodontal therapy.

Therapeutic low energy laser improves the mechanical strength of repairing medial collateral ligament.

Fung DT, Ng GY, Leung MC, Tay DK.

Lasers Surg Med. 2002;31(2):91-6.

Department of Rehabilitation Sciences, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong.

BACKGROUND AND OBJECTIVES: Low energy laser therapy has been shown to enhance collagen production but its effect on tissue strength is not well reported. We tested the effects of therapeutic laser on the strength of healing medial collateral ligaments (MCLs) in rats.

STUDY DESIGN/MATERIALS AND METHODS: Twenty-four rats received surgical transection to their right MCL and eight received sham operation. After surgery, 16 received a single dose of gallium aluminum arsenide laser to their transected MCL for 7.5 minutes (n = 8) or 15 minutes (n = 8) and eight served as control with placebo laser, while the sham group didn't receive any treatment. The MCLs were biomechanically tested at either 3 or 6 weeks post-operation.

RESULTS: The normalized ultimate tensile strength (UTS) and stiffness of laser and sham groups were larger than control (P < 0.001). The UTS of laser and sham groups were comparable. Laser and sham groups had improved in stiffness from 3 to 6 weeks (P < 0.001).

CONCLUSIONS: A single dose of low energy laser therapy improves the UTS and stiffness of repairing MCL at 3 and 6 weeks after injury.

Biochemistry and biomechanics of healing tendon: Part II. Effects of combined laser therapy and electrical stimulation.

Reddy GK, Gum S, Stehno-Bittel L, Enwemeka CS.

Med Sci Sports Exerc. 1998 Jun;30(6):794-800.

Department of Physical Therapy, University of Kansas Medical Center, Kansas City 66160-7601, USA.

PURPOSE: In previous studies we demonstrated that early mechanical loading and laser photo-stimulation independently promoted tendon healing. Thus, we tested the hypothesis that a combination of laser phototherapy and mechanical load would further accelerate healing of experimentally tenotomized and repaired rabbit Achilles tendons.

METHODS: Following surgical tenotomy and repair, the tendons of experimental and control rabbits were immobilized in polyurethane casts for 5 d. The repaired tendons of experimental rabbits received mechanical load via electrical stimulation-induced contraction of the triceps surae for 5 d. In addition, experimental tendons were treated with daily doses of 1 J.cm-2 low intensity helium-neon laser throughout the 14-d experimental period.

RESULTS: The combination of laser photostimulation and mechanical load increased the maximal stress, maximal strain, and Young's modulus of elasticity of the tendons 30, 13, and 33%, respectively. However, MANOVA revealed no statistically significant differences in these biomechanical indices of repair of control and experimental tendons. Biochemical assays showed a 32% increase in collagen levels (P < 0.05) and an 11% decrease in mature cross-links in experimental tendons compared with that in controls (P > 0.05). Electron microscopy and computer morphometry revealed no significant differences in the morphometry of the collagen fibers and no visible differences in the ultrastructure of cellular and matrical components of control and experimental tendons.

CONCLUSIONS: These findings indicate that the combination of laser photostimulation and early mechanical loading of tendons increased collagen production, with marginal biomechanical effects on repaired tendons.

Wound healing of animal and human body sport and traffic accident injuries using low-level laser therapy treatment: a randomized clinical study of seventy-four patients with control group.

Simunovic Z, Ivankovich AD, Depolo A.

J Clin Laser Med Surg. 2000 Apr;18(2):67-73.

Department of Anesthesiology, La Carita Medical Center, Laser Center, Locarno, Switzerland.

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.