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Level Laser Therapy on Collagen Deposition in Wound Healing

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Level Laser Therapy on Collagen Deposition in Wound Healing Brazilian Dental Journal (2019) 30(4): 317-324 ISSN 0103-6440 http://dx.doi.org/10.1590/0103-6440201902400 1Laboratory of Morphology Effects of Different Protocols of Low- and Experimental Pathology, UNIT - Universidade Tiradentes, Level Laser Therapy on Collagen Aracaju, SE, Brazil 2Department of Dentistry, Deposition in Wound Healing UFS - Universidade Federal de Sergipe, Aracaju, SE, Brazil Correspondence: John Lennon Silva Cunha, Avenida Murilo Dantas, 300, 49032-490 Aracaju, SE, John Lennon Silva Cunha1 , Felipe Mendes de Andrade de Carvalho1 , Brasil. Tel: +55-79-99654-0805. Rose Nely Pereira Filho1 , Maria Amália Gonzaga Ribeiro2 , Ricardo Luiz e-mail: [email protected] Cavalcanti de Albuquerque-Júnior1 The low-level laser has proven successful in stimulating the production of collagen in wound healing assays. However, diversity has been observed in the protocols used. This work has evaluated the effects of three protocols of low-level laser therapy (LLLT) in the healing of open wounds in rats. Standard-sized wounds of 1 cm2 were performed with a scalpel in the middorsal region of 60 male Wistar rats weighing 225±25 g, and they were assigned into four groups (n=15): CTR (non-irradiated animals), LT1 (20 J/cm2 daily), LT2 (16 J/cm2 daily) and LT3 (20 J/cm2 daily). After 7, 14 and 21 days, five animals/day were euthanized and the wounds analyzed histologically. Data were subjected to normality analysis of distribution using Shapiro-Wilk test. Gaussian data were analyzed using ANOVA and Bonferroni tests whereas non-Gaussian data were analyzed using Kruskal-Wallis and Dunn tests, considering significant p values less than 0.05. The LLLT in all protocols reduced the inflammation and collagen deposition increased significantly (p<0.05). However, LT2 showed the highest levels of collagen in all phases of the study (p<0.05) induced faster replacement of immature collagen III by mature collagen I in the early stages of repair and early collagen remodeling promoted by providing better organization architectural beams deposited. It was concluded that all protocols induced an increase in collagen scar. However, the protocol 2 (16 J /cm2, daily application) promoted the most significant increases in collagen deposition, accelerated Key Words: laser therapy, maturation of collagen and showed the best architecture of the final fibrous scarring. wound healing, collagen. Introduction of laser photobiomodulation is not completely clear, it The wound healing process is a complex has been proposed that LLLT stimulates mitochondrial pathophysiological process that involves a cascade of metabolism, culminating in a greater differentiation and coordinated inflammatory and proliferative events (1,2). proliferation of fibroblasts and, consequently, a greater Wounds with minimal loss of tissue, closed with sutures, deposition of collagen (9). tend to heal rapidly. However, chronic wounds, usually with Previous studies have demonstrated the beneficial infections, persistence of the inflammatory reaction and effects of LLLT on biosynthesis and collagen metabolism intense oxidative stress, exhibit delayed healing (1). The in experimental models of dermal skin injury in rodents proper care of chronic wounds has become a challenge in (10,11). However, many other controversial data have been public health, often including advanced therapies, such as reported in the literature on the laser photobiomodulator new drugs and low-level laser therapy (LLLT) (2). Because the effect on scar repair, including reduction in collagen pathophysiology of wound healing involves a wide range synthesis (12-14). This apparent paradox is most likely a of biochemical and molecular mechanisms, therapeutic result of the variety of parameters used in the experiments, strategies are challenging (3). such as energy density and intensity, irradiation time and LLLT comprises non-invasive and non-ionizing radiation irradiation mode, for example (15). that, in contact with different tissues, promotes thermal, The objective of this study was to evaluate the effect of photochemical and non-linear effects (4). It has been three LLLT protocols using gallium and aluminium arsenide reported that LLLT induces fibroblast proliferation and (GaAlAs) diode laser on the scar repair in a murine model. accelerates collagen metabolism. In addition, studies have suggested that LLLT may stimulate healing, promoting Material and Methods increased collagen deposition and accelerating the repair Ethical Aspects process (5). In addition, the tissue architecture also seems Ethical principles of the Brazilian College for Animal to be influenced by laser irradiation and has been reported Experimentation Regulation (CONCEA) were applied in this in the literature (6-8). Although the precise mechanism study, which was approved by the Ethical Committee for Braz Dent J 30(4) 2019 Animal Experimentation of Tiradentes University (UNIT) Low-Level Laser Therapy Procedures (Document approval #040508). Laser irradiation was performed using a laser diode GaAIAs (Twin Laser®, MMOptics, São Paulo, Brazil) Biological Assay previously calibrated in continuous emission mode. Two Sixty adult male Wistar rats (Rattus norvegicus albinus) different wavelengths were treated; red light (RED; 660 weighing 225±25g were randomly assigned to four nm), and infrared light (IR; 780 nm). In the experimental experimental groups (Table 1). Animals were housed in groups, the irradiation protocol was started immediately plastic cages with bedding of wood-shavings, which was after the wound confection procedure. The animals were replaced daily, under controlled temperature at 22°C and irradiated daily for 7 days and euthanized for analysis a 12 h light/dark regimen, with water and food ad libitum at 7 days, 14 days and 21 days after injury. Unirradiated (Labina®; Purina , São Paulo, Brazil). animals (control groups) underwent sham irradiation with the laser device unpowered. The irradiation parameters Surgical Procedures are shown in Table 2. The animals were subjected to dissociative anesthesia with intraperitoneal administration of 0.10 mL/100 Histological Procedures g of 10% ketamine (Ketamine®, Rhobifarma Ind. Ltd. Five animals of each group were euthanized 7, 14 and Pharmaceutical) and 0.25 mL/100 mg of xylazine 21 days after the surgical procedures in CO2 chamber (EB (Anasedan® Purina). Animals were handled in accordance 248, 400 x 320 x 350 mm, Insight, São Paulo, SP, Brazil) with the principles of aseptic chain in order to avoid any with 100% carbon dioxide continuous flux for 5 min. After possibility of exogenous bacterial contamination. Briefly, death certification, the wounded areas were surgically the animals had their dorse shaved and cleaned with 2% removed (margin of 0.5 cm), formalin-fixed and paraffin- chlorhexidine solution (Merthiolate®, Hypermarcas S.A, embedded. Twenty serial 5.0-μm-thick histological sections Barueri, São Paulo, Brazil) and a standard-sized excisional were obtained and stained in hematoxylin/eosin (HE), Sirius wounds (1 cm x 1 cm) were performed with a scalpel in red and Masson’s trichrome. The histological evaluation was the middorsal region of each rat. The wounds were treated blindly conducted by two examiners previously calibrated. as described in Table 1. Assessment of Inflammatory Profile (IP) J. L. S. Cunha et al. HE-stained sections were used for the Table 1. Distribution of the animals into the 4 groups according to the experimental descriptive analysis of the inflammatory procedures and irradiation protocol profile (IP). The intensity of the inflammatory Groups Light source response was classified as follows: 0 (absence Irradiation protocol (n=15)a type of inflammatory response), 1 (inflammatory CTRb - 0 J/cm2 b cells representing less than 10% of the cell population observed within the wound area), LT1 GaAlAs laser 20 J/cm2 per session, λ660, 40 mW, ø = 0.04 cm2, CW 2 (inflammatory cells representing between LT2 GaAlAs laser 16 J/cm2 per session, λ660, 40 mW, ø = 0.04 cm2, CW 10% and 50% of the cell population observed LT3 GaAlAs laser 20 J/cm2 per session, λ780, 40 mW, ø = 0.04 cm2, CW within the wound area), and 3 (inflammatory aEach group is divided in three subgroups (n=5) to be euthanized at 7, 14 and 21 days. cells representing more than 50% of the bThe animals were subjected to the same stress conditions of laser therapy. cell population observed within the wound Table 2. Experimental groups according to the irradiation protocol with low-level laser therapy Energy Total energy Irradiation Groups Light Average Wavelength Pulse Irradiation Applications per point density per time per (n=15) source type power (mW) (nm) parameters points per point (J/cm2) session (J/cm2) point (s) CTR* - - - - GaAlAs LT1 (18) 40 mV 660 nm CW 4 1 5 J/cm2 20 J/cm2 30 s laser GaAlAs LT2 (7) 40 mV 660 nm CW 4 1 4 J/cm2 16 J/cm2 30 s laser GaAlAs LT3 (17) 40 mV 780 nm CW 4 1 5 J/cm2 20 J/cm2 25 s laser *The animals were subjected to the same stress conditions of laser therapy. 318 Braz Dent J 30(4) 2019 area). Moreover, the inflammatory profile (IP) was classified CTR group than in the LT1 (p<0.05), LT2 (p<0.05) and LT3 as acute (predominance of polymorphonuclear cells) or (p<0.05), but no other significant difference was evident chronic (predominance of mononuclear cells) and graded among the irradiated groups (Table 3). as slighter/absent, moderate or severe. At 7 days, the HE-stained sections presented exuberant granulation reaction was observed in the four experimental Assessment of Collagen Deposition
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