Comprehensive analysis of bone tissue in extraction sockets of third molars after leukocyte and platelet rich fibrin and photobiomodulation applications.

OBJECTIVES: The aim of this study was to compare leukocyte and platelet-rich fibrin (L-PRF) and photobiomodulation (PBM) applications, which have been repeatedly reported to be superior to control groups, in terms of pain, soft tissue and bone healing in tooth extraction sockets. MATERIALS AND METHODS: This double-blind, randomized clinical study was completed with 34 patients, who had an indication for extraction of their bilaterally impacted teeth. The right and left teeth of the patients were randomly divided into L-PRF and PBM groups. L-PRF group was treated with the blood product centrifuged for 12 min at 2700 rpm, and the PBM group was treated with a diode laser at different points for 60 s with a wavelength of 940 nm in repeated sessions. Postoperative pain was evaluated using Visual Analogue Scale (VAS), soft tissue healing with Landry Index (LI), tissue healing in the distal region of mandibular second molar by probing depth measurement, and bone healing via panoramic x-ray using the Image J program. RESULTS: No statistically significant difference was found for any variable compared between the groups. CONCLUSION: L-PRF and PBM applications provide similar support in the healing of extraction sockets. Nevertheless, the advantages and disadvantages of both methods determine their usage areas. CLINICAL RELEVANCE: While L-PRF is advantageous in the early healing of extraction sockets, PBM may be preferred in terms of bone trabeculation in the long term.

Ghrelin induced by ultraviolet B exposure promotes the restoration of diabetic cutaneous wound healing.

BACKGROUND: Diabetes mellitus (DM) presents impediment to wound healing. While ultraviolet B (UVB) exposure showed therapeutic potential in various skin conditions, its capacity to mediate diabetic wound healing remains unclear. To investigate the efficacy of UVB on wound healing and its underlying basis. MATERIALS AND METHODS: Male C57BL/6 mice were subjected to the high-fat diet followed by streptozotocin administration to establish the diabetic model. Upon confirmation of diabetes, full-thickness wounds were inflicted and the treatment group received UVB radiation at 50 mJ/cm2 for 5 min every alternate day for 2 weeks. Wound healing rate was then assessed, accompanied by evaluations of blood glucose, lipid profiles, CD31 expression, and concentrations of ghrelin and leptin. Concurrently, in vitro studies were executed to evaluate the protective role of ghrelin on human umbilical vein endothelial cells (HUVEC) under high glucose (HG) conditions. RESULTS: Post UVB exposure, there was a marked acceleration in wound healing in DM mice without alterations in hyperglycemia and lipid profiles. Compared to non-UVB-exposed mice, the UVB group showed enhanced angiogenesis manifested by a surge in CD31 expression. This trend appeared to be in harmony with the elevated ghrelin levels. In vitro experiments indicated that ghrelin significantly enhanced the migratory pace and angiogenic properties of HUVEC under HG-induced stress, potentially mediated by an upregulation in vascular endothelial growth factor expression. CONCLUSION: UVB exposure bolstered wound healing in diabetic mice, plausibly mediated through augmented angiogenesis induced by ghrelin secretion. Such findings underscore the vast potential of UVB-induced ghrelin in therapeutic strategies targeting diabetic wound healing.

Photobiomodulation and amniotic membrane for treat tendon injury in rats.

Tendons, complex fibrous structures, are subjected to great tensions, which can give rise to the so-called tendinopathies. This study aimed to evaluate photobiomodulation and human Amniotic Membrane applied as single or combined therapies to treat induced Achilles tendon lesions. Seventy-five rats were divided into five groups (n=15): C- control Sham surgery; I- tendon injury; LA- tendon injury treated with photobiomodulation; AM- tendon injury treated with Amniotic Membrane; LAM- tendon injury + photobiomodulation and Amniotic Membrane, subdivided into three groups (n=5) with analysis at 3, 7, and 14 days. The tendon injuries were made with a 20 g weight released from a mini guillotine onto the ankle in dorsiflexion. AM and LAM groups received an Amniotic Membrane fragment while LA and LAM groups received transcutaneous photobiomodulation, using a 660 nm wavelength laser. The inflammatory cells showed statistical differences between groups C and I (p<0.05), I and AM (p<0.01), I and LA (p<0.05), and I and LAM (p<0.01). Both photobiomodulation and Amniotic Membrane were shown to enhance tendon repair, and the association of photobiomodulation plus Amniotic Membrane was the most effective treatment. We conclude that the association of photobiomodulation plus Amniotic Membrane was effective in accelerating and improving the tendon regeneration process.

The efficacy of high-intensity laser therapy in wound healing: a narrative review.

High-intensity laser therapy (HILT) has recently been incorporated into wound management therapeutic protocols (Mosca RC et al. (2019) Photobiomodulation Therapy for Wound Care: A Potent, Noninvasive, Photoceutical Approach. Adv Skin Wound Care 32(4):157-167. https://doi.org/10.1097/01.ASW.0000553600.97572.d2 ). Laser therapy is increasingly used as an adjunct to therapeutic interventions in clinical practice (Dundar U et al. (2015) Effect of high-intensity laser therapy in the management of myofascial pain syndrome of the trapezius: a double-blind, placebo-controlled study. Lasers Med Sci 30(1):325-332. https://doi.org/10.1007/s10103-014-1671-8 ). This study aimed to evaluate the efficacy of HILT and the potential benefits of incorporating co- interventions alongside HILT in wound management. The following databases were searched up to April 2023: Embase, MEDLINE, PubMed, and Cinahl, as well as manual searches. The search keywords included high- intensity laser therapy, high-power laser therapy, laser therapy, wound, ulcer, and wound healing. The primary measures were decreased wound surface area (WSA) and improved wound appearance (WA) or other objective wound assessment tools containing these two values. Six human studies investigating HILT in wound healing treatment and one animal study assessing the wound-healing effects of HILT in acute wounds of mice were selected (Thabet AAE, Mahran HG, Ebid AA, Alshehri MA. Effect of pulsed high intensity laser therapy on delayed caesarean section healing in diabetic women. J Phys Ther Sci.;30(4):570-575. doi:, Ebid AA, Thabet A, Helal O (2018) (2011) Efficacy of pulsed high intensity Nd: Yag Laser in Treatment of Chronic Diabetic Foot Ulcer. Energy for Health pp. 25-30); (Ebid AA, El-Kafy EM, Alayat MS (2013) Effect of pulsed Nd: YAG laser in the treatment of neuropathic foot ulcers in children with spina bifida: a randomized controlled study. Photomed Laser Surg 31(12):565-570. https://doi.org/10.1089/pho.2013.3533 ); (Hong SE et al. (2016) Effects of neodymium-yttrium-aluminum garnet (Nd: YAG) pulsed high-intensity laser therapy on full thickness wound healing in an experimental animal model. J Cosmet Laser Ther 18(8):432-437. https://doi.org/10.1080/14764172.2016.1202421 ); (Lu Q et al. (2021) Clinical effects of high-intensity laser therapy on patients with chronic refractory wounds: a randomised controlled trial. BMJ Open 11(7):e045866. https://doi.org/10.1136/bmjopen-2020-045866 ); (Pereira FLC et al. (2020) Use of a High-Power Laser for Wound Healing: A Case Report. J Lasers Med Sci 11(1):112-114. https://doi.org/10.15171/jlms.2020.19 ); (Thabet AAE et al. (2018) Effect of pulsed high intensity laser therapy on delayed caesarean section healing in diabetic women. J Phys Ther Sci 30(4):570-575. https://doi.org/10.1589/jpts.30.570 ); (Nussbaum EL, Baxter GD, Lilge L (2003) A Review of Laser Technology and Light-Tissue Interactions as a Background to Therapeutic Applications of Low Intensity Lasers and Other Light Sources. Phys Therapy Reviews 8(1):31-44. https://doi.org/10.1002/lsm.20769 ). This limited number of studies exhibited varying treatment parameters, blinding procedures, wound etiologies, irradiation protocols, and testing areas (Thabet AAE, Mahran HG, Ebid AA, Alshehri MA. Effect of pulsed high intensity laser therapy on delayed caesarean section healing in diabetic women. J Phys Ther Sci. ;30(4):570-575. doi:, Ebid AA, Thabet A, Helal O (2018) (2011) Efficacy of pulsed high intensity Nd: Yag Laser in Treatment of Chronic Diabetic Foot Ulcer. Energy for Health pp. 25-30); (Ebid AA, El-Kafy EM, Alayat MS (2013) Effect of pulsed Nd: YAG laser in the treatment of neuropathic foot ulcers in children with spina bifida: a randomized controlled study. Photomed Laser Surg 31(12):565-570. https://doi.org/10.1089/pho.2013.3533 ); (Hong SE et al. (2016) Effects of neodymium-yttrium-aluminum garnet (Nd: YAG) pulsed high-intensity laser therapy on full thickness wound healing in an experimental animal model. J Cosmet Laser Ther 18(8):432-437. https://doi.org/10.1080/14764172.2016.1202421 ); (Lu Q et al. (2021) Clinical effects of high-intensity laser therapy on patients with chronic refractory wounds: a randomised controlled trial. BMJ Open 11(7):e045866. https://doi.org/10.1136/bmjopen-2020-045866 ); (Pereira FLC et al. (2020) Use of a High-Power Laser for Wound Healing: A Case Report. J Lasers Med Sci 11(1):112-114. https://doi.org/10.15171/jlms.2020.19 ); (Thabet AAE et al. (2018) Effect of pulsed high intensity laser therapy on delayed caesarean section healing in diabetic women. J Phys Ther Sci 30(4):570-575. https://doi.org/10.1589/jpts.30.570 ); (Nussbaum EL, Baxter GD, Lilge L (2003) A Review of Laser Technology and Light-Tissue Interactions as a Background to Therapeutic Applications of Low Intensity Lasers and Other Light Sources. Phys Therapy Reviews 8(1):31-44. https://doi.org/10.1002/lsm.20769 ). All selected studies demonstrated favorable results in improving wound conditions (Thabet AAE, Mahran HG, Ebid AA, Alshehri MA. Effect of pulsed high intensity laser therapy on delayed caesarean section healing in diabetic women. J Phys Ther Sci. ;30(4):570-575. doi:, Ebid AA, Thabet A, Helal O (2018) (2011) Efficacy of pulsed high intensity Nd: Yag Laser in Treatment of Chronic Diabetic Foot Ulcer. Energy for Health pp. 25-30); (Ebid AA, El-Kafy EM, Alayat MS (2013) Effect of pulsed Nd: YAG laser in the treatment of neuropathic foot ulcers in children with spina bifida: a randomized controlled study. Photomed Laser Surg 31(12):565-570. https://doi.org/10.1089/pho.2013.3533 ); (Hong SE et al. (2016) Effects of neodymium-yttrium-aluminum garnet (Nd: YAG) pulsed high-intensity laser therapy on full thickness wound healing in an experimental animal model. J Cosmet Laser Ther 18(8):432-437. https://doi.org/10.1080/14764172.2016.1202421 ); (Lu Q et al. (2021) Clinical effects of high-intensity laser therapy on patients with chronic refractory wounds: a randomised controlled trial. BMJ Open 11(7):e045866. https://doi.org/10.1136/bmjopen-2020-045866 ); (Pereira FLC et al. (2020) Use of a High-Power Laser for Wound Healing: A Case Report. J Lasers Med Sci 11(1):112-114. https://doi.org/10.15171/jlms.2020.19 ); (Thabet AAE et al. (2018) Effect of pulsed high intensity laser therapy on delayed caesarean section healing in diabetic women. J Phys Ther Sci 30(4):570-575. https://doi.org/10.1589/jpts.30.570 ); (Nussbaum EL, Baxter GD, Lilge L (2003) A Review of Laser Technology and Light-Tissue Interactions as a Background to Therapeutic Applications of Low Intensity Lasers and Other Light Sources. Phys Therapy Reviews 8(1):31-44. https://doi.org/10.1002/lsm.20769 ). Although insufficient data support using HILT in wound management, the promising results encourage further research. HILT appears effective in wound healing, but more high-quality studies are needed to identify optimal laser protocols.

Photobiomodulation with laser and led on mesenchymal stem cells viability and wound closure in vitro.

Mesenchymal stem cells can differentiate into specific cell lineages in the tissue repair process. Photobiomodulation with laser and LED is used to treat several comorbidities, can interfere in cell proliferation and viability, in addition to promoting responses related to the physical parameters adopted. Evaluate and compare the effects of laser and LED on mesenchymal cells, with different energy doses and different wavelengths, in addition to viability and wound closure. Mesenchymal stem cells derived from human adipocytes were irradiated with laser (energy of 0.5 J, 2 J and 4 J, wavelength of 660 nm and 830 nm), and LED (energy of 0.5 J, 2 J and 4 J, where lengths are 630 nm and 850 nm). The wound closure process was evaluated through monitoring the reduction of the lesion area in vitro. Viability was determined by analysis with Hoechst and Propidium Iodide markers, and quantification of viable and non-viable cells respectively Data distributions were analyzed using the Shapiro-Wilk test. Homogeneity was analyzed using Levene's test. The comparison between the parameters used was analyzed using the Two-way ANOVA test. The T test was applied to data relating to viability and lesion area. For LED photobiomodulation, only the 630 nm wavelength obtained a significant result in 24, 48 and 72 h (p = 0,027; p = 0,024; p = 0,009). The results related to the in vitro wound closure test indicate that both photobiomodulation with laser and LED demonstrated significant results considering the time it takes to approach the edges (p < 0.05). Considering the in vitro experimental conditions of the study, it is possible to conclude that the physical parameters of photobiomodulation, such as energy and wavelength, with laser or LED in mesenchymal stem cells, can play a potential role in cell viability and wound closure.

Activation of reparative processes of chronic wounds using photobiomodulation therapy (experimental study).

OBJECTIVE: Aim: The aim of the work was to study the ef f ect of photobiomodulation therapy on the regulation of disorders in the healing of chronic wounds at the remodeling stage using indicators of platelet aggregation activity, reactive oxygen species, platelet-derived growth factor, and interleukin-1ß. PATIENTS AND METHODS: Materials and Methods: The study included 3 groups of Wistar rats: intact animals and animals of the control and experimental groups, for which chronic wounds were simulated. Rats in the experimental group received photobiomodulation therapy once a day for 5 days. Wound defects of animals in the control group were fictitiously irradiated. The levels of reactive oxygen species, platelet-derived growth factor, and interleukin-1ß in the blood serum of animals were studied by enzyme immunoassay. The functional activity of platelets was measured on a computerized platelet aggregation analyzer using the turbidimetric method. Histological studies were carried out. RESULTS: Results: Changes in the expression of the studied indicators were found in the blood serum of animals with chronic wounds when using photobiomodulation therapy: an increase in platelet-derived growth factor concentrations, the levels of reactive oxygen species and interleukin-1ß did not have statistically signif i cant differences compared to the corresponding indicators of animals in the control group. There were no significant differences in the indicators of platelet aggregation activity in the control and experimental groups of animals. CONCLUSION: Conclusions: The findings suggest that photobiomodulation therapy may promote wound healing by increasing platelet-derived growth factor levels. Histological studies have shown that using photobiomodulation therapy helps reduce inflammation and better organization of collagen fibers in animals of the experimental group.

Modulation of gene expression in skin wound healing by photobiomodulation therapy: A systematic review in vivo studies.

BACKGROUND: Wound healing is a multistep process involving coordinated responses of a variety of cell types, cytokines, growth factors, and extracellular matrix (ECM) components leading to the physiological restoration of tissue integrity. Photobiomodulation therapy (PBMT) has been highlighted as an approach to improve the healing process, nonetheless at the molecular level, the effects of PBMT are not entirely understood. AIM: To systematically review publications that investigated gene expression after PBMT during in vivo skin repair. METHODS: An electronic search was undertaken in Medline Ovid (Wolters Kluwer), PubMed (National Library of Medicine), Web of Science (Thomson Reuters), Scopus (Elsevier), Embase, and LILACS databases. The search strategy was conducted from the terms: low-level light therapy, gene expression, and wound healing and their synonyms. The databases were consulted in December 2023 and no publication year limit was used. RESULTS: Eleven studies were included in this review and the expression of 186 genes was evaluated. PBMT modified the expression of several targets genes studied, such as down-regulation of genes related to extracellular matrix proteases (MMP2 and MMP9) and pro-inflammatory cytokines (IL10 and IL6) and up-regulation of DNMT3A and BFGF. CONCLUSION: This review demonstrates that PBMT is capable of regulating gene expression during wound healing. Most evidence showed a positive impact of PBMT in regulating genes linked to inflammatory cytokines improving skin wound healing. Yet, the effects of PBMT in genes involved in other mechanisms still need to be better understood.

The features of the reparative regeneration of an oral mucosa wound created under the exposure of a laser at a wavelength of 445 nm (a pilot study).

In clinical practice, an innovative laser technology that provides contactless preparation of soft tissues with a wavelength of 445 nm has been introduced. This study aimed to investigate the morphological changes in the oral mucosa when exposed to laser radiation at a wavelength of 445 nm in the ablation mode.An experimental study was conducted to analyze the dynamics of reparative regeneration in the wound caused by that particular type of radiation, utilizing the procedure of lower lip frenuloplasty as an illustration. 48 sexually mature male laboratory rats were chosen as the research object. The procedure of preparing the oral vestibule was executed by employing a contactless laser beam with a wavelength of 445 nm and a power of 0.7 W in continuous mode (CW) and an uninitiated fiber.Histological examination showed that 25 min after the surgery, there were large areas of coagulation necrosis in the oral mucosa in the area affected by the blue laser. In 48 h, the area of necrosis decreased both in size and depth. By the 7th day after the surgery, the necrotic masses had grown into the connective tissue, while marginal regeneration of the epithelium was noted. By the 14th day, the wound surface was completely epithelialized, represented by fibrous scar tissue. Clinically, around the mandibular incisors, there was a wide area of attached keratinized gingiva.The findings of histological examination indicate a necrosis of coagulation type in the region of tissue ablation and also show the absence of phase II of the inflammatory response (the stage of exudation), which expedites the process of epithelialization of the oral mucosa wound.

Low-level laser activates Wnt/ß-catenin signaling pathway-promoting hair follicle stem cell regeneration and wound healing: Upregulate the expression of key downstream gene Lef 1.

BACKGROUND: The objective of this study is to investigate the mechanism by which low-level laser stimulation promotes the proliferation of intraepithelial hair follicle stem cells (HFSCs) in wounds. This research aims to expand the applications of laser treatment, enhance wound repair methods, and establish a theoretical and experimental foundation for achieving accelerated wound healing. METHODS: The experimental approach involved irradiating a cell model with low-level laser to assess the proliferation of HFSCs and examine alterations in the expression of proteins related to the Wnt/ß-catenin signaling pathway. A mouse back wound model was established to investigate the effects of low-level laser irradiation on wound healing rate, wound microenvironment, and the proliferation of HFSCs in relation to the Wnt/ß-catenin signaling pathway. RESULTS: The research findings indicate that low-level laser light effectively activates the Wnt signaling pathway, leading to the increased accumulation of core protein ß-catenin and the upregulation of key downstream gene Lef 1. Consequently, this regulatory mechanism facilitates various downstream biological effects, including the notable promotion of HFSC proliferation and differentiation into skin appendages and epithelial tissues. As a result, the process of wound healing is significantly accelerated. CONCLUSION: Low levels of laser activates the Wnt signalling pathway, promotes the regeneration of hair follicle stem cells and accelerates wound healing.

Investigation of alveolar osteitis and the effectiveness of laser treatment: a unified Meta-analysis and review of the literature.

BACKGROUND: Post-tooth extraction, dry socket is a frequently encountered complication, causing substantial pain and hindering the healing process. Conventional approaches to manage this condition have traditionally involved the use of antiseptic dressings to diminish bacterial presence and facilitate healing. This study aims to assess the efficacy of laser therapy in the symptomatic treatment of alveolitis. METHODS: A literature search was conducted on PubMed, Embase, Scopus, Google Scholar, Web of Science, focusing on publications from 1998 to 31/01/2024 using relevant keywords. The combination of "laser" and "dry socket" was executed through the boolean connection AND. RESULTS: At the conclusion of the study, a total of 50 studies were identified across the three search engines, with only three selected for the current systematic study and meta-analysis. The meta-analysis indicated that laser treatment proves effective in addressing alveolitis compared to Alvogyl. However, the correlation between the two was not highly significant. CONCLUSION: These findings suggest that laser therapy may serve as a viable alternative to traditional treatments for dry socket. This minimally invasive procedure has the potential to alleviate pain and promote healing with fewer associated side effects."

Altering CO2 Laser Pulse Energy Settings Did Not Influence Differential Gene Transcription in Normal Skin in a Red Duroc Pig Model.

OBJECTIVES: Fractional ablative CO2 lasers are used clinically to treat cutaneous burn scars with reported varying degrees of effectiveness. It was hypothesized that different laser pulse energy settings may lead to differential gene transcription in a porcine model. METHODS: Uninjured skin from red Duroc pigs was treated with a fractional ablative CO2 laser set to 70, 100, or 120 mJ across the abdomen (n = 4 areas per treatment). Punch biopsies of both treated and untreated sites were taken before treatment (baseline), at 30 min, and at each hour for 6 h and stored in All-Protect tissue reagent. The biopsies were then used to isolate RNA, which was subsequently used in qRT-PCR for eight genes associated with wound healing and the extracellular matrix: CCL2, IL6, FGF2, TIMP1, TIMP3, COL1A2, MMP2, and DCN. RPL13a was used as a housekeeping gene to normalize the eight genes of interest. One-way ANOVA tests were used to assess for differences among laser pulse energies and two-way ANOVA tests were used to assess the differences between treated and untreated areas. RESULTS: While six of the eight genes were upregulated after treatment (p < 0.05), there were no significant differences in gene expression between the different laser pulse energies for any of the eight genes. CONCLUSION: While laser treatment is correlated with a positive and significant upregulation for six of the eight genes 4 h after intervention, the pulse energy settings of the laser did not lead to a statistically significant difference in gene transcription among the treatment areas. Different laser pulse energies may not be required to induce similar cellular responses in a clinical setting.

Persistent eschar-like wound healing after Q-switched 1064 nm hybrid nanosecond-picosecond laser monochromatic tattoo removal: management and evolution.

Q-switched (QS) Nd: YAG lasers are frequently utilised light sources for tattoo removal due to their precise micro-confined photo-acoustic interaction with exogenous and endogenous pigments. In order to achieve optimal results, several treatment sessions are usually required. However, the number of sessions depend on tattoo size, design complexity, pigment quantity within dermal layers, and anatomical location. Higher energy settings have often been used to reduce treatment sessions to a minimum however, this approach may lead to possible post-laser skin complications such as pathological wound healing. This case report highlights the importance of recognizing early stages of pathological wound healing encountered after high fluence 1064 nm QS laser tattoo removal. Early implementation of a proportional wound care strategy with anti-neoangiogenic and anti-inflammatory properties through the unconventional use of potent topical steroids applied in a pulsed fashion resulted in positive control of the tissue repair processes. This approach led to effective wound healing re-modulation achieving near normal skin remodelling and optimal tissue healing which in turn, permitted the completion of necessary QS tattoo removal sessions to accomplish successful and safe tattoo fading whilst maintaining overall patient satisfaction.

Preventive and therapeutic vascular photobiomodulation decreases the inflammatory markers and enhances the muscle repair process in an animal model.

Photobiomodulation therapy (PBM) has shown positive effects when applied locally to modulate the inflammatory process and facilitate muscle repair. However, the available literature on the mechanisms of action of vascular photobiomodulation (VPBM), a non-invasive method of vascular irradiation, specifically in the context of local muscle repair, is limited. Thus, this study aimed to assess the impact of vascular photobiomodulation (VPBM) using a low-level laser (LLL) on the inflammatory response and the process of skeletal muscle repair whether administered prior to or following cryoinjury-induced acute muscle damage in the tibialis anterior (TA) muscles. Wistar rats (n = 85) were organized into the following experimental groups: (1) Control (n = 5); (2) Non-Injury + VPBM (n = 20); (3) Injured (n = 20); (4) Pre-VPBM + Injury (n = 20); (5) Injury + Post-VPBM (n = 20). VPBM was administered over the vein/artery at the base of the animals' tails (wavelength: 780 nm; power: 40 mW; application area: 0.04 cm2; energy density: 80 J/cm2). Euthanasia of the animals was carried out at 1, 2, 5, and 7 days after inducing the injuries. Tibialis anterior (TA) muscles were collected for both qualitative and quantitative histological analysis using H&E staining and for assessing protein expression of TNF-α, MCP-1, IL-1ß, and IL-6 via ELISA. Blood samples were collected and analyzed using an automatic hematological analyzer and a leukocyte differential counter. Data were subjected to statistical analysis (ANOVA/Tukey). The results revealed that applying VPBM prior to injury led to an increase in circulating neutrophils (granulocytes) after 1 day and a subsequent increase in monocytes after 2 and 5 days, compared to the Non-Injury + VPBM and Injured groups. Notably, an increase in erythrocytes and hemoglobin concentration was observed in the Non-Injury + VPBM group on days 1 and 2 in comparison to the Injured group. In terms of histological aspects, only the Prior VPBM + Injured group exhibited a reduction in the number of inflammatory cells after 1, 5, and 7 days, along with an increase in blood vessels at 5 days. Both the Prior VPBM + Injured and Injured + VPBM after groups displayed a decrease in myonecrosis at 1, 2, and 7 days, an increase in newly-formed and immature fibers after 5 and 7 days, and neovascularization after 1, 2, and 7 days. Regarding protein expression, there was an increase in MCP-1 after 1 and 5 days, TNF-α, IL-6, and IL-1ß after 1, 2, and 5 days in the Injured + VPBM after group when compared to the other experimental groups. The Prior VPBM + Injured group exhibited increased MCP-1 production after 2 days, in comparison to the Non-Injury + VPBM and Control groups. Notably, on day 7, the Injured group continued to show elevated MCP-1 protein expression when compared to the VPBM groups. In conclusion, VPBM effectively modulated hematological parameters, circulating leukocytes, the protein expression of the chemokine MCP-1, and the proinflammatory cytokines TNF-α and IL-1ß, ultimately influencing the inflammatory process. This modulation resulted in a reduction of myonecrosis, restoration of tissue architecture, increased formation of newly and immature muscle fibers, and enhanced neovascularization, with more pronounced effects when VPBM was applied prior to the muscle injury.

Dose-response and efficacy of 904 nm photobiomodulation on diabetic foot ulcers healing: a randomized controlled trial.

PURPOSE: This study aimed to examine the impact of a 904 nm photobiomodulation (PBM) on diabetic ulcers using varying dosages. METHODS: The study was a randomized, double-blind, placebo-controlled clinical trial that compared treatments using PBM (GaAs 904 nm 30w) with three different energy densities (4 J/cm2; 8 J/cm2; 10 J/cm2) in the healing process of non-infected diabetic foot ulcers. Eighty volunteers (48.75% female; 58.5 ± 11.1 years) were randomized into three intervention groups treated with PBM and one control group (PBM placebo). Volunteers performed up 20 interventions with PBM, either placebo or actual, in conjunction with conventional therapy, which involved dressing the wound with Helianthus annuus vegetable oil. The primary variable was the ulcer size reduction rate. RESULTS: GaAs 904 nm PBM yielded a clinically and significant ulcer size rate reduction of diabetic foot ulcers, independently of energy density range (p < 0.05). However, 10 J/cm² had 60% of completely healed ulcers and the highest proportion of patients reaching 50% of ulcer reduction rate after 5 weeks of treatment. In addition, only 10 J/cm² showed a significant difference between control group after a 10-week follow-up (p < 0.05). CONCLUSION: GaAs 904 nm PBM was effective in treating diabetic foot ulcers in this study and a dosage of 10 J/cm², after a 10-week follow-up, proved to be the most effective compared to the other groups. CLINICAL TRIAL REGISTRATION NUMBER: NCT04246814.

Investigating the Relevance of Cyclic Adenosine Monophosphate Response Element-Binding Protein to the Wound Healing Process: An In Vivo Study Using Photobiomodulation Treatment.

Monitoring inflammatory cytokines is crucial for assessing healing process and photobiomodulation (PBM) enhances wound healing. Meanwhile, cAMP response element-binding protein (CREB) is a regulator of cellular metabolism and proliferation. This study explored potential links between inflammatory cytokines and the activity of CREB in PBM-treated wounds. A total of 48 seven-week-old male SD rats were divided into four groups (wound location, skin or oral; treatment method, natural healing or PBM treatment). Wounds with a 6 mm diameter round shape were treated five times with an 808 nm laser every other day (total 60 J). The wound area was measured with a caliper and calculated using the elliptical formula. Histological analysis assessed the epidermal regeneration and collagen expression of skin and oral tissue with H&E and Masson's trichrome staining. Pro-inflammatory (TNF-α) and anti-inflammatory (TGF-ß) cytokines were quantified by RT-PCR. The ratio of phosphorylated CREB (p-CREB) to unphosphorylated CREB was identified through Western blot. PBM treatment significantly reduced the size of the wounds on day 3 and day 7, particularly in the skin wound group (p < 0.05 on day 3, p < 0.001 on day 7). The density of collagen expression was significantly higher in the PBM treatment group (in skin wound, p < 0.05 on day 3, p < 0.001 on day 7, and p < 0.05 on day 14; in oral wound, p < 0.01 on day 7). The TGF-ß/TNF-α ratio and the p-CREB/CREB ratio showed a parallel trend during wound healing. Our findings suggested that the CREB has potential as a meaningful marker to track the wound healing process.

Pulsed electromagnetic fields used in regenerative medicine: An in vitro study of the skin wound healing proliferative phase.

Numerous studies have demonstrated the efficacy of extremely low frequency-pulsed electromagnetic fields (ELF-PEMF) in accelerating the wound healing process in vitro and in vivo. Our study focuses specifically on ELF-PEMF applied with the Magnomega® device and aims to assess their effect during the main stages of the proliferative phase of dermal wound closure, in vitro. Thus, after the characterization of the EMFs delivered by the Magnomega® unit, primary culture of human dermal fibroblasts (HDFs) were exposed, or not for the control culture, to 10-12 and 100 Hz ELF-PEMF. These parameters are used in clinical practice by physiotherapists in order to enhance healing of dermal lesions in patients. HDFs proliferation was first assessed and revealed an increase in the expression of one of the two genetic markers of cell proliferation tested (PCNA and MKI67), after initial exposure of the cells to 10-12 Hz PEMF. Next, migration of HDFs was investigated by performing scratch assays on HDF layers. The observed wound closure kinetics corroborate the early organization of actin stress fibers that was revealed in the cytoplasm of HDFs exposed to 100 Hz ELF-PEMF. Also, maturation of HDFs into myofibroblasts was significantly increased in cells exposed to 10-12 or to 100 Hz PEMF. The present study is the first to demonstrate, in vitro, an early stimulation of HDFs, after their exposure to ELF-PEMF delivered by the Magnomega® device, which could contribute to an acceleration of the wound healing process.

Photodynamic therapy mediated by methylene blue-loaded PEG accelerates skin mouse wound healing: an immune response.

PURPOSE: Conventional approaches for enhancing wound healing may not always yield satisfactory results. Instead, we test the effectiveness of a newly developed photodynamic therapy (PDT) that uses methylene blue (MB) loaded with polyethylene glycol (PEG) (MB-PEG) hydrogel to accelerate wound healing process in mice. METHODS: A dorsal skin incision with 6 mm punch which topically subjected to MB-PEG hydrogel and a low-level laser light of red light to assess the regeneration process of wounded skin. A total of 63 adult male CD1 mice divided into normal group (no treatment) and other wound groups received different treatments of laser (650 ± 5 nm and power intensity of 180 mW/cm2), MB-PEG, or PDT (MB-PEG followed by laser). The wound healing parameters were investigated by histological examination of the skin and measuring of proinflammatory cytokines at the early stage (48 h) and a late one on day 21. RESULTS: at 48 h, the score of tissue granulation, inflammation, and angiogenesis process were markedly improved in wounded groups that received MB + PEG combined with laser compared to the group treated with laser alone. On day 21, a significant improvement of the inflammation was detected in the group treated with MB + PEG plus laser compared to the other groups. At 48 h, the upregulated serum levels of tumor necrosis factor (TNF)-α and interleukin (IL)-1ß in the wound group were significantly (P < 0.001) reduced in the group treated with MB + PEG combined with laser. CONCLUSION: MB-PEG based hydrogel improves and accelerates wound closure in the context of laser compared to either single treatment.

[Clinical application of photobiomodulation in trauma repair and medical aesthetics].

In recent years, with the deepening of researches on the molecular biological mechanisms of photobiomodulation (PBM), PBM has gradually been applied in clinical practice, providing effective treatment methods and approaches for various diseases. Compared with traditional photothermal therapy, PBM has the characteristics of good therapeutic effect, almost no adverse reaction, and simple operation, and its clinical efficacy is becoming increasingly significant. This article provides a detailed explanation on the mechanism of PBM, its application characteristics and development trends in trauma repair and medical aesthetics, in order to provide a theoretical basis for the extensively clinical application of this therapy.

Photobiomodulation Can Prevent Medication-Related Osteonecrosis of the Jaw Formation in Tooth Extraction Site of Rat Model.

Objective: This study aims to explore the preventive potential of photobiomodulation (PBM) in bisphosphonate-related osteonecrosis of the jaw (BRONJ) using a rat model. Methods: An experimental rat model was established, exposing rats to zoledronic acid (ZA), a primary risk factor for BRONJ. An 810 nm diode laser was applied with parameters of 0.33 W/cm2 power density and 10 J/cm2 energy density for 30 sec. PBM was initiated 1 day pre-extraction and continued for 2 weeks. The impact of PBM on wound healing in both soft and hard tissues was evaluated post tooth extraction. Results: ZA exposure hindered wound healing in both soft and hard tissues after tooth extraction. PBM intervention effectively mitigated the adverse effects of ZA, promoting healing processes in both tissue types. This suggests the potential of PBM as a preventive strategy for BRONJ in patients on long-term bisphosphonate treatment. Moreover, PBM exhibited enhanced wound healing in normal rats, indicating its broader applicability beyond BRONJ cases. Conclusions: PBM shows promise in preventing and improving wound healing in BRONJ and normal cases. These findings underscore the significance of optimizing PBM parameters and suggest its potential clinical relevance as a preventive intervention for BRONJ and a promoter of wound healing.

Long-Term Outcome of Photobiomodulation Therapy for Refractory Diabetic Wound After Secretory Carcinoma of the Parotid Gland Surgery: A Case Report.

Objective: To evaluate the efficacy and safety of photobiomodulation therapy (PBMT) in the treatment of diabetic patients with refractory wound. Background: Refractory wound is one of the most challenging clinical complications of diabetes mellitus. Studies have shown that PBMT can promote wound healing in many ways. Methods: We reported a 55-year-old male patient with refractory diabetic wound after secretory carcinoma of the parotid gland surgery responding to 810 nm laser. Results: After PBMT, the refractory diabetic wound healed gradually without adverse events. During follow-up 5-years, the healed wound remained stable and showed no signs of recurrence. Conclusions: PBMT can be potentially considered as a therapeutic method in diabetic patients with refractory diabetic wound.