photobiomodulation
manadental nutzt durch die eingesetzte Lichtquelle positive Effekte der Photobiomodulation (vgl. LLLT, Rotlichttherapie). Photobiomodulation beschreibt zellregeneriende Effekte und verbesserte Durchblutung von Gewebe die durch bestimmte Lichtwellenlängen im roten Bereich (meist 600nm) angeregt werden können. Folgend eine Übersicht zu der Studienlage rund um Photobiomodulation.
photobiomodulation
manadental nutzt durch die eingesetzte Lichtquelle positive Effekte der Photobiomodulation (vgl. LLLT, Rotlichttherapie). Photobiomodulation beschreibt zellregeneriende Effekte und verbesserte Durchblutung von Gewebe die durch bestimmte Lichtwellenlängen im roten Bereich (meist 600nm) angeregt werden können. Folgend eine Übersicht zu der Studienlage rund um Photobiomodulation.
01 | einleitung
Photobiomodulation (PBM), unter der die Bezeichnungen Low-Level Laser Treatment (LLLT) bzw. Soft Laser subsummiert werden können, bezeichnet die Anwendung von Lichtwellen zu gewebestimulierenden Zwecken. Am häufigsten werden Wellenlängen im roten bzw. nahe dem infraroten Bereich (630 – 940 nm) verwendet, die das Gewebe in einer Tiefe von 5 bis 10mm penetrieren können. Die Applikation kann durch Laser bzw. LED-Systeme erfolgen. Die Wirkung der PBM ist von einer Kombination verschiedener Parameter wie Energiedichte, Wellenlänge sowie Dauer und Häufigkeit der Einzelapplikationen abhängig.
Die nachgewiesenen Effekte entsprechen in erster Linie Entzündungshemmung und Förderung von Heilungs- und Regenerationsprozessen.
02 | wirkprinzip
PBM hat auf zellulärer Ebene photochemische Reaktionen zur Folge. So absorbiert z.B. Cytochrom C Oxidase, ein Enzym der mitochondrialen Atmungskette, Licht im roten Wellenlängenbereich. Das hat eine Steigerung der ATP-Produktion zur Folge, die erhöhte Energiebereitstellung für reparative Vorgänge bewirkt. Darüber hinaus wird die Bildung von Stickstoffmonoxid (NO) verstärkt, das einerseits durch Vasodilatation zu Verbesserung der Perfusion führt und andererseits als eines der wichtigsten Signalmoleküle für metabolische, neurale und immunologische Prozesse darstellt. Auch weitere, für das intra- und interzelluläre Signaling wichtige Moleküle wie Calciumionen und freie Radikale werden freigesetzt, die wiederum Transkriptionsfaktoren für die Regulation von Immunantwort und Entzündungsreaktionen darstellen.
03 | anwendungsbereiche
Die optimalen Anwendungsbereiche für PBM sind Läsionen, die sich innerhalb der Eindringtiefe des verwendeten Lichts befinden. Für sichtbares Licht betrifft dies Erkrankungen an oder nahe den Körperoberflächen, für Behandlung mit Infrarot-nahem Wellenlängenbereich sind auch tieferliegende Läsionen geeignet.
Es existieren bereits Studien aus verschiedenen Bereichen wie Neurologie und Neurotraumatologie, Orthopädie und Dermatologie.
Auf dem Sektor Zahnheilkunde bzw. Stomatologie wurde die erfolgreiche Anwendung bei Periodontitis in Kombination mit Scaling vielfach beschrieben. Speziell bei stark chronifizierten Formen bzw. bei Patienten mit Diabetes zeigte PBM gute Effekte hinsichtlich Abheilung und Regeneration. Auch die Einheilung von Implantaten bzw. die Osteogenese wurde durch PBM positiv beeinflusst.
Als Nebenwirkungen wurden unmittelbar nach der Behandlung leichte, lokale Rötung bzw. lokaler Juckreiz beschrieben, die nach wenigen Minuten abflauten. Eine Erhöhung der Temperatur im betroffenen Areal war damit nicht verbunden.
04 | studienlage
Zahlreiche in-vitro Studien haben nach Anwendung von PBM eine Verbesserung der Proliferation von Stammzellen gingivaler Fibroblasten, dentaler Stammzellen aus der Pulpa extrahierter, permanenter Zähne sowie exfoliierter Milchzähne gezeigt. PBM führte auch zu verstärkter Migration bzw. Proliferation epidermaler Stammzellen, während mesenchymale Stammzellen zur Differenzierung angeregt wurden.
Dementsprechend ließen sich z.B. ein Rückgang der extrazellulären Marker für Entzündung und oxidativen Stress und Steigerung der Migrationsfähigkeit und Proliferationsrate sowie geringere Apoptoseneigung von Fibroblasten und Entzündungszellen nachweisen. Auch die TNF-alpha getriggerte inflammatorische Cytokinproduktion nahm ab. Beide Effekte waren auch innerhalb von Biofilmen nachweisbar, während eine unmittelbare antibakterielle Wirkung der PBM ausblieb. Entzündungsassoziierte Genexpression in Fibroblasten, Osteoblasten und Endothelzellen wurde supprimiert, Proliferation und Osteogenese dagegen gefördert. So führte Illumination mit LED im roten Wellenlängenbereich zu Blockierung des NF-KappaB Pathways und zu Hinaufregulation von Proliferation und Osteogenes, was durch deutliche Anstiege der wichtigsten, osteogenen Marker dokumentiert wurde.
Zusätzlich waren in zahlreichen Studien Effekte auf Stammzellen und Progenitorzellen nachweisbar, die zu Differenzierung angeregt wurden, und dadurch Heilungsvorgänge unterstützten.
Besonders eingehende, experimentelle Studien wurden am periodontalen Gewebe diabetischer Mäuse durchgeführt. Es fanden sich Reduktion von Alterungs-assoziierten Faktoren sowie TNF-Alpha, Interleukin-1ß und Interleukin-6, sowie eine Hemmung des GLUT1/mTOR Pathways, somit eine multifaktorielle Herunterregulierung von Entzündungsfaktoren. Als weiterer Schlüsselfaktor der Wirkung von PBM stellte sich COX heraus, das nach Illumination von Makrophagen aus periodontalen Läsionen signifikanten Anstieg zeigte
PBM hatte bei klinischer Anwendung bei Zahnimplantaten eine Reduktion von TNF-Alpha, Interleukin-6 und einen Anstieg des vasculo-endothelialen Wachstumsfaktors (VEGF) zur Folge. Im Verlauf waren bessere Heilung des oralen Weichteilgewebes nach Implantationen zu beobachten, und auch die anhand eines visuellen Analog-Scores gemessenen, postoperativen Schmerzen waren geringer. Darüber hinaus zeigten mehrere Studien unter Anwendung von PBM eine geringere Rate an postoperativen Komplikationen und Problemen wie Infekt oder verzögerte Einheilung.
Sowohl in der experimentellen als auch in der klinischen Anwendung existiert vor allem auf dem Sektor der Zahnheilkunde eine gute Studienlage. Die Indikationen betreffen Periodontitis, Periimplantitis, Endodontitis und Mucositis, wobei fast durchgängig Standardtherapien mit Standardtherapie plus aPDT verglichen wurden. Letztere ergab bessere Wirkung auf die periodontale Immunantwort, Gewebeintegrität und Erhalt der alveolaren Knochenstruktur. Durch additive aPDT wurde bei Peridontitis die Keimzahl verringert und die Zusammensetzung des Mikrobioms des dentalen Plaque in Richtung günstigeren Spektrums verändert, während „bleeding on probing“ signifikant abnahm. Auch die postoperativen Ergebnisse bei Periimplantitis waren bei additivem Einsatz von aPDT besser als in der Vergleichsgruppe.
Claudia Dompe, Lisa Moncrieff, Jacek Matys, Kinga Grzech-Lesniak, Ievgeniia Kocherova, Artur Bryja, Małgorzata Bruska, Marzena Dominiak, Paul Mozdziak, Tarcio Hiroshi Ishimine Skiba, Jamil A. Shibli, Ana Angelova Volponi, Bartosz Kempisty, Marta Dyszkiewicz-Konwinska.
J. Clin. Med. 2020, 9, 1724; doi:10.3390/jcm9061724
https://pubmed.ncbi.nlm.nih.gov/32503238/
Abstract
The purpose of this study is to explore the possibilities for the application of laser therapy in medicine and dentistry by analyzing lasers’ underlying mechanism of action on different cells, with a special focus on stem cells and mechanisms of repair. The interest in the application of laser therapy in medicine and dentistry has remarkably increased in the last decade. There are different types of lasers available and their usage is well defined by different parameters, such as: wavelength, energy density, power output, and duration of radiation. Laser irradiation can induce a photobiomodulatory (PBM) effect on cells and tissues, contributing to a directed modulation of cell behaviors, enhancing the processes of tissue repair. Photobiomodulation (PBM), also known as low-level laser therapy (LLLT), can induce cell proliferation and enhance stem cell differentiation. Laser therapy is a non-invasive method that contributes to pain relief and reduces inflammation, parallel to the enhanced healing and tissue repair processes. The application of these properties was employed and observed in the treatment of various diseases and conditions, such as diabetes, brain injury, spinal cord damage, dermatological conditions, oral irritation, and in different areas of dentistry. Keywords: laser; low-level laser therapy; photobiomodulation; stem cells; tissue regeneration.
Sameer Mokeem.
J Investig Clin Dent 2018 Nov;9(4):e12361. doi: 10.1111/jicd.12361
https://pubmed.ncbi.nlm.nih.gov/32503238/
Abstract
The aim of the present study was to systematically review the efficacy of low-level laser therapy (LLLT) as an adjunct to scaling and root planing (SRP) vs SRP alone in the treatment of aggressive periodontitis (AgP). The addressed PICO (Population, Interventions, Comparisons and Outcomes) question was: Is LLLT as an adjunct to SRP effective in the treatment of AgP? Electronic databases, including MEDLINE via PubMed, Cochrane Central Register of Controlled Trials and Cochrane Oral Health Group Trials, and EMBASE, were searched until March 2018. Four clinical studies were included. Three studies showed significant improvement in periodontal outcomes among LLLT group compared to SRP alone, whereas only one study showed comparable periodontal outcomes between the adjunctive LLLT and SRP groups at follow up. The overall mean difference for clinical attachment level gain (weighted mean difference [WMD] = -1.69, 95% confidence interval [CI] = -3.46 to 0.07, P < 0.061) was not significant. However, significant difference for probing depth reduction (WMD = -0.95, 95% CI = -1.66 to 0.23, P = 0.009) was noticed between groups at follow up. Whether LLLT as an adjunct to SRP is more effective than SRP alone in the treatment of AgP remains debatable. Further randomized, clinical trials are required with long follow-up periods and standard laser parameters to reach a strong conclusion.
Keywords:
aggressive periodontitis; low-level laser therapy; scaling and root planing; systematic review.
F Pamuk, M Lütfioğlu, A Aydoğdu, C Z Koyuncuoglu, E Cifcibasi, O S Badur.
J Periodontal Res 2017 Oct;52(5):872-882. doi: 10.1111/jre.12457
https://pubmed.ncbi.nlm.nih.gov/28394081/
Abstract:
Background and objective:
This study aimed to investigate the effects of low-level laser therapy (LLLT) as an adjunct to scaling and root planing (SRP) on smoking and non-smoking patients with chronic periodontitis.
Material and methods:
The study was conducted using a split-mouth design with 30 patients with chronic periodontitis (15 smokers, 15 non-smokers) and 30 healthy individuals matched for age, sex and smoking status as controls. Groups were constituted as follows: Cp+SRP+Sham: non-smokers with chronic periodontitis treated with SRP; Cp+SRP+LLLT: non-smokers with chronic periodontitis treated with SRP+LLLT; SCp+SRP+Sham: smokers with chronic periodontitis treated with SRP; SCp+SRP+LLLT: smokers with chronic periodontitis treated with SRP+LLLT; C: control group comprised of periodontally healthy non-smokers; SC: control group comprised of periodontally healthy smokers. LLLT was first applied on the same day as SRP and again on days 2 and 7 after SRP treatment. Clinical parameters were recorded before non-surgical periodontal treatment (baseline) and on day 30. Gingival crevicular fluid samples were collected before periodontal treatment (baseline) and during follow-up visits on days 7, 14 and 30. Gingival crevicular fluid transforming growth factor (TGF)-β1, tissue plasminogen activator (tPA) and plasminogen activator inhibitor 1 (PAI-1) levels were measured using enzyme-linked immunosorbent assay.
Results:
All clinical parameters showed significant reductions between baseline and day 30 following SRP treatment in both the LLLT and sham groups (P<.001). No significant differences were observed between the LLLT and sham groups of either the smokers or non-smokers (P>.05). Gingival crevicular fluid PAI-1 levels decreased significantly in the SCp+SRP+sham and SCp+SRP+LLLT groups (P<.05), and gingival crevicular fluid tPA levels decreased significantly in the Cp+SRP+sham, Cp+SRP+LLLT and SCp+SRP+LLLT groups (P<.05). Gingival crevicular fluid TGF-β1 levels decreased significantly in all treatment groups (P<.05). Although no significant differences were found between the gingival crevicular fluid PAI-1, tPA and TGF-β1 levels of the LLLT versus sham groups (P>.05) at any of the time points measured, both LLLT groups showed significant reductions in tPA/PAI-1 ratios over time.
Conclusion:
Within the limits of this study, LLLT may be understood to play a role in the modulation of periodontal tissue tPA and PAI-1 gingival crevicular fluid levels, particularly in smoking patients with chronic periodontitis, and may thus be recommended as an adjunct to non-surgical periodontal treatment.
Keywords:
low-level laser therapy; periodontitis; plasminogen activator inhibitor 1; smoking; tissue plasminogen activator; transforming growth factor.
Régia Carla Medeiros da Silva, Lucas Gabriel Cunha da Silva, Agnes Andrade Martins, Cristiano Miranda de Araújo, Ana Rafaela Luz de Aquino Martins.
Lasers Med Sci 2024 Aug 2;39(1):207. doi: 10.1007/s10103-024-04148-2
https://pubmed.ncbi.nlm.nih.gov/39093490/
Abstract
To review current literature and synthesize clinical outcomes related to different low-level laser techniques as a complement to basic periodontal therapy (BPT). Electronic searches were conducted in PubMed, Cochrane, and Scopus, and clinical trials published from January 2013 to August 2023 using photobiomodulation as a complement to basic periodontal therapy, with a clear description of the laser technique, were included. The risk of bias was assessed using the Joanna Briggs Institute Critical Assessment Checklist. Estimates of interest were calculated using random effects meta-analyses. A total of 947 references were retrieved, and 22 studies were included for qualitative synthesis. Ten studies used intrasulcular laser techniques, with 89% using infrared wavelength, and 12 studies used transgingival techniques, with 61.5% using red wavelength. The frequency of photobiomodulation after BPT ranged from 1 to 9 sessions, with follow-up periods ranging from 5 days to 12 months. Risk of bias was considered low in 16 studies and moderate in six studies. Meta-analysis of 13 studies showed that BPT reduced probing depth at 4-, 12- and 24-weeks post-treatment, and improved clinical level attachment at 6-, 12- and 24-weeks post-treatment. Studies suggest that photobiomodulation may be a valuable complement in the treatment of periodontitis, especially using transgingival application technique.
Keywords:
Basic periodontal therapy; Low-level laser therapy; Periodontitis; Photobiomodulation.
Zhexian Cheng, Wei Li, Jitian Wang, Xuan Huang, Xingyuan Jia, Xuan Zhou.
J Periodontol 2025 Mar;96(3):203-216. doi: 10.1002/JPER.24-0128
https://pubmed.ncbi.nlm.nih.gov/39185693/
Background:
To compare the efficacy of combined treatment of Er:YAG laser (ERL) and low-level laser therapy (LLLT) with single laser applications, and scaling and root planing (SRP) for non-surgical periodontal treatment.
Methods:
In a randomized controlled trial, 25 non-smoking Stage II or Stage III periodontitis patients were recruited. The four intraoral quadrants were randomly assigned to four different treatments: (1) combined application with ERL plus SRP plus LLLT; (2) ERL plus SRP; (3) SRP plus LLLT; and (4) SRP. We assessed periodontal indexes, including probing depth (PD), clinical attachment level (CAL), bleeding index (BI), and plaque index (PLI), along with three cytokines (IL-1β, TNF-α, IL-10) from gingival crevicular fluid and red complex pathogens from subgingival dental plaque at baseline, 3 months, and 6 months.
Results:
For initial moderate pockets (4 mm ≤ PD ≤ 6 mm), quadrants treated with ERL+SRP+LLLT, ERL+SRP, and SRP+LLLT exhibited greater PD improvement compared to the control (SRP) quadrants at the 3-month follow-up (1.25 ± 1.06, 1.23 ± 1.12, 1.00 ± 1.21 vs. 0.98 ± 1.21 mm) and the 6-month follow-up (1.35 ± 1.06, 1.23 ± 1.17, 1.35 ± 0.98 vs. 0.98 ± 1.23 mm) (p = 0.002). Quadrants treated with ERL+SRP+LLLT and SRP+LLLT showed more CAL gain means than the control quadrants at the 3-month follow-up (0.96 ± 1.42, 0.61 ± 1.39 vs. 0.55 ± 1.57 mm) and the 6-month follow-up (0.84 ± 1.54, 0.89 ± 1.49 vs. 0.48 ± 1.68 mm) (p = 0.008). For initial deep pockets (PD ≥ 7 mm), the ERL+SRP+LLLT quadrants had more PD improvement and CAL gain compared to the control quadrants at follow-up. There were no significant differences in BI, PLI, inflammatory cytokines, and periodontal pathogens among the four groups.
Conclusion:
The combined application of ERL and LLLT demonstrated potential efficacy in reducing PD, particularly for deep pockets.
Keywords:
Er:YAG laser; diode laser; low‐level laser therapy; periodontitis.
Ievgeniia Kocherova, Artur Bryja, Katarzyna Błochowiak, Mariusz Kaczmarek, Katarzyna Stefańska, Jacek Matys, Kinga Grzech-Leśniak, Marzena Dominiak, Paul Mozdziak, Bartosz Kempisty, Marta Dyszkiewicz-Konwińska.
Materials (Basel) 2021 Jun 21;14(12):3427. doi: 10.3390/ma14123427.
https://pubmed.ncbi.nlm.nih.gov/34205573/
Abstract
Photobiomodulation (PBM), also called low-level laser treatment (LLLT), has been considered a promising tool in periodontal treatment due to its anti-inflammatory and wound healing properties. However, photobiomodulation's effectiveness depends on a combination of parameters, such as energy density, the duration and frequency of the irradiation sessions, and wavelength, which has been shown to play a key role in laser-tissue interaction. The objective of the study was to compare the in vitro effects of two different wavelengths-635 nm and 808 nm-on the human primary gingival fibroblasts in terms of viability, oxidative stress, inflammation markers, and specific gene expression during the four treatment sessions at power and energy density widely used in dental practice (100 mW, 4 J/cm2). PBM with both 635 and 808 nm at 4 J/cm2 increased the cell number, modulated extracellular oxidative stress and inflammation markers and decreased the susceptibility of human primary gingival fibroblasts to apoptosis through the downregulation of apoptotic-related genes (P53, CASP9, BAX). Moreover, modulation of mesenchymal markers expression (CD90, CD105) can reflect the possible changes in the differentiation status of irradiated fibroblasts. The most pronounced results were observed following the third irradiation session. They should be considered for the possible optimization of existing low-level laser irradiation protocols used in periodontal therapies.
Keywords:
LLLT; PBM; human gingival fibroblasts; in vitro; low-level laser treatment; photobiomodulation.
Nobuhiro Yamauchi, Emika Minagawa, Kazutaka Imai, Kenjiro Kobuchi, Runbo Li, Yoichiro Taguchi, Makoto Umeda
Life (Basel) 2022 May 15;12(5):736. doi: 10.3390/life12050736.
https://pubmed.ncbi.nlm.nih.gov/35629403/
Abstract
Periodontitis is an inflammatory lesion in the periodontal tissue. The behavior of human periodontal ligament stem cells (hPDLSCs), which play an important role in periodontal tissue regeneration, is restricted by the influence of inflammatory mediators. Photobiomodulation therapy exerts anti-inflammatory effects. The purpose of this study was to investigate the effects of light-emitting diode (LED) irradiation on the inflammatory responses of hPDLSCs. The light source was a red LED (peak wavelength: 650 nm), and the total absolute irradiance was 400 mW/cm2. The inflammatory response in hPDLSCs is induced by tumor necrosis factor (TNF)-α. Adenosine triphosphate (ATP) levels and pro-inflammatory cytokine (interleukin [IL]-6 and IL-8) production were measured 24 h after LED irradiation, and the effects of potassium cyanide (KCN) were investigated. LED irradiation at 6 J/cm2 significantly increased the ATP levels and reduced TNF-α-induced IL-6 and IL-8 production. Furthermore, the inhibitory effect of LED irradiation on the production of pro-inflammatory cytokines was inhibited by KCN treatment. The results of this study showed that high-intensity red LED irradiation suppressed the TNF-α-stimulated pro-inflammatory cytokine production in hPDLSCs by promoting ATP synthesis. These results suggest that high-intensity red LED is a useful tool for periodontal tissue regeneration in chronically inflamed tissues.
Keywords:
adenosine triphosphate; periodontal ligament stem cells; photobiomodulation therapy.
Ammaar H Abidi, Rebecca E Mayall, Cozy X Ruan, Keng Liang Ou, Christopher J Walinski
Arch Oral Biol 2021 Jan:121:104968. doi: 10.1016/j.archoralbio.2020.104968.
https://pubmed.ncbi.nlm.nih.gov/35629403/
Abstract
Objective:
Oral biofilms burden host responses by induction of inflammatory mediators, exacerbating periodontal inflammation. Photobiomodulation Therapy (PBMT) has been shown to decrease levels of pro-inflammatory cytokines and chemokines. However, optimal wavelengths and exposure doses have not been established. This study investigated the effects of PBMT on human periodontal ligament fibroblasts (hPDLFs) stimulated with inflammatory mediators (LPS, TNF-α, and IL-1β).
Methods:
Cytotoxic effects of laser wavelengths 660 nm and 810 nm were assessed by measuring their effects on cellular dehydrogenase activity. The study was expanded to include 980 nm, 660 nm + 810 nm, and 810 nm + 980 nm. P.g. LPS, TNF-α, and/or IL-1β were added one hour before irradiation, then exposed to laser irradiation to determine the most appropriate stimulus. The levels of INF-γ, IL-6, IL-8, IL-17A/F, and MCP-1 production in stimulated hPDLFs were measured and analyzed.
Results:
P.g. LPS was a poor stimulus for hPDLFs, while TNF-α and IL-1β significantly elevated the analytes. The 660 nm laser treatment induced pro-inflammatory cytokines when stimulated, while 810 nm exhibited significant suppression. IL-1β was the stimulus of choice and the 810 nm wavelength alone exhibited anti-inflammatory effects for all analytes except IL-8, while the 810 nm in combination with 660 nm and/or 980 nm exhibited effects similar to 810 nm alone.
Conclusions:
The downregulation of inflammatory mediators by the combination or individual treatment with 810 nm wavelength shows promise for the management of periodontal inflammation. PBMT may lead to the development of a novel approach in the management of periodontal disease.
Keywords:
Chemokine; Cytokine; Low level laser therapy; Periodontal inflammation; Photobiomodulation.
Yujin Ohsugi, Hiromi Niim, Tsuyoshi Shimohira, Masahiro Hatasa, Sayaka Katagiri, Akira Aoki, Takanori Iwata
Int J Mol Sci 2020 Nov 26;21(23):9002. doi: 10.3390/ijms21239002
https://pubmed.ncbi.nlm.nih.gov/33256246/
Abstract
Periodontal disease is a chronic inflammatory disease caused by periodontal bacteria. Recently, periodontal phototherapy, treatment using various types of lasers, has attracted attention. Photobiomodulation, the biological effect of low-power laser irradiation, has been widely studied. Although many types of lasers are applied in periodontal phototherapy, molecular biological effects of laser irradiation on cells in periodontal tissues are unclear. Here, we have summarized the molecular biological effects of diode, Nd:YAG, Er:YAG, Er,Cr:YSGG, and CO2 lasers irradiation on cells in periodontal tissues. Photobiomodulation by laser irradiation enhanced cell proliferation and calcification in osteoblasts with altering gene expression. Positive effects were observed in fibroblasts on the proliferation, migration, and secretion of chemokines/cytokines. Laser irradiation suppressed gene expression related to inflammation in osteoblasts, fibroblasts, human periodontal ligament cells (hPDLCs), and endothelial cells. Furthermore, recent studies have revealed that laser irradiation affects cell differentiation in hPDLCs and stem cells. Additionally, some studies have also investigated the effects of laser irradiation on endothelial cells, cementoblasts, epithelial cells, osteoclasts, and osteocytes. The appropriate irradiation power was different for each laser apparatus and targeted cells. Thus, through this review, we tried to shed light on basic research that would ultimately lead to clinical application of periodontal phototherapy in the future.
Keywords:
cell proliferation; gene expression; lasers; periodontal tissue; photobiomodulation.
Mahima Rastogi, Khageswar Sahu, Shovan Kumar Majumder
Lasers Med Sci 2025 Feb 12;40(1):83. doi: 10.1007/s10103-025-04339-5
https://pubmed.ncbi.nlm.nih.gov/39934459/
Abstract
Stem cells (SC) based therapies are proving to be the mainstay of regenerative medicine. Despite the significant potential, direct grafting or implantation of SCs for regenerative therapy encounters various translational roadblocks such as paucity of implantable cells, decreased potency, cell death post-implantation, cell damage caused by the pre-existing inflammation and immune rejection. Hence, an emerging avenue is cell-free approach; use of SC secretome. Although priming approaches based on pharmacological molecules/chemicals, cytokines and growth factors are being explored to elicit enhanced secretome production, the potential concerns include the need for continuous replenishment and potential chemical contamination during secretome isolation. To alleviate these concerns, various non-pharmacological approaches for invigorating SCs are also being investigated and among these, use of photobiomodulation (PBM) has garnered considerable interest. Notwithstanding the positive outcomes, standardized parameters are yet to be established for reproducible results. Moreover, the mechanisms of PBM based SC stimulation and secretome production are poorly elucidated and significant knowledge gaps exist on influence of cell type, culture conditions on PBM. This review aims to provide insight into the current status of this emerging field emphasizing on novel avenues and potential challenges for clinical translation. We also summarize the studies on PBM based proliferation, differentiation and secretome production according to SC cell type and culture conditions. Further, as a fixed PBM based protocol for SC proliferation, differentiation and secretome is lacking, the knowledge on functional targets and pathways in PBM based SC stimulation needs upgradation. Consequently, putative mechanisms for PBM based SC secretome have been proposed.
Keywords:
Photobiomodulation; Regenerative medicine; Secretome; Stem cells.
Younghoon Shin, Woosub Song, In Hee Shin, Dae Won Ji, Kyoung Jae Min, Sun-Hee Ahn
Biomed Opt Express 2025 Feb 6;16(3):922-934. doi: 10.1364/BOE.553671.
https://pmc.ncbi.nlm.nih.gov/articles/PMC11919360/
Abstract
This paper investigates the advanced capabilities of light-emitting diodes (LEDs) in oral care devices, emphasizing their versatility in wavelength control and ability to reach complex areas within the oral cavity. While LEDs enable precise dosage control and adjustable penetration depths, existing oral care devices are often limited to single-wavelength designs, primarily targeting anterior teeth whitening or lateral surfaces, thereby failing to provide comprehensive oral coverage. To address these limitations, this study introduces a novel LED-based oral care device integrating three distinct wavelengths: blue for antibacterial effects, green for anti-inflammatory effects, and red for preventive and therapeutic applications. Using computed tomography (CT) data, upper and lower dental arch trajectories were acquired to design a flexible printed circuit board (FPCB) that conforms to the natural curvature of the dental arch. Strategically placed LEDs on the FPCB ensure uniform light distribution and optimized irradiance across the entire oral cavity. This research systematically determines the optimal design parameters and operating conditions necessary for achieving appropriate irradiance density, including LED placement, operating time, and power control through driving current and duty cycles. The findings demonstrate a practical and effective approach to overcoming the current limitations of LED oral care devices, significantly enhancing their performance and applicability in dental phototherapy.
Aimin Cui, Yuezhang Sun, Kangjian Zhu, Haonan Zou, Ziqi Yue, Yi Ding, Xiuxiu Song, Jiao Chen, Ning Ji, Qi Wang
Lasers Med Sci 2024 Jan 18;39(1):36. doi: 10.1007/s10103-024-03987-3.
https://pubmed.ncbi.nlm.nih.gov/38236306/
Abstract
Diabetes mellitus (DM) is a chronic age-related disease that was recently found as a secondary aging pattern regulated by the senescence associated secretory phenotype (SASP). The purpose of this study is to detect the potential efficacy and the specific mechanisms of low-level laser therapy (LLLT) healing of age-related inflammation (known as inflammaging) in diabetic periodontitis. Diabetic periodontitis (DP) mice were established by intraperitoneal streptozotocin (STZ) injection and oral P. gingivalis inoculation. Low-level laser irradiation (810 nm, 0.1 W, 398 mW/cm2, 4 J/cm2, 10 s) was applied locally around the periodontal lesions every 3 days for 2 consecutive weeks. Micro-CT and hematoxylin-eosin (HE) stain was analyzed for periodontal soft tissue and alveolar bone. Western blots, immunohistochemistry, and immunofluorescence staining were used to evaluate the protein expression changes on SASP and GLUT1/mTOR pathway. The expression of aging-related factors and SASP including tumor necrosis factor-α, interleukin (IL)-1β, and IL-6 were reduced in periodontal tissue of diabetic mice. The inhibitory effect of LLLT on GLUT1/mTOR pathway was observed by detecting the related factors mTOR, p-mTOR, GLUT1, and PKM2. COX, an intracytoplasmic photoreceptor, is a key component of the anti-inflammatory effects of LLLT. After LLLT treatment a significant increase in COX was observed in macrophages in the periodontal lesion. Our findings suggest that LLLT may regulate chronic low-grade inflammation by modulating the GLUT1/mTOR senescence-related pathway, thereby offering a potential treatment for diabetic periodontal diseases.
Keywords:
Cytochrome c oxidase; Hyperglycemia; Inflammatory senescence; Periodontal disease; Photobiomodulation therapy; Senescence-associated secretory phenotype.
Liying Wang, Chen Liu, Yang Song, Fan Wu
Lasers Med Sci 2022 Dec;37(9):3591-3599. doi: 10.1007/s10103-022-03638-5.
https://pubmed.ncbi.nlm.nih.gov/36104643/
Abstract
Periodontitis often causes damage to the periodontal tissue and affects the function of human periodontal ligament stem cells (hPDLSCs). Low-level laser therapy (LLLT) has been used for periodontal treatment and can upregulate the proliferation and osteogenesis of hPDLSCs. The purpose of this study was to investigate the effects of LLLT on the proliferation, osteogenic differentiation, inflammatory reaction, and oxidative stress of hPDLSCs in an inflammatory environment (pPDLSCs). We designed one control group and three testing groups (treated with Nd:YAG laser at 4, 8, and 16 J/cm2) of hPDLSCs from periodontitis patients who were diagnosed with stable phase periodontitis. Cell proliferation was measured by colony-forming unit fibroblast (CFU-F) assays and 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyltetrazolium bromide (MTT) assays. The osteogenic capacity of the cells was determined by alkaline phosphatase (ALP) staining, ALP activity assays, Alizarin Red S staining and the mRNA transcript levels of runt-related transcription factor 2 (Runx2), ALP, and osteocalcin (OCN). The effects of LLLT on the secretion of tumor necrosis factor-α (TNF-α) and interleukin (IL)-1β by PDLSCs were measured by enzyme-linked immunosorbent assay (ELISA). We also evaluated the oxidative stress of hPDLSCs and pPDLSCs by measuring the reactive oxygen species (ROS) level, malondialdehyde (MDA) level, and superoxide dismutase (SOD) activity after treatment with LLLT at 4, 8, and 16 J/cm2. Our results demonstrated that LLLT could modulate the osteogenic potential of pPDLSCs at 8 J/cm2. Inflammatory stimuli induced excess ROS release, and LLLT at 4-8 J/cm2 promoted oxidative stress levels in hPDLSCs but decreased the expression of inflammatory cytokines and ROS levels in pPDLSCs. Moreover, LLLT at 16 J/cm2 could significantly suppress proliferation and osteogenic differentiation and promote inflammatory cytokines and ROS levels in pPDLSCs. In conclusion, LLLT could regulate proliferation, osteogenesis, inflammatory reaction, and oxidative stress of human periodontal ligament stem cells under inflammatory conditions.
Keywords:
Human periodontal ligament stem cells; Inflammation; Low-level laser therapy; Osteogenesis; Proliferation; Reactive oxygen species.
Selma Dervisbegovic, Susanne Bloch, Vera Maierhofer, Christian Behm, Xiaohui Rausch-Fan, Andreas Moritz, Christina Schäffer , Oleh Andrukhov.
Int J Mol Sci 2025 Jul 16;26(14):6803. doi: 10.3390/ijms26146803.
Abstract
Low-level laser therapy (LLLT) is gaining attention as an effective adjunct to non-surgical periodontal treatment. This study evaluates the potential of LLLT to reduce bacterial load in a clinically relevant in vitro subgingival biofilm model and its impact on the inflammatory response. A subgingival biofilm model consisting of seven bacterial species was established. Primary human gingival fibroblasts (GFs) and periodontal ligament cells (PDLs) were cultured. Both biofilms and host cells were treated with the DenLase Diode Laser (980 nm) under various clinically relevant settings. The composition and structure of the seven-species biofilms were evaluated using quantitative PCR and fluorescence microscopy, respectively. The inflammatory response in host cells was analyzed by measuring the gene and protein expression levels of various inflammatory mediators. Laser treatment at power outputs ranging from 0.3 to 2 W had no significant effect on biofilm composition or architecture. LLLT, particularly at higher power settings, reduced the viability in both GFs and PDLs up to 70%. Gene expression levels of inflammatory mediators were only minimally influenced by laser treatment. However, LLLT significantly decreased the secretion of all examined cytokines. These findings suggest that LLLT with a 980 nm diode laser, under clinically relevant conditions, exerts anti-inflammatory rather than antimicrobial effects.
Keywords:
gingival fibroblasts; inflammatory mediators; low level laser therapy; periodontal ligament cells; seven-species biofilms.
Sung-Bin Lee, Hyunjin Lee, Jun-Beom Park.
Sci Rep 2025 Jul 2;15(1):23326. doi: 10.1038/s41598-025-05889-y.
https://pubmed.ncbi.nlm.nih.gov/40604048/
Abstract
Modulation of cellular activity by low-level laser therapy (LLLT) has been widely studied, particularly in regenerative medicine. This study examined the effects of LLLT on the viability, osteogenic differentiation, and mineralization of gingiva-derived mesenchymal stem cells (GMSCs) in two-(2D) and three-dimensional (3D) cultures. GMSCs were treated with LLLT at 980 nm and 808 nm using different energy densities and irradiation frequencies. Cell viability was assessed using a colorimetric assay and live/dead staining. Osteogenic differentiation was assessed through alkaline phosphatase activity and real-time polymerase chain reaction (RT-PCR) analysis of RUNX2 and COL1A1 mRNA expression. Mineralization was analyzed using Alizarin Red S staining. LLLT enhanced cell viability without inducing significant morphological changes, with more pronounced effects in 3D spheroids than in 2D monolayers. Osteogenic differentiation and mineralization were significantly increased in LLLT-treated groups. Gene expression analyses confirmed the upregulation of key osteogenic markers, reinforcing LLLT's role in promoting osteogenesis. These findings indicate that LLLT is a non-invasive and effective approach to promoting osteogenic differentiation and mineralization. Notably, its effects were more evident in 3D culture systems, which better mimic in vivo conditions. This study highlights the therapeutic potential of LLLT in tissue engineering and regenerative medicine, emphasizing its applications in bone regeneration.
Yuan Liu, Juan Yang, Bing Jiang, Genzi Zheng, Yao Wang.
Lasers Med Sci 2023 Oct 18;38(1):240. doi: 10.1007/s10103-023-03880-5.
https://pubmed.ncbi.nlm.nih.gov/37851127/
Abstract
There are few studies on the effect of low-energy LED red light on periodontal tissue regeneration in an inflammatory environment. In this study, Cell Counting Kit-8 (CCK-8) assays were used to detect the effects of TNF-α at three different concentrations (0, 10 ng/ml, and 20 ng/ml) on the proliferation of human periodontal ligament stem cells (hPDLSCs), and 10 ng/ml was selected as the subsequent experimental stimulation concentration. CCK-8 assays were used to detect the effect of LED red light with energy density of 1 J/ cm2, 3 J/ cm2, and 5 J/cm2 on the proliferation of hPDLSCs. The promotion effect of energy density of 5 J/cm2 on the proliferation of hPDLSCS was the most obvious (p < 0.05). Set CON group, ODM group, ODM + 10 ng/ml TNF-α group, and ODM + 10 ng/ml TNF-α + 5 J/ cm2 LED red light group. Alkaline phosphatase staining and activity detection, alizarin red staining and calcium nodules quantitative detection of osteoblast differentiation products, real-time fluorescence quantitative PCR detection of osteoblast gene expression (Runx2, Col-I, OPN, OCN). The results showed that ODM showed the strongest osteoblast ability, followed by ODM + 10 ng/ml TNF-α + 5 J/ cm2 LED red light group. The osteoblast ability of ODM + 10 ng/ml TNF-α was decreased, but was not found in CON group. Western blot was used to detect the expression of NF-κB pathway protein and osteoblast-related proteins (Runx2, Col-I, OPN, OCN) after addition of PDTC inhibitor. The results showed that the expression of p-IκBα was increased and the expression of IκBα was decreased (p < 0.05). The expression of osteoblast protein increased after the addition of inhibitor (p < 0.05). Therefore, in an inflammatory environment constructed by 10 ng/ml TNF-α, 5 J/cm2 LED red light can upregulate the proliferation and osteogenesis of hPDLSCs by inhibiting NF-κB signaling pathway.
Keywords: LED red light; NF-κB; Osteogenic differentiation; Proliferation; TNF-α; hPDLSCs.
Qiaoru Zou, Shengxiang Zhang, Chunwen Jiang, Shan Xiao, Yue Wang, Bing Wen.
BMC Oral Health 2024 Dec 5;24(1):1477. doi: 10.1186/s12903-024-05258-7.
https://pubmed.ncbi.nlm.nih.gov/39639276/
Abstract
Background:
To explore the effect of low-level laser therapy (LLLT) on the healing of soft tissue around the implant after flap implantation and explore the possible mechanism.
Methods:
A total of 58 patients who underwent implant surgery were enrolled, with a total of 70 implants. They were randomly divided into the LLLT group and the control group. The LLLT group underwent LLLT with Nd:YAG (Fotona, 1064 nm) immediately after surgery and on the 2nd and 3rd day in the surgical area, while the control group did not receive any intervention. Pain assessment was performed in the first 3 days after surgery. The weight of peri-implant crevicular fluid (PICF), modified sulcus bleeding index (mSBI), gingival index (GI), and the expression levels of tumor necrosis factor-α (TNF-α), and vascular endothelial growth factor (VEGF) on the 7th and 14th days after surgery were evaluated.
Results:
On the first 3 days after surgery, the pain score of the LLLT group was significantly lower than that of the control group. On the 7th and 14th day after surgery, the PICF volume, mSBI, GI, and TNF-α levels of the LLLT group were lower than those of the control group. The VEGF levels in the LLLT group were significantly higher than that in the control group.
Conclusions:
LLLT can promote the healing of the soft tissue after implantation, effectively relieve postoperative pain, improve clinical indicators, reduce TNF-α, and increase the expression level of VEGF, which is worthy of clinical application.
Trial registration:
Retrospectively Registered Trials ChiCTR2400087562 (07/30/2024).
Keywords:
Low-level laser therapy; Pain; Soft tissue healing; TNF-α; VEGF.
Esraa S Mahmoud, Amal M Abd El-Baky, Osama M Gouda, Hussein G Hussein.
Head Face Med 2025 Apr 23;21(1):29. doi: 10.1186/s13005-025-00502-z.
https://pubmed.ncbi.nlm.nih.gov/40269949/
Abstract
Background:
Low-intensity pulsed ultrasound (LIPUS) and low-level laser therapy (LLLT) are proposed adjunctive therapies to enhance healing after dental implant surgery. However, direct comparisons of their effects on peri-implant marginal bone preservation and soft tissue healing remain limited. This randomized controlled trial aimed to compare the effectiveness of LIPUS and LLLT on peri-implant marginal bone preservation, soft tissue healing, pain levels, and oral health-related quality of life following dental implant placement.
Methods:
This single-blind, randomized controlled trial included 63 patients undergoing maxillary or mandibular implant placement, randomly allocated to LIPUS (n = 21), LLLT (n = 21), or control (n = 21) groups. LIPUS was applied twice weekly for 4 weeks, while LLLT was administered in 4 sessions over 2 weeks post-implant. Marginal bone loss (MBL) and OHRQoL (OHIP-14) were assessed at baseline, 6, and 12 weeks. Soft tissue healing (Landry Healing Index) and pain (VAS) were evaluated at baseline, 7-, 14-, 21-, and 30-days post-implant.
Results:
LIPUS significantly reduced marginal bone loss at 6 weeks and 3 months post-implant compared to LLLT and control groups (p < 0.05). LLLT demonstrated superior soft tissue healing at 7-, 14-, 21-, and 30-days post-implant (p < 0.05). Both interventions significantly decreased pain intensity and improved OHRQoL at various time points compared to the control group (p < 0.05).
Conclusions: LIPUS and LLLT significantly enhance peri-implant marginal bone preservation, soft tissue healing, pain management, and OHRQoL in dental implant patients compared to standard care. LIPUS was more effective for peri-implant marginal bone preservation, while LLLT excelled in soft tissue healing.
Trial registration:
This study was registered at ClinicalTrials.gov (NCT05938868) on July 11, 2023.
Keywords:
Dental implants; Low-intensity pulsed ultrasound; Low-level laser therapy; Oral health-related quality of life; Osseointegration; Pain; Soft tissue healing.
Alain Chaple Gil, Leonardo Díaz, Alfredo Von Marttens, Claudio Sotomayor Javier Basualdo, Víctor Beltrán, Gilbert Jorquera, Rodrigo Caviedes, Eduardo Fernández.
Photodiagnosis Photodyn Ther 2025 Jun:53:104594. doi: 10.1016/j.pdpdt.2025.104594.
https://pubmed.ncbi.nlm.nih.gov/40288479/
Abstract
Background:
Low-Level Laser Therapy (LLLT) has gained attention as a non-invasive adjunctive treatment in oral surgery due to its potential to enhance tissue healing, reduce postoperative pain, and modulate inflammation.
Objective:
This systematic review aimed to evaluate the clinical efficacy of LLLT in improving postoperative wound healing, alleviating pain, and controlling inflammation in patients undergoing oral surgical procedures. It also aimed to identify optimal laser parameters for future clinical application.
Methods:
A systematic review of randomized controlled trials (RCTs) was performed following PRISMA 2020 guidelines and the PROPS framework. Literature searches were conducted in five electronic databases and grey literature sources up to March 2025. Studies included adult patients undergoing oral surgery, treated with LLLT, and reporting outcomes related to healing, pain, inflammation, or complications.
Results:
Eighteen RCTs comprising 771 patients were included. LLLT consistently demonstrated superior outcomes compared to placebo, sham, or standard care. All studies reported enhanced wound healing, particularly with wavelengths between 660 and 810 nm and energy densities of 3-12 J/cm². Postoperative pain was reduced by 30-55 % within the first 3-7 days post-surgery, according to Visual Analog Scale scores. Studies that assessed inflammatory biomarkers showed reductions in TNF-α and IL-6, and increased VEGF expression. Additionally, several studies indicated a lower incidence of postoperative complications such as infection and delayed healing in LLLT-treated groups.
Conclusion:
LLLT appears to be a safe and effective adjunct in oral surgery. Further high-quality studies with standardized protocols and longer follow-up periods are needed to support its broader clinical implementation.
Keywords: Inflammation; Low Level Light therapy; Low-level laser therapy; Oral surgery; PRISMA; PROPS Framework; Pain; Systematic review; Wound healing.