Clinical outcome is influenced by many factors and can be enhanced to improve the results utilizing the body and its natural factors. Diet and managing the patient’s health play a key role in how their systems react to clinical treatment that affects the soft and hard tissues of the body. But there are ways to enhance the bodies healing and regeneration by influencing cells within the soft (gingiva, muscle, skin) and hard tissue (bone). Photobiomodulation (PBM) has been increasingly reported to provide positive effects to various areas of the body when applied to that tissue without any side effects in a non-invasive manner.
Photobiomodulation is defined as the utilization of non-ionizing electromagnetic energy to trigger cellular photochemical changes within structures that are receptive to those photons. In particular, mitochondria are receptive to this process, where at the cellular level, near infrared light (NIR) and visible red energy is absorbed by the cell’s mitochondria. Those mitochondria produce energy called “ATP” (adenosine triphosphate) for cellular use. PBM may result in the increased production of mild oxidants (ROS), nitric oxide (NO), (ATP), and cyclic adenosine monophosphate (cAMP) which initiate cell proliferation and induce the signal cascade effect. Khorsandi K, Hosseinzadeh R, Abrahamse H, Fekrazad R. Biological Responses of Stem Cells to Photobiomodulation Therapy. Curr Stem Cell Res Ther. 2020;15(5):400-413. doi: 10.2174/1574888X15666200204123722. PMID: 32013851. The process additionally creates ROS, which leads to cellular repair and healing. This process unclogs the chain that has been clogged by NO which is then released back into the system. Huang YY, Sharma SK, Carroll J, Hamblin MR. Biphasic dose response in low level light therapy - an update. Dose Response. 2011;9(4):602-18. doi: 10.2203/dose-response.11-009.Hamblin. Epub 2011 Sep 2. PMID: 22461763; PMCID: PMC3315174. Nitric oxide is a molecule that our body produces to help its cells communicate with each other with communication occurring by transmission of signals throughout the body. Hamblin MR. Mechanisms and Mitochondrial Redox Signaling in Photobiomodulation. Photochem Photobiol. 2018 Mar;94(2):199-212. doi: 10.1111/php.12864. Epub 2018 Jan 19. PMID: 29164625; PMCID: PMC5844808. Additionally, nitric oxide helps to dilate the blood vessels and improve blood circulation. Those factors can lead to increased expression of genes related to protein synthesis, cell migration and proliferation, anti-inflammatory signaling, anti-apoptotic proteins, antioxidant enzymes. Stem cells and progenitor cells appear to be particularly susceptible to LLLT. de Freitas LF, Hamblin MR. Proposed Mechanisms of Photobiomodulation or Low-Level Light Therapy. IEEE J Sel Top Quantum Electron. 2016 May-Jun;22(3):7000417. doi: 10.1109/JSTQE.2016.2561201. PMID: 28070154; PMCID: PMC5215870. The key to the entire process is a mitochondrial enzyme called cytochrome oxidase c, a chromophore, which accepts photonic energy of specific wavelengths when functioning below par. As the mitochondria absorb those wavelengths of light energy, producing more ATP energy transportation in the cells is boosted leading to increased cell proliferation. That cell proliferation via photobiomodulation increases the body’s natural healing process.
Wavelengths and their effects on tissue:
Light is measured in nanometers (nm) and expressed as a wavelength. Natural light (white light) is a combination of various wavelengths. But specific wavelengths have different penetration and affects on the body when exposed to it and fall into color specific ranges. (Figure 1) As the wavelength increases deeper penetration is observed and different tissue is affected, with near-infrared (NIR) having the deepest penetration and ultraviolet (UV) the least. Sunburns and tans are caused by UV (100 to 380 nm) light and thus the superficial skin is affected with little to no affect on deeper tissues and in some individuals may lead to skin cancer. Guerra KC, Zafar N, Crane JS. Skin Cancer Prevention. 2021 Aug 14. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan–. PMID: 30137812.
Blue (450-470 nm) light has been surrounded by controversy relating to the premise that the margin between ‘safe’ blue light and potentially damaging (UV) light has not been well defined. Clinical results have reported benefits on inflammatory lesions on subjects with acne. This wavelength of light can induce beneficial and adverse effects, depending on the dose and on the spectrum width of the exposure. Magali Bonnans, Linda Fouque, Michele Pelletier, Rachel Chabert, Sandrine Pinacolo, Laura Restellini, Karine Cucumel.: Blue light: Friend or foe ?, Journal of Photochemistry and Photobiology B: Biology, Volume 212, 2020, 112026, ISSN 1011-1344. Reports have demonstrated that blue light has a positive effect to partially prevent skin flap necrosis and when combined with red light can enhance the survival of random skin flap by improving angiogenesis. Hamushan M, Cai W, Lou T, Cheng P, Zhang Y, Tan M, Chai Y, Zhang F, Lineaweaver WC, Han P, Ju J. Postconditioning With Red-Blue Light Therapy Improves Survival of Random Skin Flaps in a Rat Model. Ann Plast Surg. 2021 May 1;86(5):582-587. doi: 10.1097/SAP.0000000000002501. PMID: 32756256. So, utilization of PBM with blue light can augment the affects of red light aiding in healing of incisions, cuts and other alterations to the surface tissue (skin and gingiva). Blue light was reported to stimulate keratinocyte differentiation aiding in restoring the skin barrier function. Castellano-Pellicena, I.; Uzunbajakava, N.E.; Mignon, C.; Raafs, B.; Botchkarev, V.A.; Thornton, M.J. Does blue light restore human epidermal barrier function via activation of opsin during cutaneous wound healing? Lasers Surg. Med. 2018.
Green (510-540 nm) light is absorbed into the skin where it helps to lighten hyper-pigmentation spots revealing a brighter complexion. Pigmented areas on the skin (brown spots or freckles),have many causes and can occur in all skin types. Hyperpigmentation is characterized by darker areas of the skin or gingiva related to overproduction of melanin. The green wavelengths target melanocytes, the melanin-producing cells located in the deeper layer of the skin’s epidermis, inhibiting production of excess melanin, thereby preventing it from travelling to the skin’s surface, and breaking up melanin clusters to lessen existing discoloration. As a result, dark spots slightly fade while blending with the surrounding tissue tone. Cios A, Cieplak M, Szyma?ski ?, Lewicka A, Cierniak S, Stankiewicz W, Mendrycka M, Lewicki S. Effect of Different Wavelengths of Laser Irradiation on the Skin Cells. Int J Mol Sci. 2021 Feb 28;22(5):2437. doi: 10.3390/ijms22052437. PMID: 33670977; PMCID: PMC7957604. Additionally, the light aids in increasing cell growth enabling wound repair of the skin and gingiva. The effect also has anti-inflammatory properties that soothe the surface of the skin. Green light has shown a therapeutic effect on basal cell carcinoma. JalalKamali, M.; Nematollahi-Mahani, S.N.; Shojaei, M.; Shamsoddini, A.; Arabpour, N. Effect of light polarization on the efficiency of photodynamic therapy of basal cell carcinomas: An In Vitro cellular study. Lasers Med. Sci. 2018, 33, 305–313. Additionally, it accelerates wound healing and has positive effects on treatment of acne and other skin irritation issues. Fushimi, T.; Inui, S.; Nakajima, T.; Ogasawara, M.; Hosokawa, K.; Itami, S. Green light emitting diodes accelerate wound healing: Characterization of the effect and its molecular basis In Vitro and In Vivo. Wound Repair. Regen. 2012, 20, 226–235. Reported that green light was more potent stimulating proliferation and migration of endothelial cells than clinically well-established red light therapy. Wang Y, Huang YY, Wang Y, Lyu P, Hamblin MR. Photobiomodulation (blue and green light) encourages osteoblastic-differentiation of human adipose-derived stem cells: role of intracellular calcium and light-gated ion channels. Sci Rep. 2016 Sep 21;6:33719. doi: 10.1038/srep33719. PMID: 27650508; PMCID: PMC5030629. Further they reported that blue and green wavelengths produced a stimulating effect with increased osteoblast differentiation. With the shallower depth of penetration of those two wavelength ranges compared to red and NIR, this works well intraorally where the osseous structure is below gingival tissue with no interspersed muscle that may prevent contact with the boney area. Ideally, it may be considered to utilize red/NIR light for expansion and proliferation of stem cells and use blue/green light for differentiation into progenitor cells with a combination of those for the best overall effects.
Yellow (580-600 nm) light has slightly deeper penetration then blue and green light reaching the dermal area with has a healing, anti-inflammatory and analgesic effects with regenerative affect on the skin. This wavelength is effective with skin conditions involving redness, swelling, and other effects related to pigmentation. Opel DR, Hagstrom E, Pace AK et al (2015) Light-emitting diodes: a brief review and clinical experience. J Clin Aesthetic Dermatol 8:36–44 Ablon G. Phototherapy with Light Emitting Diodes: Treating a Broad Range of Medical and Aesthetic Conditions in Dermatology. J Clin Aesthet Dermatol. 2018 Feb;11(2):21-27. Epub 2018 Feb 1. PMID: 29552272; PMCID: PMC5843358. In vitro and in vivo studies have demonstrated the ability of yellow LED therapy to trigger skin collagen synthesis and to reduce MMP expression Lee SY, Park KH, Choi JW et al (2007) A prospective, randomized, placebocontrolled, double-blinded, and split-face clinical study on LED phototherapy for skin rejuvenation: clinical, profilometric, histologic, ultrastructural, and biochemical evaluations and comparison of three different treatment settings. J Photochem Photobiol B 27:51–67 Rejuvenation effects have been reported followed by treatment with yellow. Weiss RA, McDaniel DH, Geronemus RG, Weiss MA, Beasley KL, Munavalli GM, Bellew SG. Clinical experience with light-emitting diode (LED) photomodulation. Dermatol Surg. 2005 Sep;31(9 Pt 2):1199-205. doi: 10.1111/j.1524-4725.2005.31926. PMID: 16176771.
Acne, whether in adolescents or adults can be challenging to eliminate with traditional methods and create esthetic issues that and LLLT treatment utilizing light in the yellow range has demonstrated to be effective in treatment of acne. Fabbrocini G, Annunziata MC, D'Arco V, De Vita V, Lodi G, Mauriello MC, Pastore F, Monfrecola G. Acne scars: pathogenesis,and treatment. Dermatol Res Pract. 2010;2010:893080. doi: 10.1155/2010/893080. Epub 2010 Oct 14. PMID: 20981308; PMCID: PMC2958495. Dermal scars are also an esthetic issue especially when present on the face and may not be coverable by makeup in female patients and an issue for male patients too. Scar reduction has been reported using this wavelength of light and has esthetic implications in those patients who are concerned with the presence of scars related to either prior surgical treatment or previous trauma. Sobanko JF, Alster TS. Laser treatment for scars and wounds. G Ital Dermatol Venereol. 2009 Oct;144(5):583-93. PMID: 19834436. This also applies to treatment of keloid. Bouzari N, Davis SC, Nouri K. Laser treatment of keloids and hypertrophic scars. Int J Dermatol. 2007 Jan;46(1):80-8. doi: 10.1111/j.1365-4632.2007.03104.x. PMID: 17214728. Additionally, it has been reported yellow wavelengths are an effective treatment for thinning hair and baldness related to androgenetic alopecia and alopecia areata. Tzung TY, Chen CY, Tzung TY, Kao FJ, Chen WC. Infrared irradiation as an adjuvant therapy in recalcitrant alopecia areata. Dermatol Surg. 2009 Apr;35(4):721-3. doi: 10.1111/j.1524-4725.2009.01120.x. Erratum in: Dermatol Surg. 2009 Jun;35(6):1019. PMID: 19400891.
Red (610-775 nm) light has been documented to provide healing to the irradiated tissues with deep penetration into the skin and underlying structures, where the cells can absorb and use it. Mitochondria in the cells absorb those light particles, which then produce ATP, which is the energy source for the cells. The extra energy creates a cellular response allowing the cells to better respond to damage and rejuvenate themselves. Irradiation with red light generated a much lower amount of ROS when compared to the nonirradiated cells. George, S.; Hamblin, M.R.; Abrahamse, H. Effect of red light and near infrared laser on the generation of reactive oxygen species in primary dermal fibroblasts. J. Photochem. Photobiol. B Biol. 2018, 188, 60–68. Another study suggested that the more stressed fibroblasts cells are the better they respond to photobiomodulation with red wavelengths. Ayuk, S.M.; Houreld, N.N.; Abrahamse, H. Collagen production in diabetic wounded fibroblasts in response to low-intensity laser irradiation at 660 Nm. Diabetes Technol. 2012, 14, 1110–1117. Those red wavelengths increased cell proliferation and viability while aiding in wound healing via accelerated cell migration rate. Fortuna, T.; Gonzalez, A.C.; Sá, M.F.; de Andrade, Z.A.; Reis, S.R.A.; Medrado, A.R.A.P. Effect of 670 Nm laser photobiomodulation on vascular density and fibroplasia in late stages of tissue repair. Int. Wound, J. 2018, 15, 274–282. It modulates dermal fibroblasts to increase gene expression responsible for enhancing the adaptive response to redox, inflammatory balance, and, additionally, those genes that play a major part in DNA repair processes. Red laser irradiation enhanced the synthesis of procollagen, the expression of collagen, and the release of basic fibroblast growth factor.
Near infrared (NIR) (800-835 nm) light has two main types of chromophores which are intracellular water and cytochrome c oxidase that results in an increase in intracellular temperature. Thus, cell or tissue biological response to NIR irradiation is in part caused by a generated thermal effect. NIR, at the cellular level, activates cytochrome c oxidase (COX) the primary mitochondrial photoacceptor of light. This activation results in various cellular responses, including increased mitochondrial ATP production. Houreld NN, Masha RT, Abrahamse H. Low-intensity laser irradiation at 660 nm stimulates cytochrome c oxidase in stressed fibroblast cells. Lasers Surg Med. 2012 Jul;44(5):429-34. doi: 10.1002/lsm.22027. Epub 2012 Apr 5. PMID: 22488690. NIR light therapy has demonstrated increased mitochondrial metabolism, Dias FJ, Issa JP, Vicentini FT, Fonseca MJ, Leão JC, Siéssere S, Regalo SC, Iyomasa MM. Effects of low-level laser therapy on the oxidative metabolism and matrix proteins in the rat masseter muscle. Photomed Laser Surg. 2011 Oct;29(10):677-84. doi: 10.1089/pho.2010.2879. Epub 2011 Jul 11. PMID: 21745137. with skin and gingival angiogenesis stimulation, Kohale BR, Agrawal AA, Raut CP. Effect of low-level laser therapy on wound healing and patients' response after scalpel gingivectomy: A randomized clinical split-mouth study. J Indian Soc Periodontol. 2018 Sep-Oct;22(5):419-426. doi: 10.4103/jisp.jisp_239_18. PMID: 30210191; PMCID: PMC6128133. improvement in bone quality with stimulation of osteoblastic cell activity, Liu N, Lu W, Qu X, Zhu C. LLLI promotes BMSC proliferation through circRNA_0001052/miR-124-3p. Lasers Med Sci. 2021 Apr 21. doi: 10.1007/s10103-021-03322-0. Epub ahead of print. PMID: 33884524. regeneration of muscle tissues. Borzabadi-Farahani A. Effect of low-level laser irradiation on proliferation of human dental mesenchymal stem cells; a systemic review. J Photochem Photobiol B. 2016 Sep;162:577-582. doi: 10.1016/j.jphotobiol.2016.07.022. Epub 2016 Jul 25. PMID: 27475781. Those increased ATP levels accelerates bone remodeling. This relates to elevation of metabolic activity, with accompanying angiogenesis, increasing the blood supply necessary for remodeling. Impellizzeri A, Horodynski M, Fusco R, Palaia G, Polimeni A, Romeo U, Barbato E, Galluccio G. Photobiomodulation Therapy on Orthodontic Movement: Analysis of Preliminary Studies with a New Protocol. Int J Environ Res Public Health. 2020 May 19;17(10):3547. doi: 10.3390/ijerph17103547. PMID: 32438716; PMCID: PMC7277382. Additionally, wound healing is improved so incisions created during periodontal and oral surgery or traumatic injuries heal at a faster rate. Silveira PC, Silva LA, Fraga DB, Freitas TP, Streck EL, Pinho R. Evaluation of mitochondrial respiratory chain activity in muscle healing by low-level laser therapy. J Photochem Photobiol B. 2009 May 4;95(2):89-92. doi: 10.1016/j.jphotobiol.2009.01.004. Epub 2009 Jan 21. PMID: 19232497. Pain is a common occurrence following surgery as well as during orthodontic treatment as aligners are changed or the fixed appliance is adjusted. NIR has demonstrated a reduction in pain and should be a consideration in those patients undergoing extractions, implant placement and periodontal procedures. Ezzati K, Fekrazad R, Raoufi Z. The Effects of Photobiomodulation Therapy on Post-Surgical Pain. J Lasers Med Sci. 2019 Spring;10(2):79-85. doi: 10.15171/jlms.2019.13. Epub 2019 Feb 25. PMID: 31360374; PMCID: PMC6499566. Ezzati K, Laakso EL, Salari A, Hasannejad A, Fekrazad R, Aris A. The Beneficial Effects of High-Intensity Laser Therapy and Co-Interventions on Musculoskeletal Pain Management: A Systematic Review. J Lasers Med Sci. 2020 Winter;11(1):81-90. doi: 10.15171/jlms.2020.14. Epub 2020 Jan 18. PMID: 32099632; PMCID: PMC7008744. Additionally, reduction in post-operative swelling has also been reported and with a reduction in said swelling pain is also reduced. Hosseinpour S, Tunér J, Fekrazad R. Photobiomodulation in Oral Surgery: A Review. Photobiomodul Photomed Laser Surg. 2019 Dec;37(12):814-825. doi: 10.1089/photob.2019.4712. Epub 2019 Nov 21. PMID: 31750798.
Both red and NIR have demonstrated an ability to accelerate orthodontic tooth movement by promoting alveolar bone remodeling on the compression side of the teeth. PBM using energy in the red range accelerated bone remodeling to a greater extent than NIR at an early stage. But, over time use of the two wavelengths together provided better results than using only a single wavelength. Yang H, Liu J, Yang K. Comparative Study of 660 and 830?nm Photobiomodulation in Promoting Orthodontic Tooth Movement. Photobiomodul Photomed Laser Surg. 2019 Jun;37(6):349-355. doi: 10.1089/photob.2018.4615. PMID: 31188090.
Figure : Depth of penetration for the various wavelengths