Evaluation of bradykinin, VEGF, and EGF biomarkers in gingival crevicular fluid and comparison of PhotoBioModulation with conventional techniques in periodontitis: a split-mouth randomized clinical trial
Periodontal disease is a chronic progressive inflammatory process leading to damage of tooth-supporting tissues. This comparative study assessed the effect of PhotoBioModulation (PBM) versus conventional therapy, and investigated biomarkers involved in the healing process. The test group comprised twenty systemically-healthy non-smoking subjects with chronic periodontitis with the presence of two matched contro-lateral premolar sites (probing depth > 5 mm); twenty subjects without chronic periodontitis (CP) served as control group. Patients were treated at baseline, either with scaling and root planing (SRP group) or with a procedure entailing SRP supported by PBM (PBM group). The laser used was a diode laser operating at 645 nm wavelength, 10 J/cm2, and 0.5 W/cm2 with a 600 μm fiber optic. Crevicular fluid levels of bradykinin (BK), vascular endothelial growth factor (VEGF), and epidermal growth factor z (EGF) were determined at both sites. Crevicular fluid specimens from both groups were analyzed with the ELISA TEST. Clinical differences in analyzed outcomes were observed in favor of PBM treatment. Taking average values as 100%, the reduction in BK concentration was 47.68% with SRP and 68.43% with PBM on day 3; the VEGF concentration decreased by 35.73% with SRP and 48.59% with PBM on day 7; the EGF concentration increased by 55.58% with SRP and by 58.11% with PBM on day 21.
Clinical parameters improved significantly in both groups (pooled mean values of probing depth decreased from 5.6 to 4.5 mm; gingival index from 1.92 to 1.1; and bleeding on probing from 49.67 to 23.23) but did not vary significantly between the PBM and the SRP group. The results confirmed that PBM have beneficial effects in the early phases of the healing process playing a role in modulation of BK, EGF, and VEGF in gingival crevicular fluid levels; both groups had significant clinical improvement over control but there was no significant difference between them, only a trend for PBM group. The overall results of the study suggest a potential benefit of PBM in conjunction with SRP in treating chronic periodontitis.
Periodontology Low-level laser therapy Wound healing Dentistry Effect of Lasers in Tissue Lasers in Dentistry Lasers Diode PhotoBioModulation
This is a preview of subscription content, log in to check access.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
The study was approved by the Local Ethics Committee, Milan, no. PR246.
Written informed consent was obtained from all study participants in accordance with the Helsinki Declaration (1975; revised, 2002).
Heitz-Mayfield LJA, Lang NP (2013) Surgical and nonsurgical periodontal therapy. Learned and unlearned concepts. Periodontol 2000(62):218–231CrossRefGoogle Scholar
Badersten A, Nileus R, Egelberg J (1981) Effect of nonsurgical periodontal therapy. I. Moderately advanced periodontitis. J Clin Periodontol 8:57–72CrossRefGoogle Scholar
Lindhe J, Nyman S (1985) Scaling and granulation tissue removal in periodontal therapy. J Clin Periodontol 12:374–388CrossRefGoogle Scholar
O’Leary TJ (1985) The impact of research on scaling and root planing. J Periodontol 57:69–75CrossRefGoogle Scholar
Kaldahl WB, Kalkwarf KL, Patil KD, Molvar MP, Dyer JK (1996) Long-term evaluation of periodontal therapy: I. Response to 4 therapeutic modalities. J Periodontol 67:93–102CrossRefGoogle Scholar
Ren C, McGrath C, Jin L, Zhang C, Yang Y (2017) The effectiveness of low-level laser therapy as an adjunct to non-surgical periodontal treatment: a meta-analysis. J Periodontal Res 52:8–20CrossRefGoogle Scholar
Vladimirov YA, Osipov AN, Klebanov GI (2004) Photobiological principles of therapeutic applications of laser radiation. Biochemistry (Mosc) 69:81–90CrossRefGoogle Scholar
Peplow PV, Chung T-Y, Baxter GD (2012) Photodynamic modulation of wound healing: a review of human and animal studies. Photomed Laser Surg 30:118–148CrossRefGoogle Scholar
Silveira PC, Streck EL, Pinho RA (2007) Evaluation of mitochondrial respiratory chain activity in wound healing by low-level laser therapy. J Photochem Photobiol B 86:279–282CrossRefGoogle Scholar
Alexandratou E, Yova D, Handris P, Kletsas D, Loukas S (2002) Human fibroblast alterations induced by low power laser irradiation at the single cell level using confocal microscopy. Photochem Photobiol Sci 1:547–552CrossRefGoogle Scholar
Hawkins D, Abrahamse H (2006) Effect of multiple exposures of low-level laser therapy on the cellular responses of wounded human skin fibroblasts. Photomed Laser Surg 24:705–714CrossRefGoogle Scholar
Pereira AN, Eduardo CP, Matson E, Marques MM (2002) Effect of low-power laser irradiation on cell growth and procollagen synthesis of cultured fibroblasts. Lasers Surg Med 31:263–267CrossRefGoogle Scholar
Kuffer DP (2016) Photobiomodulation in promoting wound healing: a review. Regen Med 11:107–122CrossRefGoogle Scholar
Lilge L, Tierney K, Nussbaum E (2000) Low-level laser therapy for wound healing: feasibility of wound dressing transillumination. J Clin Laser Med Surg 18:235–240CrossRefGoogle Scholar
Qadri T, Miranda L, Tuner J, Gustafsson A (2005) The short-term effects of low-level lasers as adjunct therapy in the treatment of periodontal inflammation. J Clin Periodontol 32:714–719CrossRefGoogle Scholar
Pesevska S, Nakova M, Gjorgoski I, Angelov N, Ivanovski K, Nares S, Andreana S (2012) Effect of laser on TNF-alpha expression in inflamed human gingival tissue. Lasers Med Sci 27:377–381CrossRefGoogle Scholar
Calderin S, Garcia-Nunez JA, Gomez C (2013) Short-term clinical and osteoimmunological effects of scaling and root planing complemented by simple or repeated laser phototherapy in chronic periodontitis. Lasers Med Sci 28:157–166CrossRefGoogle Scholar
Aykol G, Baser U, Maden I, Kazak Z, Onan U, Tanrikulu-Kucuk S, Ademoglu E, Issever H, Yalcin F (2011) The effect of low-level laser therapy as an adjunct to non-surgical periodontal treatment. J Periodontol 82:481–488CrossRefGoogle Scholar
Makhlouf M, Dahaba MM, Tunér J, Eissa SA, Harhash TA (2012) Effect of adjunctive low level laser therapy (PBM) on nonsurgical treatment of chronic periodontitis. Photomed Laser Surg 30:160–166CrossRefGoogle Scholar
Gündoğar H, Şenyurt SZ, Erciyas K, Yalım M, Üstün K (2016) The effect of low-level laser therapy on non-surgical periodontal treatment: a randomized controlled, single-blind, split-mouth clinical trial. Lasers Med Sci 31:1767–1773CrossRefGoogle Scholar
Pamuk F, Lütfioğlu M, Aydoğdu A, Koyuncuoglu CZ, Cifcibasi E, Badur OS (2017) The effect of low-level laser therapy as an adjunct to non-surgical periodontal treatment on gingival crevicular fluid levels of transforming growth factor-beta 1, tissue plasminogen activator and plasminogen activator inhibitor 1 in smoking and non-smoking chronic periodontitis patients: a split-mouth, randomized control study. J Periodontal Res 52:872–882CrossRefGoogle Scholar
Armitage GC (1999) Development of a classification system for periodontal diseases and conditions. Ann Periodontol 4:1–6CrossRefGoogle Scholar
Jiang J (2007) Linear and generalized linear mixed models and their applications. Springer-Verlag, New York, NYGoogle Scholar
Maurer M, Bader M, Bas M (2011) New topics in bradykinin research. Eur J Allergy clin Immunol 66:1397–1406CrossRefGoogle Scholar
Lerner UH, Jones IL, Gustafson GT (1987) Bradykinin, a new potential mediator of inflammatory-induced bone resorption. Studies on the effects on mouse calvarial bones and articular cartilage in vitro. Arthritis Rheum 30:530–540CrossRefGoogle Scholar
Hoeben A, Landuyt B, Ms H, Wildiers H, Van Oosterom AT, De Bruijn EA (2004) Vascular endothelial growth factor and angiogenesis. Pharmacol Rev 56:549–580CrossRefGoogle Scholar
Johnson KE, Wilgus TA (2014) Vascular endothelial growth factor and angiogenesis in the regulation of cutaneous wound repair. Advances in wound care 3:647–661CrossRefGoogle Scholar
Matsuda N, Yokoyama K, Takeshita S, Watanabe M (1998) Role of epidermal growth factor and its receptor in mechanical stress-induced differentiation of human periodontal ligament cells in vitro. Arch Oral Biol 43:987–997CrossRefGoogle Scholar
Nguyen NT, Byarlay MR, Reinhardt RA, Marx DB, Meinberg TA, Kaldahl WB (2015) Adjunctive non-surgical therapy of inflamed periodontal pockets during maintenance therapy using diode laser: a randomized clinical trial. J Periodontol 86:1133–1140CrossRefGoogle Scholar
Koçak E, Sağlam M, Kayış SA, Dündar N, Kebapçılar L, Loos BG, Hakkı SS (2016) Nonsurgical periodontal therapy with/without diode laser modulates metabolic control of type 2 diabetics with periodontitis: a randomized clinical trial. Lasers Med Sci 31:343–353CrossRefGoogle Scholar
Demirturk-Gocgun O, Baser U, Aykol-Sahin G, Dinccag N, Issever H, Yalcin F (2017) Role of low-level laser therapy as an adjunct to initial periodontal treatment in type 2 diabetic patients: a split-mouth, randomized, controlled clinical trial. Photomed Laser Surg 35:111–115CrossRefGoogle Scholar
Saglam M, Kantarci A, Dundar N, Hakki SS (2014) Clinical and biochemical effects of diode laser as an adjunct to nonsurgical treatment of chronic periodontitis: a randomized, controlled clinical trial. Lasers Med Sci 29:37–46CrossRefGoogle Scholar
Üstün K, Erciyas K, Sezer U, Şenyurt SZ, Gündoğar H, Üstün Ö, Öztuzcu S (2014) Clinical and biochemical effects of 810 nm diode laser as an adjunct to periodontal therapy: a randomized split-mouth clinical trial. Photomed. Laser Surg 32:61–66CrossRefGoogle Scholar
Matarese G, Ramaglia L, Cicciù M, Cordasco G, Isola G (2017) The effects of diode laser therapy as an adjunct to scaling and root planing in the treatment of aggressive periodontitis: a 1-year randomized controlled clinical trial. Photomed Laser Surg 35:702–709CrossRefGoogle Scholar