Abstract
Pressure ulcers (PU) are wounds located mainly on bone surfaces where the tissue under pressure suffers ischemia leading to cellular lesion and necrosis , its causes and the healing process depend on several factors. The aim of this study was evaluating the gene expression of inflammatory/reparative factors: IL6, TNF, VEGF, and TGF, which take part in the tissue healing process under effects of low-level laser therapy (LLLT). In order to perform lesion area analysis, PUs were photographed and computer analyzed. Biochemical analysis was performed sa.mpling ulcer border tissue obtained through biopsy before and after laser therapy and quantitative real-time PCR (qRT-PCR) analysis. The study comprised eight individuals, mean age sixty-two years old, and sacroiliac and calcaneous PU, classified as degree III and IV according to the National Pressure Ulcer Advisory Panel (NPUAP). PUs were irradiated with low-level laser (InGaAIP, 100 mW, 660 nm), energy density 2 J/cm2, once a day, with intervals of 24 h, totaling 12 applications. The lesion area analysis revealed averaged improvement of the granulation tissue size up to 50% from pre- to post-treatment. qRT-PCR analysis revealed that IL6 values were not significantly different before and after treatment, TNF gene expression was reduced, and VEFG and TGF-β gene expression increased after treatment. After LLLT, wounds presented improvement in gross appearance, with increase in factors VEFG and TGF-β, and reduction of TNF; despite our promising results, they have to be analyzed carefully as this study did not have a control group.
Similar content being viewed by others
References
Calil JA, Ferreira LM, Neto MS, Castilho HD, Garcia EB (2001) Clinical application of the VY posterior thigh fasciocutaneous flap. Rev Assoc Méd Bras 47(4):311–319
Edsberg LE, Black JM, Goldberg M, McNichol L, Moore L, Sieggreen M (2016) Revised national pressure ulcer advisory panel pressure injury staging system: revised pressure injury staging system. J Wound, Ostomy Continence Nurs 43(6):585
Singer AJ, Clark RA (1999) Cutaneous wound healing. N Engl J Med 341(10):738–746
Robson MC (1997) The role of growth factors in the healing of chronic wounds. Wound Repair Regen 5(1):12–17
Trengove NJ, Bielefeldt-Ohmann H, Stacey MC (2000) Mitogenic activity and cytokine levels in non-healing and healing chronic leg ulcers. Wound Repair Regen 8(1):13–25
de Braekt MM, van Alphen FA, Kuijpers-Jagtman AM, Maltha JC (1991) Effect of low level laser therapy on wound healing after palatal surgery in beagle dogs. Lasers Surg Med 11(5):462–470
Mester E, Mester AF, Mester A (1985) The biomedical effects of laser application. Lasers Surg Med 5(1):31–39
Yu W, Naim JO, Lanzafame RJ (1997) Effects of photostimulation on wound healing in diabetic mice. Lasers Surg Med 20(1):56–63
Maiya GA, Kumar P, Rao L (2005) Effect of low intensity helium-neon (He-Ne) laser irradiation on diabetic wound healing dynamics. Photomed Laser Ther 23(2):187–190
Posten W, Wrone DA, Dover JS, Arndt KA, Silapunt S, Alam M (2005) Low-level laser therapy for wound healing: mechanism and efficacy. Dermatol Surg 31(3):334–340
Viegas VN, Abreu MER, Viezzer C, Machado DC, Filho MSA, Silva DN, Pagnoncelli RM (2007) Effect of low-level laser therapy on inflammatory reactions during wound healing: comparison with meloxicam. Photomed Laser Surg 25(6):467–473
Machado RS, Viana S, and Sbruzzi G (2017) Low-level laser therapy in the treatment of pressure ulcers: systematic review. Lasers Med Sci 32(4):937–944
Taradaj J, Halski T, Kucharzewski M, Urbanek T, Halska U, Kucio C (2013) Effect of laser irradiation at different wavelengths (940, 808, and 658 nm) on pressure ulcer healing: results from a clinical study. Evid Based Complement Alternat Med 2013:960240
Nussbaum EL, Biemann I, Mustard B (1994) Comparison of ultrasound/ultraviolet-C and laser for treatment of pressure ulcers in patients with spinal cord injury. Phys Ther 74(9):812–823
Taly AB, Nair KPS, Murali T, John A (2004) Efficacy of multiwavelength light therapy in the treatment of pressure ulcers in subjects with disorders of the spinal cord: a randomized double-blind controlled trial. Arch Phys Med Rehabil 85(10):1657–1661
Lucas C, Van Gemert MJC, De Haan RJ (2003) Efficacy of low-level laser therapy in the management of stage III decubitus ulcers: a prospective, observer-blinded multicentre randomised clinical trial. Lasers Med Sci 182:72–77
Huang YY, Chen ACH, Carroll JD, Hamblin MR (2009) Biphasic dose response in low level light therapy. Dose-Response 7(4):358–383 dose-response
Saygun I, Nizam N, Ural AU, Serdar MA, Avcu F, Tözüm TF (2012) Low-level laser irradiation affects the release of basic fibroblast growth factor (bFGF), insulin-like growth factor-I (IGF-I), and receptor of IGF-I (IGFBP3) from osteoblasts. Photomed Laser Surg 30(3):149–154
Dang Y, Liu B, Liu L, Ye X, Bi X, Zhang Y, Gu J (2011) The 800-nm diode laser irradiation induces skin collagen synthesis by stimulating TGF-β/Smad signaling pathway. Lasers Med Sci 26(6):837–843
Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2− ΔΔCT method. Methods 25(4):402–408
Wang CJ, Ko JY, Kuo YR, Yang YJ (2011) Molecular changes in diabetic foot ulcers. Diabetes Res Clin Pract 94(1):105–110
Rocha J, Miranda M, Andrade M (2006) Pressure ulcer management—evidence-based interventions. Acta Med Port 19(1):29–38
Costa MP, Sturtz G, Costa FPPD, Ferreira MC, Barros Filho TE (2005) Epidemiological profile and treatment of pressure ulcers: experience with 77 cases. Acta Ortop Bras 13(3):124–133
Lopes LDF (2011) Utilização do laser de 660 nm, 17 J/cm2 em úlceras por pressão− Um relato de caso. Rev Neurocienc 19(4):668–674
Santoianni P, Monfrecola G, Martellotta D, Ayala F (1984) Inadequate effect of helium-neon laser on venous leg ulcers. Photo-Dermatology 1(5):245–249
Malm M, Lundeberg T (1991) Effect of low power gallium arsenide laser on healing of venous ulcers. Scand J Plast Reconstr Surg Hand Surg 25(3):249–251
Lundeberg T, Malm M (1991) Low-power HeNe laser treatment of venous leg ulcers. Ann Plast Surg 27(6):537–539
Gupta AK, Filonenko N, Salansky N, Sauder DN (1998) The use of low energy photon therapy (LEPT) in venous leg ulcers: a double-blind, placebo-controlled study. Dermatol Surg 24(12):1383–1386
Kirtschig G, Brink A, Scheper R, Jaspars E (2005) Low level laser: does it influence wound healing in venous leg ulcers? A randomized, placebo-controlled, double-blind study. J Clin Microbiol 40:779–787
Sobanko JF, Alster TS (2008) Efficacy of low-level laser therapy for chronic cutaneous ulceration in humans: a review and discussion. Dermatol Surg 34(8):991–1000
Lucas C, Van Gemert MJC, De Haan RJ (2003) Efficacy of low-level laser therapy in the management of stage III decubitus ulcers: a prospective, observer-blinded multicentre randomised clinical trial. Lasers Med Sci 18(2):72–77
Lanzafame RJ, Stadler I, Kurtz AF, Connelly R, Brondon P, Olson D (2007) Reciprocity of exposure time and irradiance on energy density during photoradiation on wound healing in a murine pressure ulcer model. Lasers Surg Med 39(6):534–542
Kaviani A, Djavid GE, Ataie-Fashtami L, Fateh M, Ghodsi M, Salami M, Zand N, Kashef N, Larijani B (2011) A randomized clinical trial on the effect of low-level laser therapy on chronic diabetic foot wound healing: a preliminary report. Photomed Laser Surg 29(2):109–114
Minatel DG, Frade MAC, França SC, Enwemeka CS (2009) Phototherapy promotes healing of chronic diabetic leg ulcers that failed to respond to other therapies. Lasers Surg Med 41(6):433–441
Saied GM, Kamel RM, Labib AM, Said MT, Mohamed AZ (2011) The diabetic foot and leg: combined He-Ne and infrared low-intensity lasers improve skin blood perfusion and prevent potential complications. A prospective study on 30 Egyptian patients. Lasers Med Sci 26(5):627–632
Carvalho PDTCD, Silva ISD, Reis FAD, Perreira DM, Aydos RD (2010) Influence of ingaalp laser (660nm) on the healing of skin wounds in diabetic rats. Acta Cir Bras 25(1):71–79
Dixit S, Maiya A, Umakanth S, Borkar S (2013) Photobiomodulation of surgical wound dehiscence in a diabetic individual by low-level laser therapy following median sternotomy. Indian J Palliat Care 19(1):71
Dixit S, Agrawal PR, Sharma DK, Singh RP (2014) Closure of chronic non healing ankle ulcer with low level laser therapy in a patient presenting with thalassemia intermedia: case report. Indian J Plast Surg 47(3):432
Kipshidze N, Nikolaychik V, Keelan MH, Shankar LR, Khanna A, Kornowski R et al (2001) Low-power helium: neon laser irradiation enhances production of vascular endothelial growth factor and promotes growth of endothelial cells in vitro. Lasers Surg Med 28(4):355–364
Sekhejane PR, Houreld NN, Abrahamse H (2011) Irradiation at 636 nm positively affects diabetic wounded and hypoxic cells in vitro. Photomed Laser Surg 29(8):521–530
Houreld NN, Sekhejane PR, Abrahamse H (2010) Irradiation at 830 nm stimulates nitric oxide production and inhibits pro-inflammatory cytokines in diabetic wounded fibroblast cells. Lasers Surg Med 42(6):494–502
Pallotta RC, Bjordal JM, Frigo L, Junior ECPL, Teixeira S, Marcos RL et al (2012) Infrared (810-nm) low-level laser therapy on rat experimental knee inflammation. Lasers Med Sci 27(1):71–78
Carvalho MHCD, Colaço AL, Fortes ZB (2006) Cytokines, endothelial dysfunction, and insulin resistance. Arq Bras Endocrinol Metabol 50(2):304–312
Tonnesen MG, Feng X, & Clark RA (2000) Angiogenesis in wound healing. In Journal of Investigative Dermatology Symposium Proceedings Vol. 5, No. 1. Nature Publishing Group, pp. 40–46
Riedel K, Riedel F, Goessler UR, Germann G, Sauerbier M (2007) TGF-β antisense therapy increases angiogenic potential in human keratinocytes in vitro∗. Arch Med Res 38(1):45–51
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
The Research Ethics Committee of Ponta Grossa University (COEP-UEPG) approved this study (protocol number 07897/11, decision 48/2011) that was performed in accordance with the ethical standards suggested by the Guidelines and Norms Regulating Research Involving Human Beings according to the Resolution of the National Health Council, n. 466 of 2012. Informed consent was obtained from all individual participants included in the study.
Conflict of interest
Professor Ernesto Cesar Pinto Leal-Junior receives research support from Multi Radiance Medical (Solon, OH-USA), a laser device manufacturer. Multi Radiance Medical had no role in the planning of this study, and the laser device used was not theirs. They had no influence on study design, data collection and analysis, decision to publish, or preparation of the manuscript. The remaining authors declare that they have no conflict of interests.
Rights and permissions
About this article
Cite this article
Ruh, A.C., Frigo, L., Cavalcanti, M.F.X.B. et al. Laser photobiomodulation in pressure ulcer healing of human diabetic patients: gene expression analysis of inflammatory biochemical markers. Lasers Med Sci 33, 165–171 (2018). https://doi.org/10.1007/s10103-017-2384-6
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10103-017-2384-6