Combination treatment of dendrosomal nanocurcumin and low-level laser therapy develops proliferation and migration of mouse embryonic fibroblasts and alter TGF-β, VEGF, TNF-α and IL-6 expressions involved in wound healing process

Abstract

Introduction Pressure ulcer (PU) is known as the third most costly disorder usually caused by prolonged pressure and stagnation in various parts of the body. Although several therapeutic approaches are employing, obstacles in appropriate healing for skin lesions still exist which necessitates new practical alternative or adjunctive treatments. Low level laser therapy (LLLT) as one of the mentioned new strategies have gained attention. Besides, curcumin is an herbal medicine extracted from turmeric with anti-inflammatory and antioxidative properties with promising beneficial therapeutic effects in wound healing. Employing dendrosomal nanoparticles, we overcome the hydrophobicity of curcumin in the present study. We hypothesized that combination treatment of DNC+LLLT (450 nm) simultaneously may promote the wound healing process. Material and methods MTT assay, PI staining followed by flowcytometry, scratch assay and intracellular ROS measurement were used to investigate the effects caused by DNC and LLLT (450 nm) alone and in combination, on proliferation, cell cycle, migration and oxidative stress mouse embryonic fibroblast cells, respectively. The levels of growth factors and pro-inflammatory cytokines were evaluated by qRT-PCR and ELISA. Results Our results indicated that combination exposure with DNC and LLLT leads to increased proliferation and migration of MEFs as well as being more efficient in significantly upregulating growth factors (TGF-β, VEGF) and decline in inflammatory cytokines (TNF-α, IL-6). Moreover, findings of this research provide persuasive support for the notion that DNC could reduce the LLLT-induced enhancement in intracellular ROS in mouse embryonic fibroblasts. Conclusion Concurrent exposure to anti-oxidant concentrations of DNC and LLLT enriched S phase entry and therefor increased proliferation as well as migration on MEFs through regulating the expression levels growth factors and shortening the inflammatory phase by modulating of cytokines. It should be noted that DNC were able to reduce the laser-induced oxidative stress, during wound healing, representing an informative accompaniment with LLLT.

Keratinocyte and Fibroblast Wound Healing In Vitro Is Repressed by Non-Optimal Conditions but the Reparative Potential Can Be Improved by Water-Filtered Infrared A

“…Photobiomodulation has been shown to exert beneficial effects on wound healing [ 26 , 27 ], matrix deposition, and cell layers [ 29 , 30 , 90 , 91 ]. Significant induction of wound healing processes in acute and chronic wounds by wIRA treatment have been reported [ 26 , 27 ].…”

“…In accordance, scratch wound healing after IL-4/IL-13 stimulation was found to be decreased and could be re-initiated by wIRA treatment, which induced IL1A gene expression under anti-inflammatory conditions at one hour. Similarly, low-level laser therapy and cold atmospheric plasma were able to induce IL-8 secretion and increase wound healing in vitro [ 90 , 113 ].…”

Latest Innovations and Nanotechnologies with Curcumin as a Nature-Inspired Photosensitizer Applied in the Photodynamic Therapy of Cancer

“…This combined therapy (DNC + PDT) also highlighted the modulating role of nanocurcumin on the production and excessive accumulation of ROS generated by the action of the laser. In conclusion, the authors consider that additional in vivo studies are needed to confirm the hypothesis that the combined treatment of DNC simultaneously with PDT (450 nm) may favor the wound healing process [155].…”

“…Table 2 highlights some of the effects of PDT and curcumin nanoformulations in skin cancers, by significantly improving the bioavailability and stability of nanocurcumin, increasing cytotoxicity on malignant cells, but with low phototoxicity on normal keratinocytes, the apoptotic effects and molecular mechanisms by generating high levels of ROS, along with the significant depolarization of mitochondrial membranes, while other in vitro experiments on mice demonstrated significant cell migration in the denuded area and highlighted the modulatory role of nanocurcumin on excessive production and the accumulation of ROS generated by laser irradiation [145,146,155,159,160,162].…”

“…Total Energy (J) Applied Analyzed Parameters Conclusions [155] In vitro experiments on mouse embryonic fibroblasts (MEFs) cells Diode laser device with a wavelength of 450 nm and an output power of 75 mW. Dendrosomal Nano-Curcumin (DNC) Cells were irradiated for 224 s (for getting a dose of 17.9 J, with an energy density of 0.63 J/cm 2 ), and 337 s (for getting a dose of 26.9 J, with an energy density of 0.95 J/cm 2 ).…”