Non-Invasive Physical Plasma Reduces the Inflammatory Response in Microbially Prestimulated Human Gingival Fibroblasts.

Non-invasive physical plasma (NIPP), an electrically conductive gas, is playing an increasingly important role in medicine due to its antimicrobial and regenerative properties. However, NIPP is not yet well established in dentistry, although it has promising potential, especially for periodontological applications. The aim of the present study was to investigate the effect of NIPP on a commercially available human gingival fibroblast (HGF) cell line and primary HGFs in the presence of periodontitis-associated bacteria. First, primary HGFs from eight patients were characterised by immunofluorescence, and cell numbers were examined by an automatic cell counter over 5 days. Then, HGFs that were preincubated with Fusobacterium nucleatum (F.n.) were treated with NIPP. Afterwards, the IL-6 and IL-8 levels in the cell supernatants were determined by ELISA. In HGFs, F.n. caused a significant increase in IL-6 and IL-8, and this F.n.-induced upregulation of both cytokines was counteracted by NIPP, suggesting a beneficial effect of physical plasma on periodontal cells in a microbial environment. The application of NIPP in periodontal therapy could therefore represent a novel and promising strategy and deserves further investigation

Modulation of the Tumor-Associated Immuno-Environment by Non-Invasive Physical Plasma

Over the past 15 years, investigating the efficacy of non-invasive physical plasma (NIPP) in cancer treatment as a safe oxidative stress inducer has become an active area of research. So far, most studies focused on the NIPP-induced apoptotic death of tumor cells. However, whether NIPP plays a role in the anti-tumor immune responses need to be deciphered in detail. In this review, we summarized the current knowledge of the potential effects of NIPP on immune cells, tumor–immune interactions, and the immunosuppressive tumor microenvironment. In general, relying on their inherent anti-oxidative defense systems, immune cells show a more resistant character than cancer cells in the NIPP-induced apoptosis, which is an important reason why NIPP is considered promising in cancer management. Moreover, NIPP treatment induces immunogenic cell death of cancer cells, leading to maturation of dendritic cells and activation of cytotoxic CD8+ T cells to further eliminate the cancer cells. Some studies also suggest that NIPP treatment may promote anti-tumor immune responses via other mechanisms such as inhibiting tumor angiogenesis and the desmoplasia of tumor stroma. Though more evidence is required, we expect a bright future for applying NIPP in clinical cancer management

Plasma–liquid interactions: a review and roadmap

Plasma–liquid interactions represent a growing interdisciplinary area of research involving plasma science, fluid dynamics, heat and mass transfer, photolysis, multiphase chemistry and aerosol science. This review provides an assessment of the state-of-the-art of this multidisciplinary area and identifies the key research challenges. The developments in diagnostics, modeling and further extensions of cross section and reaction rate databases that are necessary to address these challenges are discussed. The review focusses on non-equilibrium plasmas

Non-Invasive Physical Plasma Treatment after Tooth Extraction in a Patient on Antiresorptive Medication Promotes Tissue Regeneration

Postoperative tissue regeneration can be negatively affected by bisphosphonate administration, especially in patients with oncologic diseases. A serious complication of bisphosphonate therapy is the medication-related osteonecrosis of the jaw (MRONJ), which can be observed mainly after dental surgery. MRONJ is a progressive destruction of the bone that requires patients to stay in hospital for extended periods of time. For this reason, primary wound closure is particularly important in surgical procedures. In the case of wound dehiscence, there is a very high risk for MRONJ. In recent years, non-invasive physical plasma (NIPP) has become known for improving wound healing on the one hand, but also for its promising efficacy in cancer therapy on the other hand. We report on a 63-year-old patient with a history of multiple myeloma and receiving zoledronate, who developed wound dehiscence after tooth extraction. NIPP treatment resulted in complete epithelialization of the entire wound dehiscence. In conclusion, the use of NIPP in patients receiving antiresorptive drugs seems to support tissue regeneration and thus could be an important tool for the prevention of MRONJ

Effect of Cold Atmospheric Plasma (CAP) on Osteogenic Differentiation Potential of Human Osteoblasts

Bone regeneration after oral and maxillofacial surgery is a long-term process, which involves various mechanisms. Recently, cold atmospheric plasma (CAP) has become known to accelerate wound healing and have an antimicrobial effect. Since the use of CAP in dentistry is not yet established, the aim of the present study was to investigate the effect of CAP on human calvaria osteoblasts (HCO). HCO were treated with CAP for different durations of time and distances to the cells. Cell proliferation was determined by MTT assay and cell toxicity by LDH assay. Additionally, RT-qPCR was used to investigate effects on osteogenic markers, such as alkaline phosphatase (ALP), bone morphogenic protein (BMP)2, collagen (COL)1A1, osteonectin (SPARC), osteoprotegerin (OPG), osterix (OSX), receptor activator of NF-κB (RANK), RANK Ligand (RANKL), and Runt-related transcription factor (RUNX)2. There were small differences in cell proliferation and LDH release regarding treatment duration and distance to the cells. However, an increase in the expression of RANK and RANKL was observed at longer treatment times. Additionally, CAP caused a significant increase in mRNA expression of genes relevant to osteogenesis. In conclusion, CAP has a stimulating effect on osteoblasts and may thus represent a potential therapeutic approach in the regeneration of hard tissue defects

Influence of cold atmospheric plasma on dental implant materials — an in vitro analysis

Background and objectives!#!Alterations in the microenvironment of implant surfaces could influence the cellular crosstalk and adhesion patterns of dental implant materials. Cold plasma has been described to have an influence on cells, tissues, and biomaterials. Hence, the mechanisms of osseointegration may be altered by non-thermal plasma treatment depending on different chemical compositions and surface coatings of the biomaterial. The aim of the present study is to investigate the influence of cold atmospheric plasma (CAP) treatment on implant surfaces and its biological and physicochemical side effects.!##!Materials and methods!#!Dental implant discs from titanium and zirconia with different surface modifications were treated with CAP at various durations. Cell behavior and adhesion patterns of human gingival fibroblast (HGF-1) and osteoblast-like cells (MG-63) were examined using scanning electron microscopy and fluorescence microscopy. Surface chemical characterization was analyzed using energy-dispersive X-ray spectroscopy (EDS). Quantitative analysis of cell adhesion, proliferation, and extracellular matrix formation was conducted including real-time PCR.!##!Results!#!CAP did not affect the elemental composition of different dental implant materials. Additionally, markers for cell proliferation, extracellular matrix formation, and cell adhesion were differently regulated depending on the application time of CAP treatment in MG-63 cells and gingival fibroblasts.!##!Conclusions!#!CAP application is beneficial for dental implant materials to allow for faster proliferation and adhesion of cells from the surrounding tissue on both titanium and zirconia implant surfaces with different surface properties.!##!Clinical relevance!#!The healing capacity provided through CAP treatment could enhance osseointegration of dental implants and has the potential to serve as an effective treatment option in periimplantitis therapy

Non-Invasive Physical Plasma Generated by a Medical Argon Plasma Device Induces the Expression of Regenerative Factors in Human Gingival Keratinocytes, Fibroblasts, and Tissue Biopsies

After oral surgery, intraoral wound healing and tissue regeneration is an important factor for the success of the entire therapy. In recent years, non-invasive medical plasma (NIPP) has been shown to accelerate wound healing, which would be particularly beneficial for patients with wound healing disorders. Since the application of NIPP in dentistry has not been sufficiently understood, the aim of the present study was to investigate the effect of a medical argon plasma device on gingival cells. Human gingival fibroblasts, keratinocytes, and tissue biopsies were treated with NIPP for different durations. Crucial markers associated with wound healing were examined at the mRNA and protein levels by real-time PCR, ELISA and immunohistochemistry. NIPP treatment led to an increase in Ki67 and MMP1 at mRNA and protein levels. NIPP application lasting longer than 60 s resulted in an increase in apoptotic genes at mRNA level and superficial damage to the epithelium in the tissue biopsies. Overall, our experimental setup demonstrated that NIPP application times of 30 s were most suitable for the treatment of gingival cells and tissue biopsies. Our study provides evidence for potential use of NIPP in dentistry, which would be a promising treatment option for oral surgery

Modulation of the Tumor-Associated Immuno-Environment by Non-Invasive Physical Plasma

Over the past 15 years, investigating the efficacy of non-invasive physical plasma (NIPP) in cancer treatment as a safe oxidative stress inducer has become an active area of research. So far, most studies focused on the NIPP-induced apoptotic death of tumor cells. However, whether NIPP plays a role in the anti-tumor immune responses need to be deciphered in detail. In this review, we summarized the current knowledge of the potential effects of NIPP on immune cells, tumor–immune interactions, and the immunosuppressive tumor microenvironment. In general, relying on their inherent anti-oxidative defense systems, immune cells show a more resistant character than cancer cells in the NIPP-induced apoptosis, which is an important reason why NIPP is considered promising in cancer management. Moreover, NIPP treatment induces immunogenic cell death of cancer cells, leading to maturation of dendritic cells and activation of cytotoxic CD8+ T cells to further eliminate the cancer cells. Some studies also suggest that NIPP treatment may promote anti-tumor immune responses via other mechanisms such as inhibiting tumor angiogenesis and the desmoplasia of tumor stroma. Though more evidence is required, we expect a bright future for applying NIPP in clinical cancer management