scholarly journals Synthetic Calcium Phosphate Ceramics as a Potential Treatment for Bisphosphonate-Related Osteonecrosis of the Jaw

Materials ◽  
2019 ◽  
Vol 12 (11) ◽  
pp. 1840 ◽  
Author(s):  
Siri Paulo ◽  
Mafalda Laranjo ◽  
Ana M. Abrantes ◽  
João Casalta-Lopes ◽  
Kathleen Santos ◽  
...  
Keyword(s):  
Calcium Phosphate ◽  
Protective Effect ◽  
Cell Viability ◽  
Metabolic Activity ◽  
Soft Tissues ◽  
Calcium Phosphates ◽  
Osteonecrosis Of The Jaw ◽  
Human Gingival Fibroblasts ◽  
Gingival Fibroblasts ◽  
Migration Ability

(1) Background: Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is one of the most often seen side effects in patients treated with nitrogen-containing bisphosphonates (BPs), a post-surgical non-healing wound condition. Since calcium phosphate (CP) compounds are able to adsorb zoledronate (ZOL) when used as a drug delivery vehicle, we aimed to verify if these ceramics might have a potential protective effect for soft tissues surrounding surgical osseous wounds. (2) Methods: The chemical reaction between ZOL and CP compounds was evaluated through ultraviolet-visible spectroscopy and elemental analysis. A primary culture of human gingival fibroblasts (HGF) was established as a model to evaluate the cytotoxicity of the association of ZOL (5–500 μM) and of ZOL/biphasic calcium phosphates (BCP). Metabolic activity, cell viability, types of cell death, the cell cycle through, and the migration ability of human gingival fibroblasts were evaluated. (3) Results: ZOL was adsorbed by biphasic calcium phosphate compounds in an aqueous solution. The HGF were sensitive to ZOL toxicity; nevertheless, ZOL/BCP showed a significant protective effect regarding metabolic activity, cell viability, and cell migration. (4) Conclusions: BCP interaction with ZOL reduces or abolishes its toxicity in HGF. This finding represents a potential solution for BRONJ in the case of patients undergoing therapy with ZOL.

scholarly journals Calcium Phosphate Ceramics Can Prevent Bisphosphonate-Related Osteonecrosis of the Jaw

Materials ◽  
2020 ◽  
Vol 13 (8) ◽  
pp. 1955
Author(s):  
Siri Paulo ◽  
Mafalda Laranjo ◽  
Anabela Paula ◽  
Ana Margarida Abrantes ◽  
João Martins ◽  
...  
Keyword(s):  
Nuclear Medicine ◽  
Calcium Phosphate ◽  
Tooth Extraction ◽  
Soft Tissues ◽  
Calcium Phosphates ◽  
Test Group ◽  
Osteonecrosis Of The Jaw ◽  
In Vivo Model ◽  
Calcium Phosphate Ceramics

Bisphosphonate-associated osteonecrosis of the jaw (BRONJ), a post-surgical non-healing wound condition, is one of the most common side effects in patients treated with nitrogen-containing bisphosphonates. Its physiopathology has been related with suppression of bone turnover, of soft tissue healing and infection. Biphasic calcium phosphates (BCP) are used as a drug delivery vehicle and as a bone substitute in surgical wounds. Due to their capacity to adsorb zoledronate, it was hypothesized these compounds might have a protective effect on the soft tissues in BRONJ wounds. To address this hypothesis, a reproducible in vivo model of BRONJ in Wistar rats was used. This model directly relates chronic bisphosphonate administration with the development of osteonecrosis of the jaw after tooth extraction. BCP granules were placed in the alveolus immediately after tooth extraction in the test group. The animals were evaluated through nuclear medicine, radiology, macroscopic observation, and histologic analysis. Encouragingly, calcium phosphate ceramics were able to limit zoledronate toxicity in vivo and to favor healing, which was evidenced by medical imaging (nuclear medicine and radiology), macroscopically, and through histology. The studied therapeutic option presented itself as a potential solution to prevent the development of maxillary osteonecrosis.

Effects of alendronate and pamidronate on apoptosis and cell proliferation in cultured primary human gingival fibroblasts

2015 ◽  
Vol 34 (11) ◽  
pp. 1073-1082 ◽  
Author(s):  
SS Soydan ◽  
K Araz ◽  
FV Senel ◽  
E Yurtcu ◽  
F Helvacioglu ◽  
...  
Keyword(s):  
Oral Mucosa ◽  
Mtt Assay ◽  
In Vitro Study ◽  
Osteonecrosis Of The Jaw ◽  
Human Gingival Fibroblasts ◽  
Gingival Tissue ◽  
Proliferation Index ◽  
Gingival Fibroblasts ◽  
Inhibition Of Proliferation

Data arising from the recent literature directed the researchers to study on the degree and extent of bisphosphonate toxicity on oral mucosa in further detail. The aim of this study is to determine the half maximal inhibitory concentration of pamidronate (PAM) and alendronate (ALN) on human gingival fibroblasts in vitro using 3-[4.5-thiazol-2-yl]-2.5-diphenyltetrazolium bromide (MTT) assay and to evaluate the effects of both agents on the proliferation and apoptotic indices. Cells used in the study were generated from human gingival specimens and divided into alendronate ( n = 240), PAM ( n = 240), and control groups ( n = 60). Based on the MTT assay results, 10−4, 10−5, 10−6, and 10−7 M concentrations of both drugs were administered and the effects were evaluated for 6, 12, 24, 48, or 72 h periods. An indirect immunofluorescence technique was used to evaluate apoptotic (anti-caspase 3) and proliferation (anti-Ki67) indices. Toxicity of both PAM and ALN was found to be the most potent at 10−4–10−5 M range. The apoptotic index of PAM group was found to be significantly higher than ALN group for all concentrations especially at 24 h incubation time ( p < 0.05). The decrease in the proliferation index was found similar in first 48 h for both drugs; however, after 72 h of incubation decrease in proliferation index in PAM group was found to be significantly higher ( p < 0.05). Micromolar concentrations of not only PAM but also ALN rapidly affect cells generated from human oral gingival tissue by inducing apoptosis together with inhibition of proliferation. Cytotoxic effects of both ALN and PAM on primary human gingival fibroblasts, which cause significant changes in apoptotic and proliferative indices as shown in this in vitro study, suggests that the defective epithelialization of oral mucosa is possibly a major factor on the onset of bisphosphonate-related osteonecrosis of the jaw cases.

scholarly journals In vitro Analysis of Cytotoxicity of Temporary Resilient Relining Materials

2016 ◽  
Vol 17 (6) ◽  
pp. 457-462 ◽  
Author(s):  
Isleine P Caldas ◽  
Miriam Z Scelza ◽  
Marco A Gallito ◽  
Gutemberg Alves ◽  
Licínio Silva
Keyword(s):  
Cell Viability ◽  
Human Fibroblasts ◽  
Primary Cultures ◽  
Polystyrene Latex ◽  
Test Method ◽  
Human Gingival Fibroblasts ◽  
Control Group ◽  
Gingival Fibroblasts ◽  
Significant Difference

ABSTRACT Aims The aim of this study is to evaluate the in vitro response of human gingival fibroblasts in primary cultures to two materials for temporary relining of dentures: Temporary Soft (TDV, Brazil) and Trusoft (Bosworth, USA) for 24 hours, 7 and 30 days by using a multi-parametric analysis. Materials and methods Each material sample (TDV, TS, Polystyrene, Latex) was prepared and incubated in a culture medium for 1, 7, and 30 days at 37°C. Human gingival fibroblasts were exposed to the extracts and cell viability was evaluated by a multi-parametric assay, which allowed sequential analysis of mitochondrial activity (XTT), membrane integrity [neutral red (NR)], and cell density [crystal violet dye exclusion (CVDE)] in the same cells. Analysis of variance (ANOVA) was used to test the interactions of the three sources of variation (material, test method, and time) with the proportions of viable cells for each relining material. Results Both evaluated materials (TDV and TS) had low cytotoxic effects during 1, 7, and 30 days after manipulation of the material, as assessed by all three methods used. A statistical difference was found when comparing the negative control group (latex fragments) with the other groups, which showed high toxicity and low percentage of cell viability in all tests used. There was no significant difference among other materials (p > 0.05). Conclusion Low cytotoxicity levels were detected by representatives of the major groups of temporary prosthetic relining materials, as evaluated by multiple cellular viability parameters in human fibroblasts. Clinical significance There are various soft materials on the market for relining prostheses; however, the effects of these materials on tissues need to be clarified to avoid problems for patients. How to cite this article Caldas IP, Scelza MZ, Gallito MA, Alves G, Silva L. In vitro Analysis of Cytotoxicity of Temporary Resilient Relining Materials. J Contemp Dent Pract 2016;17(6):457-462.

scholarly journals Cytotoxic and Genotoxic Effects of Composite Resins on Cultured Human Gingival Fibroblasts

Materials ◽  
2021 ◽  
Vol 14 (18) ◽  
pp. 5225
Author(s):  
Francesco De Angelis ◽  
Domitilla Mandatori ◽  
Valeria Schiavone ◽  
Francesco Paolo Melito ◽  
Silvia Valentinuzzi ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Metabolic Activity ◽  
Triethylene Glycol ◽  
Composite Resins ◽  
Dental Composite ◽  
Human Gingival Fibroblasts ◽  
Gingival Fibroblasts ◽  
Cell Metabolic Activity ◽  
Genotoxic Potential

The aim of the study was to evaluate the cytotoxic and genotoxic potential of five commercially available dental composite resins (CRs), investigating the effect of their quantifiable bisphenol-A-glycidyl-methacrylate (Bis-GMA) and/or triethylene glycol dimethacrylate (TEGDMA) release. Experiments were performed using the method of soaking extracts, which were derived from the immersion of the following CRs in the culture medium: Clearfil-Majesty-ES-2, GrandioSO, and Enamel-plus-HRi (Bis-GMA-based); Enamel-BioFunction and VenusDiamond (Bis-GMA-free). Human Gingival Fibroblasts (hGDFs) were employed as the cellular model to mimic in vitro the oral cavity milieu, where CRs simultaneously release various components. Cell metabolic activity, oxidative stress, and genotoxicity were used as cellular outcomes. Results showed that only VenusDiamond and Enamel-plus-HRi significantly affected the hGDF cell metabolic activity. In accordance with this, although no CR-derived extract induced a significantly detectable oxidative stress, only VenusDiamond and Enamel-plus-HRi induced significant genotoxicity. Our findings showed, for the CRs employed, a cytotoxic and genotoxic potential that did not seem to depend only on the actual Bis-GMA or TEGDMA content. Enamel-BioFunction appeared optimal in terms of cytotoxicity, and similar findings were observed for Clearfil-Majesty-ES-2 despite their different Bis-GMA/TEGDMA release patterns. This suggested that simply excluding one specific monomer from the CR formulation might not steadily turn out as a successful approach for improving their biocompatibility.

scholarly journals Effect of Ions Released and pH of Two Glass Ionomer Cements in Human Gingival Fibroblasts

2019 ◽  
Vol 21 (1) ◽  
pp. 67-77
Author(s):  
Alejandro L. Vega-Jiménez DDS, MSc, PhD ◽  
Ana G. Rodríguez-Hernández DDS, MSc, PhD ◽  
María Cristina Piña-Barba PhD ◽  
Javier Ambrosio-Hernández PhD
Keyword(s):  
Metabolic Activity ◽  
Culture Media ◽  
Biological Response ◽  
Human Gingival Fibroblasts ◽  
Glass Ionomer Cements ◽  
Glass Ionomer ◽  
Gingival Fibroblasts ◽  
Cellular Metabolic Activity ◽  
Ph Variations

Conventional glass ionomer cements are used as dental provisional restorative materials, which present several advantages such as adhesion to the tooth mineral phase among others. On the other hand, the knowledge about biological property of glass ionomers shows various approaches and results. In this work, it was studied the in vitro biological response of human gingival fibroblasts in contact with commercial cements of glass ionomer: Mirafil® and Ionglass® and with their extracts, according to ISO 10993. The extracts of the cements, in which the cells were cultured, were adjusted at different concentrations ranging 0.1% to 100%. The cellular metabolic activity of gingival fibroblasts was measured using the Alamar Blue® reagent. The results showed a significant effect on the cellular metabolic activity correlated with the concentration of liberated ions (Al³+ and Ca²+) for both ionomers, as well as the pH variations of the culture media. This could mean that the cellular metabolic activity is substantially influenced by ions and pH of the cell culture.

scholarly journals Cytotoxicity Evaluation of Two Bis-Acryl Composite Resins Using Human Gingival Fibroblasts

2016 ◽  
Vol 27 (5) ◽  
pp. 492-496 ◽  
Author(s):  
Fabiano Palmeira Gonçalves ◽  
◽  
Gutemberg Alves ◽  
Vladi Oliveira Guimarães Júnior ◽  
Marco Antônio Gallito ◽  
...  
Keyword(s):  
Cell Viability ◽  
Membrane Integrity ◽  
Composite Resins ◽  
Human Gingival Fibroblasts ◽  
Control Group ◽  
Mitochondrial Activity ◽  
Human Gingival Fibroblast ◽  
Gingival Fibroblast ◽  
Gingival Fibroblasts ◽  
Xtt Assay

Abstract Bis-acryl resins are used for temporary dental restorations and have shown advantages over other materials. The aim of this work was to evaluate the in vitro cytotoxicity of two bis-acryl composite resins (Protemp 4 and Luxatemp Star), obtained at 1, 7 and 40 days after mixing the resin components, using a standardized assay employing human primary cells closely related to oral tissues. Human gingival fibroblast cell cultures were exposed for 24 h to either bis-acryl composite resins, polystyrene beads (negative control) and latex (positive control) extracts obtained after incubation by the different periods, at 37 °C under 5% CO2. Cell viability was evaluated using a multiparametric procedure involving sequential assessment (using the same cells) of mitochondrial activity (XTT assay), membrane integrity (neutral red test) and total cell density (crystal violet dye exclusion test). The cells exposed to the resin extracts showed cell viability indexes exceeding 75% after 24 h. Even when cells were exposed to extracts prepared with longer conditioning times, the bis-acryl composite resins showed no significant cytotoxic effects (p>0.05), compared to the control group or in relation to the first 24 h of contact with the products. There were no differences among the results obtained for the bis-acryl composite resins evaluated 24 h, 7 days and 40 days after mixing. It may be concluded that the bis-acryl resins Protemp 4 and Luxatemp Star were cytocompatible with human gingival fibroblasts, suggesting that both materials are suitable for use in contact with human tissues.

scholarly journals Influence of Nano, Micro and Macro Topography of Dental Implant Surfaces on Human Gingival Fibroblasts

2021 ◽  
Vol 22 (18) ◽  
pp. 9871
Author(s):  
Morena Petrini ◽  
Tania Vanessa Pierfelice ◽  
Emira D’Amico ◽  
Natalia Di Pietro ◽  
Assunta Pandolfi ◽  
...  
Keyword(s):  
Soft Tissues ◽  
Titanium Implant ◽  
Sem Analysis ◽  
Human Gingival Fibroblasts ◽  
Dependent Manner ◽  
Gingival Fibroblasts ◽  
Force Microscopy ◽  
Atomic Force

Current research on dental implants has mainly focused on the influence of surface roughness on the rate of osseointegration, while studies on the development of surfaces to also improve the interaction of peri-implant soft tissues are lacking. To this end, the first purpose of this study was to evaluate the response of human gingival fibroblasts (hGDFs) to titanium implant discs (Implacil De Bortoli, Brazil) having different micro and nano-topography: machined (Ti-M) versus sandblasted/double-etched (Ti-S). The secondary aim was to investigate the effect of the macrogeometry of the discs on cells: linear-like (Ti-L) versus wave-like (Ti-W) surfaces. The atomic force microscopy (AFM) and scanning electron microscopy (SEM) analysis showed that the Ti-S surfaces were characterized by a significantly higher micro and nano roughness and showed the 3D macrotopography of Ti-L and Ti-W surfaces. For in vitro analyses, the hGDFs were seeded into titanium discs and analyzed at 1, 3, and 5 days for adhesion and morphology (SEM) viability and proliferation (Cck-8 and MTT assays). The results showed that all tested surfaces were not cytotoxic for the hGDFs, rather the nano-micro and macro topography favored their proliferation in a time-dependent manner. Especially, at 3 and 5 days, the number of cells on Ti-L was higher than on other surfaces, including Ti-W surfaces. In conclusion, although further studies are needed, our in vitro data proved that the use of implant discs with Ti-S surfaces promotes the adhesion and proliferation of gingival fibroblasts, suggesting their use for in vivo applications.

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