Kwang-Mahn Kim

Targeting to carcinoma cells with chitosan- and starch-coated magnetic nanoparticles for magnetic hyperthermia

The delivery of hyperthermic thermoseeds to a specific target site with minimal side effects is an important challenge in targeted hyperthermia, which employs magnetic method and functional polymers. An external magnetic field is used to control the site-specific targeting of the magnetic nanoparticles. Polymer-coated magnetic nanoparticles can confer a higher affinity to the biological cell membranes. In this study, uncoated, chitosan-coated, and starch-coated magnetic nanoparticles were synthesized for use as a hyperthermic thermoseed. Each sample was examined with respect to their applications to hyperthermia using XRD, VSM, and FTIR. In addition, the temperature changes under an alternating magnetic field were observed. As in vitro tests, the magnetic responsiveness of chitosan- and starch-coated magnetite was determined by a simple blood vessel model under various intensities of magnetic field. L929 normal cells and KB carcinoma cells were used to examine the cytotoxicity and affinity of each sample using the MTT method. The chitosan-coated magnetic nanoparticles generated a higher DeltaT of 23 degrees C under an AC magnetic field than the starch-coated magnetite, and the capturing rate of the particles was 96% under an external magnetic field of 0.4 T. The highest viability of L929 cells was 93.7%. Comparing the rate of KB cells capture with the rate of L929 cells capture, the rate of KB cells capture relatively increased with 10.8% in chitosan-coated magnetic nanoparticles. Hence, chitosan-coated magnetic nanoparticles are biocompatible and have a selective affinity to KB cells. The targeting of magnetic nanoparticles in hyperthermia was improved using a controlled magnetic field and a chitosan-coating. Therefore, chitosan-coated magnetic nanoparticles are expected to be promising materials for use in magnetic targeted hyperthermia.

Catechol-Functionalized Synthetic Polymer as a Dental Adhesive to Contaminated Dentin Surface for a Composite Restoration.

This study reports a synthetic polymer functionalized with catechol groups as dental adhesives. We hypothesize that a catechol-functionalized polymer functions as a dental adhesive for wet dentin surfaces, potentially eliminating the complications associated with saliva contamination. We prepared a random copolymer containing catechol and methoxyethyl groups in the side chains. The mechanical and adhesive properties of the polymer to dentin surface in the presence of water and salivary components were determined. It was found that the new polymer combined with an Fe3+ additive improved bond strength of a commercial dental adhesive to artificial saliva contaminated dentin surface as compared to a control sample without the polymer. Histological analysis of the bonding structures showed no leakage pattern, probably due to the formation of Fe–catechol complexes, which reinforce the bonding structures. Cytotoxicity test showed that the polymers did not inhibit human gingival fibroblast cells proliferation. Results from this study suggest a potential to reduce failure of dental restorations due to saliva contamination using catechol-functionalized polymers as dental adhesives.

Acid neutralizing, mechanical and physical properties of pit and fissure sealants containing melt-derived 45S5 bioactive glass

OBJECTIVES The aim of this study was to examine the effects of 45S5 bioactive glass (BAG) on the acid neutralizing, mechanical and physical properties of pit and fissure sealants. METHODS 45S5BAG (<25 μm) was mixed with the silanized glass (180 ± 30 nm) and added into a resin matrix [Bis-GMA/TEGDMA 50/50 (wt%) containing 1% of DMAEMA/CQ 2:1 (wt%)] with varying filler proportions; 0% 45S5BAG+50% glass (BAG0); 12.5% 45S5BAG+37.5% glass (BAG12.5); 25% 45S5BAG+25% glass (BAG25); 37.5% 45S5BAG+12.5% glass (BAG37.5); and 50% 45S5BAG+0% glass (BAG50). To evaluate the acid neutralizing properties, specimens were immersed in lactic acid solution (pH 4.0). Then, the change in pH and the time required to raise the pH from 4.0 to 5.5 were measured. In addition, flexural strength, water sorption and solubility were analyzed. RESULTS The acid neutralizing properties of each group exhibited increasing pH values as more 45S5BAG was added, and the time required to raise the pH from 4.0 to 5.5 became shorter as the proportion of 45S5BAG increased (P<0.05). Additionally, the flexural strength decreased according to the increasing proportions of 45S5BAG added (P<0.05). Water sorption showed an increasing trend with increasing proportions of 45S5 BAG added (P<0.05). However, the solubility results were similar among the groups (P>0.05), except for BAG50. SIGNIFICANCE The novel pit and fissure sealants neutralized the acid solution (pH 4.0) and exhibited appropriate mechanical and physical properties. Therefore, these compounds are suitable candidates for caries-inhibiting dental materials.

Dimensional changes of dental impression materials by thermal changes

Dental impression materials for prosthodontic treatment must be easy to use, precisely replicate of oral tissue, be dimensionally stable, and be compatible with gypsum materials. The dimensional accuracy of all materials is affected by thermal changes; impression materials shrink during cooling from mouth temperature (37 degrees C) to room temperature (23 degrees C). Five kinds of light body addition-reaction silicone impression materials [Contrast (CT), Voco Co., Germany; Examix (EM), GC Co., Japan; Extrude (EX), Kerr Co., USA; Imprint II (IM), 3M Co., USA; Perfect (PF), Handae Chemical, Korea] were tested by making cylindrical specimens (6 mm diameter and 12 mm height). The thermal expansion of the impression materials was measured with a thermomechanical analyzer (TMA 2940, TA Instruments, USA) between 23-37 degrees C. Data were analyzed via the Mann-Whitney Usage Test. To simulate actual dental impressions, tooth and tray shapes were modeled to measure the linear shrinkage of impression materials at anterior and posterior locations. The thermal expansion of impression materials tested decreased as follows: CT >or= PF >or= EM >or= EX >or= IM (p < 0.05). The anterior region changed more than the posterior region for the same impression materials. The dimensional changes averaged more than 40 microm in the anterior region, but less than 40 microm in the posterior region for all materials. Thermal expansion coefficients of some impression materials were significantly different from each other (p < 0.05), and the anterior region had more dimensional change than the posterior region for the same impression materials.

Effect of non-thermal air atmospheric pressure plasma jet treatment on gingival wound healing

Non-thermal atmospheric pressure plasmas have been applied in the biomedical field for the improvement of various cellular activities. In dentistry, the healing of gingival soft tissue plays an important role in health and aesthetic outcomes. While the biomedical application of plasma has been thoroughly studied in dentistry, a detailed investigation of plasma-mediated human gingival fibroblast (HGF) migration for wound healing and its underlying biological mechanism is still pending. Therefore, the aim of this study is to apply a non-thermal air atmospheric pressure plasma jet (NTAAPPJ) to HGF to measure the migration and to reveal the underlying biological mechanisms involved in the migration. After the characterization of NTAAPPJ by optical emission spectroscopy, the adherent HGF was treated with NTAAPPJ or air with a different flow rate. Cell viability, lipid peroxidation, migration, intracellular reactive oxygen species (ROS), and the expression of migration-related genes (EGFR, PAK1, and MAPK3) were investigated. The level of statistical significance was set at 0.05. NTAAPPJ and air treatment with a flow rate of 250–1000 standard cubic centimetres per minute (sccm) for up to 30 s did not induce significant decreases in cell viability or membrane damage. A significant increase in the migration of mitomycin C-treated HGF was observed after 30 s of NTAAPPJ treatment compared to 30 s air-only treatment, which was induced by high levels of intracellular reactive oxygen species (ROS). An increase in migration-related gene expression and EGFR activation was observed following NTAAPPJ treatment in an air flow rate-dependent manner. This is the first report that NTAAPPJ treatment induces an increase in HGF migration without changing cell viability or causing membrane damage. HGF migration was related to an increase in intracellular ROS, changes in the expression of three of the migration-related genes (EGFR, PAK1, and MAPK1), and EGFR activation. Therefore, NTAAPPJ for gingival tissue healing is a promising method for health and aesthetic outcomes.

Modification of TiO2 nanotube surfaces by electro-spray deposition of amoxicillin combined with PLGA for bactericidal effects at surgical implantation sites

OBJECTIVE To fabricate the antibiotic-releasing coatings on TiO(2) nanotube surfaces for wide applications of implant and bone plate in medical and dental surgery, the optimal deposition time of amoxicillin/PLGA solution simultaneously performing non-toxicity and a high bactericidal effect for preventing early implant failures was found. MATERIALS AND METHODS FE-SEM, ESD and FT-IR were used for confirming deposition of amoxicillin/PLGA on the TiO(2) surface. Also, the elution of amoxicillin/PLGA in a TiO(2) nanotube surface was measured by a UV-VIS spectrophotometer. The bactericidal effect of amoxicillin on the TiO(2) nanotube surface was evaluated by using Staphylococcus aureus (S. aureus). The cytotoxicity and cell proliferation were observed by WST assay using MC3T3-E1 osteoblast cells. RESULTS The results indicated that the TiO(2) nanotube surface controlled by electro-spray deposition time with amoxicillin/PLGA solution could provide a high bactericidal effect against S. aureus by the bactericidal effect of amoxicillin, as well as good osteoblast cell proliferation at the TiO(2) nanotube surface without toxicity. CONCLUSIONS This study used electro-spray deposition (ESD) methodology to obtain amoxicillin deposition in nanotube structures of TiO(2) and found the optimal deposition time of amoxicillin/PLGA solution simultaneously performing non-toxicity and a high bactericidal effect for preventing early implant failures.

Bioactivity and mechanical properties of collagen composite membranes reinforced by chitosan and β-tricalcium phosphate†

In this study, we analyzed the effects of varying concentrations of chitosan (CS) and β-tricalcium phosphate [β-TCP, Ca(3)(PO(4))(2)] on the mechanical and cell-adhesion properties of a collagen (CG) matrix for use in guided bone regeneration (GBR). Three different CS concentrations (0.5, 1, and 2%) and five different contents of β-TCP (0, 17, 29, 38, and 44%) were investigated. The composite membranes were analyzed by scanning electron microscopy and cell-adhesion, flexural-strength, and tear-strength assays. The results show that the cell-adhesion and mechanical properties of the composite membranes improved with increasing β-TCP and CS contents, yielding suitable levels of the adhesion of cells and adequate mechanical stability to ensure successful GBR. The CS adhered to the microsized β-TCP, which was distributed uniformly in the composite membranes. The β-TCP and CS have no negative effect on the cell morphology, viability, and proliferation and possess good biocompatibility. This study demonstrates that β-TCP/CS/CG composite membranes are good candidates for GBR membranes in future applications.

BMP-2 Promotes Oral Squamous Carcinoma Cell Invasion by Inducing CCL5 Release

Bone morphogenetic protein-2 (BMP-2)-containing bone grafts are useful regenerative materials for oral and maxillofacial surgery; however, several in vitro and in vivo studies previously reported cancer progression-related adverse effects caused by BMP-2. In this study, by quantifying the rhBMP-2 content released from bone grafts, the rhBMP-2 concentration that did not show cytotoxicity in each cell line was determined and applied to the in vitro monoculture or coculture model in the invasion assay. Our results showed that 1 ng/ml rhBMP-2, while not affecting cancer cell viability, significantly increased the invasion ability of the cancer cells cocultured with fibroblasts. Cocultured medium with rhBMP-2 also contained increased levels of matrix metalloproteinases. rhBMP-2-treated cocultured fibroblasts did not show a prominent difference in mRNA expression profile. Some cytokines, however, were detected in the conditioned medium by a human cytokine antibody array. Among them, the cancer invasion-related factor CCL5 was quantified by ELISA. Interestingly, CCL5 neutralizing antibodies significantly reduced the invasion of oral cancer cells. In conclusion, our results suggest that 1 ng/ml rhBMP-2 may induce invasion of oral squamous cell carcinoma (OSCC) cells by CCL5 release in coculture models. Therefore, we propose that a careful clinical examination before the use of rhBMP-2-containing biomaterials is indispensable for using rhBMP-2 treatment to prevent cancer progression.

Selective Killing Effects of Cold Atmospheric Pressure Plasma with NO Induced Dysfunction of Epidermal Growth Factor Receptor in Oral Squamous Cell Carcinoma

The aim of this study is to investigate the effects of cold atmospheric pressure plasma (CAP)-induced radicals on the epidermal growth factor receptor (EGFR), which is overexpressed by oral squamous cell carcinoma, to determine the underlying mechanism of selective killing. CAP-induced highly reactive radicals were observed in both plasma plume and cell culture media. The selective killing effect was observed in oral squamous cell carcinoma compared with normal human gingival fibroblast. Degradation and dysfunction of EGFRs were observed only in the EGFR-overexpressing oral squamous cell carcinoma and not in the normal cell. Nitric oxide scavenger pretreatment in cell culture media before CAP treatment rescued above degradation and dysfunction of the EGFR as well as the killing effect in oral squamous cell carcinoma. CAP may be a promising cancer treatment method by inducing EGFR dysfunction in EGFR-overexpressing oral squamous cell carcinoma via nitric oxide radicals.

Cytotoxicity and anti-inflammatory effects of zinc ions and eugenol during setting of ZOE in immortalized human oral keratinocytes grown as three-dimensional spheroids

OBJECTIVES The objective of this study is to assess the cytotoxic and anti-inflammatory effects of ZOE cement during setting in two-dimensional (2D) or three-dimensional (3D) cultures of immortalized human oral keratinocytes (IHOKs) with determining the extract components responsible for these effects. METHODS Extracts of mixed ZOE at different stages of setting were analyzed by a digital pH meter, ICP-MS, and GC-MS. Serial concentrations of extract and their mixture of ZnCl2, ZnSO4·H2O, and eugenol liquid were added to the 2D and 3D IHOK cultures to determine the half maximal effective concentration in investigating the cause of cytotoxicity by means of WST assay and to investigate mRNA expression levels of inflammatory cytokines by RT-PCR. RESULTS Zn(2+) and eugenol (4-19 ppm) were detected in the extracts. In the early setting stage, significant cytotoxicity was observed in the 2D and 3D IHOK cultures (P<0.05). The EC50 of Zn(2+) from ZnCl2 was 5-44 ppm in both cultures, whereas the EC50 of eugenol was not detectable under 100 ppm. Along with the lower levels of inflammatory cytokine gene expressions in the extract, treatment of the 2D IHOKs with Zn(2+) alone and treatment of the 3D IHOKs with Zn(2+) plus eugenol resulted in significantly lower expression levels of IL-1β, IL-6, and IL-8 (P<0.05). SIGNIFICANCE The cytotoxic effect of ZOE on IHOKs was greater during the setting stage owing to the presence of Zn(2+). The anti-inflammatory response to ZOE was induced by a combination of Zn(2+) and eugenol. Cytotoxic and anti-inflammatory effects differed between the 2D and 3D IHOK cultures.