Publications by authors named "Hae-Hyoung Lee"

69 Publications

Comparison of Mechanical Properties of Chairside CAD/CAM Restorations Fabricated Using a Standardization Method.

Materials (Basel) 2021 Jun 6;14(11). Epub 2021 Jun 6.

Institute of Tissue Regeneration Engineering (ITREN), Dankook University, Cheonan 31116, Korea.

The aim of this in vitro study was to investigate the fracture resistance, fracture failure pattern, and fractography of four types of chairside computer-aided design/computer-aided manufacturing (CAD/CAM) restoration materials in teeth and titanium abutments fabricated using a standardization method. An artificial mandibular left first premolar prepared for all-ceramic crown restoration was scanned. Forty extracted mandibular molars and cylindrical titanium specimens were milled into a standardized shape. A total of eighty CAD/CAM restoration blocks were milled into a crown and twenty pieces of each lithium disilicate (LS), polymer-infiltrated-ceramic-network (PICN), resin nano ceramic (RNC), and zirconia-reinforced lithium silicate (ZLS) materials were used. Crowns were bonded to abutments, and all specimens underwent thermal cycling treatment for 10,000 cycles. Fracture resistance was measured using a universal testing machine and fracture failure patterns were analyzed using optical microscopy and scanning electron microscopy. Statistical differences were analyzed using appropriate ANOVA, Tukey HSD post hoc tests, and independent sample -tests (α = 0.05). The results indicated that, in both teeth abutments and titanium abutments, the fracture resistances showed significantly the highest values in LS and the second highest in ZLS ( < 0.05). The fracture resistances based on teeth abutments and titanium abutments were significantly different in all the CAD/CAM restoration materials ( < 0.05). There are statistically significant correlations between the types of materials and the types of abutments ( < 0.05). Each of the different materials showed different fracture failure patterns, and there was no noticeable difference in fractographic analysis. Lithium disilicates and zirconia-reinforced lithium silicates exhibited statistically high fracture resistance, indicating their suitability as restoration materials for natural teeth or implant abutments. There were no distinct differences in the fracture pattern based on the restoration and abutment materials showed that the fracture initiated at the groove where the ball indenter was toughed and propagated toward the axial wall.
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http://dx.doi.org/10.3390/ma14113115DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8200951PMC
June 2021

Electricity auto-generating skin patch promotes wound healing process by activation of mechanosensitive ion channels.

Biomaterials 2021 Aug 9;275:120948. Epub 2021 Jun 9.

Institute of Tissue Regeneration Engineering (ITREN), Dankook University, Cheonan, 31116, Republic of Korea; Department of Nanobiomedical Science and BK21 NBM Global Research Center for Regenerative Medicine, Dankook University, Cheonan, 31116, Republic of Korea; Department of Biomaterials Science, College of Dentistry, Dankook University, Cheonan, 31116, Republic of Korea; Department of Regenerative Dental Medicine, College of Dentistry, Dankook University, Cheonan, 31116, Republic of Korea; Cell & Matter Institute, Dankook University, Cheonan, 31116, Republic of Korea; Mechanobiology Dental Medicine Research Center, Cheonan, 31116, Republic of Korea; UCL Eastman-Korea Dental Medicine Innovation Centre, Dankook University, Cheonan, 31116, Republic of Korea. Electronic address:

Electricity constitutes a natural biophysical component that preserves tissue homeostasis and modulates many biological processes, including the repair of damaged tissues. Wound healing involves intricate cellular events, such as inflammation, angiogenesis, matrix synthesis, and epithelialization whereby multiple cell types sense the environmental cues to rebuild the structure and functions. Here, we report that electricity auto-generating glucose-responsive enzymatic-biofuel-cell (EBC) skin patch stimulates the wound healing process. Rat wounded-skin model and in vitro cell cultures showed that EBC accelerated wound healing by modulating inflammation while stimulating angiogenesis, fibroblast fuctionality and matrix synthesis. Of note, EBC-activated cellular bahaviors were linked to the signalings involved with calcium influx, which predominantly dependent on the mechanosensitive ion channels, primarily Piezo1. Inhibition of Piezo1-receptor impaired the EBC-induced key functions of both fibroblasts and endothelial cells in the wound healing. This study highlights the significant roles of electricity played in wound healing through activated mechanosensitive ion channels and the calcium influx, and suggests the possibility of the electricity auto-generating EBC-based skin patch for use as a wound healing device.
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http://dx.doi.org/10.1016/j.biomaterials.2021.120948DOI Listing
August 2021

Emerging biogenesis technologies of extracellular vesicles for tissue regenerative therapeutics.

J Tissue Eng 2021 Jan-Dec;12:20417314211019015. Epub 2021 May 25.

Institute of Tissue Regeneration Engineering (ITREN), Dankook University, Chungcheongnam-do, Cheonan, Republic of Korea.

Extracellular vesicles (EVs), including exosomes, carry the genetic packages of RNA, DNA, and proteins and are heavily involved in cell-cell communications and intracellular signalings. Therefore, EVs are spotlighted as therapeutic mediators for the treatment of injured and dysfunctional tissues as well as biomarkers for the detection of disease status and progress. Several key issues in EVs, including payload content and bioactivity, targeting and bio-imaging ability, and mass-production, need to be improved to enable effective therapeutics and clinical translation. For this, significant efforts have been made recently, including genetic modification, biomolecular and chemical treatment, application of physical/mechanical cues, and 3D cultures. Here we communicate those recent technological advances made mainly in the biogenesis process of EVs or at post-collection stages, which ultimately aimed to improve the therapeutic efficacy in tissue healing and disease curing and the possibility of clinical translation. This communication will help tissue engineers and biomaterial scientists design and produce EVs optimally for tissue regenerative therapeutics.
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http://dx.doi.org/10.1177/20417314211019015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8155774PMC
May 2021

Ceria-Incorporated Biopolymer for Preventing Fungal Adhesion.

ACS Biomater Sci Eng 2021 05 4;7(5):1808-1816. Epub 2020 Dec 4.

Institute of Tissue Regeneration Engineering (ITREN), Dankook University, Cheonan 31116, South Korea.

Although biopolymers are widely used in biomedical fields, the issue of poor antimicrobial properties remains unsolved, leading to a potential increase in infections. Here, ceria nanoparticles (CNPs) were incorporated into a representative biopolymer, poly(methyl methacrylate) (PMMA), for drug-free antimicrobial properties. After characterizing the CNPs and surface/mechanical properties of the CNP-PMMA nanocomposite, antiadhesive effects against , the most common fungal species responsible for fungal infections, were determined using metabolic activity assays, and the underlying microbial antiadhesive mechanism was revealed. Hydrothermally fabricated CNPs showed a size of ∼20 nm with a zeta potential of 12 ± 2.3 mV and showed catalytic properties as a ROS modulator. Successful incorporation of CNPs into PMMA up to 2 wt % was confirmed by EDS analysis. The surface roughness and mechanical properties such as flexural strength and modulus were relatively unchanged up to 2 wt %. In contrast, the surface energy increased, and the Vickers hardness decreased in the 2 wt % PMMA compared with the control. A drop of up to 90% of adherent was observed in CNP-incorporated PMMA, which was confirmed and quantified via fungus staining images. The antiadhesive mechanism was revealed from the direct antimicrobial effects of CNP via the upregulation of the intracellular ROS level. Taken together, the antimicrobial-adhesive properties of the CNP-PMMA nanocomposite suggest the potential usefulness of CNP as a promising drug-free antimicrobial ingredient for biopolymers, which could lead to the prevention of microbial-induced complications in clinical settings.
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http://dx.doi.org/10.1021/acsbiomaterials.0c01039DOI Listing
May 2021

Influence of Sequential CAD/CAM Milling on the Fitting Accuracy of Titanium Three-Unit Fixed Dental Prostheses.

Materials (Basel) 2021 Mar 13;14(6). Epub 2021 Mar 13.

Department of Biomaterials Science, College of Dentistry, Dankook University, 119 Dandaero, Cheonan 31116, Korea.

This study investigated the fitting accuracy of titanium alloy fixed dental prostheses (FDP) after sequential CAD/CAM (Computer Aided Design/Computer Aided Manufacturing) fabrication. A three-unit FDP model connecting mandibular second premolars and molars was prepared and scanned to fabricate titanium FDPs by CAD/CAM milling. A total of six FDPs were sequentially milled in one titanium alloy disk using a new set of burs every time (n = 4). The fitting accuracy of FDPs was mesiodistally evaluated by a silicone replica technique and the measurement was triplicated at four different locations: MO (marginal opening), MG (marginal gap), AG (axial gap), and OG (occlusal gap). Data were statistically analyzed using ANOVA and Tukey's HSD test. The fitting accuracy of PMMA (polymethyl methacrylate) FDPs milled using the worn or new bur were evaluated by the same procedure (n = 6). The mean dimensions of titanium FDP for all measuring positions, except for AG, were significantly increased from the third milling. However, no difference was noted between the first FDP and the second FDP milled with the same set of burs. Severe edge chippings were observed in all milling burs. Detrimental effects of the worn burs on the fitting accuracy were demonstrated in the CAD/CAM-milled PMMA FDP. The results recommend proper changing frequency of cutting burs to achieve the quality of fit and predictable outcomes for dental CAD/CAM prostheses.
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http://dx.doi.org/10.3390/ma14061401DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7998422PMC
March 2021

Digital image correlation in dental materials and related research: A review.

Dent Mater 2021 05 11;37(5):758-771. Epub 2021 Mar 11.

Department of Biomaterials Science, College of Dentistry, Dankook University, 119 Dandaero, Cheonan, Chungnam 31116, Republic of Korea; Institute of Tissue Regeneration Engineering, Dankook University, 119 Dandaero, Cheonan, Chungnam 31116, Republic of Korea. Electronic address:

Objective: Digital image correlation (DIC) is a non-contact image processing technique for full-field strain measurement. Although DIC has been widely used in engineering and biomechanical fields, it is in the spotlight only recently in dental materials. Therefore, the purpose of this review paper is introducing the working principle of the DIC technique with some modifications and providing further potential applications in various dental materials and related fields.

Methods: The accuracy of the algorithm depending on the environmental characteristics of the DIC technique, as well as the advantages and disadvantages of strain measurement using optical measurements, have been elaborated in dental materials and related fields. Applications to those researches have been classified into the following categories: shrinkage behavior of light-cured resin composite, resin-tooth interface, mechanical properties of tooth structure, crack extension and elastic properties of dental materials, and deformation of dental restoration and prosthesis. This classification and discussion were performed using literature survey and review based on numerous papers in the international journals published over the past 20 years. The future directions for predicting the precise deformation of dental materials under various environments, as well as limitations of the DIC technique, was presented in this review.

Results: The DIC technique was demonstrated as a more effective tool to measure full-field polymerization shrinkage of composite resin, even in a simulated clinical condition over the existing methods. Moreover, the DIC combined with other technologies can be useful to evaluate the mechanical behavior of material-tooth interface, dentine structure and restorative and prosthetic materials with high accuracy. Three-dimensional DIC using two cameras extended the measurement range in-plane to out-of-plane, enabling measure of the strain directly on the surface of dental restorations or prosthesis.

Significance: DIC technique is a potential tool for measuring and predicting the full-field deformation/strain of dental materials and actual prostheses in diverse clinical conditions. The versatility of DIC can replace the existing complex sensor devices in those studies.
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http://dx.doi.org/10.1016/j.dental.2021.02.024DOI Listing
May 2021

Calcium Silicate-Based Biocompatible Light-Curable Dental Material for Dental Pulpal Complex.

Nanomaterials (Basel) 2021 Feb 27;11(3). Epub 2021 Feb 27.

Institute of Tissue Regeneration Engineering (ITREN), Dankook University, 119 Dandae-ro, Cheonan 31116, Chungcheongnam-do, Korea.

Dental caries causes tooth defects and clinical treatment is essential. To prevent further damage and protect healthy teeth, appropriate dental material is a need. However, the biocompatibility of dental material is needed to secure the oral environment. For this purpose, biocompatible materials were investigated for incorporated with dental capping material. Among them, nanomaterials are applied to dental materials to enhance their chemical, mechanical, and biological properties. This research aimed to study the physicochemical and mechanical properties and biocompatibility of a recently introduced light-curable mineral trioxide aggregate (MTA)-like material without bisphenol A-glycidyl methacrylate (Bis-GMA). To overcome the compromised mechanical properties in the absence of Bis-GMA, silica nanoparticles were synthesized and blended with a dental polymer for the formation of a nano-network. This material was compared with a conventional light-curable MTA-like material that contains Bis-GMA. Investigation of the physiochemical properties followed ISO 4049. Hydroxyl and calcium ion release from the materials was measured over 21 days. The Vickers hardness test and three-point flexural strength test were used to assess the mechanical properties. Specimens were immersed in solutions that mimicked human body plasma for seven days, and surface characteristics were analyzed. Biological properties were assessed by cytotoxicity and biomineralization tests. There was no significant difference between the tested materials with respect to overall physicochemical properties and released calcium ions. The newly produced material released more calcium ions on the third day, but 14 days later, the other material containing Bis-GMA released higher levels of calcium ions. The microhardness was reduced in a low pH environment, and differences between the specimens were observed. The flexural strength of the newly developed material was significantly higher, and different surface morphologies were detected. The recently produced extract showed higher cell viability at an extract concentration of 100%, while mineralization was clear at the conventional concentration of 25%. No significant changes in the physical properties between Bis-GMA incorporate material and nanoparticle incorporate materials.
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http://dx.doi.org/10.3390/nano11030596DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7997209PMC
February 2021

The Effect of Selenium Nanoparticles on the Osteogenic Differentiation of MC3T3-E1 Cells.

Nanomaterials (Basel) 2021 Feb 23;11(2). Epub 2021 Feb 23.

Institute of Tissue Regeneration Engineering (ITREN), Dankook University, 119 Dandae-ro, Cheonan, Chungcheongnam-do 31116, Korea.

Reactive oxygen species (ROS) regulate various functions of cells, including cell death, viability, and differentiation, and nanoparticles influence ROS depending on their size and shape. Selenium is known to regulate various physiological functions, such as cell differentiations and anti-inflammatory functions, and plays an important role in the regulation of ROS as an antioxidant. This study aims to investigate the effect of selenium nanoparticles (SeNPs) on the differentiation of osteogenic MC3T3-E1 cells. After fabrication of SeNPs with a size of 25.3 ± 2.6 nm, and confirmation of its oxidase-like activity, SeNPs were added to MC3T3-E1 cells with or without HO: 5~20 μg/mL SeNPs recovered cells damaged by 200 μM HO via the intracellular ROS downregulating role of SeNPs, revealed by the ROS staining assay. The increase in osteogenic maturation with SeNPs was gradually investigated by expression of osteogenic genes at 3 and 7 days, Alkaline phosphatase activity staining at 14 days, and Alizarin red S staining at 28 days. Therefore, the role of SeNPs in regulating ROS and their therapeutic effects on the differentiation of MC3T3-E1 cells were determined, leading to possible applications for bone treatment.
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http://dx.doi.org/10.3390/nano11020557DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7926403PMC
February 2021

Grapefruit Seed Extract as a Natural Derived Antibacterial Substance against Multidrug-Resistant Bacteria.

Antibiotics (Basel) 2021 Jan 18;10(1). Epub 2021 Jan 18.

Institute of Tissue Regeneration Engineering (ITREN), Dankook University, Cheonan, Chungcheongnam-do 31116, Korea.

Multidrug-resistant (MDR) bacteria are increasing due to the abuse and misuse of antibiotics, and nosocomial infections by MDR bacteria are also increasing. The aim of this study was to identify new substances that can target MDR bacteria among 12 plant extracts that are known to have antibacterial effects. The experiments were performed by the disk diffusion test and microdilution minimum inhibitory concentration (MIC) test, as described by the Clinical and Laboratory Standards Institute (CLSI). By screening against methicillin-sensitive (MSSA), grapefruit seed extract (GSE) was selected from 12 plant extracts for subsequent experiments. GSE showed antibacterial effects against methicillin-resistant (MRSA) and vancomycin-resistant (VRSA) in the disk diffusion test. Even at the lowest concentration, GSE showed antibacterial activity in the microdilution MIC test. As a result, we can conclude that GSE is a naturally derived antibacterial substance that exhibits a favorable antibacterial effect even at a very low concentration, so it is a good candidate for a natural substance that can be used to prevent or reduce nosocomial infections as coating for materials used in medical contexts or by mixing a small amount with other materials.
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http://dx.doi.org/10.3390/antibiotics10010085DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7830962PMC
January 2021

Antibacterial, proangiogenic, and osteopromotive nanoglass paste coordinates regenerative process following bacterial infection in hard tissue.

Biomaterials 2021 01 9;268:120593. Epub 2020 Dec 9.

Institute of Tissue Regeneration Engineering (ITREN), Dankook University, Cheonan, 31116, Republic of Korea; Department of Nanobiomedical Science and BK21 PLUS NBM Global Research Center for Regenerative Medicine, Dankook University, Cheonan, 31116, Republic of Korea; Department of Biomaterials Science, College of Dentistry, Dankook University, Cheonan, 31116, Republic of Korea; UCL Eastman-Korea Dental Medicine Innovation Centre, Dankook University, Cheonan, 31116, Republic of Korea; Cell & Matter Institute, Dankook University, Cheonan, 31116, South Korea. Electronic address:

Bacterial infection raises serious concerns in tissue repair settings involved with implantable biomaterials, devastating the regenerative process and even life-threatening. When hard tissues are infected with bacteria (called 'osteomyelitis'), often the cases in open fracture or chronic inflammation, a complete restoration of regenerative capacity is significantly challenging even with highly-dosed antibiotics or surgical intervention. The implantable biomaterials are thus needed to be armored to fight bacteria then to relay regenerative events. To this end, here we propose a nanoglass paste made of ~200-nm-sized silicate-glass (with Ca, Cu) particles that are hardened in contact with aqueous medium and multiple-therapeutic, i.e., anti-bacterial, pro-angiogenic and osteopromotive. The nanoglass paste self-hardened via networks of precipitated nano-islands from leached ions to exhibit ultrahigh surface area (~300 m/g), amenable to fill tunable defects with active biomolecular interactions. Also, the nanoglass paste could release multiple ions (silicate, calcium, and copper) at therapeutically relevant doses and sustainably (for days to weeks), implying possible roles in surrounding cells/tissues as a therapeutic-ions reservoir. The osteopromotive effects of nanoglass paste were evidenced by the stimulated osteogenic differentiation of MSCs. Also, the nanoglass paste promoted angiogenesis of endothelial cells in vitro and vasculature formation in vivo. Furthermore, the significant bactericidal effect of nanoglass paste, as assessed with E. coli and S. aureus, highlighted the role of copper played in elevating ROS level and destroying homeostasis, which salvaged tissue cells from co-cultivated bacteria contamination. When administered topically to rat tibia osteomyelitis defects, the nanoglass paste enhanced in vivo bone healing and fracture resistance. The developed nanoglass paste, given its self-setting property and the coordinated therapeutic actions, is considered to be a promising drug-free inorganic biomaterial platform for the regenerative therapy of bacteria-infected hard tissues.
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http://dx.doi.org/10.1016/j.biomaterials.2020.120593DOI Listing
January 2021

Biological Effects of Tricalcium Silicate Nanoparticle-Containing Cement on Stem Cells from Human Exfoliated Deciduous Teeth.

Nanomaterials (Basel) 2020 Jul 14;10(7). Epub 2020 Jul 14.

Department of Pediatric Dentistry, College of Dentistry, Dankook University, 119 Dandae-ro, Cheonan, Chungcheongnam-do 31116, Korea.

Nanomaterials can enhance interactions with stem cells for tissue regeneration. This study aimed to investigate the biological effects of tricalcium silicate nanoparticle-containing cement (Biodentine™) during or after setting on stem cells from human exfoliated deciduous teeth (SHED) to mimic clinically relevant situations in which materials are adapted. Specimens were divided into four groups depending on the start of extraction time (during (3, 6 and 12 min) or after setting (24 h)) and extracted in culture medium for 24 h for further physicochemical and biological analysis. After cell viability in serially diluted extracts was evaluated, odontogenic differentiation on SHED was evaluated by ARS staining using nontoxic conditions. A physicochemical analysis of extracts or specimens indicated different Ca ion content, pH, and surface chemistry among groups, supporting the possibility of different biological functionalities depending on the extraction starting conditions. Compared to the 'after setting' group, all 'during setting' groups showed cytotoxicity on SHED. The during setting groups induced more odontogenic differentiation at the nontoxic concentrations compared to the control. Thus, under clinically simulated extract conditions at nontoxic concentrations, Biodentine™ seemed to be a promising odontoblast differentiating biomaterial that is helpful for dental tissue regeneration. In addition, to simulate clinical situations when nanoparticle-containing cement is adjusted, biological effects during setting need to be considered.
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http://dx.doi.org/10.3390/nano10071373DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7408117PMC
July 2020

Mechanophysical and biological properties of a 3D-printed titanium alloy for dental applications.

Dent Mater 2020 07 29;36(7):945-958. Epub 2020 May 29.

Department of Biomaterials Science, College of Dentistry, Dankook University, 119 Dandae-ro, Cheonan, Chungcheongnam-do 31116, Republic of Korea; Institute of Tissue Regeneration Engineering (ITREN), Dankook University, 119 Dandae-ro, Cheonan, Chungcheongnam-do 31116, Republic of Korea. Electronic address:

Objective: Titanium and its alloys are widely used for dental and medical biomaterials due to their excellent mechanical and biological advantages. After the introduction of direct laser metal sintering (DLMS) 3D printing technology and its use over conventional machine-cut processes, questions remain regarding whether 3D-printed titanium (alloy) devices have similar biological properties to machine-cut counterparts for dental applications. Thus, this work focuses on comparing the biological activities of machine-cut and 3D-printed specimens after optimizing the DLMS 3D-printing conditions in terms of the mechanophysical characteristics.

Methods: The DLMS 3D-printing (as a function of the laser spacing from 30-100μm) and post-surface treatment (as-given or sand-blasted) conditions were optimized using medical-grade Ti-6Al-4V powders in terms of the inner pore amount, mechanical properties, roughness and hydrophilicity. Then, the initial cell adhesion of the optimized DLMS 3D-printed Ti-6Al-4V specimen was compared with that of the machine-cut Ti-6Al-4V specimen against human dermal fibroblasts (hDFs) and mesenchymal stem cells (hMSCs), which are representative of direct-contact cell types of orofacial mucosa and bone, respectively. hMSC differentiation on the specimens was conducted for up to 21 days to measure the osteogenic gene expression and biomineralization.

Results: Laser spacings of 30-40μm had fewer inner defects and consequently a higher three-point flexural strength and elastic modulus compared to other larger laser spacings. Depending on the span width (0.3-1mm) in the lattice architecture, the elastic modulus of the 3D-printed cuboid specimen can be further controlled (up to ∼30 times). The sand-blasted specimens after 3D printing revealed lower surface roughness and higher hydrophilicity compared to the as-3D printed specimen, which were considered optimal conditions for biological study. Initial hDF and hMSC adhesion for 12 hr and hMSC differentiation on the surface were comparable between the sand-blasted 3D-printed and machine-cut specimens in terms of adherent cell numbers, vinculin intensity, osteogenic gene expression and biomineralization.

Significance: The optimized DLMS 3D-printed Ti-6Al-4V specimen had similar biological properties to those of the machine-cut counterpart, suggesting the potential usefulness of 3D printing technology for a wide range of dental applications.
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http://dx.doi.org/10.1016/j.dental.2020.04.027DOI Listing
July 2020

Nano-graphene oxide/polyurethane nanofibers: mechanically flexible and myogenic stimulating matrix for skeletal tissue engineering.

J Tissue Eng 2020 Jan-Dec;11:2041731419900424. Epub 2020 Jan 23.

Institute of Tissue Regeneration Engineering (ITREN), Dankook University, Cheonan, Republic of Korea.

For skeletal muscle engineering, scaffolds that can stimulate myogenic differentiation of cells while possessing suitable mechanical properties (e.g. flexibility) are required. In particular, the elastic property of scaffolds is of importance which helps to resist and support the dynamic conditions of muscle tissue environment. Here, we developed highly flexible nanocomposite nanofibrous scaffolds made of polycarbonate diol and isosorbide-based polyurethane and hydrophilic nano-graphene oxide added at concentrations up to 8%. The nano-graphene oxide incorporation increased the hydrophilicity, elasticity, and stress relaxation capacity of the polyurethane-derived nanofibrous scaffolds. When cultured with C2C12 cells, the polyurethane-nano-graphene oxide nanofibers enhanced the initial adhesion and spreading of cells and further the proliferation. Furthermore, the polyurethane-nano-graphene oxide scaffolds significantly up-regulated the myogenic mRNA levels and myosin heavy chain expression. Of note, the cells on the flexible polyurethane-nano-graphene oxide nanofibrous scaffolds could be mechanically stretched to experience dynamic tensional force. Under the dynamic force condition, the cells expressed significantly higher myogenic differentiation markers at both gene and protein levels and exhibited more aligned myotubular formation. The currently developed polyurethane-nano-graphene oxide nanofibrous scaffolds, due to their nanofibrous morphology and high mechanical flexibility, along with the stimulating capacity for myogenic differentiation, are considered to be a potential matrix for future skeletal muscle engineering.
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http://dx.doi.org/10.1177/2041731419900424DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7001895PMC
January 2020

Development of Bis-GMA-free biopolymer to avoid estrogenicity.

Dent Mater 2020 01 30;36(1):157-166. Epub 2019 Nov 30.

Department of Biomaterials Science, School of Dentistry, Dankook University, Cheonan 330-714, South Korea; Institute of Tissue Regeneration Engineering (ITREN), Dankook University, Cheonan 330-714, South Korea. Electronic address:

Objective: Although bisphenol A-glycidyl methacrylate (Bis-GMA)-based dental materials are widely used in dentistry, Estrogenicity from released bisphenol A remains a concern due to possibility of adversely affecting the growth of children and homeostasis of adults. Here, a new family of isosorbide-derived biomonomers were synthesized and experimentally utilized as a matrix of dental sealants to provide physico-mechanical and biological properties comparable to those of a conventional Bis-GMA-based material but without the the potential estrogenicity.

Methods: After synthesis of isosorbide-derived biomonomers (ISDB) by light polymerization, an experimental dental sealant with different silica filler concentrations (0-15wt%) was characterized and compared to a commercially available Bis-GMA-based sealant. Cytotoxicity and estrogenicity assays were conducted with human oral keratinocytes and estrogen-sensitive MCF-7 cells, respectively.

Results: ISDB-based dental sealants exhibited typical initially smooth surfaces with depth of cure, Vickers hardness, compressive strength/modulus, water resorption/solubility, and flowability comparable to those of the commercial sealant and met the ISO standard for dental sealants and polymer-based restorative materials. Indirect cytotoxicity tests using an extract showed comparable viability among experimental ISDB-based materials and a commercial Bis-GMA-incorporated control. DNA synthesis in MCF-7 cells (a marker of estrogenicity) and the release of bisphenol A under enzymatic incubation were not detected in ISDB-based materials.

Significance: In conclusion, the comparable physico-mechanical properties of ISDB-based materials with their cytocompatibility and lack of estrogenicity suggest the potential usefulness of ISDBs as a newly developed and safe biomaterial.
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http://dx.doi.org/10.1016/j.dental.2019.11.016DOI Listing
January 2020

Depth-Dependent Cellular Response from Dental Bulk-Fill Resins in Human Dental Pulp Stem Cells.

Stem Cells Int 2019 24;2019:1251536. Epub 2019 Oct 24.

Department of Biomaterials Science, College of Dentistry, Dankook University, Chungnam, Cheonan 31116, Republic of Korea.

The proper choice of dental composite resins is necessary based on the minimal cytotoxicity and antiodontogenesis on human dental pulp stem cells for dental pulp-dentin tissue repair and regeneration. The aim of this study was to evaluate the cytotoxicity and antidifferentiation effects of dental bulk-fill resins, able to be polymerized as a bulk status for filling deep cavity of a tooth by single light curing, against human dental pulp stem cells (hDPSCs) from three compartments corresponding to depth (0-2, 2-4, and 4-6 mm) from the light-curing site. Three bulk-fill composite resins (SDR, Venus bulk-fill (VBF), and Beautifil Bulk Flowable (BBF)) and a conventional flowable composite resin (Filtek Z350 XT flowable restorative (ZFF)) were individually filled into a cylindrical hole ( = 2 mm, = 10 mm), and three compartments (total ~6 mm of height) were combined as a single assembly for light curing. The resin samples from the three layers were separated and eluted in the culture medium. The extracts were exposed to hDPSCs, and cytotoxicity and differentiation capability were evaluated. Depth of cure and surface hardness according to depth were determined. All bulk-fill resins except BBF revealed cytotoxicity from 4 to 6 or 2 to 4 mm, while ZFF was cytotoxic at over 2 mm. Depth of cure was detected from 3.55 to 4.02 mm in the bulk-fill resins (vs. ~2.25 mm in conventional resin), and 80% hardness compared with that of a fully polymerized top surface was determined from 4.2 to 6 mm in the bulk-fill resin (vs. 2.4 mm in conventional resin). Antidifferentiation was revealed at a depth of 4-6 mm in the bulk-fill resin. There was a difference in depth of cytotoxicity and antidifferentiation between the bulk-fill composite resins, which was mainly due to different cure depths and ingredients. Therefore, careful consideration of choice of bulk-fill resins is necessary especially for restoration of deep cavities for maintaining the viability and differentiation ability of dental pulp stem cells.
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http://dx.doi.org/10.1155/2019/1251536DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6854224PMC
October 2019

Author Correction: Performance of a glucose-reactive enzyme-based biofuel cell system for biomedical applications.

Sci Rep 2019 Nov 27;9(1):18044. Epub 2019 Nov 27.

Department of Chemistry, College of Natural Science, Dankook University, Chungnam, Cheonan, 31116, Republic of Korea.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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http://dx.doi.org/10.1038/s41598-019-54377-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6879505PMC
November 2019

Characterization of an anti-foaming and fast-setting gypsum for dental stone.

Dent Mater 2019 12 19;35(12):1728-1739. Epub 2019 Sep 19.

Department of Biomaterials Science, College of Dentistry, Dankook University, Chungnam, Cheonan, 31116, Republic of Korea; Institute of Tissue Regeneration Engineering (ITREN), Dankook University, Cheonan, 31116, Republic of Korea; UCL Eastman-Korea Dental Medicine Innovation Centre, Dankook University, Cheonan, 31116, Republic of Korea. Electronic address:

Objective: An anti-foaming and fast-setting gypsum for dental stone recently became available on the market. Interestingly, this product can be mixed by the cocktail shaking method, providing a more convenient way to obtain high reproducibility when fabricating error-free study models for digital dentistry. The aim of this study is to investigate setting time, surface bubble formation, and other gypsum characteristics of three dental stone products with different mixing methods.

Methods: Shake mix stone (SM), new plastone 2 white (NP), and Hi-Koseton (HK) were chosen. Using different mixing methods (cocktail shaking, hand mixing, hand mixing+vibrating, and hand mixing+vacuum process), the characteristics of dental stone were investigated according to ISO 6873. Powder size, morphology, and thermo/chemical analyses were performed.

Results: Regardless of the method of mixing, SM exhibited the fastest setting time (3-4min) and the smallest number (˜10% versus HK) and area (˜30% versus HK) of surface bubbles among the investigated products, while setting expansion, mechanical properties such as compressive/impact strength and microhardness and detail reproduction before and after digital scanning were similar. A smaller size (˜1.5μm) and unidentified additives were revealed as possible reasons for the above anti-foaming and fast-setting characteristics.

Significance: Anti-foaming and fast-setting characteristics of a developed gypsum for dental stone were confirmed even with shaking.
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http://dx.doi.org/10.1016/j.dental.2019.08.110DOI Listing
December 2019

Performance of a glucose-reactive enzyme-based biofuel cell system for biomedical applications.

Sci Rep 2019 07 26;9(1):10872. Epub 2019 Jul 26.

Department of Chemistry, College of Natural Science, Dankook University, Chungnam, Cheonan, 31116, Republic of Korea.

A glucose-reactive enzyme-based biofuel cell system (EBFC) was recently introduced in the scientific community for biomedical applications, such as implantable artificial organs and biosensors for drug delivery. Upon direct contact with tissues or organs, an implanted EBFC can exert effects that damage or stimulate intact tissue due to its byproducts or generated electrical cues, which have not been investigated in detail. Here, we perform a fundamental cell culture study using a glucose dehydrogenase (GDH) as an anode enzyme and bilirubin oxidase (BOD) as a cathode enzyme. The fabricated EBFC had power densities of 15.26 to 38.33 nW/cm depending on the enzyme concentration in media supplemented with 25 mM glucose. Despite the low power density, the GDH-based EBFC showed increases in cell viability (~150%) and cell migration (~90%) with a relatively low inflammatory response. However, glucose oxidase (GOD), which has been used as an EBFC anode enzyme, revealed extreme cytotoxicity (~10%) due to the lethal concentration of HO byproducts (~1500 µM). Therefore, with its cytocompatibility and cell-stimulating effects, the GDH-based EBFC is considered a promising implantable tool for generating electricity for biomedical applications. Finally, the GDH-based EBFC can be used for introducing electricity during cell culture and the fabrication of organs on a chip and a power source for implantable devices such as biosensors, biopatches, and artificial organs.
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http://dx.doi.org/10.1038/s41598-019-47392-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6659637PMC
July 2019

Ceria-incorporated MTA for accelerating odontoblastic differentiation via ROS downregulation.

Dent Mater 2019 09 27;35(9):1291-1299. Epub 2019 Jun 27.

Department of Biomaterials Science, School of Dentistry, Dankook University, Cheonan 330-714, South Korea; Institute of Tissue Regeneration Engineering (ITREN), Dankook University, Cheonan 330-714, South Korea; UCL Eastman-Korea Dental Medicine Innovation Centre, Dankook University, Cheonan 31116, Republic of Korea. Electronic address:

Objective: Odontoblast differentiation from dental pulp stem cells (DPSCs) is involved in a cascade of key biological events for maintaining pulp-dentin homeostasis, repair and regeneration. A pulp regeneration biomaterial (mineral trioxide aggregate (MTA)) increased intracellular reactive oxygen species (ROS) levels during differentiation, ameliorating the differentiating of DPSCs into odontoblasts. Here, ceria nanoparticles (CNP) were incorporated as an insoluble antioxidant into commercially available MTA (CMTA), and the odontoblastic differentiation of human DPSCs was investigated.

Methods: The CMTA was fabricated from MTA and CNP conjugation up to 4wt%, and the compressive strength, surface morphology after setting and setting time were investigated. Furthermore, the alkaline phosphatase (ALP) assay, Alizarin Red staining (ARS) and quantitative real-time polymerase chain reaction (qPCR) were performed to evaluate odontoblastic differentiation in an indirect co-culture system using inserts with pores. To reveal the underlying mechanism, the ROS levels and ion release were measured. Statistical analysis was performed by one-way analysis of variance with a Tukey post hoc test (P<0.05).

Results: CMTA significantly elevated the odontoblastic differentiation of hDPSCs measured by ALP activity, ARS, and odontoblastic gene expression, whereas the other physico-mechanical properties were relatively maintained. Upregulation of gene expression from CMTA was reversed with hydrogen peroxide. CMTA could reduce the increased intracellular ROS levels of hDPSCs by approximately 70% during differentiation, similar to when an antioxidant was used, without changing the ion release and pH of the media.

Significance: CMTA could be useful dental materials for regenerating dentin-pulp complexes by instructing intracellular ROS during differentiation to achieve beneficial biological functions. This study suggests a new direction of dental nanomaterials in treating pulp-dentin complexes.
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http://dx.doi.org/10.1016/j.dental.2019.05.024DOI Listing
September 2019

Carbon nanotube incorporation in PMMA to prevent microbial adhesion.

Sci Rep 2019 03 20;9(1):4921. Epub 2019 Mar 20.

Department of Biomaterials Science, School of Dentistry, Dankook University, Cheonan, 31116, South Korea.

Although PMMA-based biomaterials are widely used in clinics, a major hurdle, namely, their poor antimicrobial (i.e., adhesion) properties, remains and can accelerate infections. In this study, carboxylated multiwalled carbon nanotubes (CNTs) were incorporated into poly(methyl methacrylate) (PMMA) to achieve drug-free antimicrobial adhesion properties. After characterizing the mechanical/surface properties, the anti-adhesive effects against 3 different oral microbial species (Staphylococcus aureus, Streptococcus mutans, and Candida albicans) were determined for roughened and highly polished surfaces using metabolic activity assays and staining for recognizing adherent cells. Carboxylated multiwalled CNTs were fabricated and incorporated into PMMA. Total fracture work was enhanced for composites containing 1 and 2% CNTs, while other mechanical properties were gradually compromised with the increase in the amount of CNTs incorporated. However, the surface roughness and water contact angle increased with increasing CNT incorporation. Significant anti-adhesive effects (35~95%) against 3 different oral microbial species without cytotoxicity to oral keratinocytes were observed for the 1% CNT group compared to the PMMA control group, which was confirmed by microorganism staining. The anti-adhesive mechanism was revealed as a disconnection of sequential microbe chains. The drug-free antimicrobial adhesion properties observed in the CNT-PMMA composite suggest the potential utility of CNT composites as future antimicrobial biomaterials for preventing microbial-induced complications in clinical settings (i.e., Candidiasis).
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http://dx.doi.org/10.1038/s41598-019-41381-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6427005PMC
March 2019

Role of nuclear mechanosensitivity in determining cellular responses to forces and biomaterials.

Biomaterials 2019 03 8;197:60-71. Epub 2019 Jan 8.

Institute of Tissue Regeneration Engineering (ITREN), Dankook University, Cheonan 31116, Republic of Korea; Department of Biomaterials Science, College of Dentistry, Dankook University, Cheonan 31116, Republic of Korea; Department of Nanobiomedical Science & BK21 PLUS Global Research Center for Regenerative Medicine, Dankook University, Cheonan 31116, Republic of Korea; UCL Eastman-Korea Dental Medicine Innovation Centre, Dankook University, Cheonan 31116, Republic of Korea. Electronic address:

Tissue engineers use biomaterials or apply forces to alter cell behaviors and cure damaged/diseased tissues. The external physical cues perceived by cells are transduced intracellularly along the mechanosensitive machineries, including subcellular adhesion molecules and cytoskeletons. The signals are further channeled to a nucleus through the physical links of nucleoskeleton and cytoskeleton or the biochemical translocation of transcription factors. Thus, the external cues are thought to affect directly or indirectly the nucleus and the genetic transcriptional process, ultimately determining cell fate. Here we communicate the importance of such mechanotransductory processes in cell and tissue engineering where external forces- or biomaterials-related physical cues essentially regulate cellular behaviors, with an emphasis on the mechanosensing and signaling along the road to a nucleus.
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http://dx.doi.org/10.1016/j.biomaterials.2019.01.010DOI Listing
March 2019

Uniaxial/biaxial flexure strengths and elastic properties of resin-composite block materials for CAD/CAM.

Dent Mater 2019 02 7;35(2):389-401. Epub 2018 Dec 7.

Department of Biomaterials Science, College of Dentistry, Dankook University, Cheonan 31116, South Korea; Institute of Tissue Regeneration Engineering, Dankook University, Cheonan 31116, South Korea. Electronic address:

Objective: Comparing strengths under different loading conditions provides useful information on the mechanical behaviour of restorative materials under multiaxial masticatory loading in the oral cavity. The aims of this study was to investigate the flexural strengths and the reliability of resin-composite blocks for CAD/CAM by uniaxial and biaxial flexure tests and to compare the elastic properties measured by different methods including digital image correlation (DIC).

Methods: Four resin-composite blocks for CAD/CAM, namely, VE (Vita Enamic), LU (Lava Ultimate), MD (Mazic Duro), and CS (Cerasmart), were investigated. Beam specimens (4.0×1.4×18.0mm) and disks (12-14mmϕ×1.5mm) were prepared to determine the uniaxial (three-point bending) and biaxial (ball-on-ring, BOR) flexural strengths and flexural moduli. A compression test (8×4×18mm) with DIC analysis was utilized to measure the elastic modulus and Poisson's ratio. Data were analysed by a 2-parameter Weibull function and ANOVA with Scheffe's test.

Results: The mean uniaxial and biaxial strengths and Weibull moduli of the specimen groups were as follows: uniaxial VE (140.1±7.0, 24.1), LU (159.1±6.3, 31.5), MD (144.9±13.3, 13.6), and CS (165.4±16.9, 11.2) and biaxial VE (153.6±10.4, 19.0), LU (231.0±29.3, 9.7), MD (148.9±23.8, 7.4), and CS (249.7±22.4, 13.8). Although the ranking of both sets of strength data remained unchanged, the strength reliability was significantly affected by the loading; the Weibull moduli of the specimens decreased when they were subjected to biaxial tests (except for that of CS). The elastic modulus values of the materials varied significantly under the different test loadings, although they were in the same order regardless of the test method: VE>>LU≈MD>CS. The DIC technique yielded elastic moduli that were in good agreement with those measured by the uniaxial flexure test.

Significance: The flexural strength, reliability, and elastic modulus of resin-composite block materials differed with the uniaxial and biaxial flexural loading and the test method. The different behaviours under both loadings should be considered in the evaluation of the mechanical performance of those materials.
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http://dx.doi.org/10.1016/j.dental.2018.11.032DOI Listing
February 2019

Dual-ion delivery for synergistic angiogenesis and bactericidal capacity with silica-based microsphere.

Acta Biomater 2019 01 19;83:322-333. Epub 2018 Nov 19.

Institute of Tissue Regeneration Engineering (ITREN), Dankook University, Cheonan 330-714, Republic of Korea; Department of Nanobiomedical Science & BK21 PLUS NBM Global Research Center for Regenerative Medicine, Dankook University, Cheonan 330-714, Republic of Korea; UCL Eastman-Korea Dental Medicine Innovation Centre, Dankook University, Cheonan, Republic of Korea; Department of Biomaterials Science, College of Dentistry, Dankook University, Cheonan 330-714, Republic of Korea. Electronic address:

Inhibition of bacterial growth with the simultaneous promotion of angiogenesis has been challenging in the repair and regeneration of infected tissues. Here, we aim to tackle this issue through the use of cobalt-doped silicate microspheres that can sustainably release dual ions (silicate and cobalt) at therapeutically-relevant doses. The cobalt was doped up to 2.5 wt% within a sol-gel silicate glass network, and microspheres with the size of ∼300 μm were generated by an emulsification method. The cobalt and silicate ions released were shown to synergistically upregulate key angiogenic genes, such as HIF1-α, VEGF and the receptor KDR. Moreover, the incorporation of ions promoted the polarization, migration, homing and sprouting angiogenesis of endothelial cells. Neo-vascular formation was significantly higher in the dual-ion delivered microspheres, as evidenced in a chicken chorioallantoic membrane model. When cultured with bacterial species, the cobalt-doped microspheres effectively inhibited bacteria growth in both indirect or direct contacts. Of note, the bacteria/endothelial cell coculture model proved the efficacy of dual-ion releasing microcarriers for maintaining the endothelial survivability against bacterial contamination and their cell-cell junction. The current study demonstrates the multiple actions (proangiogenic and antibacterial) of silicate and cobalt ions released from microspheres, and the concept provided here can be extensively applied to repair and regenerate infected tissues as a growth factor- or drug-free delivery system. STATEMENT OF SIGNIFICANCE: While several ions have been introduced to biomaterials for therapeutic purposes, relaying the effects of antibacterial into tissue regenerative (e.g., angiogenesis) has been a significant challenge. In this study, we aim to develop a biomaterial platform that has the capacity of both 'antibacterial' and 'proangiogenic' from a microsphere sustainably releasing multiple ions (herein cobalt and silicate). Here, dual-actions of the microspheres revealed the stimulated endothelial functions as well as the inhibited growth of different bacterial species. In particular, protecting endothelial survivability against bacterial contamination was reported using the bacterial/endothelial co-culture model. The current concept of drug-free yet multiple-ion delivery biomaterials can be applicable for the repair and regeneration of infected tissues with dual actions of angiogenesis and suppressing bacterial activity.
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http://dx.doi.org/10.1016/j.actbio.2018.11.025DOI Listing
January 2019

Reformulated mineral trioxide aggregate components and the assessments for use as future dental regenerative cements.

J Tissue Eng 2018 Jan-Dec;9:2041731418807396. Epub 2018 Oct 30.

Institute of Tissue Regeneration Engineering (ITREN), Dankook University, Cheonan, Republic of Korea.

Mineral trioxide aggregate, which comprises three major inorganic components, namely, tricalcium silicate (C3S), dicalcium silicate (C2S), and tricalcium aluminate (C3A), is promising regenerative cement for dentistry. While mineral trioxide aggregate has been successfully applied in retrograde filling, the exact role of each component in the mineral trioxide aggregate system is largely unexplored. In this study, we individually synthesized the three components, namely, C3S, C2A, and C3A, and then mixed them to achieve various compositions (a total of 14 compositions including those similar to mineral trioxide aggregate). All powders were fabricated to obtain high purity. The setting reaction of all cement compositions was within 40 min, which is shorter than for commercial mineral trioxide aggregate (~150 min). Over time, the pH of the composed cements initially showed an abrupt increase and then plateaued (pH 10-12), which is a typical behavior of mineral trioxide aggregate. The compression and tensile strength of the composed cements increased (2-4 times the initial values) with time for up to 21 days in an aqueous medium, the degree to which largely depended on the composition. The cell viability test with rat mesenchymal stem cells revealed no toxicity for any composition except C3A, which contained aluminum. To confirm the in vivo biological response, cement was retro-filled into an extracted rat tooth and the complex was re-implanted. Four weeks post-operation, histological assessments revealed that C3A caused significant tissue toxicity, while good tissue compatibility was observed with the other compositions. Taken together, these results reveal that of the three major constituents of mineral trioxide aggregate, C3A generated significant toxicity in vitro and in vivo, although it accelerated setting time. This study highlights the need for careful consideration with regard to the composition of mineral trioxide aggregate, and if possible (when other properties are satisfactory), the C3A component should be avoided, which can be achieved by the mixture of individual components.
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http://dx.doi.org/10.1177/2041731418807396DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6207958PMC
October 2018

Intra-articular biomaterials-assisted delivery to treat temporomandibular joint disorders.

J Tissue Eng 2018 Jan-Dec;9:2041731418776514. Epub 2018 May 13.

Institute of Tissue Regeneration Engineering (ITREN), Dankook University, Cheonan, South Korea.

The temporomandibular joint disorder, also known as myofascial pain syndrome, is considered one of the prevalent chronic pain diseases caused by muscle inflammation and cartilage degradation in head and neck, and thus influences even biopsychosocial conditions in a lifetime. There are several current treatment methodologies relieving inflammation and preventing degradation of the joint complex. One of the promising non-surgical treatment methods is an intra-articular injection of drugs such as corticosteroids, analgesics, and anti-depressants. However, the side effects of drugs due to frequent injections and over-doses, including dizziness, dry mouth, and possible drug dependency are considered limitations. Thus, the delivery of therapeutic molecules through the use of nano/microparticles is currently considered as a promising strategy primarily due to the controlled release. This review highlights the nano/microparticle systems for effective intra-articular therapeutics delivery to prevent cartilage degradation and protect subchondral bone in a temporomandibular joint.
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http://dx.doi.org/10.1177/2041731418776514DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5954570PMC
May 2018

Multi-functional nano-adhesive releasing therapeutic ions for MMP-deactivation and remineralization.

Sci Rep 2018 04 4;8(1):5663. Epub 2018 Apr 4.

Department of Biomaterials Science, School of Dentistry, Dankook University, Cheonan 31116, South Korea.

Restoration of hard tissue in conjunction with adhesive is a globally challenging issue in medicine and dentistry. Common clinical therapies involving application of adhesive and substitute material for functional or anatomical recovery are still suboptimal. Biomaterials with bioactivity and inhibitory effects of enzyme-mediated adhesive degradation can render a solution to this. Here, we designed a novel copper-doped bioactive glass nanoparticles (CuBGn) to offer multifunction: metalloproteinases (MMP) deactivation and remineralization and incorporated the CuBGn in resin-dentin adhesive systems, which showed most common failure of MMP mediated adhesive degradation among hard tissue adhesives, to evaluate proposed therapeutic effects. A sol-gel derived bioactive glass nanoparticles doping 10 wt% of Cu (Cu-BGn) for releasing Cu ions, which were well-known MMP deactivator, were successfully created and included in light-curing dental adhesive (DA), a filler-free co-monomer resin blend, at different concentrations (up to 2 wt%). These therapeutic adhesives (CuBGn-DA) showed enhanced (a)cellular bioactivity, cytocompatibility, microtensile bond strength and MMP deactivation-ability. In conclusion, the incorporation of Cu ions releasing nano-bioactive glass demonstrated multifunctional properties at the resin-dentin interface; MMP deactivation and remineralization, representing a suitable strategy to extend the longevity of adhesive-hard tissue (i.e. resin-dentin) interfaces.
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http://dx.doi.org/10.1038/s41598-018-23939-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5884793PMC
April 2018

Evaluation of the flexural mechanical properties of various thermoplastic denture base polymers.

Dent Mater J 2018 Nov 7;37(6):950-956. Epub 2018 Mar 7.

Department of Removable Prosthodontics, School of Dental Medicine, Tsurumi University.

This study evaluated the flexural mechanical properties of various thermoplastic denture base polymers (six polyamides, four acrylic resins, polyester, polypropylene, and polycarbonate) by three different testing conditions; specimens were tested in water bath at 37°C (Wet/Water, by ISO 20795-1), or in ambient air (Wet/Air) after being immersed in distilled water for 50 h, or after desiccation for 7 days (Dry/Air). The mean ultimate flexural strength (UFS) and flexural modulus (FM) for most products ranged from 27 to 61 MPa and from 611 to 1,783 MPa respectively, which failed to meet the minimum requirements of the international standard, except for polycarbonate (89 and 2,245 MPa). The mean UFS and FM values were ranked Dry/Air>Wet/Air>Wet/Water (p<0.05). In conclusion, the flexural mechanical properties of denture base polymers varied with the products and were significantly affected by the testing medium (air or water) and specimen conditions (wet or dry).
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http://dx.doi.org/10.4012/dmj.2017-373DOI Listing
November 2018

Evaluation of mold-enclosed shear bond strength between zirconia core and porcelain veneer.

Dent Mater J 2018 Sep 7;37(5):783-788. Epub 2018 Mar 7.

Department of Biomaterials Science, College of Dentistry, Dankook University.

This study aimed to evaluate the mold-enclosed shear bond strength (ME-SBS) of zirconia to veneering porcelain with different surface treatments. Colored or uncolored zirconia coupons were either highly polished or airborne-particle abraded. The specimens were divided into groups with/without application of liner. Veneering porcelain was fired into an alumina ring mold on the zirconia coupons. The assembled specimens were subjected to the ME-SBS test. The mean ME-SBS for groups ranged from 7-10 MPa with no significant difference (p>0.05). A three-way ANOVA showed that coloring and surface roughening of the zirconia specimen had no significant influence on the ME-SBS value, but liner application exhibited a significant effect with a minor decrease in the MESBS (p=0.049). Surface treatments (coloring, airborne-particle abrasion, and liner application) were found to not cause a significant increase to the zirconia-porcelain bond strength. The application of zirconia liner had a slight negative influence on the ME-SBS results.
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http://dx.doi.org/10.4012/dmj.2017-339DOI Listing
September 2018

Silk fibroin/collagen protein hybrid cell-encapsulating hydrogels with tunable gelation and improved physical and biological properties.

Acta Biomater 2018 03 2;69:218-233. Epub 2018 Feb 2.

Institute of Tissue Regeneration Engineering (ITREN), Dankook University, South Korea; Department of Nanobiomedical Science & BK21 PLUS NBM Global Research Center for Regenerative Medicine, Dankook University, South Korea; Department of Biomaterials Science, College of Dentistry, Dankook University, South Korea. Electronic address:

Cell encapsulating hydrogels with tunable mechanical and biological properties are of special importance for cell delivery and tissue engineering. Silk fibroin and collagen, two typical important biological proteins, are considered potential as cell culture hydrogels. However, both have been used individually, with limited properties (e.g., collagen has poor mechanical properties and cell-mediated shrinkage, and silk fibroin from Bombyx mori (mulberry) lacks cell adhesion motifs). Therefore, the combination of them is considered to achieve improved mechanical and biological properties with respect to individual hydrogels. Here, we show that the cell-encapsulating hydrogels of mulberry silk fibroin / collagen are implementable over a wide range of compositions, enabled simply by combining the different gelation mechanisms. Not only the gelation reaction but also the structural characteristics, consequently, the mechanical properties and cellular behaviors are accelerated significantly by the silk fibroin / collagen hybrid hydrogel approach. Of note, the mechanical and biological properties are tunable to represent the combined merits of individual proteins. The shear storage modulus is tailored to range from 0.1 to 20 kPa along the iso-compositional line, which is considered to cover the matrix stiffness of soft-to-hard tissues. In particular, the silk fibroin / collagen hydrogels are highly elastic, exhibiting excellent resistance to permanent deformation under different modes of stress; without being collapsed or water-squeezed out (vs. not possible in individual proteins) - which results from the mechanical synergism of interpenetrating networks of both proteins. Furthermore, the role of collagen protein component in the hybrid hydrogels provides adhesive sites to cells, stimulating anchorage and spreading significantly with respect to mulberry silk fibroin gel, which lacks cell adhesion motifs. The silk fibroin / collagen hydrogels can encapsulate cells while preserving the viability and growth over a long 3D culture period. Our findings demonstrate that the silk / collagen hydrogels possess physical and biological properties tunable and significantly improved (vs. the individual protein gels), implying their potential uses for cell delivery and tissue engineering.

Statement Of Significance: Development of cell encapsulating hydrogels with excellent physical and biological properties is important for the cell delivery and cell-based tissue engineering. Here we communicate for the first time the novel protein composite hydrogels comprised of 'Silk' and 'Collagen' and report their outstanding physical, mechanical and biological properties that are not readily achievable with individual protein hydrogels. The properties include i) gelation accelerated over a wide range of compositions, ii) stiffness levels covering 0.1 kPa to 20 kPa that mimic those of soft-to-hard tissues, iii) excellent elastic behaviors under various stress modes (bending, twisting, stretching, and compression), iv) high resistance to cell-mediated gel contraction, v) rapid anchorage and spreading of cells, and vi) cell encapsulation ability with a long-term survivability. These results come from the synergism of individual proteins of alpha-helix and beta-sheet structured networks. We consider the current elastic cell-encapsulating hydrogels of silk-collagen can be potentially useful for the cell delivery and tissue engineering in a wide spectrum of soft-to-hard tissues.
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http://dx.doi.org/10.1016/j.actbio.2017.12.026DOI Listing
March 2018

Nano-graphene oxide incorporated into PMMA resin to prevent microbial adhesion.

Dent Mater 2018 04 3;34(4):e63-e72. Epub 2018 Feb 3.

Institute of Tissue Regeneration Engineering (ITREN), Dankook University, Cheonan 330-714, South Korea; Department of Biomaterials Science, School of Dentistry, Dankook University, Cheonan 330-714, South Korea. Electronic address:

Objective: Although polymethyl methacrylate (PMMA) is widely used as a dental material, a major challenge of using this substance is its poor antimicrobial (anti-adhesion) effects, which increase oral infections. Here, graphene-oxide nanosheets (nGO) were incorporated into PMMA to introduce sustained antimicrobial-adhesive effects by increasing the hydrophilicity of PMMA.

Methods: After characterizing nGO and nGO-incorporated PMMA (up to 2wt%) in terms of morphology and surface characteristics, 3-point flexural strength and hardness were evaluated. The anti-adhesive effects were determined for 4 different microbial species with experimental specimens and the underlying anti-adhesive mechanism was investigated by a non-thermal oxygen plasma treatment. Sustained antimicrobial-adhesive effects were characterized with incubation in artificial saliva for up to 28 days.

Results: The typical nanosheet morphology was observed for nGO. Incorporating nGO into PMMA roughened its surface and increased its hydrophilicity without compromising flexural strength or surface hardness. An anti-adhesive effect after 1h of exposure to microbial species in artificial saliva was observed in nGO-incorporated specimens, which accelerated with increasing levels of nGO without significant cytotoxicity to oral keratinocytes. Plasma treatment of native PMMA demonstrated that the antimicrobial-adhesive effects of nGO incorporation were at least partially due to increased hydrophilicity, not changes in the surface roughness. A sustained antimicrobial-adhesive property against Candida albicans was observed in 2% nGO for up to 28 days.

Significance: The presence of sustained anti-adhesion properties in nGO-incorporated PMMA without loading any antimicrobial drugs suggests the potential usefulness of this compound as a promising antimicrobial dental material for dentures, orthodontic devices and provisional restorative materials.
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http://dx.doi.org/10.1016/j.dental.2018.01.019DOI Listing
April 2018
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