Registration of digital dental models and cone-beam computed tomography images using 3-dimensional planning software: Comparison of the accuracy according to scanning methods and software.

INTRODUCTION: The registration of cone-beam computed tomography (CBCT) images and digital dental models is required for the design and manufacturing of dental devices such as implant guides and surgical wafers. This study aims to register intraoral scan (IS) models and cast scan (CS) models onto CBCT images using 3-dimensional (3D) planning software and evaluate the registration accuracy according to scanning methods and 3D planning software. METHODS: The CBCT image of an artificial skull model with reference markers was taken. The CS model and the IS model were obtained from the same skull model, registered onto the CBCT image using 3D planning software packages providing manual registration (MR) function and point-based registration (PR) functions, and set as the experimental groups. After registration, shell to shell deviations and positional differences between the reference model and the experimental models were evaluated. RESULTS: The shell to shell deviations ranged from 0.03 to 0.18 mm. Deviations in both the maxilla and mandible were significantly different according to scanning methods and software packages. In the anteroposterior direction, the IS-MR and CS-MR groups showed significantly different positions. In the superoinferior direction, the MR and PR groups showed significantly different positions. CONCLUSIONS: The registration using the PR function of the 3D planning software packages was significantly more accurate than the registration using the MR function. There was no significant difference between the registrations using the IS model and the CS model when using the PR functions.

Smart Microcapsules with Molecular Polarity- and Temperature-Dependent Permeability.

Microcapsules with molecule-selective permeation are appealing as microreactors, capsule-type sensors, drug and cell carriers, and artificial cells. To accomplish molecular size- and charge-selective permeation, regular size of pores and surface charges have been formed in the membranes. However, it remains an important challenge to provide advanced regulation of transmembrane transport. Here, smart microcapsules are designed that provide molecular polarity- and temperature-dependent permeability. With capillary microfluidic devices, water-in-oil-in-water (W/O/W) double-emulsion drops are prepared, which serve as templates to produce microcapsules. The oil shell is composed of two monomers and dodecanol, which turns to a polymeric framework whose continuous voids are filled with dodecanol upon photopolymerization. One of the monomers provides mechanical stability of the framework, whereas the other serves as a compatibilizer between growing polymer and dodecanol, preventing macrophase separation. Above melting point of dodecanol, molecules that are soluble in the molten dodecanol are selectively allowed to diffuse across the shell, where the rate of transmembrane transport is strongly influenced by partition coefficient. The rate is drastically lowered for temperatures below the melting point. This molecular polarity- and temperature-dependent permeability renders the microcapsules potentially useful as drug carriers for triggered release and contamination-free microreactors and microsensors.

Magnetophoretic Delivery of a Tumor-Priming Agent for Chemotherapy of Metastatic Murine Breast Cancer.

Tumor microenvironment is a significant physical barrier to the effective delivery of chemotherapy into solid tumors. To overcome this challenge, tumors are pretreated with an agent that reduces cellular and extracellular matrix densities prior to chemotherapy. However, it also comes with a concern that metastasis may increase due to the loss of protective containment. We hypothesize that timely priming at the early stage of primary tumors will help control metastasis. To test this, we primed orthotopic 4T1 breast tumors with a paclitaxel (PTX)-loaded iron-oxide-decorated poly(lactic- co-glycolic acid) nanoparticle (NP) composite (PTX@PINC), which can be quickly concentrated in target tissues with the aid of an external magnet, and monitored its effect on the delivery of subsequently administered NPs. Magnetic resonance imaging and optical whole-body imaging confirmed that PTX@PINC was efficiently delivered to tumors by the external magnet and help loosen the tumors to accommodate subsequently delivered NPs. Consistently, the primed tumors responded to Doxil better than nonprimed tumors. In addition, lung metastasis was significantly reduced in the animals PINC-primed prior to Doxil administration. These results support that PINC combined with magnetophoresis can facilitate the timely management of primary tumors with a favorable secondary effect on metastasis.

Development of Liposomal Gemcitabine with High Drug Loading Capacity.

Liposomes are widely used for systemic delivery of chemotherapeutic agents to reduce their nonspecific side effects. Gemcitabine (Gem) makes a great candidate for liposomal encapsulation due to the short half-life and nonspecific side effects; however, it has been difficult to achieve liposomal Gem with high drug loading capacity. Remote loading, which uses a transmembrane pH gradient to induce an influx of drug and locks the drug in the core as a sulfate complex, does not serve Gem as efficiently as doxorubicin (Dox) due to the low p Ka value of Gem. Existing studies have attempted to improve Gem loading capacity in liposomes by employing lipophilic Gem derivatives or creating a high-concentration gradient for active loading into the hydrophilic cores (small volume loading). In this study, we combine the remote loading approach and small volume loading or hypertonic loading, a new approach to induce the influx of Gem into the preformed liposomes by high osmotic pressure, to achieve a Gem loading capacity of 9.4-10.3 wt % in contrast to 0.14-3.8 wt % of the conventional methods. Liposomal Gem showed a good stability during storage, sustained-release over 120 h in vitro, enhanced cellular uptake, and improved cytotoxicity as compared to free Gem. Liposomal Gem showed a synergistic effect with liposomal Dox on Huh7 hepatocellular carcinoma cells. A mixture of liposomal Gem and liposomal Dox delivered both drugs to the tumor more efficiently than a free drug mixture and showed a relatively good anti-tumor effect in a xenograft model of hepatocellular carcinoma. This study shows that bioactive liposomal Gem with high drug loading capacity can be produced by remote loading combined with additional approaches to increase drug influx into the liposomes.

In Situ Polymerization of Dopamine on Graphene Framework for Charge Storage Applications.

Polydopamine, a functional coating material, is redox active as cathode materials for both Li- and Na-ion batteries or hybrid capacitors. Here, a polydopamine coating onto 3D graphene framework is introduced through a simple hydrothermal process, during which graphene oxide serves not only as an oxidant for assisting the polymerization of dopamine, but also as a template for the conformal growth of polydopamine. High-density films are fabricated by compressing the polydopamine-coated graphene aerogels, which can be directly used as free-standing and flexible cathodes in both Li- and Na-cells. The compact electrodes deliver high capacities of ≈230 mAh g-1 in Li-cells and ≈211 mAh g-1 in Na-cells based on the total mass of electrodes. These compact electrodes also exhibit exceptional cycling stability and high rate performance due to the unique structure in which polydopamine is uniformly coated on the 3D structured graphene.

Development of Surface-Variable Polymeric Nanoparticles for Drug Delivery to Tumors.

To develop nanoparticle drug carriers that interact with cells specifically in the mildly acidic tumor microenvironment, we produced polymeric nanoparticles modified with amidated TAT peptide via a simple surface modification method. Two types of core poly(lactic-co-glycolic acid) nanoparticles (NL and NP) were prepared with a phospholipid shell as an optional feature and covered with polydopamine that enabled the conjugation of TAT peptide on the surface. Subsequent treatment with acid anhydrides such as cis-aconitic anhydride (CA) and succinic anhydride (SA) converted amines of lysine residues in TAT peptide to ß-carboxylic amides, introducing carboxylic groups that undergo pH-dependent protonation and deprotonation. The nanoparticles modified with amidated TAT peptide (NLpT-CA and NPpT-CA) avoided interactions with LS174T colon cancer cells and J774A.1 macrophages at pH 7.4 but restored the ability to interact with LS174T cells at pH 6.5, delivering paclitaxel efficiently to the cells following a brief contact time. In LS174T tumor-bearing nude mice, NPpT-CA showed less accumulation in the lung than NPpT, reflecting the shielding effect of amidation, but tumor accumulation of NPpT and NPpT-CA was equally minimal. Comparison of particle stability and protein corona formation in media containing sera from different species suggests that NPpT-CA has been activated and opsonized in mouse blood to a greater extent than those in bovine serum-containing medium, thus losing the benefits of pH-sensitivity expected from in vitro experiments.

A drug-delivery strategy for overcoming drug resistance in breast cancer through targeting of oncofetal fibronectin.

A major problem with cancer chemotherapy begins when cells acquire resistance. Drug-resistant cancer cells typically upregulate multi-drug resistance proteins such as P-glycoprotein (P-gp). However, the lack of overexpressed surface biomarkers has limited the targeted therapy of drug-resistant cancers. Here we report a drug-delivery carrier decorated with a targeting ligand for a surface marker protein extra-domain B(EDB) specific to drug-resistant breast cancer cells as a new therapeutic option for the aggressive cancers. We constructed EDB-specific aptide (APTEDB)-conjugated liposome to simultaneously deliver siRNA(siMDR1) and Dox to drug-resistant breast cancer cells. APTEDB-LS(Dox,siMDR1) led to enhanced delivery of payloads into MCF7/ADR cells and showed significantly higher accumulation and retention in the tumors. While either APTEDB-LS(Dox) or APTEDB-LS(siMDR1) did not lead to appreciable tumor retardation in MCF7/ADR orthotropic model, APTEDB-LS(Dox,siMDR1) treatment resulted in significant reduction of the drug-resistant breast tumor. Taken together, this study provides a new strategy of drug delivery for drug-resistant cancer therapy.

Development of Porous Beads to Provide Regulated BMP-2 Stimulation for Varying Durations: In Vitro and In Vivo Studies for Bone Regeneration.

It is commonly accepted that the sustained release of bone morphogenetic protein-2 (BMP-2) can enhance bone regeneration and minimize its safety issues. However, little is known regarding the appropriate duration of BMP-2 stimulation for sufficient osteogenic differentiation and new bone formation because of the short half-life of BMP-2 in the physiological environment and the lack of a well-defined delivery matrix that can regulate the release period of BMP-2. In this study, we prepared porous poly(lactic-co-glycolic acid) (PLGA) beads with different surface pore sizes that can regulate the release period of BMP-2 (i.e., 7, 17, and 30 days) while providing the BMP-2 concentration required for bone regeneration. Our findings in both in vitro cell culture and in vivo animal studies using these BMP-2-loaded beads demonstrate that release of BMP-2 within 7 days affects only the initial differentiation of human periosteum-derived cells (hPDCs) and does not significantly enhance their subsequent differentiation into mature functional cells. However, extending the duration of BMP-2 stimulation over 17 days can provide a suitable environment for osteogenic differentiation of hPDCs and new bone formation.

Autophagy Has a Beneficial Role in Relieving Cigarette Smoke-Induced Apoptotic Death in Human Gingival Fibroblasts.

The deleterious role of cigarette smoke has long been documented in various human diseases including periodontal complications. In this report, we examined this adverse effect of cigarette smoke on human gingival fibroblasts (HGFs) which are critical not only in maintaining gingival tissue architecture but also in mediating immune responses. As well documented in other cell types, we also observed that cigarette smoke promoted cellular reactive oxygen species in HGFs. And we found that this cigarette smoke-induced oxidative stress reduced HGF viability through inducing apoptosis. Our results indicated that an increased Bax/Bcl-xL ratio and resulting caspase activation underlie the apoptotic death in HGFs exposed to cigarette smoke. Furthermore, we detected that cigarette smoke also triggered autophagy, an integrated cellular stress response. Interesting, a pharmacological suppression of the cigarette smoke-induced autophagy led to a further reduction in HGF viability while a pharmacological promotion of autophagy increased the viability of HGFs with cigarette smoke exposures. These findings suggest a protective role for autophagy in HGFs stressed with cigarette smoke, highlighting that modulation of autophagy can be a novel therapeutic target in periodontal complications with cigarette smoke.

Bilirubin Nanoparticles as a Nanomedicine for Anti-inflammation Therapy.

Despite the high potency of bilirubin as an endogenous anti-inflammatory compound, its clinical translation has been hampered because of its insolubility in water. Bilirubin-based nanoparticles that may overcome this critical issue are presented. A polyethylene glycol compound (PEG) was covalently attached to bilirubin, yielding PEGylated bilirubin (PEG-BR). The PEG-BR self-assembled into nanoscale particles with a size of approximately 110 nm, termed bilirubin nanoparticles (BRNPs). BRNPs are highly efficient hydrogen peroxide scavengers, thereby protecting cells from H2 O2 -induced cytotoxicity. In a murine model of ulcerative colitis, intravenous injection of BRNPs showed preferential accumulation of nanoparticles at the sites of inflammation and significantly inhibited the progression of acute inflammation in the colon. Taken together, BRNPs show potential for use as a therapeutic nanomedicine in various inflammatory diseases.

Case report: Omphalitis caused by Trueperella pyogenes infection in a Korean indigenous calf.

Omphalitis, commonly caused by opportunistic bacteria has been significantly associated with morbidity and mortality in neonatal calves. Trueperella pyogenes is a commensal and opportunistic pathogen that can cause suppurative infection in farm animals. Our case involved a 10-day-old female Korean indigenous calf that presented with umbilical enlargement accompanied by a greenish-yellow purulent discharge and right forelimb lameness. The calf was diagnosed with failure of passive transfer at 24 h of age. Physical examination found hypothermia (38.1°C), tachycardia (110 beats/min), tachypnea (47 cycles/min), and open mouth breathing. Ultrasonography revealed hyperechoic pus in the 9th and 10th right intercostals, for which a liver abscess due to omphalophlebitis was suspected. After 3 days, the calf died. T. pyogenes was detected in the umbilical cord, lung, liver, kidney, intestine, mesenteric lymph node, urinary bladder, and bladder ligament. All genes related to the virulent factors (i.e., plo, cbpA, fimA, fimC, fimG, nanH, and nanP) were also identified, with plo and fimA being associated with pathogenicity. A final diagnosis of omphalitis was established based on the identification of virulent T. pyogenes and umbilical cord dilatation on ultrasonography. Antimicrobial susceptibility tests showed that the isolated T. pyogenes was susceptible to amoxicillin, ceftiofur, florfenicol, enrofloxacin, ofloxacin, and ciprofloxacin, suggesting the suitability of these antibiotics for treating T. pyogenes-induced omphalitis. Hence, accurate and rapid diagnosis of the involved bacteria and antimicrobial susceptibility patterns can help guide therapeutic decisions. Our case provides useful information that could aid large animal clinicians in the diagnosis and treatment of T. pyogenes-induced omphalitis.

BMP-2-immobilized PCL 3D printing scaffold with a leaf-stacked structure as a physically and biologically activated bone graft.

Although three-dimensional (3D) printing techniques are used to mimic macro- and micro-structures as well as multi-structural human tissues in tissue engineering, efficient target tissue regeneration requires bioactive 3D printing scaffolds. In this study, we developed a bone morphogenetic protein-2 (BMP-2)-immobilized polycaprolactone (PCL) 3D printing scaffold with leaf-stacked structure (LSS) (3D-PLSS-BMP) as a bioactive patient-tailored bone graft. The unique LSS was introduced on the strand surface of the scaffold via heating/cooling in tetraglycol without significant deterioration in physical properties. The BMP-2 adsorbed on3D-PLSS-BMPwas continuously released from LSS over a period of 32 d. The LSS can be a microtopographical cue for improved focal cell adhesion, proliferation, and osteogenic differentiation.In vitrocell culture andin vivoanimal studies demonstrated the biological (bioactive BMP-2) and physical (microrough structure) mechanisms of3D-PLSS-BMPfor accelerated bone regeneration. Thus, bioactive molecule-immobilized 3D printing scaffold with LSS represents a promising physically and biologically activated bone graft as well as an advanced tool for widespread application in clinical and research fields.

Bioactive Porous Particles as Biological and Physical Stimuli for Bone Regeneration.

Even though bony defects can be recovered to their original condition with full functionality, critical-sized bone injuries continue to be a challenge in clinical fields due to deficiencies in the scaffolding matrix and growth factors at the injury region. In this study, we prepared bone morphogenetic protein-2 (BMP-2)-loaded porous particles as a bioactive bone graft for accelerated bone regeneration. The porous particles with unique leaf-stacked morphology (LSS particles) were fabricated by a simple cooling procedure of hot polycaprolactone (PCL) solution. The unique leaf-stacked structure in the LSS particles provided a large surface area and complex release path for the sufficient immobilization of BMP-2 and sustained release of BMP-2 for 26 days. The LSS was also recognized as a topographical cue for cell adhesion and differentiation. In in vitro cell culture and in vivo animal study using a canine mandible defect model, BMP-2-immobilized LSS particles provided a favorable environment for osteogenic differentiation of stem cells and bone regeneration. In vitro study suggests a dual stimulus of bone mineral-like (leaf-stacked) structure (a physical cue) and continuously supplied BMP-2 (a biological cue) to be the cause of this improved healing outcome. Thus, LSS particles containing BMP-2 can be a promising bioactive grafting material for effective new bone formation.

Redescription of Paraclimenes gorgonicola (Bruce, 1969) (Crustacea: Decapoda: Palaemonidae) and establishing P. franklini (Bruce, 1990) as its junior synonym.

The octocoral associated species Paraclimenes gorgonicola is a deep-sea palaemonid shrimp briefly described in Bruce (1969) without illustrations. Paraclimenes franklini, the type species of the genus Paraclimenes, has been considered as a valid species and distinguished from P. gorgonicola by the presence of articulated postrostral teeth on the carapace. Paraclimenes gorgonicola is herein fully redescribed and illustrated on the basis of the type series which is deposited in Naturalis Biodiversity Center, Leiden, The Netherlands and recently collected specimens from shallow waters around Jejudo Island, Korea, and compared with P. franklini. It is demonstrated that both taxa are conspecific and thus P. franklini is considered to be a junior synonym of P. gorgonicola.

Two New Species and a Further Country Record of the Caridean Shrimp Genus Periclimenaeus Borradaile, 1915 from Korea (Decapoda: Palaemonidae).

Two new species of the palaemonid genus Periclimenaeus are described and illustrated from Korea; additionally, a third species is recorded from Korea for the first time. Periclimenaeus karantina sp. nov. was obtained from ascidian hosts. The species has a denticulate dactylus on both second pereiopods, considered to be typical for ascidian associates. It can be separated from related species by the combination of the following characters: the carpocerite overreaching the anterior margin of the scaphocerite; the distolateral tooth of the scaphocerite exceeding the anterior margin of the lamella; the dactylus of the minor chela exceeding the fixed finger; and the ambulatory dactyli furnished with a minute proximal tooth. Periclimenaeus apomonosi sp. nov. was obtained from sponge hosts, and belongs to the P. robustus species-group, on account of the developed anterior median lobe on the tergite of the first abdominal somite. It can be distinguished from related species by the combination of the presence of a supraorbital tooth; the presence of a pointed process on the inferior orbital angle; the distolateral tooth of the scaphocerite terminating level with the anterior margin of the lamella; the antennal carpocerite reaching about 0.6 of the scaphocerite; the first and second chelae with non-serrated cutting edges; the ischium and merus of the second pereiopods harbouring tubercles on the ventral margin; and the ambulatory dactyli with a distal accessory tooth and the corpus furnished with denticles, ventrally. The sponge associated species, Periclimenaeus djboutensis, relatively widespread across the Indo-Pacific, is reported for the first time from Korea in Geomundo Island. Asides from a morphological description of all three species, molecular information of two genetic markers (16S + COI) is provided to aid in future phylogenetic reconstructions of the genus.

Surgical treatment of a skeletal Class III patient using customized brackets based on the CAD/CAM virtual orthodontic system.

The computer-aided design/computer-aided manufacturing (CAD/CAM) virtual orthodontic system produces customized brackets, indirect bonding jigs, and archwires based on a three-dimensional virtual setup. In surgical cases, this system helps to visualize the final occlusion during diagnosis and to efficiently plan individualized presurgical orthodontic treatments. A 20-year-old female patient with a skeletal Class III malocclusion, maxillary protrusion, and lip protrusion was successfully treated with orthognathic surgery and orthodontic treatment with maxillary first premolar extractions. The CAD/CAM system was applied for efficient treatment, with a total active treatment time of 16 months. In this case report, the applicability of the CAD/CAM virtual orthodontic system for orthognathic surgery cases is demonstrated. Suggestions are also made to overcome the limitations and to maximize the advantages of this system during orthodontic treatment of patients undergoing orthognathic surgery.

A new species of the genus Cristimenes Duris & Horká, 2017 (Decapoda, Caridea, Palaemonidae).

A new species of crinoid-associated shrimp, Cristimenesbrucei sp. nov., is described based on specimens from Korea, although the species also occurs in Hong Kong and is likely more widespread. The new species is morphologically very similar to C.commensalis, but can be distinguished by the reduced supraorbital tooth on the carapace. Cristimenesbrucei sp. nov. is clearly recovered as a monophyletic species through COI barcode and molecular phylogenetic analyses based on four genetic markers (COI, 16S, H3, 18S).

Advanced Colorimetric Paper Sensors Using Color Focusing Effect Based on Asymmetric Flow of Fluid.

Although paper-based colorimetric sensors utilizing enzymatic reactions are well suited for real-field diagnosis, their widespread use is hindered by signal blurring at the detection spot due to the action of capillary forces on the liquid and the corresponding membrane. In this study, we eliminated signal losses commonly observed during enzyme-mediated colorimetric sensing and achieved pattern-free quantitative analysis of glucose and uric acid by mixing enzymes and color-forming reagents with chitosan oligosaccharide lactate (COL), which resulted in perfectly focused colorimetric signals at the detection spot, using asymmetric flow induced by changing the flow rate of the COL-treated paper. The targets were calibrated with 0-500 mg/dL of glucose and 0-200 mg/dL of uric acid, and the limit of detection was calculated to be 0.6 and 0.03 mg/dL, respectively. In human urine, the correlation has a high response between the measured and spiked concentrations, and the stability of the enzyme mixture including COL increased by 41% for glucose oxidase mixture and 29% for uricase mixture, compared to the corresponding mixtures without COL. Thus, the color focusing and pattern-free sensor, which have the advantages of easy fabrication, easy handling, and high stability, should be applied to real-field diagnosis.

Preparation and properties of fluorine-containing colorless polyimide nanocomposite films with organo-modified montmorillonites for potential flexible substrate.

We prepared transparent polyimide (PI) and organo-modified montmorillonite (OMMT) nanocomposite films from the solution of poly(amic acid) and various amounts (0.5-2 wt%) of OMMT in N,N-dimethylacetamide (DMAc). The Poly(amic acid) was prepared from the reaction of 4,4'-(hexafluoroisopropylidene)diphthalic anhydride (6FDA) and 2,2'-bis (trifluoromethyl)-4,4'-diamino phenyl (TFDB). Dodecylamine (C12-) and dodecyltriphenylphosphonium chloride (C12PPh-Cl-) were used as organic modifiers in OMMT. The PI/OMMT nanocomposite films were characterized by Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), transmission electron microscope (TEM), UV-Vis transmission spectra, thermomechanical analysis (TMA), and rheometric dynamic analysis (RDA). As the OMMT contents is increased, PI/OMMT nanocomposites generally show better properties compared to pristine PI films, although the transparency of the PI/OMMT nanocomposite films is sacrificed slightly. However, it is concluded that these nanocomposite films are good candidates for potential flexible substrates.

Small molecule delivery to solid tumors with chitosan-coated PLGA particles: A lesson learned from comparative imaging.

For polymeric nanoparticles (NPs) to deliver more drugs to tumors than free drug solution, it is critical that the NPs establish interactions with tumor cells and avoid removal from the tumors. Since traditional polyethylene glycol (PEG) surface layer interferes with the cell-NP interaction in tumors, we used a water-soluble and blood-compatible chitosan derivative called zwitterionic chitosan (ZWC) as an alternative surface coating for poly(lactic-co-glycolic acid) (PLGA) NPs. The ZWC-coated PLGA NPs showed pH-dependent surface charge profiles and differential cellular interactions according to the pH of the medium. The in vivo delivery of ZWC-coated NPs was evaluated in mice bearing LS174T-xenografts using magnetic resonance (MR) imaging and fluorescence whole body imaging, which respectively tracked iron oxide particles and indocyanine green (ICG) encapsulated in the NPs as tracers. MR imaging showed that ZWC-coated NPs were more persistent in tumors than PEG-coated NPs, in agreement with the in vitro results. However, the fluorescence imaging indicated that the increased NP retention in tumors by the ZWC coating did not significantly affect the ICG distribution in tumors due to the rapid release of the dye. This study shows that stable drug retention in NPs during circulation is a critical prerequisite to successful translation of the potential benefits of surface-engineered NPs.