Diboronic-Acid-Based Electrochemical Sensor for Enzyme-Free Selective and Sensitive Glucose Detection.

A diboronic acid anthracene-based fluorescent system for detecting blood glucose could be used for 180 days. However, there has not yet been a boronic acid immobilized electrode to selectively detect glucose in a signal-increased way. Considering malfunctions of sensors at high sugar levels, the electrochemical signal should be increased proportionally to the glucose concentration. Therefore, we synthesized a new diboronic acid derivative and fabricated the derivative-immobilized electrodes for the selective detection of glucose. We performed cyclic voltammetry and electrochemical impedance spectroscopy with an Fe(CN)63-/4- redox pair for detecting glucose in the range of 0-500 mg/dL. The analysis revealed increased electron-transfer kinetics such as increased peak current and decreased semicircle radius of Nyquist plots as the glucose concentration increased. The cyclic voltammetry and impedance spectroscopy showed that the linear detection range of glucose was 40 to 500 mg/dL with limits of detection of 31.2 mg/dL and 21.5 mg/dL, respectively. We applied the fabricated electrode to detect glucose in artificial sweat and obtained 90% of the performance of the electrodes in PBS. Cyclic voltammetry measurements of other sugars such as galactose, fructose, and mannitol also showed linear increased peak currents proportional to the concentrations of the tested sugars. However, the slopes of the sugars were lower than that of glucose, indicating selectivity for glucose. These results proved the newly synthesized diboronic acid is a promising synthetic receptor for developing a long-term usable electrochemical sensor system.

Highly bioactive bone cement microspheres based on α-tricalcium phosphate microparticles/mesoporous bioactive glass nanoparticles: Formulation, physico-chemical characterization and in vivo bone regeneration.

Calcium phosphate cement (CPC) is a self-setting, biocompatible and osteoconductive bone cement, however its use as a bone substitute is still limited owing to its low bioactivity (i.e. its slow in vivo resorption and slow new bone formation rate) which is a challenging issue to be addressed. Herein, we report for the first time highly bioactive bone cement microspheres formulated from a cement paste containing α-tricalcium phosphate microparticles (α-TCP) and mesoporous calcium silicate bioactive glass nanoparticles (mesoporous BGn) using a water-in-oil emulsion method. Indeed, bioactive microspheres possess high potential as bone defect fillers for bone regeneration. The α-TCP microparticles were prepared by a solid state synthesis at 1400 ºC while mesoporous BGn were synthesized by template-assissted ultrasound-mediated sol-gel method. The particle size distribution of as-prepared cement microspheres was in the range of 200 - 450 µm with a sphericity index in the range of 0.92 - 0.94. The surface morphology of α-TCP microspheres revealed α-TCP micoparticles with smooth surfaces whereas α-TCP/BGn microspheres unveiled nano-roughened α-TCP microparticles. The as-prepared α-TCP/BGn cement microspheres exhibited larger specific surface area ca 18.6 m2/g, sustained release of soluble silicate (SiO44-) ions (118 ppm within a week) and high protein adsorption capacity (252 mg/g). Notably, the α-TCP/BGn cement microspheres showed excellent in vitro surface bioactivity via formation of massive amounts of bone-like hydroxyapatite spherules and aggregates on their surfaces after soaking in simulated body fluid. Importantly, the in vivo implantation of as-prepared α-TCP/BGn cement microspheres in rat calvarial critical size bone defects for 6 weeks unveiled high in vivo bioactivity in terms of substantial new bone ingrowth and significant new bone formation within the bone defect as evidenced by histological analyses, X-ray radiography and micro-computed tomography evaluations.

Evaluation of Biomechanical Properties and Morphometric Structures of the Trachea in Pigs and Rabbits.

BACKGROUND/AIM: Animals differ in the biochemical composition, attachments, and mechanical properties of tracheal cartilage. This study examined the biomechanical properties and morphological structure of the trachea of pigs, and rabbits as preclinical models. MATERIALS AND METHODS: The trachea in pigs and rabbits can be divided into four regions, cranial cervical, middle cervical, thoracic inlet, and intra-thoracic parts. RESULTS: The total number of tracheal rings in pigs and rabbits was 32-35 and 34-38 rings, respectively. The pig bronchus first branches from the trachea, reaching the cranial lobe of the lungs before branching to the main bronchus, while the rabbit bronchus branched after the main bronchus. A comparison of the posterior region of the crosssectional trachea shows that the rabbit has a C-shape with cartilage connected to the tracheal muscle, and the pig has the tracheal muscle covered with cartilage. The trachea of pigs and rabbits decreased in tracheal thickness and size from the thoracic inlet toward the lungs. The stress-strain in the longitudinal and transverse tensile test was higher in rabbits than in pigs. The tensile stress of the four regions was significantly different in the transverse tensile test (p<0.001). In the bending test, more force was required to bend pig than rabbit tracheas. Microscopic and scanning electron microscopy showed no structural differences in tracheal cartilage between the two species. CONCLUSION: These results suggest that there is great variation in morphology and physical properties of the trachea in pigs and rabbits. We found porcine tracheas have similar biomechanical properties to those of humans.

Toxicological Evaluation of a Probiotic-Based Delivery System for P8 Protein as an Anti-Colorectal Cancer Drug.

PURPOSE: This study aimed to toxicological evaluate a probiotics-based delivery system for p8 protein as an anti-colorectal cancer drug. INTRODUCTION: Lactic acid bacteria (LAB) have been widely ingested for many years and are regarded as very safe. Recently, a Pediococcus pentosaceus SL4 (PP) strain that secretes the probiotic-derived anti-cancer protein P8 (PP-P8) has been developed as an anti-colorectal cancer (CRC) biologic by Cell Biotech. We initially identified a Lactobacillus rhamnosus (LR)-derived anti-cancer protein, P8, that suppresses CRC growth. We also showed that P8 penetrates specifically into CRC cells (DLD-1 cells) through endocytosis. We then confirmed the efficacy of PP-P8, showing that oral administration of this agent significantly decreased tumor mass (~42%) relative to controls in a mouse CRC xenograft model. In terms of molecular mechanism, PP-P8 induces cell-cycle arrest in G2 phase through down-regulation of Cyclin B1 and Cdk1. In this study, we performed in vivo toxicology profiling to obtain evidence that PP-P8 is safe, with the goal of receiving approval for an investigational new drug application (IND). METHODS: Based on gene therapy guidelines of the Ministry of Food and Drug Safety (MFDS) of Korea, the potential undesirable effects of PP-P8 had to be investigated in intact small rodent or marmoset models prior to first-in-human (FIH) administration. The estimated doses of PP-P8 for FIH are 1.0×1010 - 1.0×1011 CFU/person (60 kg). Therefore, to perform toxicological investigations in non-clinical animal models, we orally administered PP-P8 at doses of 3.375 × 1011, 6.75 × 1011, and 13.5×1011 CFU/kg/day; thus the maximum dose was 800-8000-fold higher than the estimated dose for FIH. RESULTS: In our animal models, we observed no adverse effects of PP-P8 on clinicopathologic findings, relative organ weight, or tissue pathology. In addition, we observed no inflammation or ulceration during pathological necropsy. CONCLUSION: These non-clinical toxicology studies could be used to furnish valuable data for the safety certification of PP-P8.

Highly Stable and Fine-Textured Hybrid Microspheres for Entrapment of Cosmetic Active Ingredients.

This study details the preparation and application of supramolecular host-guest inclusion complexes entrapping biomineralized microspheres for long-term storage and their pH-responsive behavior. The microspheres were assembled using a CaCO3 synthesis process coupled with cyclodextrin-tetrahydrocurcumin (CD-THC) inclusion complexes, forming fine-textured and mechanically stable hybrid materials. The products were successfully characterized using field-emission scanning electron microscopy (FE-SEM), energy-dispersive X-ray spectroscopy (EDS), Fourier transform infrared (FT-IR) spectroscopy, X-ray diffraction (XRD), and particle size analysis (PSA). Various parameters such as the Brunauer-Emmett-Teller (BET) surface area, single point total pore volume, and pore size via adsorption/desorption analysis were also determined. The obtained THC-entrapped hybrid microspheres contained as high as 20 wt % THC loading and were very stable, preserving 90% of the initial concentration over four weeks of storage at different temperatures, largely limiting THC leaching and indicating high stability in a physiological environment. In addition, the pH-responsive release of THC from the hybrid microspheres was observed, showing potential use for application to weakly acidic skin surfaces. To our knowledge, this is the first demonstration of antiaging cosmetic formulation technology using biomineralization based on the co-synthesis of CaCO3 and CD-THC complexes.

Combined Delivery of Two Different Bioactive Factors Incorporated in Hydroxyapatite Microcarrier for Bone Regeneration.

BACKGROUND: The delivery of growth factors using a carrier system presents a promising and innovative tool in tissue engineering and dentistry today. Two of the foremost bioactive factors, bone morphogenetic protein-2 and vascular endothelial growth factor (VEGF), are widely applied using a ceramic scaffold. The aim of this study was to determine the use of hydroxyapatite microcarrier (MC) for dual delivery of osteogenic and angiogenic factors to accelerate hard tissue regeneration during the regenerative process. METHODS: Two MCs of different sizes were fabricated by emulsification of gelatin and alpha-tricalcium phosphate (α-TCP). The experimental group was divided based on the combination of MC size and growth factors. For investigating the in vitro properties, rat mesenchymal stem cells (rMSCs) were harvested from bone marrow of the femur and tibia. For in vivo experiments, MC with/without growth factors was applied into the standardized, 5-mm diameter defects, which were made bilaterally on the parietal bone of the rat. The animals were allowed to heal for 8 weeks, and samples were harvested and analyzed by micro-computed tomography and histology. RESULTS: Improved proliferation of rat mesenchymal stem cells was observed with VEGF loaded MC. For osteogenic differentiation, dual growth factors delivered by MC showed higher osteogenic gene expression, alkaline phosphatse production and calcium deposition. The in vivo results revealed statistically significant increase in new bone formation when dual growth factors were delivered by MC. Dual growth factors administered on a calcium phosphate matrix showed significantly enhanced osteogenic potential. CONCLUSION: We propose this system has potential clinical utility in providing solutions for craniofacial bone defects, with the added benefit of early availability.

Preclinical Voxel-Based Dosimetry in Theranostics: a Review.

Due to the increasing use of preclinical targeted radionuclide therapy (TRT) studies for the development of novel theranostic agents, several studies have been performed to accurately estimate absorbed doses to mice at the voxel level using reference mouse phantoms and Monte Carlo (MC) simulations. Accurate dosimetry is important in preclinical theranostics to interpret radiobiological dose-response relationships and to translate results for clinical use. Direct MC (DMC) simulation is believed to produce more realistic voxel-level dose distribution with high precision because tissue heterogeneities and nonuniform source distributions in patients or animals are considered. Although MC simulation is considered to be an accurate method for voxel-based absorbed dose calculations, it is time-consuming, computationally demanding, and often impractical in daily practice. In this review, we focus on the current status of voxel-based dosimetry methods applied in preclinical theranostics and discuss the need for accurate and fast voxel-based dosimetry methods for pretherapy absorbed dose calculations to optimize the dose computation time in preclinical TRT.

Novel bone-mimetic nanohydroxyapatite/collagen porous scaffolds biomimetically mineralized from surface silanized mesoporous nanobioglass/collagen hybrid scaffold: Physicochemical, mechanical and in vivo evaluations.

Bone-mimetic scaffolds are receiving much interest as such scaffolds exhibit excellent biocompatibility and very close mimic to bone structure and composition. Here, novel bone-mimetic nanohydroxyapatite (nHA)/collagen (Col) porous scaffolds (nHA/Col) were prepared from surface silanized mesoporous nanobioglass (NBG)/Col hybrid scaffold by biomimetic mineralization. Surface silanized mesoporous NBG was prepared by ultrasound-assisted sol-gel method and post treatment with 3-aminopropyltriethylsilane (APTS). The surface silanized mesoporous NBG was characterized by transmission electron microscopy (TEM), transmission electron microscopy-selected area electron diffraction (TEM-SAED) and X-ray photoelectron spectroscopy (XPS). The physicochemical/mechanical characterizations of the scaffolds included scanning electron microscopy (SEM) and TEM imaging of micro/nanostructure, energy dispersive X-ray (EDX) analysis of chemical composition, TEM-SAED and X-ray diffraction/Attenuated total Reflectance-Fourier Infrared spectroscopy (XRD/ATR-FTIR) analyses of amorphous-to-crystalline transformations, thermogravimetric/differential scanning calorimetric (TGA/DSC) analyses of thermal behaviour , porosity and dynamic mechanical analyses. The presence of NBG in collagen fibrillar network enabled progressive growth of HA nanocrystals and generation of a novel bone-mimetic hybrid structures while preserving the highly porous structure of collagen scaffold. The crystallinity, crystallite size and crystal morphology of the grown HA nanocrystals were controllable by regulation of the mineralization time. Furthermore, the osteogenic properties of the non-mineralized (NBG/Col) and mineralized (nHA/Col) hybrid porous scaffolds were examined in vivo using critical-sized calvarial bone defect model in rat. Histological and micro-computed tomography (Micro-CT) analyses after 6 weeks of implantation revealed that the mineralized scaffolds possess excellent in vivo osteogenic potential compared to the non-mineralized one. Collectively, by using surface silanized mesoporous NBG hybridization with collagen fibrillar network, we successfully introduced a new approach for developing novel bone-mimetic nanohydroxyapatite/collagen hybrid scaffolds that possess significant potential for bone tissue regeneration.

Correction: Dynamic mechanical and nanofibrous topological combinatory cues designed for periodontal ligament engineering.

[This corrects the article DOI: 10.1371/journal.pone.0149967.].

SIS/aligned fibre scaffold designed to meet layered oesophageal tissue complexity and properties.

With donor organs not readily available, the need for a tissue-engineered oesophagus remains high, particularly for congenital childhood conditions such as atresia. Previous attempts have not been successful, and challenges remain. Small intestine submucosa (SIS) is an acellular matrix material with good biological properties; however, as is common with these types of materials, they demonstrate poor mechanical properties. In this work, electrospinning was performed to mechanically reinforce tubular SIS with polylactic-co-glycolic acid (PLGA) nanofibres. It was hypothesised that if attachment could be achieved between the two materials, then this would (i) improve the SIS mechanical properties, (ii) facilitate smooth muscle cell alignment to support directional growth of muscle cells and (iii) allow for the delivery of bioactive molecules (VEGF in this instance). Through a relatively simple multistage process, adhesion between the layers was achieved without chemically altering the SIS. It was also found that altering mandrel rotation speed affected the alignment of the PLGA nanofibres. SIS-PLGA scaffolds performed mechanically better than SIS alone; yield stress improvement was 200% and 400% along the longitudinal and circumferential directions, respectively. Smooth muscle cells cultured on the aligned fibres showed resultant unidirectional alignment. In vivo the SIS-PLGA scaffolds demonstrated limited foreign body reaction judged by the type and proportion of immune cells present and lack of fibrous encapsulation. The scaffolds remained intact at 4 weeks in vivo, and good cellular infiltration was observed. The incorporation of VEGF within SIS-PLGA scaffolds increased the blood vessel density of the surrounding tissues, highlighting the possible stimulation of endothelialisation by angiogenic factor delivery. Overall, the designed SIS-PLGA-VEGF hybrid scaffolds might be used as a potential matrix platform for oesophageal tissue engineering. In addition to this, achieving improved attachment between layers of acellular matrix materials and electrospun fibre layers offers the potential utility in other applications. STATEMENT OF SIGNIFICANCE: Because of its multi-layered nature and complex structure, the oesophagus tissue poses several challenges for successful clinical grafting. Therefore, it is promising to utilise tissue engineering strategies to mimic and form structural compartments for its recovery. In this context, we investigated the use of tubular small intestine submucosa (SIS) reinforced with polylactic-co-glycolic acid (PLGA) nanofibres by using electrospinning and also, amongst other parameters, the integrity of the bilayered structure created. This was carried out to facilitate smooth muscle cell alignment, support directional growth of muscle cells and allow the delivery of bioactive molecules (VEGF in this study). We evaluated this approach by using in vitro and in vivo models to determine the efficacy of this new system.

Deep-dose: a voxel dose estimation method using deep convolutional neural network for personalized internal dosimetry.

Personalized dosimetry with high accuracy is crucial owing to the growing interests in personalized medicine. The direct Monte Carlo simulation is considered as a state-of-art voxel-based dosimetry technique; however, it incurs an excessive computational cost and time. To overcome the limitations of the direct Monte Carlo approach, we propose using a deep convolutional neural network (CNN) for the voxel dose prediction. PET and CT image patches were used as inputs for the CNN with the given ground truth from direct Monte Carlo. The predicted voxel dose rate maps from the CNN were compared with the ground truth and dose rate maps generated voxel S-value (VSV) kernel convolution method, which is one of the common voxel-based dosimetry techniques. The CNN-based dose rate map agreed well with the ground truth with voxel dose rate errors of 2.54% ± 2.09%. The VSV kernel approach showed a voxel error of 9.97% ± 1.79%. In the whole-body dosimetry study, the average organ absorbed dose errors were 1.07%, 9.43%, and 34.22% for the CNN, VSV, and OLINDA/EXM dosimetry software, respectively. The proposed CNN-based dosimetry method showed improvements compared to the conventional dosimetry approaches and showed results comparable with that of the direct Monte Carlo simulation with significantly lower calculation time.

Preclinical voxel-based dosimetry through GATE Monte Carlo simulation using PET/CT imaging of mice.

Internal dosimetry is of critical importance to obtain an accurate absorbed dose-response relationship during preclinical molecular imaging and targeted radionuclide therapy (TRT). Conventionally, absorbed dose calculations have been performed using organ-level dosimetry based on the Medical Internal Radiation Dose (MIRD) schema. However, recent research has focused on developing more accurate voxel-level calculation methods. Geant4 application for emission tomography (GATE) Monte Carlo (MC) is a simulation toolkit gaining attention in voxel-based dosimetry. In this study, we used PET/CT images of real mice to estimate the absorbed doses in sensitive organs at voxel-level to evaluate the suitability of GATE MC simulation for preclinical dosimetry. Thirteen normal C57BL/6 mice (male, body weight: 27.71 ± 4.25 g) were used to acquire dynamic positron emission tomography/computed tomography (PET/CT) images after IV injection of 18F-FDG. GATE MC toolkit was applied to estimate the absorbed doses in various organs of mice at voxel-level using CT and PET images as voxelized phantom and voxelized source, respectively. In addition, mean absorbed dose at organ-level was calculated using MIRD schema for comparison purposes. The differences in the respective absorbed doses (mGy MBq-1) between GATE MC and MIRD schema for brain, heart wall, liver, lungs, stomach wall, spleen, kidneys, and bladder wall were 1.36, 12.3, -22.4, -11.2, -16.9, -2.87, -4.29, and 3.71%, respectively. Considering that the PET/CT data of real mice were used for GATE simulation, the absorbed doses estimated in this study are mouse-specific. Therefore, the GATE-based Monte Carlo is likely to allow for more accurate internal dosimetry calculations. This method can be used in TRT for personalized dosimetry because it considers patient-specific heterogeneous tissue compositions and activity distributions.

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

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.

Fast and simple method for screening of single-stranded DNA breaking photosensitizers using graphene oxide.

A fast and simple method for screening of ssDNA-breaking photosensitizers was developed using graphene oxide. The ultraviolet light-induced DNA breaks are one of the most harmful DNA damages and cause skin cancer if they are left unrepaired. Since graphene oxide showed relatively strong affinity to the broken DNA than intact DNA, and it quenched fluorescence of the DNA labeling dye effectively, the degree of ultraviolet light-induced broken DNAs could be analyzed by measuring decreased fluorescence after mixing the DNA with graphene oxide. The decrease of fluorescence was highly correlated with the ultraviolet light-irradiating time and concentration of the added drugs. As a result, it was possible to evaluate the efficacy of different ssDNA-breaking photosensitizers in a high-throughput manner. However, conventional methods for the damaged-DNA analysis are time-consuming and require additional manipulations such as purification, radio-labeling, enzymatic digestion, or chemical modification of DNA. The phototoxicity of five drugs such as benzophenone, ketoprofen, indomethacin, naproxen, and norfloxacin was tested using the proposed method. The ssDNA-breaking efficiency of the drugs was well matched with reported efficiency of the tested drugs. In contrast to naked gold nanoparticles, graphene oxide is stably dispersed in the presence of salt, the phototoxicity of the drugs could be successfully tested at a physiological condition using the graphene oxide based method.

Biodistribution and Internal Radiation Dosimetry of 99mTc-IDA-D-[c(RGDfK)]2 (BIK-505), a Novel SPECT Radiotracer for the Imaging of Integrin αvß3 Expression.

BACKGROUND: Integrin αvß3 is a molecular marker for the estimation of tumor angiogenesis. 99mTc-IDA-D-[c(RGDfK)]2 (also known as BIK-505) is a recently developed radiotracer for single-photon emission computed tomography, with good affinity for integrin αvß3. In this study, the authors investigated the whole-body distribution and internal radiation dosimetry of 99mTc-IDA-D-[c(RGDfK)]2 in elderly human participants. MATERIALS AND METHODS: Six healthy volunteers underwent whole-body simultaneous anterior and posterior scans, preceded by transmission scans using cobalt-57 flood source, with a dual head gamma camera system, at 0, 1, 2, 4, 8, and 24 h postinjection of 99mTc-IDA-D-[c(RGDfK)]2 (injected radioactivity [mean ± SD] = 388.7 ± 29.3 MBq). Anterior and posterior images were geometrically averaged and attenuation corrected to delineate the regions of interest in the liver, gallbladder, kidneys, urinary bladder, spleen, brain, and large intestine. Radiation dose for each organ and the effective doses (EDs) were estimated using OLINDA/EXM 1.1 software. RESULTS: High radiation doses of renal and biliary excretion tracks such as the urinary bladder wall, upper large intestine, kidneys, liver, and gallbladder wall (19.15 ± 6.84, 19.28 ± 4.78, 15.67 ± 0.90, 9.13 ± 1.71, and 9.09 ± 2.03 µGy/MBq, respectively) were observed. The ED and effective dose equivalent were 5.08 ± 0.53 and 7.11 ± 0.58 µSv/MBq, respectively. CONCLUSIONS: Dosimetry results were comparable to other radiolabeled peptides and were considered safe and efficient for clinical usage.

Vertical Bone Augmentation Using Three-dimensionally Printed Cap in the Rat Calvarial Partial Defect.

BACKGROUND/AIM: Lost alveolar bone is commonly restored by distraction osteogenesis or bone blocks for substantial vertical bone augmentation (VBA), that is applied in conjunction with a barrier system. This study was performed to determine whether volume control of a three-dimensional (3D) printed nylon cap in the rat calvarial partial thickness bone defect would induce qualitative and quantitative differences in vertical bone regeneration. MATERIALS AND METHODS: A rat calvarial partial thickness bone defect was prepared and the 3D cap covered the defect to induce VBA, while the control group was left without cap placement. After six weeks the animals were sacrificed, and the calvaria were prepared for micro-CT (µCT) and histology. RESULTS: Quantitative µCT results showed that our cap system has significant osteoconductive properties, and the histology slide revealed new bone filled inside the cap. CONCLUSION: The results clearly showed that this system was successful for VBA in a research animal model.

One-step isothermal detection of multiple KRAS mutations by forming SNP specific hairpins on a gold nanoshell.

We developed a one-step isothermal method for typing multiple KRAS mutations using a designed set of primers to form a hairpin on a gold nanoshell upon being ligated by a SNP specific DNA ligase after binding of targets. As a result, we could detect as low as 20 attomoles of KRAS mutations within 1 h.

Dual growth factor-immobilized asymmetrically porous membrane for bone-to-tendon interface regeneration on rat patellar tendon avulsion model.

Insufficient repair of the bone-to-tendon interface (BTI) with structural/compositional gradients has been a significant challenge in orthopedics. In this study, dual growth factor (platelet-derived growth factor-BB [PDGF-BB] and bone morphogenetic protein-2 [BMP-2])-immobilized polycaprolactone (PCL)/Pluronic F127 asymmetrically porous membrane was fabricated to estimate its feasibility as a potential strategy for effective regeneration of BTI injury. The growth factors immobilized (via heparin-intermediated interactions) on the membrane were continuously released for up to ∼80% of the initial loading amount after 5 weeks without a significant initial burst. From the in vivo animal study using a rat patellar tendon avulsion model, it was observed that the PDGF-BB/BMP-2-immobilized membrane accelerates the regeneration of the BTI injury, probably because of the continuous release of both growth factors (biological stimuli) and their complementary effect to create a multiphasic structure (bone, fibrocartilage, and tendon) like a native structure, as well as the role of the asymmetrically porous membrane as a physical barrier (nanopore side; prevention of fibrous tissue invasion into the defect site) and scaffold (micropore side; guidance for tissue regeneration). © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 115-125, 2018.

Whole-Body Voxel-Based Personalized Dosimetry: The Multiple Voxel S-Value Approach for Heterogeneous Media with Nonuniform Activity Distributions.

Personalized dosimetry with high accuracy is becoming more important because of the growing interest in personalized medicine and targeted radionuclide therapy. Voxel-based dosimetry using dose point kernel or voxel S-value (VSV) convolution is available. However, these approaches do not consider the heterogeneity of the medium. Here, we propose a new method for whole-body voxel-based personalized dosimetry in heterogeneous media with nonuniform activity distributions-a method we refer to as the multiple VSV approach. Instead of using only a single VSV, as found in water, the method uses multiple numbers (N) of VSVs to cover media of various density ranges, as found in the whole body. Methods: The VSVs were precalculated using GATE Monte Carlo simulation and were convoluted with the time-integrated activity to generate density-specific dose maps. CT-based segmentation was performed to generate a binary mask image for each density region. The final dose map was acquired by the summation of N segmented density-specific dose maps. We tested several sets of VSVs with different densities: N = 1 (single water VSV), 4, 6, 8, 10, and 20. To validate the proposed method, phantom and patient studies were conducted and compared with the direct Monte Carlo approach, which was considered the ground truth. Finally, dosimetry on 10 patients was performed using the multiple VSV approach and compared with the single VSV and organ-based approaches. Errors at the voxel and organ levels were reported for 8 organs. Results: In the phantom and patient studies, the multiple VSV approach showed significant decreases in voxel-level errors, especially for the lung and bone regions. As the number of VSVs increased, voxel-level errors decreased, although some overestimations were observed at the lung boundaries. For the multiple VSVs (N = 8), we achieved a voxel-level error of 2.06%. In the dosimetry study, our proposed method showed greatly improved results compared with single VSV and organ-based dosimetry. Errors at the organ level were -6.71%, 2.17%, and 227.46% for single VSV, multiple VSV, and organ-based dosimetry, respectively. Conclusion: The multiple VSV approach for heterogeneous media with nonuniform activity distributions offers fast personalized dosimetry at the whole-body level, yielding results comparable to those of the direct Monte Carlo approach.

In situ synthesis of silver nanoparticles on the surface of PDMS with high antibacterial activity and biosafety toward an implantable medical device.

We developed a straightforward method to fabricate antibacterial silicon films via the in situ synthesis of silver nanoparticles (AgNPs) on a polydimethylsiloxane (PDMS) film. To grow AgNPs attached on the film, AgNP seeds were synthesized through the reduction of silver ions electrostatically bound to hydroxyl groups formed on the surface of the film after treatment with air plasma. In the growth reaction, silver ions were reduced on the seeds of AgNPs by sodium citrate in a solution of AgNO3, which allowed for the formation of AgNPs with sizes of up to ~ 500 nm, which The formed AgNPs on the films were characterized using UV-vis spectrophotometer, scattering electron microscope and induced coupled mass spectrometer. The amount of AgNPs was estimated to be less than 0.05% of the total film weight. Even though it was coated with a small amount of AgNPs, the PDMS film exhibited reduction of E. coli and S. aureus with values of log10 4.8 and log10 5.7, respectively. The biosafety of the AgNP-attached PDMS film was examined by contact of cells with the film or film eluent. Counting of viable cells revealed no significant cytotoxicity of the in situ-fabricated AgNPs on the PDMS film.