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This study explores the application of synchrotron radiation and conventional microcomputed tomography (SR-µCT and C-µCT, respectively) in evaluating bone-biopsy specimens. Bone-biopsy specimens were obtained using a trephine bur during bone-graft removal for implant placement six months after performing a maxillary sinus bone-graft procedure. Image data of specimens were obtained using SR-µCT and C-µCT. SR-µCT was performed using the 6C biomedical imaging beamline at the Pohang Accelerator Laboratory with a monochromatic X-ray beam of 23 keV, and C-µCT was performed using a table-top CT scanner (Skyscan 1272). Reconstruction images obtained using the two methods were qualitatively compared with 2D images evaluated under 3D visualization. The SR-µCT images, especially of the new-bone–graft–woven-bone formation, were less noisy and sharper than the C-µCT images. To evaluate the new-bone–graft–woven-bone formation, only the SR-µCT images showed areas of new bone (NB) formation with bone substitute (BS; Bio-Oss) and woven bone (WB) contact, and correctly visualized true 3D structures of bone formation. Hence, µCT techniques are non-destructive and can provide detailed images of bone biopsy. In particular, SR-µCT can be used to obtain improved image quality with contrast of NB, BS and WB, demonstrating a level of detail comparable with bone formation. SR-µCT could be an unbiased 3D alternative for imaging WB formation and for high-throughput analysis.

The hydrophilicity of bone graft material generally used as a carrier can play an important role in regulating bone morphogenetic protein (BMP) expression at the bone graft site. The hydrophilicity, altering physicochemical properties, and enhancing biological capabilities, can be increased via surface modification through ultraviolet (UV) photofunctionalization and the effect on de novo osteogenesis could be further improved. Therefore, this study aimed to assess the effects of UV-irradiated TiO2 -coated hydroxyapatite (HA) in combination with rhBMP-2 on bone regeneration in rabbit calvarial defects. The hydrophilicity of HA and TiO2 -coated HA pellets was evaluated by measuring the contact angle of water droplets with UV irradiation. To compare de novo osteogenesis in rabbit calvarial defects, the rabbits were segregated into four different groups: negative control, HA, TiO2 -coated HA, and TiO2 -coated HA with UV; histomorphometric analysis and micro-computed tomography (μCT) imaging were performed after 4 and 8 weeks. In vivo analysis revealed that de novo osteogenesis occurred on the critical size defects in all groups and was significantly increased in the TiO2 -coated HA with UV group than in other groups (p < 0.05). The present results indicate that UV photofunctionalization promotes de novo osteogenesis. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 1953-1959, 2019.

Bone homeostasis is maintained by concerted actions of bone-forming osteoblasts and bone-resorbing osteoclasts. A wide range of evidence indicates that a proinflammatory cytokine IL-17 promotes osteoclastogenesis. However, the role of IL-17 in osteoblasts is less well-understood. In the current study, the effect of IL-17 on osteogenic differentiation was investigated in mouse calvarial cells. IL-17 stimulated osteoblast differentiation, mineralization, proliferation, motility, and osteoblast-dependent osteoclastogenesis in vitro. The pro-osteogenic role of IL-17 was dependent on Act1 and the generation of reactive oxygen species. In a critical size calvarial defect model, IL-17 significantly augmented bone regeneration. Importantly, IL-17 also remarkably increased bone remodeling and restored osteoclastogenesis in zoledronate-treated mice. Furthermore, IL-17 conspicuously stimulated the formation of lamellar bones. These data not only provide a clue to understand the role of IL-17 in bone metabolism but also suggest possible applications in bone augmentation therapies.

In this paper, we propose an intravitreal implantable magnetic micropump integrated with micro check valve capable of on-demand vascular endothelial growth factor receptor (VEGFR)-targeted drug delivery for the treatment of age-related macular degeneration, diabetic retinopathy and other eye pathologies characterized by ocular neoangiogenesis. Precise on-demand drug release is realized by the deflection of the magnetic membrane assembly according to the external magnetic field, and the membrane assembly consists of a thin elastic polydimethylsiloxane (PDMS) membrane and a cylindrical magnetic nanoparticle-PDMS composite block. Additionally, a micro check valve composed of two PDMS layers was integrated into the micropump to realize a diode-like one-directional drug delivery and prevent undesired drug diffusion. For specifically targeting VEGFR and suppression of VEGF-induced proliferation of microvascular endothelial cells, anti-Flt1 gold nanocomplexes are synthesized. In vitro and in vivo experiments and quantitative analysis are carried out in order to verify our proposed concept: precise drug release control according to the external magnetic field, targeting to microvascular endothelial cells, and efficient and on-demand drug delivery from the proposed micropump to the macular area of rabbit's eye.

The Coulomb nanoradiator (CNR) effect produces the dose enhancement effects from high-Z nanoparticles under irradiation with a high-energy ion beam. To gain insight into the radiation dose and biological significance of the CNR effect, the enhancement of reactive oxygen species (ROS) production from iron oxide or gold NPs (IONs or AuNPs, respectively) in water was investigated using traversing proton beams.The dependence of nanoradiator-enhanced ROS production on the atomic Z value and proton energy was investigated. Two biologically important ROS species were measured using fluorescent probes specific to •OH or [Formula: see text] in a series of water phantoms containing either AuNPs or IONs under irradiation with a 45- or 100-MeV proton beam.The enhanced generation of hydroxyl radicals (•OH) and superoxide anions ([Formula: see text]) was determined to be caused by the dependence on the NP concentration and proton energy. The proton-induced Au or iron oxide nanoradiators exhibited different ROS enhancement rates depending on the proton energy, suggesting that the CNR radiation varied. The curve of the superoxide anion production from the Au-nanoradiator showed strong non-linearity, unlike the linear behavior observed for hydroxyl radical production and the X-ray photoelectric nanoradiator. In addition, the 45-MeV proton-induced Au nanoradiator exhibited an ROS enhancement ratio of 8.54/1.50 ([Formula: see text] / •OH), similar to that of the 100-KeV X-ray photoelectric Au nanoradiator (7.68/1.46).The ROS-based detection of the CNR effect revealed its dependence on the proton beam energy, dose and atomic Z value and provided insight into the low-linear energy transfer (LET) CNR radiation, suggesting that these factors may influence the therapeutic efficacy via chemical reactivities, transport behaviors, and intracellular oxidative stress.

The regeneration of bone defects caused by periodontal disease or trauma is an important goal. Porous hydroxyapatite (HA) is an osteoconductive graft material. However, the hydrophobic properties of HA can be a disadvantage in the initial healing process. HA can be coated with TiO2 to improve its hydrophilicity, and ultraviolet irradiation (UV) can further increase the hydrophilicity by photofunctionalization. This study was designed to evaluate the effect of 5% TiO2-coated HA on rabbit calvarial defects and compare it with that of photofunctionalization on new bone in the early stage. The following four study groups were established, negative control, HA, TiO2-coated HA, and TiO2-coated HA with UV. The animals were sacrificed and the defects were assessed by radiography as well as histologic and histomorphometric analyses. At 2 and 8 weeks postoperatively, the TiO2-coated HA with UV group and TiO2-coated HA group showed significantly higher percentages of new bone than the control group (p &lt, 0.05). UV irradiation increased the extent of new bone formation, and there was a significant difference between the TiO2-coated HA group and TiO2-coated HA with UV group. The combination of TiO2/HA and UV irradiation in bone regeneration appears to induce a favorable response.

Purpose This randomized controlled study aimed to evaluate the effects of an electric toothbrush with 3 colors of light-emitting diodes (LEDs) on antiplaque and bleeding control. Methods This randomized, placebo-controlled, double-blinded, parallel-group clinical trial included 50 healthy adults with gingivitis, who were randomly assigned to 2 groups. The experimental group used electric toothbrushes with 3 colors of LEDs and the control group used the same electric toothbrush as the experimental group, but with LED sources with one-hundredth of the strength. The subjects used the electric toothbrush 3 times a day for 4 minutes each time. As clinical indices, bleeding on marginal probing (BOMP), the Löe-Silness gingival index (GI), and the Turesky-Quigley-Hein plaque index (QHI) were assessed at baseline, at 3 weeks, and at 6 weeks. Results There were significant decreases in all clinical indices (BOMP, GI, QHI) in both the experimental and control groups compared to baseline at 3 weeks and at 6 weeks. In a comparison between the experimental and control groups, no statistically significant differences were observed for any clinical indices at 3 weeks (P>0.05). However, at 6 weeks, statistically significant differences were observed between the experimental and control groups in BOMP and GI, which are indicators of gingival inflammation (P, Graphical Abstract

Anti-Flt1 peptide of GNQWFI binds to vascular endothelial growth factor receptor 1 (VEGFR1 or Flt1) and prevents binding of VEGF, inhibiting VEGFR1-mediated endothelial cell migration and tube formation. Bare gold nanoparticle (AuNP) was known to have anti-angiogenic properties by specific binding with VEGF. In this study, anti-Flt1 peptide (GGNQWFI) and cyanine were chemically conjugated to AuNPs (Flt1@AuNP-cyanine 5.5 or Flt1@AuNP-hydrocyanine 5.5 [HCy5.5]) to enhance antiangiogenic properties with targeting to VEGFR-1 as well as producing Coulomb nanoradiator therapeutic effect on the retinal endothelial cells. Anti-Flt1 AuNP complex showed binding with VEGFR-1 and showed more protein-induced fluorescence enhancement (PIFE) by various VEGFs compared with bare AuNPs, suggesting enhanced antiangiogenic properties compared to bare AuNP. Nonfluorescent Flt1@AuNP-HCy5.5 successfully reacted with reactive oxygen species (ROS) produced from Fenton reactions or a proton-induced Coulomb nanoradiator, enabling quenching-free oxidant fluorescence ROS imaging in HRMECs under oxidative stress. Flt1@AuNP-HCy5.5 alone induced 50% greater cytotoxicity for HRMECs compared to bare AuNPs and 80% greater cell death by the Au-nanoradiator effect. In conclusion, this study describes a new therapeutic anti-Flt1 gold nanocomplex with enhanced antiangiogenic properties and nanoradiator-mediated cytotoxicity on retinal endothelial cells. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 1272-1283, 2019.

An x-ray fluorescence computed tomography using a pinhole collimator (p-XFCT) for medical use depicts the 3-D distribution of imaging agent by collecting the x-ray fluorescence photons emitted from the imaging agent accumulated in an organ using a pinhole collimator and a 2-D detector. However, the number of the fluorescent x-ray photons are restricted by the pinhole, leading to acquisition of low S/N projections due to the photon starvation. Simultaneous acquisition of multiple projections using a multi-pinhole scheme overcomes the photon starvation. In this research, we clarified the measurement process and described the quantitative linear relationship between the quantities to be estimated and to be measured. We solved the multi-pinhole based XFCT (mp-XFCT) as a linear inverse problem regarding the described measurement process using ML-EM (maximum likelihood expectation-maximization) algorithm. We actually constructed an mp-XFCT imaging system at beamline AR-NE7A in KEK, and performed imaging experiment using a physical phantom to demonstrate the efficacy of mp-XFCT.

High-resolution tomographic images using synchrotron X-rays are expected to provide detailed reflection of microstructures, thereby allowing for the examination of histologic structures without destruction of the specimen. This study aims to evaluate the synchrotron tomographic images of mixed ground-glass opacity excised on 5-mm sections in comparison to pathologic examination. The Institutional Review Board of our institute approved this retrospective study, and written informed consent was obtained from each patient whose lung tissue would be used. Obtained lung cancer specimens were brought to the multiple Wiggler 6C beam line at the Pohang Light Source (PLS-II) in Korea, and phase contrast X-ray images were obtained in November 2016. The X-ray emanated from a bending magnet of the electron storage ring with electron energy of 3 GeV, and a typical beam current was 320 mA. Reconstructed tomographic images were compared with images from histologic slides obtained from the same samples. Pulmonary microstructures including terminal bronchioles, alveolar sacs, and vasculature were identified with phase contrast X-ray images. Images from normal lung tissue and mixed ground-glass opacity were clearly distinguishable. Hyperplasia of the interalveolar septum and dysplasia of microstructure were clearly identified. The imaging findings correlated well with hematoxylin-eosin stained specimens. Tomographic images using synchrotron radiation have the potential for clinical applications. With refinement, this technique may become a diagnostic tool for detection of lung cancer.

It is crucial to overcome the skull-based contrast loss of cerebral structures in the development of high-resolution X-ray phase-contrast transcranial brain imaging. The present study aimed to determine the consequence of microporous skull-based scattering and its correlation with the contrast loss in a dark-field imaging-computed tomography transcranial brain imaging setup and to suggest methods for visualizing interior structures in analyzer-based X-ray transcranial brain CT imaging. Virtual-skull brain phantoms that mimic the microporous structure of the skull and internal structures including gray/white matter, glioma edema, and the central necrosis of glioma were prepared for wave-propagation simulation of dark-field computed tomography imaging. Reconstruction of refraction angle images and sinogram analysis of angle deviation showed microporous skull-mediated increases in the right-left angle mismatch and out-of-range values in curve fitting with a rocking curve, which was correlated with the contrast loss for internal structures. Correcting the angle mismatch and artificially widening the rocking curve both restored contrast to the internal structures in the reconstructed images. In conclusion, the contrast loss in analyzer-based X-ray diffraction for transcranial brain imaging was related to increases in microporous skull-mediated angle mismatches and out-of-range values when calculating refraction angles using the analyzer rocking curve. This contrast loss may be resolved by using refraction angle measurements from an analyzer crystal with a wider rocking curve or by using an algorithm such as a neural network that can distinguish the left/right refraction angle for a given intensity in a rocking curve.

This paper describes an X-ray phase contrast imaging technique using analyzer-based optics called X-ray Dark-Field Imaging that has been under development for the past 10 years. We describe the theory behind XDFI, the X-ray optics required for implementing it in practice, and algorithms used for 2D, 2.5D, and 3D image reconstruction. The XDFI optical chain consists of an asymmetrically cut, Bragg-type monochromator-collimator that provides a planar monochromatic X-ray beam, a positioning stage for the specimens, a Laue-case angle analyzer, and one or two cameras to capture the dark and bright field images. We demonstrate the soft-tissue discrimination capabilities of XDFI by reconstructing images with absorption and phase contrast. By using a variety of specimens such as breast tissue with cancer, joints with articular cartilage, ex-vivo human eye specimen, and others, we show that refraction-based contrast derived from XDFI is more effective in characterizing anatomical features, articular pathology, and neoplastic disease than conventional absorption-based images. For example, XDFI of breast tissue can discriminate between the normal and diseased terminal duct lobular unit, and between invasive and in-situ cancer. The final section of this paper is devoted to potential future developments to enable clinical and histo-pathological applications of this technique.

BACKGROUND Recombinant human bone morphogenetic proteins (rhBMPs) have been widely used in regenerative therapies to promote bone formation. The production of rhBMPs using bacterial systems such as Escherichia coli (E. coli) is estimated to facilitate clinical applications by lowering the cost without compromising biological activity. In clinical practice, rhBMP-2 and osteoconductive carriers (e.g., hydroxyapatite [HA] and bovine bone xenograft) are used together. This study examined the effect of E. coli-derived rhBMP-2 combined with porous HA-based ceramics on calvarial defect in rabbits. METHODS Six adult male New Zealand white rabbits were used in this study. The experimental groups were divided into the following 4 groups: untreated (NC), bovine bone graft (BO), porous HA (HA) and porous HA with rhBMP-2 (HA-BMP). Four transosseous defects of 8 mm in diameter were prepared using stainless steel trephine bur in the frontal and parietal bones. Histological and histomorphometric analyses at 4 weeks after surgery revealed significant new bone formation by porous HA alone. RESULTS HA-BMP showed significantly higher degree of bone formation compared with BO and HA group (P