Rapid Flow Synthesis of a Biomimetic Carbonate Apatite as an Effective Drug Carrier.

A facile synthesis of apatite nanocrystals analogous to bioapatites with increased biocompatibility and biodegradability can remedy the shortcomings of the widely applied synthetic hydroxyapatite (HAp) for bone defect treatment. Here, we propose an expeditious synthesis method to develop a biomimetic B-type carbonate apatite (CAp) with a simple capillary microfluidic device at room temperature. The process not only eliminates fluctuations with the addition of carbonate but also produces safe CAp drug carriers through simultaneous alendronate incorporation to the CAp structure. CAp displayed superior mineralization on osteoblast-like MG-63 cells when compared with HAp and HAp drug carriers that were produced using identical methods. Furthermore, alendronate-incorporated CAp drug carriers potentially displayed higher cancer cell suppression when applied to breast cancer cells attached to the bone tissue model, which signifies enhanced cancer metastasis to bone suppression due to the likelihood of increased alendronate release of CAp owing to its faster dissolution. Overall, our results may provide promising opportunities for enhanced clinical CAp application for bone defect treatment, particularly for bone loss and cancer to bone metastasis.

Rapid Single-Step Growth of MOF Exoskeleton on Mammalian Cells for Enhanced Cytoprotection.

Mammalian cells are promising agents for cell therapy, diagnostics, and drug delivery. For full utilization of the cells, development of an exoskeleton may be beneficial to protecting the cells against the environmental stresses and cytotoxins to which they are susceptible. We report here a rapid single-step method for growing metal-organic framework (MOF) exoskeletons on a mammalian cell surface under cytocompatible conditions. The MOF exoskeleton coating on the mammalian cells was developed via a one-pot biomimetic mineralization process. With the exoskeleton on, the individual cells were successfully protected against cell protease (i.e., Proteinase K), whereas smaller-sized nutrient transport across the exoskeleton was maintained. Moreover, vital cellular activities mediated by transmembrane GLUT transporter proteins were also unaffected by the MOF exoskeleton formation on the cell surfaces. Altogether, this ability to control the access of specific molecules to a single cell through the porous exoskeleton, along with the cytoprotection provided, should be valuable for biomedical applications of mammalian cells.

Correction: Correlative microscopy of the constituents of a dinosaur rib fossil and hosting mudstone: Implications on diagenesis and fossil preservation.

[This corrects the article DOI: 10.1371/journal.pone.0186600.].

Correlative microscopy of the constituents of a dinosaur rib fossil and hosting mudstone: Implications on diagenesis and fossil preservation.

We have applied correlative microscopy to identify the key constituents of a dorsal rib fossil from Koreanosaurus boseongensis and its hosting mudstone discovered at the rich fossil site in Boseong, South Korea, to investigate the factors that likely contributed to diagenesis and the preservation of fossil bone. Calcite and illite were the commonly occurring phases in the rib bone, hosting mudstone, and the boundary region in-between. The boundary region may have contributed to bone preservation once it fully formed by acting as a protective shell. Fluorapatite crystals in the rib bone matrix signified diagenetic alteration of the original bioapatite crystals. While calcite predominantly occupied vascular channels and cracks, platy illite crystals widely occupied miniscule pores throughout the bone matrix. Thorough transmission electron microscopy (TEM) study of illite within the bone matrix indicated the solid-state transformation of 1M to 2M without composition change, which was more evident from the lateral variation of 1M to 2M within the same layer. The high level of lattice disordering of 2M illite suggested an early stage of 1M to 2M transformation. Thus, the diagenetic alteration of both apatite and illite crystals within the bone matrix may have increased its overall density, as the preferred orientation of apatite crystals from moderate to strong degrees was evident despite the poor preservation of osteohistological features. The combined effects of rapid burial, formation of a boundary region, and diagenesis of illite and apatite within the bone matrix may have contributed to the rib bone preservation.

Disparities in correlating microstructural to nanostructural preservation of dinosaur femoral bones.

Osteohistological researches on dinosaurs are well documented, but descriptions of direct correlations between the bone microstructure and corresponding nanostructure are currently lacking. By applying correlative microscopy, we aimed to verify that well-preserved osteohistological features correlate with pristine fossil bone nanostructures from the femoral bones of Koreanosaurus boseongensis. The quality of nanostructural preservation was evaluated based on the preferred orientation level of apatite crystals obtained from selected area electron diffraction (SAED) patterns and by measuring the "arcs" from the {100} and {002} diffraction rings. Unlike our expectations, our results revealed that well-preserved microstructures do not guarantee pristine nanostructures and vice versa. Structural preservation of bone from macro- to nanoscale primarily depends on original bioapatite density, and subsequent taphonomical factors such as effects from burial, pressure, influx of external elements and the rate of diagenetic alteration of apatite crystals. Our findings suggest that the efficient application of SAED analysis opens the opportunity for comprehensive nanostructural investigations of bone.

Influence of external electric field on optical properties of Dy3+ embedded in chalcogenide glass modified with Ga and CsBr.

In sulfur-based chalcogenide glass, i.e., a covalent amorphous solid, the addition of a small amount of Ga + CsBr switches the nearest neighbors of the Dy3+ dopant from S to Br, which results in significant enhancement in the lifetime of the excited 4f configurational states of Dy3+. The chemical preference between [GaS3Br]- and Dy3+ alters only the local structures of the involved rare earth ion. This atomic restructuring occurs spontaneously at a nanoscale during the melt-quenching process, without the need for further heat treatment, and thus improves the luminescence properties of the activator while keeping the thermal and mechanical properties of the parent host material unchanged. In this study, it is experimentally verified that externally applied DC electric fields can further tune the oscillator strengths of Dy3+ in Ge-S glass that contains Ga + CsBr. This experimental finding proves that mass transports driven by electric fields influence the optical properties of rare earth doped in the chalcogenide glass that is compositionally engineered in this study.

Design and characterization of a high resolution microfluidic heat flux sensor with thermal modulation.

A complementary metal-oxide semiconductor-compatible process was used in the design and fabrication of a suspended membrane microfluidic heat flux sensor with a thermopile for the purpose of measuring the heat flow rate. The combination of a thirty-junction gold and nickel thermoelectric sensor with an ultralow noise preamplifier, a low pass filter, and a lock-in amplifier can yield a resolution 20 nW with a sensitivity of 461 V/W. The thermal modulation method is used to eliminate low-frequency noise from the sensor output, and various amounts of fluidic heat were applied to the sensor to investigate its suitability for microfluidic applications. For sensor design and analysis of signal output, a method of modeling and simulating electro-thermal behavior in a microfluidic heat flux sensor with an integrated electronic circuit is presented and validated. The electro-thermal domain model was constructed by using system dynamics, particularly the bond graph. The electro-thermal domain system model in which the thermal and the electrical domains are coupled expresses the heat generation of samples and converts thermal input to electrical output. The proposed electro-thermal domain system model is in good agreement with the measured output voltage response in both the transient and the steady state.