3D multi-nozzle system with dual drives highly potential for 3D complex scaffolds with multi-biomaterials

Recently, additive manufacturing is one of the most focused research topics due to its explosive development, especially in manufacturing engineering and medical science. In order to build 3D complex scaffolds with multi-biomaterials for clinical application, a new 3D multi-nozzle system with dual-mode drives, i.e. ejection and extrusion was developed. In this paper, much effort was made to gain fine control of droplet and excellent coordination during fabrication. Specifically, the parameters that influence the size and stability of droplet most was intensively studied. Considering that the biomaterials used in the future may have much difference in properties, the combination of parameters was investigated to facilitate the settings for certainsized droplets, which are potentially eligible for bio-printing. The dispensing nozzles can work well both in independent and convergent mode, which can be freely switched. Outstanding to the most currently used 3D bio-printing techniques, this system can fabricate scaffolds with multi-materials of both low viscosity (by pneumatic dispensing) and high viscosity (through motor extrusion). It is highly expected that this system can satisfy clinical application in the near future

Fabrication and characterisation of 3D complex hydroxyapatite scaffolds with hierarchical porosity of different features for optimal bioactive performance

To improve the biological performance of hydroxyapatite scaffolds in bone tissue engineering, graphite was used as porogen to create additional micro/nanoporosity to macroporosity, resulting in hierarchical porosity. For maximum imitation of natural bone structures, scaffolds with different porosity features were fabricated using micron/nano-sized graphite. The sintering profile of graphite treated scaffolds was optimised to reduce the influence of shrinkage. To confirm the porosity features, the micro/nanostructures of scaffolds were characterised by scanning electron microscopy and Brunauer-Emmett-Teller method. Considering that hydroxyapatite is resistant to biodegradation in vivo, the degradation rate of scaffolds in modified simulated body fluid was examined. Furthermore, biological evaluations based on myoblasts were carried out to investigate the influence of porosity features on the essential performance such as adhesion, proliferation and differentiation. The results indicate that the scaffolds with dominant microporosity and little nanoporosity formed inside had high potential for clinical applications due to improved performance in bioactivity

Novel fabrication of hierarchically porous hydroxyapatite scaffolds with refined porosity and suitable strength

Based on extrusion deposition and foaming technique, a novel method for biological hydroxyapatite (HA) scaffolds was introduced in this paper. The scaffolds were primarily characterised by interconnected and hierarchically porous structures with high porosity, adjustable distribution of pore sizes, as well as considerable mechanical strength. In order to confirm that fine control of bulk porosity and mechanical strength was possible and feasible, further analysis of obtained scaffolds was carried out by field emission scanning electron microscope (FESEM), compressive test and calculation of volumetric shrinkage; in particular, the additional porosity resulting from the introduction of pore former was evaluated. The results indicated that this method can have a great potential to construct HA scaffolds of suitable quality for spongy bone in bone tissue engineering

Data_Sheet_1_Targeted Methotrexate Prodrug Conjugated With Heptamethine Cyanine Dye Improving Chemotherapy and Monitoring Itself Activating by Dual-Modal Imaging.docx

<p>Theranostic prodrug plays a vital role in reducing the side effects and evaluating the therapeutic efficiency of prodrug in vivo. In particular, small conjugate-based theranostic prodrugs have attracted much attention because of their clear and simple structures. In this work, we synthesized a novel tumor-targeting and glutathione-activated conjugate-based theranostic prodrug (Cy-SS-MTX). The prodrug was constructed by conjugating Cy (IR780) to methotrexate (MTX) via a disulfide bond. The Cy dye as targeting molecule bring prodrug to cancer cells and then the prodrug was activated by the high levels of glutathione in tumor. In cell experiments, the results showed the excellent ability of prodrug to target tumor. Meanwhile, the prodrug apparently improved the anti-tumor ability and hugely reduced toxicity of free MTX on normal cells. Furthermore, owing to intramolecular charge transfer between Cy and MTX, the Cy structure in the prodrug showed an absorption peak at 654 nm in UV-Vis spectroscopy. However, when the disulfide bond of prodrug was broken by glutathione, a new UV-Vis absorption peak at 802 nm of Cy structure in prodrug was arised. At the same time, the fluorescence (FL) emission peak at 750 nm (excitation at 640 nm) would turn into 808 nm (excitation at 745 nm). What's more, the photoacoustic (PA) signal with excitation at 680 and 808 nm also changed. The experimental results in vivo showed that the prodrug has been successfully utilized for real-timely tracking MTX activation by FL and PA imaging upon near infrared laser excitation and cancer targeting therapy. Our studies further encourage application of small conjugate-based prodrug based on tumor-targeted heptamethine cyanine dye as reporter group for targeted therapy and real-timely tracking activation of drug.</p

Spatio-Temporal Pattern and Influencing Factors of Hemorrhagic Fever with Renal Syndrome (HFRS) in Hubei Province (China) between 2005 and 2014

<div><p>Hemorrhagic Fever with Renal Syndrome (HFRS) is considered as a globally distributed infectious disease, which results in many deaths annually in Hubei Province, China. The outbreak of HFRS is usually characterized with spatio-temporal heterogeneity and is seasonally distributed. Further, it might also be impacted by the influencing factors such as socio-economic and geographical environment. To better understand and predict the outbreak of HFRS in the Hubei Province, the spatio-temporal pattern and influencing factors were investigated in this study. Moran’s <i>I</i> Index value was adopted in spatial global autocorrelation analysis to identify the overall spatio-temporal pattern of HFRS outbreak. Kulldorff scan statistical analysis was performed to further identify the changing trends of the clustering patterns of HFRS outbreak. Spearman's rank correlation analysis was used to explore the possible influencing factors on HFRS epidemics such as climate and geographic. The results demonstrated that HFRS outbreak in Hubei Province decreased from 2005 to 2012 in general while increasing slightly from 2012 to 2014. The spatial and temporal scan statistical analysis indicated that HFRS epidemic was temporally clustered in summer and autumn from 2005 to 2014 except 2008 and 2011. The seasonal epidemic pattern of HFRS in Hubei Province was characterized by a bimodal pattern (March to May and September to November) while peaks often occurring in the spring time. SEOV-type HFRS was presumed to influence more on the total number of HFRS incidence than HTNV-type HFRS do. The average humidity and human population density were the main influencing factors during these years. HFRS outbreaks were more in plains than in other areas of Hubei Province. We did not find that whether the terrain of the wetland (water system) plays a significant role in the outbreak of HFRS incidence. With a better understanding of rodent infection rate, socio-economic status and ecological environment characteristics, this study may help to reduce the outbreak of HFRS disease.</p></div

Distribution pattern of HFRS according to Moran's Index from 2005–2014.

<p>Each point represents the Moran’s <i>I</i> value in a specific year. All of the points are lined to indicate the trend of the Moran’s <i>I</i> in Hubei Province.</p

The ratio of rural population over the total population of Hubei Province from 2005–2014.

<p>Each point represents the ratio in a specific year. All of the points are lined to indicate the trend of the rural population ratio in Hubei Province from 2005 to 2014.</p

The Most Likely Clusters (Cluster one in Fig 4) of HFRS cases from 2005–2014 in Hubei Province.

<p>The Most Likely Clusters (Cluster one in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0167836#pone.0167836.g004" target="_blank">Fig 4</a>) of HFRS cases from 2005–2014 in Hubei Province.</p

Monthly HFRS cases from 2005 to 2014.

<p>(A) Average monthly HRFS cases from 2005 to 2009. (B) Average monthly HRFS cases from 2009 to 2014.</p

Comparison of the humidity of Yicheng County with the average humidity of Hubei Province.

<p>Average monthly humidity values for Hubei Province and Yicheng County are depicted by dotted line and solid line, respectively.</p