Biomimetic Approaches for Bone Tissue Engineering

Bone tissue engineering is an attractive alternative to transplanting harvested tissue for bone defect repair. Various signals are involved in the regulation of stem/progenitor cell behavior, development and healing, which could be beneficially utilized in bone tissue engineering. However, bone tissue engineering research has very limited success in translation into the clinic, which often stems from the inappropriate administration of these signaling molecules due to the lack of optimal delivery systems. Therefore, this project is aimed at the development of new approaches to bone tissue engineering by mimicking advantageous features of the native extracellular matrix and signaling processes involved in development and natural healing. The author first develops preprogrammed drug delivery systems to achieve long-term pulsatile delivery of parathyroid hormone (PTH). A series of techniques, including polymer synthesis, drug formulation and device fabrication are developed to control the physical and chemical properties of the delivery devices so as to achieve spatiotemporal controlled drug release. Systemic pulsatile PTH release from the delivery device is demonstrated to increase bone volume and mineralized bone density, thereby providing a promising complying-friendly alternative to the standard daily PTH injection treatment for osteoporosis. Then PTH is repurposed successfully for local bone regeneration in a mouse calvarial bone defect regeneration model by using the pulsatile delivery system in combination with a biomimetic nanofibrous PLLA scaffold developed in our lab. Such system could possibly be utilized to regenerate various bone defects. Considering that the native bone defect healing process is initiated by macrophages via engulfing dead cells, the author develops a novel bioconjugation strategy to fabricate biodegradable microspheres to mimic apoptotic cells to target macrophages to initiate a biomimetic bone healing process. The biodegradable apoptotic cell-mimicking microspheres (BAM) are decorated with “eat me signal” and are shown to significantly enhance macrophage phagocytosis and enhance bone marrow stromal cell (BMSCs) migration via increased secretion of chemokines. Implanting a 3D space-defining biomimetic nanofiberous (NF) scaffold loaded with BAM results in a drastic increase in endogenous mesenchymal stem/progenitor cell recruitment into the scaffold compared to the same scaffold loaded with control microspheres, leading to critical-sized bone defect repair. This novel biomimetic approach opens a potential new avenue for bone regeneration without the need for exogenous cells.PHDMacromolecular Science & EngineeringUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttps://deepblue.lib.umich.edu/bitstream/2027.42/144083/1/dangming_1.pd

Optimal Power Control Model of Direct Driven PMSG

AbstractIn order to analyze the performances of direct driven PMSG, an optimal power control model which includes maximum power extraction control model under low wind speed and pitch angle control model under high wind speed is established. The concept of the model is analyzed in a 1.5 MW direct drive variable speed permanent magnet synchronous generator (D-PMSG) WECS with back-to-back IGBT frequency converter. Vector control of the generator side rectifier is realized in the grid voltage vector reference frame. Confirmation of models and control schemes is demonstrated by using the EMTDC/PSCAD environment

Oncometabolites:linking altered metabolism with cancer

The discovery of cancer-associated mutations in genes encoding key metabolic enzymes has provided a direct link between altered metabolism and cancer. Advances in mass spectrometry and nuclear magnetic resonance technologies have facilitated high-resolution metabolite profiling of cells and tumors and identified the accumulation of metabolites associated with specific gene defects. Here we review the potential roles of such "oncometabolites" in tumor evolution and as clinical biomarkers for the detection of cancers characterized by metabolic dysregulation

Phosphorus fractions in the sediments of yuecheng reservoir, china

As a result of the inexorable development of the economy and the ever-increasing population, the demand for water in the urban and rural sectors has increased, and this in turn has caused the water quality and eutrophication of the reservoir to become a legitimate concern in the water environment management of river basins. Phosphorus (P) is one of the limiting nutrients in aquatic ecosystems; P in the sediment is a primary factor for eutrophication. Yuecheng Reservoir is located in one of the most productive and intensively cultivated agricultural regions in North China. Detailed knowledge of the sediment is lacking at this regional reservoir. The first study to look into the different P fractions and its diffusion fluxes at the water sediment interface of the Yuecheng Reservoir makes it possible to learn about the internal P loading. According to the results, the concentrations of total phosphorus (TP) ranged from 1576.3 to 2172.6 mg kg and the P fraction concentration sequence is as follows: P associated with calcium (Ca–Pi) > organic P (Po) > P bound to aluminum (Al), ferrum (Fe) and manganese (Mn) oxides and hydroxides (Fe/Al–Pi). The results demonstrated that, although the construction of a large number of water conservancy projects in the upper reaches of the river resulted in the decrease of inflow runoff, the pollutions from terrestrial plants or materials played a key role in the sediment phosphorus fraction, and they should be emphasized on the water environment management of river basin

The role of the neutrophil Fcγ receptor I (CD64) index in diagnosing spontaneous bacterial peritonitis in cirrhotic patients

SummaryObjectiveTo investigate the role of the neutrophil Fcγ receptor I (CD64) index in the diagnosis of spontaneous bacterial peritonitis (SBP) in cirrhotic patients.MethodsA total of 123 cirrhotic patients with ascites who fulfilled the inclusion criteria were enrolled in this study. Ascites and blood samples were collected; the polymorphonuclear neutrophil (PMN) count, bacterial culture, and related laboratory tests were performed. The CD64 index was determined for each sample using flow cytometry.ResultsThe neutrophil CD64 index results were significantly higher in cirrhotic patients with SBP than in those without SBP (p<0.001). There was a positive correlation between the neutrophil CD64 index and the PMN count in ascites. In the receiver operating characteristic curve (ROC) analysis, the area under the curve (AUC) was 0.894 (95% confidence interval 0.823–0.964, p<0.001). The optimal cut-off value for the neutrophil CD64 index was 2.02. The sensitivity and specificity of the neutrophil CD64 index for cirrhotic patients with SBP were 80.49% and 93.90%, respectively. The elevated neutrophil CD64 index was down-regulated by antibiotic therapy (p=0.002).ConclusionsThe neutrophil CD64 index could be used as a sensitive and specific indicator for the diagnosis of SBP in cirrhotic patients with ascites and is also modulated by antibiotic therapy

Individual Differences in Dopamine Are Associated with Reward Discounting in Clinical Groups But Not in Healthy Adults.

Some people are more willing to make immediate, risky, or costly reward-focused choices than others, which has been hypothesized to be associated with individual differences in dopamine (DA) function. In two studies using PET imaging, one empirical (Study 1: N = 144 males and females across 3 samples) and one meta-analytic (Study 2: N = 307 across 12 samples), we sought to characterize associations between individual differences in DA and time, probability, and physical effort discounting in human adults. Study 1 demonstrated that individual differences in DA D2-like receptors were not associated with time or probability discounting of monetary rewards in healthy humans, and associations with physical effort discounting were inconsistent across adults of different ages. Meta-analytic results for temporal discounting corroborated our empirical finding for minimal effect of DA measures on discounting in healthy individuals but suggested that associations between individual differences in DA and reward discounting depend on clinical features. Addictions were characterized by negative correlations between DA and discounting, but other clinical conditions, such as Parkinson's disease, obesity, and attention-deficit/hyperactivity disorder, were characterized by positive correlations between DA and discounting. Together, the results suggest that trait differences in discounting in healthy adults do not appear to be strongly associated with individual differences in D2-like receptors. The difference in meta-analytic correlation effects between healthy controls and individuals with psychopathology suggests that individual difference findings related to DA and reward discounting in clinical samples may not be reliably generalized to healthy controls, and vice versa.SIGNIFICANCE STATEMENT Decisions to forgo large rewards for smaller ones due to increasing time delays, uncertainty, or physical effort have been linked to differences in dopamine (DA) function, which is disrupted in some forms of psychopathology. It remains unclear whether alterations in DA function associated with psychopathology also extend to explaining associations between DA function and decision making in healthy individuals. We show that individual differences in DA D2 receptor availability are not consistently related to monetary discounting of time, probability, or physical effort in healthy individuals across a broad age range. By contrast, we suggest that psychopathology accounts for observed inconsistencies in the relationship between measures of DA function and reward discounting behavior