Geometrical guidance of stem cell fate : elucidation studies and implication in tissue engineering

Tissue engineering and regenerative medicine aims to construct functional tissues replacement through precise control of local environment that promotes proliferation and differentiation of cells. Widespread attention has been focused on using stem cells as the primary source for tissue engineering due to its self-renewal capability and multipotency. Stem cells are highly responsive to the microenvironment signals and given the right condition, it is possible to direct stem cell differentiation into a particular cell type in the body. Recent findings have underscored the important role of mechanical environment in directing stem cell lineage commitment. For instance it has been shown that materials compliance, applied mechanical stimulus (e.g. stretch, strain, and shear) and regulation of cell shape can exert significant influences in regulating tissue specific gene expression and protein translation. The objective of this project is to employ a simple and versatile technique to control the spatial arrangement, orientation and geometry of stem cell for the purpose of elucidating the basis of cell shape distortion, cytoskeleton rearrangement and focal adhesions distribution on bone marrow derived human mesenchymal stem cells (hMSCs) lineage commitment in the absence of exogenous soluble factors. To achieve this, microcontact printing was employed to control cell spreading on extracellular matrix protein defined regions. It was found that hMSCs cultured on 20μm wide fibronectin lanes printed on poly (lactide-co-glycolide) substrate adopted a highly elongated morphology with concomitant upregulation of myogenic mRNA transcripts and protein, indicative of muscle differentiation. Further elucidation studies revealed that repression of the FAK-ERK signaling events may serve as a molecular basis for the cell shape induced muscle lineage commitment hMSCs.DOCTOR OF PHILOSOPHY (MSE

Multitrack Compressed Sensing for Faster Hyperspectral Imaging

Hyperspectral imaging (HSI) provides additional information compared to regular color imaging, making it valuable in areas such as biomedicine, materials inspection and food safety. However, HSI is challenging because of the large amount of data and long measurement times involved. Compressed sensing (CS) approaches to HSI address this, albeit subject to tradeoffs between image reconstruction accuracy, time and generalizability to different types of scenes. Here, we develop improved CS approaches for HSI, based on parallelized multitrack acquisition of multiple spectra per shot. The multitrack architecture can be paired up with either of the two compatible CS algorithms developed here: (1) a sparse recovery algorithm based on block compressed sensing and (2) an adaptive CS algorithm based on sampling in the wavelet domain. As a result, the measurement speed can be drastically increased while maintaining reconstruction speed and accuracy. The methods were validated computationally both in noiseless as well as noisy simulated measurements. Multitrack adaptive CS has a ∼10 times shorter measurement plus reconstruction time as compared to full sampling HSI without compromising reconstruction accuracy across the sample images tested. Multitrack non-adaptive CS (sparse recovery) is most robust against Poisson noise at the expense of longer reconstruction times

Molecular design and medicinal applications of nano-nitric oxide delivery systems

Background: Nitric oxide (NO) plays important regulatory roles in a plethora of biological functions and thus holds tremendous potential to be exploited for clinical uses. However, the chemistries in the molecular design of nano-nitric oxide delivery systems is currently lacking. Objective: The overarching aim of this review is to provide the readers with the fundamentals that relate to the design of NO release molecules (NORMs), loading and releasing mechanism, as well as delivery of NORMs for nanotherapeutics. Methods: We conducted a thorough literature search on the design and synthesis of NORMs, as well as the current state-of-the-art NO compatible delivery platforms to address various clinical needs. Results: N-diazeniumdiolate and S-nitrosothiol based NO molecules are among the most widely used NORMs for anti-cancer and anti-microbial applications. The innovative integration of these NORMs with cytocompatible organic and inorganic nanocarriers enabled controlled spatiotemporal delivery and release of NO at the targeted diseased sites. Conclusion: We have provided a comprehensive summary of the fundamental chemistries underpinning the molecular design of the NORMs and critically assessed the recent advancements of nano-NO delivery systems for advanced biomedical applications.MOE (Min. of Education, S’pore

Value-added products from thermochemical treatments of contaminated e-waste plastics

International audienceThe rise of electronic waste (e-waste) generation around the globe has become a major concern in recent times and their recycling is mostly focussed on the recovery of valuable metals such as gold (Au), silver (Ag) and copper (Cu) etc. However, a significant weight fraction of e-waste consists of plastics (25-30%) that are either discarded or incinerated. There is a growing need for recycling of these e-waste plastics majority of them are made from high-quality polymers (composites) such as acrylonitrile butadiene styrene (ABS), high impact polystyrene (HIPS); polycarbonate (PC); polyamide (PA); polypropylene (PP); and epoxies. However, these plastics are contaminated with hazardous materials such as brominated flame retardants (BFRs) and heavy metals (such as lead and mercury). Under any thermal stress, the bromine element (Br) present in the e-waste plastics produces environmentally hazardous pollutants, such as hydrogen bromide or polybrominated diphenyl ethers/furans (PBDE/Fs). The discarded plastics can lead to the leaching of toxins into the environment. Therefore, removal of the toxics chemicals from the e-waste plastics is prerequisite before considering any thermal process. This review article gives a detailed account of e-waste plastics recycling and recovery using thermochemical processes, such as extraction and pyrolysis. A basic framework of the existing processes has been established by reviewing the most interesting findings in recent times and the prospects that they open in the field recycling of e-waste plastics

Machine learning-assisted optimization of TBBPA-bis-(2,3-dibromopropyl ether) extraction process from ABS polymer

The increasing amount of e-waste plastics needs to be disposed of properly, and removing the brominated flame retardants contained in them can effectively reduce their negative impact on the environment. In the present work, TBBPA-bis-(2,3-dibromopropyl ether) (TBBPA-DBP), a novel brominated flame retardant, was extracted by ultrasonic-assisted solvothermal extraction process. Response Surface Methodology (RSM) achieved by machine learning (support vector regression, SVR) was employed to estimate the optimum extraction conditions (extraction time, extraction temperature, liquid to solid ratio) in methanol or ethanol solvent. The predicted optimum conditions of TBBPA-DBP were 96 min, 131 mL g-1, 65 °C, in MeOH, and 120 min, 152 mL g-1, 67 °C in EtOH. And the validity of predicted conditions was verified.Ministry of National Development (MND)National Environmental Agency (NEA)National Research Foundation (NRF)This work was supported by the National Research Foundation, Prime Minister’s Office, Singapore, the Ministry of National Development, Singapore, and National Environment Agency - Singapore, Ministry of Sustainability and the Environment, Singapore under the Closing the Waste Loop R&D Initiative as part of the Urban Solutions & Sustainability - Integration Fund (Award No. USS-IF-2018-4)

Clarifying the in-situ cytotoxic potential of electronic waste plastics

Plastics in waste electronics (E-plastics) account for approximately 20% of the entire global electronic waste (E-waste) stream. Most of the E-plastics are not recycled as the presence of toxic additives (e.g. heavy metals, brominated flame retardants (BFRs), antimony, etc.) have associated environmental and health concerns. However, the majority of the studies are focused on quantitative assessment of the toxic constituents in E-plastics, while empirical information regarding the potential toxic effects in humans is largely lacking. To gain a deeper appreciation into the toxicological profile of E-plastics, in situ time-dependent exposures of 6 different human cell lines to a panel of 8 representative E-plastics recovered from liquid crystal displays (LCD), keyboards, screen frames, and wire insulators were conducted. Although several hazardous elements (e.g. Pb, As, Sb, Zn, Cu, etc) were detected at concentrations that far exceed the limit values permitted by the Restriction of Hazardous Substances Directive and EU Directives in the panel E-plastics, in-depth analysis of the 144 unique cell viability data points and live-dead staining experiments suggest that the acute and sub-chronic toxic effects of E-plastics in direct contact with human cells are negligible. These observations agreed with the inductively coupled plasma-optical emission spectrometry data, which revealed that leaching of these toxic additives into the biological milieu is not sufficiently high to trigger a cytotoxic response up to a continuous culture period of 2 weeks. The novel insights gained from this study are posited to further clarify the uncertainty associated with the safety and circular economy implementation of E-plastics.Ministry of National Development (MND)Nanyang Technological UniversityNational Environmental Agency (NEA)National Research Foundation (NRF)This work was financially supported by a grant award from “Singapore eCEA Alliance for Research in Circular Economy (SCARCE)”, which is a joint lab set up between Nanyang Technological University (NTU, Singapore) and the French Alternative Energies and Atomic Energy Commission (CEA, France). SCARCE is supported by the National Research Foundation, Prime Minister’s Office, Singapore, the Ministry of National Development, Singapore, and National Environment Agency, Ministry of the Environment and Water Resource, Singapore under the Closing the Waste Loop R&D Initiative as part of the Urban Solutions & Sustainability e Integration Fund (award number USS-IF-2018-4)

Biomimicry 3D gastrointestinal spheroid platform for the assessment of toxicity and inflammatory effects of zinc oxide nanoparticles

10.1002/smll.201401915Small116702-71

Nature-Inspired DNA Nanosensor for Real-Time <i>in Situ</i> Detection of mRNA in Living Cells

Rapid and precise <i>in situ</i> detection of gene expressions within a single cell is highly informative and offers valuable insights into its state. Detecting mRNA within single cells in real time and nondestructively remains an important challenge. Using DNA nanotechnology and inspired by nature’s many examples of “protective-yet-accessible” exoskeletons, we designed our mRNA nanosensor, nano-snail-inspired nucleic acid locator (nano-SNEL), to illustrate these elements. The design of the nano-SNEL is composed of a sensory molecular beacon module to detect mRNA and a DNA nanoshell component, mimicking the functional anatomy of a snail. Accurate and sensitive visualization of mRNA is achieved by the exceptional protection conferred by the nanoshell to the sensory component from nucleases-mediated degradation by approximately 9–25-fold compared to its unprotected counterpart. Our nano-SNEL design strategy improved cell internalization is a demonstration of accurate, dynamic spatiotemporal resolved detection of RNA transcripts in living cells