- Recruitment for Master and PhD student -

研究計畫 Major projects (Collaborative Research)

• 半導體微影技術 (Photolithography) 

╴微圖案化生物材料 (Fabrication of micropattern)

╴仿細胞外基質之微環境 (Niche mimicking extracellular matrix)

• 誘導幹細胞分化 (Induction of cell differentiation)

╴成脂分化 (Adipogenic differentiation)

╴成骨分化 (Osteogenic differentiation)

╴神經細胞分化 (Neurogenic differentiation)

• 3D 生物列印 (3D biomaterial printing)

╴生物反應器 (Bioreactor)

╴小鼠心臟列印 (3D bio-printing of heart)

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Unveiling the Topographic Cue Rendered by Micropatterns for Steering Cell Differentiation by Using Extrinsic Photobiomodulation, Guan-Ying Tsai, Thipwadee Klom-In, Meng-Jiy Wang*, and Szu-yuan Chen*, Journal of Photochemistry and Photobiology, (2024) 

It is known that cell culture micropatterns have the ability to facilitate stem cell differentiation induced by specialized chemical factors and different differentiation directions have different optimal micropattern shapes. In this study, by utilizing extrinsic photobiomodulation (EPM) with verteporfin as photosensitizer and light irradiation of 690 nm wavelength as a universal, unbiased, and synchronizing way of inducing differentiation of human umbilical cord Wharton's Jelly mesenchymal stem cells (WJ-MSCs), the topographic cue for cell type specification conveyed in microislands is investigated. It is found that the topographic cues are encoded in the symmetry and aspect ratio of microislands and conformation of cells to microislands is necessary for acquiring the cue. F-actin vertical columns form and cell thickness increases for cells on microislands, and the two effects are enhanced by EPM and correlate with cell differentiation. EPM treatment poises cells in a stationary state to initiate differentiation and the process of making commitment takes two days. Our findings reveal the way to fully exploit topographic cues for promoting and controlling cell differentiation.

Interleukin-6 Electrochemical Sensor using Poly(o-phenylenediamine)-Based Molecularly Imprinted Polymer, Wei-Ting Ting, Meng-Jiy Wang*, and Matiar M.R. Howlader*, Sensors and Actuators B: Chemical, (2024) 

Interleukin-6 (IL-6) is an important cytokine involved in immune responses and maintaining body homeostasis. Elevated IL-6 levels, exceeding ∼ 40 pg/mL in bodily fluids, are associated with inflammation and diseases such as COVID-19, cardiovascular disorders, and Alzheimer’s, necessitating real-time health monitoring for personalized healthcare. In this study, we developed a highly sensitive and selective IL-6 sensing platform by depositing a poly(o-phenylenediamine) (P(o-PD))-based molecularly imprinted polymer (MIP) onto an oxygen-functionalized screen-printed carbon electrode with gold nanoparticles, 3-aminopropyltriethoxysilane (APTES), and glutaraldehyde (GA). While APTES enhanced the peak current due to redox probe adsorption, GA reduced it due to non-conductive aldehyde groups. This functionalized surface improved hydrophilicity due to the presence of amino and carbonyl groups. We identified that a 120-minute NaCl treatment effectively removed IL-6 templates, ensuring the successful embedding of IL-6 in the P(o-PD) matrix. We calculated an imprinting factor of 11.2, indicating the effective imprinting of IL-6 by P(o-PD) and the presence of IL-6 specific binding sites within the MIP, resulting in a robust current response to IL-6. After optimizing the MIP deposition through five cycles, we detected IL-6 concentrations ranging from 2 to 400 pg/mL, with a sensitivity of 3.48 μA/log(pg/mL) and a limit of detection of 1.74 pg/mL. When tested in real human serum, the sensor encountered challenges due to P(o-PD) matrix adsorbing other active molecules. Despite this challenge, our platform demonstrates high selectivity and long-term stability in IL-6 detection. These qualities position our sensor well-suited for point-of-care diagnostics, emphasizing its potential as a reliable tool for real-world applications.

Effects of Cancer Cell-Derived Nanovesicle Vaccines Produced by the Oxidative Stress-Induced Expression of DAMP and Spontaneous Release/Filter Extrusion in the Interplay of Cancer Cells and Macrophages, Song-Hsien Lin, Guan-Ying Tsai, Meng-Jiy Wang*, and Szu-Yuan Chen*, Biomedicines, (2022) 

Photodynamic therapy (PDT)-based cancer vaccines are shown to be more effective modalities for treating cancer in animal models compared to other methods used to generate cancer cell-derived vaccines. The higher efficacy seems to stem from the generation of cell membrane nanovesicles or fragments that carry both cancer cell-specific antigens and high surface content of damage-associated molecular pattern (DAMP) molecules induced by oxidative stress. To develop more effective cancer vaccines in this direction, we explored the generation of cancer vaccines by applying different sources of oxidative stress on cancer cell cultures followed by spontaneous release or filter extrusions to produce cancer cell-derived DAMP-expressing nanovesicles. Through an in-vitro test based on the co-culture of cancer cells and macrophages, it was found that the nanovesicle vaccines generated by H2O2 are as effective as those generated by PDT in diminishing cancer cell culture masses, providing a simpler way to manufacture vaccines. In addition, the nanovesicle vaccines produced by filter extrusion are as potent as those produced by spontaneous release, rendering a more stable way for vaccine production.

Fabrication and Characterizations of Axial View Liquid Electrode Plasma Atomic Emission Spectrometry for the Sensitive Determination of Trace Zinc, Cadmium, and Lead, Yueh-Han Huang, Daisuke Hirose, Jun Minami, Meng-Jiy Wang*, and Yuzuru Takamura*, Analytical Chemistry, (2022) 

Control of Stem Cell Differentiation by Using Extrinsic Photobiomodulation in Conjunction with Cell Adhesion Pattern, Saitong Muneekaew, Meng-Jiy Wang*, and Szu-yuan Chen*, Scientific Reports, (2022) 

The induction and direction of stem cell differentiation into needed cell phenotypes is the central pillar of tissue engineering for repairing damaged tissues or organs. Conventionally, a special recipe of chemical factors is formulated to achieve this purpose for each specific target cell type. In this work, it is demonstrated that the combination of extrinsic photobiomodulation and collagen-covered microislands could be used to induce differentiation of Wharton’s jelly mesenchymal stem cells (WJ-MSCs) with the differentiation direction dictated by the specific island topography without use of chemical factors. Both neurogenic differentiation and adipogenic differentiation could be attained with a rate surpassing that using chemical factors. Application of this method to other cell types is possible by utilizing microislands with a pattern tailored particularly for each specific cell type, rendering it a versatile modality for initiating and guiding stem cell differentiation.

Calcium Phosphate Composites to Synergistically Promote Osteoconduction and Corrosion Resistance on Bone Materials via Plasma Polymerized Hexamethyldisilazane Coatings, Wei-Ting Ting, Tzu-Hsien Yang, Yuan Cheng, Ko-Shao Chen*, Shiu-Huey Chou*, Mu-Rong Yang, and Meng-Jiy Wang*, Surface and Coatings Technology, (2021) 

A facile and effective plasma polymerized hexamethyldisilazane (ppHMDSZ) combining with calcium phosphate (Casingle bondP) coating to promote osteoconduction meanwhile provide resistance to corrosion is developed in this study. The composites of Casingle bondP and ppHMDSZ thin films were deposited on bone substitutes to investigate the osteoblast compatibility. The amount of the Casingle bondP coatings was modulated with a linear deposition rate of 7.37 μg/(cm2∙cycle) by alternative immersion cycles (1, 2, 5, and 10) in solutions containing calcium and phosphate, measured by quartz crystal microbalance (QCM). Importantly, cell behaviors including cell adhesion, proliferation, and functional activity responded positively toward the surface wettability and roughness of the Casingle bondP layers. Moreover, the human osteoblast cells (hFOB1.19) revealed excellent compatibility on the stainless steel coated with Ca-P/ppHMDSZ composite films. The combination of bioceramics and corrosion resistance plasma polymerized HMDSZ films showed a synergistic effect on the biocompatibility and osteoconductive for bone tissue engineering applications.

Micropatterning of Mammalian Cells on Plasma Polymerized Polypyrrole Thin Films, Chien-Hung Kuo, Yueh‐Han Huang, Wen-Pin Lin, Tsung-Jen Wang, and Meng-Jiy Wang*, IEEE Transactions on Plasma Science, (2021) 

Microscaled patterns have been used to construct exquisite intelligent biomaterials and can be applied in tissue engineering to create different biological signals and modulate cell behavior. This study proposed to create micropatterns for cell attachment and proliferation by combining 3-D printed mask with the plasma polymerized pyrrole (ppPy) on an antifouling polymer-modified substrate. The antifouling moieties selected in this study are the zwitterionic molecules of sulfobetaine methacrylate (SBMA) copolymerized with acrylic acid (AAc). The cell-pattern interactions were facilitated by cultivating L-929 mouse fibroblasts on the substrates with the well-defined chemical features providing by the multilayers composed of plasma polymers and zwitterionic copolymers. The results showed that both the attachment and proliferation of L-929 fibroblast cells were excellently confined within the ppPy functionalized patterns. Moreover, the cell density per unit area increased as a function of the ppPy deposition time, indicating cell proliferation was modulated by amine functionality. This study provides an alternative method to pattern biomolecules using plasma deposition which could be further applied in fields of biomaterials and biosensing.

Selective Killing Effects of Atmospheric Pressure Plasma Jet on Human Melanoma and Lewis Lung Carcinoma Cells, Saitong Muneekaew, Yueh‐Han Huang, and Meng-Jiy Wang*, Plasma Chemistry and Plasma Processing, (2021) 

Melanoma is one type of skin cancer that develops from melanocytes and has been reported as the cause of deaths in different continents globally. This study aims to selectively “kill” only skin cancer cells by applying a customer designed and portable atmospheric pressure plasma jet (APPJ). Human melanoma (A375) and Lewis lung carcinoma (LLC) were selected as the target cancer cells to compare with the effects of APPJ toward L-929 mouse fibroblasts. The impacts of APPJ treatments on the cell viability and morphology of three types of cells were evaluated quantitatively by LDH and MTT assays whereas the qualitative cell behavior was provided by cell morphological changes. Importantly, the mechanism of evolution in cell fate resulted from APPJ treatments for the three types of cells was elucidated by cell apoptosis integrated with caspase-9 activities, which determined the threshold of APPJ treatment time toward individual cell type. Furthermore, it was found that the cell culture time assisted benign cells (L-929 fibroblasts) to resume proliferation activities from the impact of APPJ treatment. Therefore, the selective impacts on tumor and benign cells demonstrated in this study shed lights of APPJ treatments for the future developments of direct plasma skin cancer therapy.

Dense and Anti-Corrosion Thin films Prepared by Plasma Polymerized Hexamethyldisilazane for Applications in Metallic Implants, Wei-Ting Ting, Kao Shoa Chen*, and Meng-Jiy Wang*, Surface and Coatings Technology, (2021) 

Plasma polymerized hexamethyldisilazane (ppHMDSZ) thin films with specific thickness and density coated on substrates (ppHMDSZ/substrate) to promote the corrosion resistance for the potential applications in metallic implants is reported in this study. Comparing with the conventional anti-corrosion thin film coatings, plasma polymerization method provided an effective, dry, and simpler process, which allowed to prepare dense thin films with the thickness of a few hundred nanometers. This study proposed that the anti-corrosion behavior could be correlated closely to the density of thin film coated on stainless steel (SS) that can be precisely controlled by the plasma deposition time. The physico-chemical properties of the as-prepared ppHMDSZ thin films were evaluated by field-emission scanning electron microscope (FE-SEM), water contact angle (WCA), attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR), and electron spectroscopy for chemical analysis (ESCA). The corrosion resistance of the ppHMDSZ coated stainless steel (ppHMDSZ/SS) was improved by depositing ~140 nm in thickness and 1.15 g/cm3 in density which reduced 90% of the original corrosion performance against the corrosion in Hank's solution, measured by potentiodynamic polarization tests. The resultant ppHMDSZ thin film coatings allowed to protect substrates toward corrosion and can be further applied in implants for tissue engineering and biomaterials.