Browsing by Author "Lo, Yu-Chih"

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Conductive nanogel-interfaced neural microelectrode arrays with electrically controlled in-situ delivery of manganese ions enabling high-resolution MEMRI for synchronous neural tracing with deep brain stimulation
(2017-04)
Huang, Wei-Chen
;
Lo, Yu-Chih
;
Chu, Chao-Yi
;
Lai, Hsin-Yi
;
Chen, You-Yin
Chronic brain stimulation has become a promising physical therapy with increased efficacy and efficiency in the treatment of neurodegenerative diseases. The application of deep brain electrical stimulation (DBS) combined with manganese-enhanced magnetic resonance imaging (MEMRI) provides an unbiased representation of the functional anatomy, which shows the communication between areas of the brain responding to the therapy. However, it is challenging for the current system to provide a real-time high-resolution image because the incorporated MnCl2 solution through microinjection usually results in image blurring or toxicity due to the uncontrollable diffusion of Mn2+. In this study, we developed a new type of conductive nanogel-based neural interface composed of amphiphilic chitosan-modified poly(3,4 -ethylenedioxythiophene) (PMSDT) that can exhibit biomimic structural/mechanical properties and ionic/electrical conductivity comparable to that of Au. More importantly, the PMSDT enables metal-ligand bonding with Mn2+ ions, so that the system can release Mn2+ ions rather than MnCl2 solution directly and precisely controlled by electrical stimulation (ES) to achieve real-time high resolution MEMRI. With the integration of PMSDT nanogel-based coating in polyimide-based micro electrode arrays, the post-implantation DBS enables frequency-dependent MR imaging in vivo, as well as small focal imaging in response to channel site-specific stimulation on the implant. The MR imaging of the implanted brain treated with 5-min electrical stimulation showed a thalamocortical neuronal pathway after 36 h, confirming the effective activation of a downstream neuronal circuit following DBS. By eliminating the susceptibility to artifact and toxicity, this system, in combination with a MR-compatible implant and a bio-compliant neural interface, provides a harmless and synchronic functional anatomy for DBS. The study demonstrates a model of MEMRI-functionalized DBS based on functional neural interface engineering and controllable delivery technology, which can be utilized in more detailed exploration of the functional anatomy in the treatment of neurodegenerative diseases. (C) 2017 Elsevier Ltd. All rights reserved.
Development of a computational promoter with highly efficient expression in tumors
(2018-04-27)
Ho, Shu-Yi
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Chang, Bo-Hau
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Chung, Chen-Han
;
Lin, Yu-Ling
;
Chuang, Cheng-Hsun
Background: Gene therapy is a potent method to increase the therapeutic efficacy against cancer. However, a gene that is specifically expressed in the tumor area has not been identified. In addition, nonspecific expression of therapeutic genes in normal tissues may cause side effects that can harm the patients' health. Certain promoters have been reported to drive therapeutic gene expression specifically in cancer cells; however, low expression levels of the target gene are a problem for providing good therapeutic efficacy. Therefore, a specific and highly expressive promoter is needed for cancer gene therapy. Methods: Bioinformatics approaches were utilized to analyze transcription factors (TFs) from high-throughput data. Reverse transcription polymerase chain reaction, western blotting and cell transfection were applied for the measurement of mRNA, protein expression and activity. C57BL/6JNarl mice were injected with pD5-hrGFP to evaluate the expression of TFs. Results: We analyzed bioinformatics data and identified three TFs, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappa B), cyclic AMP response element binding protein (CREB), and hypoxia-inducible factor-1 alpha (HIF-1 alpha), that are highly active in tumor cells. Here, we constructed a novel mini-promoter, D5, that is composed of the binding sites of the three TFs. The results show that the D5 promoter specifically drives therapeutic gene expression in tumor tissues and that the strength of the D5 promoter is directly proportional to tumor size. Conclusions: Our results show that bioinformatics may be a good tool for the selection of appropriate TFs and for the design of specific mini-promoters to improve cancer gene therapy.
Elastin-like Polypeptide-based Hydrogel Actuator for Cardiac Tissue Engineering
(2017-01-01)
Lo, Yu-Chih
;
Chiang, Min-Yu
;
Chen, Wen-Liang
;
Chen, San-Yuan
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材料科學與工程學系
Cardiac tissue engineering aims to reconstruct functional construction with resembling native tissue to replace damaged myocardium. To mimic native myocardium, cells with phenotypes of mature cardiomyocytes and scaffolds with elastic, electro-conductive, highly porous, and biodegradable plays two major roles. So far, although a number of cell types have been evaluated in the reports of cardiac repair, most of them cannot form functional cardiomyocytes with mature cardiac phenotypes including the formation of the myocytic syncytium with surrounding cardiomyocytes, and expression of cardiac specific proteins in completely organized pattern. The maturation of cardiomyocytes can be achieved by multiple stimuli such as electrical stimulation, mechanical stretching, and chemical stimulation. Therefore, in this study, we aimed to develop a conductive hydrogel actuator based on elastin-like polypeptide (ELP) consisting of repeating elastin-derived sequences Val-Pro-Gly-Ile-Gly (VPGIG), combining near-infrared light (NIR)-induced mechanical stretching and electrical stimulation for the simulation of immature cardiomyocytes. The hydrogel actuator can be fabricated by rapidly crosslinking by tetrakis(hydroxymethyl) phosphonium chloride (THPC) to form a high density porous structure, providing cardiac muscle cell an extracellular matrix (ECM)-like nanostructure with bioactive Arg-Gly-Asp (RGD) peptide. It showed appropriate mechanical strength and sufficient electroactivity, which is suitable for myocardial cell culture system. In addition, the actuation leads a specific and efficient way to regulate activity in cardiac muscle cell by physical cue of the hydrogel. In the future, we expect the ELP-baesd hydrogel actuator to show great potential to be used in the differentiation and maturation of cardiomyocytes.