Browsing by Author "Sun, Jui-Sheng"

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3D laser-printed porous Ti6Al4V dental implants for compromised bone support
(2020-01-01)
Tu, Che Chang
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Tsai, Pei-, I
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Chen, San-Yuan
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Kuo, Mark Yen-Ping
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Sun, Jui-Sheng
Background/Purpose: Alveolar bone loss following peri-implantitis remains a clinical challenge. We aimed to design a novel bioactive dental implant to accommodate the large bone defect caused by removal of previously failed implant. Methods: Bio-Active(ITRI) dental implant was manufactured with laser-sintered additive 3D printing technique. A 7.5 mm diameter x 7.0 mm depth osteotomy defect was created at the lateral aspect of distal femur of 20 New Zealand white rabbits to simulate the bony defect after removal of failed dental implant. One side of distal femurs was randomly selected for the commercially pure titanium NobelActive (TM) implant (control group) and the other side with Bio-Active(ITRI) Ti-6 Al4V porous dental implant (ITRI group). Animals were sacrificed at 4, 8 and 12 weeks after the implants' insertion. The samples were processed for gross morphological analysis, radiographic examination, micro-CT evaluation, and mechanical testing. Results: In histomorphometrical evaluation and micro-CT analysis, active new bone formation and good osseointegration within the ITRI implants were observed at the bone gap surrounding the dental implants. The biomechanical parameters in the Bio-Active(ITRI) dental implants were significantly higher than those of the commercially control samples. For the Bio-Active(ITRI) dental implants, the trabecular thickness decreased, while the trabecular separation and total porosity increased from the prescribed 1-month to 3-month time points; reflecting the natural remodeling of surrounding bony tissue in the Bio-Active(ITRI) dental implants. Conclusion: The novel porous structured Bio-Active(ITRI) dental implants may have a great potential for the prosthetic reconstruction where bone support is compromised after removal of a previously failed implant. Copyright (C) 2019, Formosan Medical Association. Published by Elsevier Taiwan LLC.
3D Porous Calcium-Alginate Scaffolds Cell Culture System Improved Human Osteoblast Cell Clusters for Cell Therapy
(2015-01-01)
Chen, Ching-Yun
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Ke, Cherng-Jyh
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Yen, Ko-Chung
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Hsieh, Hui-Chen
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Sun, Jui-Sheng
Age-related orthopedic disorders and bone defects have become a critical public health issue, and cell-based therapy is potentially a novel solution for issues surrounding bone tissue engineering and regenerative medicine. Long-term cultures of primary bone cells exhibit phenotypic and functional degeneration; therefore, culturing cells or tissues suitable for clinical use remain a challenge. A platform consisting of human osteoblasts (hOBs), calcium-alginate (Ca-Alginate) scaffolds, and a self-made bioreactor system was established for autologous transplantation of human osteoblast cell clusters. The Ca-Alginate scaffold facilitated the growth and differentiation of human bone cell clusters, and the functionally-closed process bioreactor system supplied the soluble nutrients and osteogenic signals required to maintain the cell viability. This system preserved the proliferative ability of cells and cell viability and up-regulated bone-related gene expression and biological apatite crystals formation. The bone-like tissue generated could be extracted by removal of calcium ions via ethylenediaminetetraacetic acid (EDTA) chelation, and exhibited a size suitable for injection. The described strategy could be used in therapeutic application and opens new avenues for surgical interventions to correct skeletal defects.
A Microfabricated Coil for Implantable Applications of Magnetic Spinal Cord Stimulation
(2015)
Fu, Yu-Min
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Chen, Che-Yu
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Qian, Xin-Hong
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Cheng, Yu-Ting
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Wu, Chung-Yu
In this paper, a microfabricated inductive coil comprising of 125-turn coil windings and a MnZn-based magnetic core in a volume of 200 mm(3) is presented for the magnetic neural stimulation in a spinal cord. The coil winding with the parallel-linkage design instead of the typical serial-linkage one is proposed not only to provide better design flexibility to the current mode driving circuit but also to simplify the fabrication process of the 3-D inductive coil, which can further advance the coil miniaturization. Experimental results show the microcoil with a 1.5 A, 1 kHz square-wave current input can induce a voltages of 220 mu V on the conducting wire with an impedance of similar to 0.2 Omega @ kHz, 1 mm separation.
Arthropod steroid hormone (20-Hydroxyecdysone) suppresses IL-1 beta-induced catabolic gene expression in cartilage
(2015-01-24)
Sheu, Shiow-Yunn
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Ho, Shin-Rong
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Sun, Jui-Sheng
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Chen, Ching-Yun
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Ke, Cherng-Jyh
Background: In osteoarthritis (OA), the imbalance of chondrocytes' anabolic and catabolic factors can induce cartilage destruction. Interleukin-1 beta (IL-1 beta) is a potent pro-inflammatory cytokine that is capable of inducing chondrocytes and synovial cells to synthesize MMPs. The hypoxia-inducible factor-2alpha (HIF-2alpha, encoded by Epas1) is the catabolic transcription factor in the osteoarthritic process. The purpose of this study is to validate the effects of ecdysteroids (Ecd) on IL-1 beta-induced cartilage catabolism and the possible role of Ecd in treatment or prevention of early OA. Methods: Chondrocytes and articular cartilage was harvested from newborn ICR mice. Ecd effect on chondrocytes viability was tested and the optimal concentration was determined by MTT assay. The effect of HIF-2 alpha (EPAS1) in cartilage catabolism simulated by IL-1 beta (5 ng/ml) was evaluated by articular cartilage explants culture. The effects of Ecd on IL-1 beta-induced inflammatory conditions and their related catabolic genes expression were analyzed. Results: Interleukin-1 beta (IL-1 beta) treatment on primary mouse articular cartilage explants enhanced their Epas1, matrix metalloproteinases (MMP-3, MMP-13) and ADAMTS-5 genes expression and down-regulated collagen type II (Col2a1) gene expression. With the pre-treatment of 10(-8)M Ecd, the catabolic effects of IL-1 beta on articular cartilage were scavenged. Conclusion: In conclusions, Ecd can reduce the IL-1 beta-induced inflammatory effect of the cartilage. Ecd may suppress IL-1 beta-induced cartilage catabolism via HIF-2a pathway.
Augmentation of DMLS Biomimetic Dental Implants with Weight-Bearing Strut to Balance of Biologic and Mechanical Demands: From Bench to Animal
(2019-01-01)
Chang, Jenny Zwei-Chieng
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Tsai, Pei-I
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Kuo, Mark Yen-Ping
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Sun, Jui-Sheng
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Chen, San-Yuan
A mismatch of elastic modulus values could result in undesirable bone resorption around the dental implant. The objective of this study was to optimize direct metal laser sintering (DMLS)-manufactured Ti6Al4V dental implants' design, minimize elastic mismatch, allow for maximal bone ingrowth, and improve long-term fixation of the implant. In this study, DMLS dental implants with different morphological characteristics were fabricated. Three-point bending, torsional, and stability tests were performed to compare the mechanical properties of different designs. Improvement of the weaker design was attempted by augmentation with a longitudinal 3D-printed strut. The osseointegrative properties were evaluated. The results showed that the increase in porosity decreased the mechanical properties, while augmentation with a longitudinal weight-bearing strut can improve mechanical strength. Maximal alkaline phosphatase gene expression of MG63 cells attained on 60% porosity Ti6Al4V discs. In vivo experiments showed good incorporation of bone into the porous scaffolds of the DMLS dental implant, resulting in a higher pull-out strength. In summary, we introduced a new design concept by augmenting the implant with a longitudinal weight-bearing strut to achieve the ideal combination of high strength and low elastic modulus; our results showed that there is a chance to reach the balance of both biologic and mechanical demands.
Developing intelligent human-machine interface for next generation ICU by using user-centered system development approach
(2014-01-01)
Hsu, Shang Hwa
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Sun, Jui-Sheng
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Chou Yi-Jing
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Weng, Chun-Wei
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工業工程與管理學系
For medical staffs, ICU is a high-risk and high-demanding environment. To reduce the medical staff's workload and improve their efficiency, we propose a user-centered approach for next generation ICU system development. The user-centered approach contains four phases: (1) user problem exploration; (2) user needs and requirements identification; (3) human-machine interface solution generation; and (4) user evaluation. The results from user evaluation of human-machine interface concepts showed that the user-centered approach is effective incorporating user needs and requirements into product development.
Dose-dependent regulation of cell proliferation and collagen degradation by estradiol on ligamentum flavum
(2014-07-15)
Chen, Mei-Hsiu
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Hu, Chao-Kai
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Chen, Pei-Ru
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Chen, Yu-Shan
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Sun, Jui-Sheng
Background: Estradiol plays an important role in the regulation of collagen metabolism. Deficiency of estradiol has been reported to be associated with the degeneration of many connective tissues. However, the association of estradiol and hypertrophy of the ligamentum flavum was seldom explored. Therefore, we studied the effects of estradiol on cultured cells from the ligamentum flavum. Methods: Primary cultures of human ligamentum flavum cells obtained from surgical specimens of 14 patients undergoing spinal surgery were used to investigate the effect of estradiol on cell proliferation and the expression of collagen, elastin, and matrix metalloproteinases. Downstream pathways of estrogen receptor underlying the regulation of metalloproteinases were also investigated. Results: In our study, we revealed the existence of estrogen receptors on both female and male ligamentum flavum cells with a gender difference. 17 beta-estradiol increased early (24 hours) proliferation of ligamentum flavum cells in a dose dependent manner and the effect could not be seen when the cell density increased. Estradiol with a concentration of 10-9 M decreased collagen levels and increased the expression of MMP-13. Adding an antagonist of PI3K downstream pathway could reverse the expression of MMP-13 caused by estradiol. Conclusions: The results implied estradiol regulated the expression of MMP-13 via PI3K pathway and contributed to the homeostasis of extracellular matrix in the ligamentum flavum.
Glycosaminoglycan-based hybrid hydrogel encapsulated with polyelectrolyte complex nanoparticles for endogenous stem cell regulation in central nervous system regeneration
(2018-08-01)
Jian, Wei-Hong
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Wang, Huan-Chih
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Kuan, Chen-Hsiang
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Chen, Ming-Hong
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Wu, Hsi-Chin
The poor regenerative capability of stem cell transplantation in the central nervous system limits their therapeutic efficacy in brain injuries. The sustained inflammatory response, lack of structural support, and trophic factors deficiency restrain the integration and long-term survival of stem cells. Instead of exogenous stem cell therapy, here we described the synthesis of nanohybrid hydrogel containing sulfated glycosaminoglycan-based polyelectrolyte complex nanoparticles (PCN) to mimic the brain extracellular matrix and control the delivery of stromal-derived factor-1 alpha (SDF-1 alpha) and basic fibroblast factor (bFGF) in response to matrix metalloproteinase (MMP) for recruiting endogenous neural stem cells (NSC) and regulating their cellular fate. Bioactive factors are delivered by electrostatic sequestration on PCN to amplify the signaling of SDF-1 alpha and bFGF to regulate NSC in vitro. In in vivo ischemic stroke model, the factors promoted neurological behavior recovery by enhancing neurogenesis and angiogenesis. These combined strategies may be applied for other tissue regenerations by regulating endogenous progenitors through the delivery of different kinds of glycosaminoglycan-binding molecules. (C) 2018 Elsevier Ltd. All rights reserved.
Improved Intrinsic Motivation and Muscle Activation Patterns in Reaching Task Using Virtual Reality Training for Stroke Rehabilitation: A Pilot Randomized Control Trial
(2014-01-01)
Fan, Shih-Chen
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Su, Fong-Chin
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Chen, Sheng-Shiung
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Hou, Wen-Hsuan
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Sun, Jui-Sheng
In long-term rehabilitation, stoke survivors might experience low motivation and poor adhesion to treatments. In such cases, off-the-shelf virtual reality (OTSVR) gaming systems can be a viable solution. The purpose of this exploratory study was to evaluate the effects of an affordable OTSVR treatment on patients\' motivation and motor capacities. The ultimate goal is to apply the advantages of the OTSVR system to the design of future systems. Twenty participants completed the follow-up assessment. Four parallel groups received treatments for three weeks: 1) virtual reality (VR) via Wii gaming; 2) conventional therapy; 3) a placebo board game; 4) no treatment. The training effects were evaluated immediately after and four weeks after treatment. Surface electromyographic activity for a reaching task was obtained from five muscles, and the time-to-peak (TTP) contractions, time that a muscle takes to reach maximum contractions, was used as a kinesiological parameter. Any functional gains were evaluated using the Jebsen-Taylor Hand Function Test and the Stroke Impact Scale. The VR group immediately demonstrated significantly shorter TTP contractions in their biceps and flexor carpi radialis compared to the those of the board game and no treatment groups (p < 0.05). The TTP contraction change between the VR group and the conventional therapy group did not have significant differences. The VR group having a marginally retentional improvement in the deltoids (p = 0.059). No long-term benefits persisted in any other muscle. However, the VR group showed higher intrinsic motivation than those of the other groups. In this pilot study, OTSVR gaming had immediate effects on motor recovery and provided motivation for treatment compliance in stroke patients.
Improvement of bone-tendon fixation by porous titanium interference screw: A rabbit animal model
(2018-10-01)
Tsai, Pei-I
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Chen, Chih-Yu
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Huang, Shu-Wei
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Yang, Kuo-Yi
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Lin, Tzu-Hung
The interference screw is a widely used fixation device in the anterior cruciate ligament (ACL) reconstruction surgeries. Despite the generally satisfactory results, problems of using interference screws were reported. By using additive manufacturing (AM) technology, we developed an innovative titanium alloy (Ti6Al4V) interference screw with rough surface and inter-connected porous structure designs to improve the bone-tendon fixation. An innovative Ti6Al4V interference screws were manufactured by AM technology. In vitro mechanical tests were performed to validate its mechanical properties. Twenty-seven New Zealand white rabbits were randomly divided into control and AM screw groups for biomechanical analyses and histological analysis at 4, 8, and 12 weeks postoperatively; while micro-CT analysis was performed at 12 weeks postoperatively. The biomechanical tests showed that the ultimate failure load in the AM interference screw group was significantly higher than that in the control group at all tested periods. These results were also compatible with the findings of micro-CT and histological analyses. In micro-CT analysis, the bone-screw gap was larger in the control group; while for the additive manufactured screw, the screw and bone growth was in close contact. In histological study, the bone-screw gaps were wider in the control group and were almost invisible in the AM screw group. The innovative AM interference screws with surface roughness and inter-connected porous architectures demonstrated better bone-tendon-implant integration, and resulted in stronger biomechanical characteristics when compared to traditional screws. These advantages can be transferred to future interference screw designs to improve their clinical performance. The AM interference screw could improve graft fixation and eventually result in better biomechanical performance of the bone-tendon-screw construct. The innovative AM interference screws can be transferred to future interference screw designs to improve the performance of implants. (c) 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:2633-2640, 2018.
Magnetic hyperthermia enhance the treatment efficacy of peri-implant osteomyelitis
(2017-07-25)
Fang, Chih-Hsiang
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Tsai, Pei-I
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Huang, Shu-Wei
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Sun, Jui-Sheng
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Chang, Jenny Zwei-Chieng
Background: When bacteria colony persist within a biofilm, suitable drugs are not yet available for the eradication of biofilm-producing bacteria. The aim of this study is to study the effect of magnetic nano-particles-induced hyperthermia on destroying biofilm and promoting bactericidal effects of antibiotics in the treatment of osteomyelitis. Methods: Sixty 12-weeks-old male Wistar rats were used. A metallic 18G needle was implanted into the bone marrow cavity of distal femur after the injection of Methicillin-sensitive Staphylococcus aureus (MSSA). All animals were divided into 5 different treatment modalities. The microbiological evaluation, scanning electron microscope examination, radiographic examination and then micro-CT evaluation of peri-implant bone resorption were analyzed. Results: The pathomorphological characteristics of biofilm formation were completed after 40-days induction of osteomyelitis. The inserted implants can be heated upto 75 degrees C by magnetic heating without any significant thermal damage on the surrounding tissue. We also demonstrated that systemic administration of vancomycin [VC (i.m.)] could not eradicate the bacteria; but, local administration of vancomycin into the femoral canal and the presence of magnetic nanoparticles hyperthermia did enhance the eradication of bacteria in a biofilm-based colony. In these two groups, the percent bone volume (BV/TV: %) was significantly higher than that of the positive control. Conclusions: For the treatment of chronic osteomyelitis, we developed a new modality to improve antibiotic efficacy; the protection effect of biofilms on bacteria could be destroyed by magnetic nanoparticles-induced hyperthermia and therapeutic effect of systemic antibiotics could be enhanced.
Multi-scale mapping for collagen-regulated mineralization in bone remodeling of additive manufacturing porous implants
(2019-05-15)
Tsai, Pei-I.
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Lam, Tu-Ngoc
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Wu, Meng-Huang
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Tseng, Kuan-Ying
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Chang, Yuan-Wei
Long term success of metallic fusion cages depends on mechanobiological processes through the bone incorporation and rich osseointegration. An optimal configuration of porous titanium-aluminum-vanadium (Ti-6Al-4V) implant fabricated via the additive manufacturing was evaluated in complimentary structure examinations to investigate the growth of autologous osseous at multi-length scales. X-ray microcomputed tomography (micro-CT) and transmission X-ray microscopy (TXM) using newly-built analysis method indicate the porous Ti-6Al-4V is much better for bone ingrowth compared to commercially non-porous titanium (Ti) and porous tantalum (Ta) implants at the ultramicrostructural level. The evolution of bone formation and remodeling acquired by nano X-ray Laue diffraction mapping exhibits the isotropic orientation and low crystallinity of all newly formed bone whereas mature bone in Ti-6Al-4V discloses the preferential alignment and higher crystallinity volumes of constituent hydroxyapatite (HA) crystallites. The high degree in mineral crystallinity of the fully mature bone suggests additive manufactured Ti-6Al-4V pores enhance the collagen-regulated mineralization.
Radix Scrophulariae extracts (harpagoside) suppresses hypoxia-induced microglial activation and neurotoxicity
(2015-09-14)
Sheu, Shiow-Yunn
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Hong, Yi-Wen
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Sun, Jui-Sheng
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Liu, Man-Hai
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Chen, Ching-Yun
Background: Hypoxia could lead to microglia activation and inflammatory mediators' overproduction. These inflammatory molecules could amplify the neuroinflammatory process and exacerbate neuronal injury. The aim of this study is to find out whether harpagoside could reduce hypoxia-induced microglia activation. Methods: In this study, primary microglia cells harvested from neonatal ICR mice were activated by exposure to hypoxia (1 % O-2 for 3 h). Harpagoside had been shown to be no cytotoxicity on microglia cells by MTT assay. The scavenger effect of harpagoside on hypoxia-enhanced microglial cells proliferation, associated inflammatory genes expression (COX-II, IL-1 beta and IL-6 genes) and NO synthesis were also examined. Results: Hypoxia enhances active proliferation of microglial cells, while harpagoside can scavenge this effect. We find that harpagoside could scavenge hypoxia-enhanced inflammatory genes expression (COX-2, IL-1 beta and IL-6 genes) and NO synthesis of microglial cells. Under 3 h' hypoxic stimulation, the nuclear contents of p65 and hypoxia inducible factor-1 alpha (HIF-1 alpha) significantly increase, while the cytosol I kappa B-alpha content decreases; these effects can be reversed by 1 h's pre-incubation of 10(-8) M harpagoside. Harpagoside could decrease I kappa B-alpha protein phosphorylation and inhibit p65 protein translocation from the cytosol to the nucleus, thus suppress NF-kappa B activation and reduce the HIF-1 alpha generation. Conclusion: These results suggested that the anti-inflammatory mechanism of harpagoside might be associated with the NF-kappa B signaling pathway. Harpagoside protect against hypoxia-induced toxicity on microglial cells through HIF-alpha pathway.
Tissue transglutaminase is involved in mechanical load-induced osteogenic differentiation of human ligamentum flavum cells
(2016)
Chao, Yuan-Hung
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Huang, Shih-Yung
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Yang, Ruei-Cheng
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Sun, Jui-Sheng
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友訊交大聯合研發中心
Mechanical load-induced osteogenic differentiation might be the key cellular event in the calcification and ossification of ligamentum flavum. The aim of this study was to investigate the influence of tissue transglutaminase (TGM2) on mechanical load-induced osteogenesis of ligamentum flavum cells. Human ligamentum flavum cells were obtained from 12 patients undergoing lumbar spine surgery. Osteogenic phenotypes of ligamentum flavum cells, such as alkaline phosphatase (ALP), Alizarin red-S stain, and gene expression of osteogenic makers were evaluated following the administration of mechanical load and BMP-2 treatment. The expression of TGM2 was evaluated by real-time PCR, Western blotting, and enzyme-linked immunosorbent assay (ELISA) analysis. Our results showed that mechanical load in combination with BMP-2 enhanced calcium deposition and ALP activity. Mechanical load significantly increased ALP and OC gene expression on day 3, whereas BMP-2 significantly increased ALP, OPN, and Runx2 on day 7. Mechanical load significantly induced TGM2 gene expression and enzyme activity in human ligamentum flavum cells. Exogenous TGM2 increased ALP and OC gene expression; while, inhibited TG activity significantly attenuated mechanical load-induced and TGM2-induced ALP activity. In summary, mechanical load-induced TGM2 expression and enzyme activity is involved in the progression of the calcification of ligamentum flavum.
Wing-augmentation reduces femoral head cutting out of dynamic hip screw
(2017-06-01)
Chen, Chih-Yu
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Huang, Shu-Wei
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Sun, Jui-Sheng
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Lin, Shin-Yiing
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Yu, Chih-Sheng
The dynamic hip screw (DHS) is commonly used in the treatment of femoral intertrochanteric fracture with high satisfactory results. However, post-operative failure does occur and result in poor prognosis. The most common failure is femoral head varus collapse, followed by lag screw cut-out through the femoral head. In this study, a novel-designed DHS with two supplemental horizontal blades was used to improve the fixation stability. In this study, nine convention DHS and 9 Orthopaedic Device Research Center (ODRC) DHSS were tested in this study. Each implant was fixed into cellular polyurethane rigid foam as a surrogate of osteoporotic femoral head. Under biaxial rocking motion, all constructs were loaded to failure point (12 mm axial displacement) or up to 20,000 cycles of 1.45 kN peak magnitude were achieved, whichever occurred first. The migration kinematics was continuously monitored and recorded. The final tip-to-apex distance, rotational angle and varus deformation were also recorded. The results showed that the ODRC DHS sustained significantly more loading cycles and exhibited less axial migration in comparison to the conventional DHS. The ODRC DHS showed a significantly smaller bending strain and larger torsional strain compared to the conventional DHS. The changes in tip-to-apex distance (TAD), post-study varus angle, post-study rotational angle of the ODRC DHS were all significantly less than that of the conventional DHS (p < 0.05). We concluded that the ODRC DHS augmented with two horizontal wings would increase the bone-implant interface contact surface, dissipate the load to the screw itself, which improves the migration resistance and increases the anti-rotational implant effect. In conclusion, the proposed ODRC DHS demonstrated significantly better migration resistance and anti-rotational effect in comparison to the conventional DHS construct. (C) 2017 IPEM. Published by Elsevier Ltd. All rights reserved.