43 results on '"Jung-Youn Shin"'
Search Results
2. A 14-year-old male with rhabdomyolysis associated with psychogenic polydipsia and hyponatremia
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Jung, Youn Shin, primary, Choi, Yunha, additional, Ha, Jihyun, additional, Yoo, Eun-Gyong, additional, Paek, So Hyun, additional, and Jung, Mo Kyung, additional
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- 2023
- Full Text
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3. Regeneration of Osteochondral Defects Using Developmentally Inspired Cartilaginous Templates
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Rossana Schipani, Jung-Youn Shin, Aidan McAlinden, Daniel J. Kelly, Pedro J. Díaz-Payno, Daniel Withers, Eben Alsberg, Gráinne M. Cunniffe, Susan E. Critchley, and Adam O'Reilly
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Cartilage, Articular ,0206 medical engineering ,Biomedical Engineering ,Bioengineering ,02 engineering and technology ,Biology ,Mesenchymal Stem Cell Transplantation ,Biochemistry ,Bone and Bones ,Biomaterials ,03 medical and health sciences ,Tissue engineering ,Animals ,Regeneration ,Endochondral ossification ,030304 developmental biology ,0303 health sciences ,Regeneration (biology) ,Mesenchymal stem cell ,Mesenchymal Stem Cells ,Chondrogenesis ,020601 biomedical engineering ,Cell biology ,Female ,Rabbits - Abstract
Successfully treating osteochondral defects involves regenerating both the damaged articular cartilage and the underlying subchondral bone, in addition to the complex interface that separates these tissues. In this study, we demonstrate that a cartilage template, engineered using bone marrow-derived mesenchymal stem cells, can enhance the regeneration of such defects and promote the development of a more mechanically functional repair tissue. We also use a computational mechanobiological model to understand how joint-specific environmental factors, specifically oxygen levels and tissue strains, regulate the conversion of the engineered template into cartilage and bone in vivo.
- Published
- 2019
4. Scaffold-free human mesenchymal stem cell construct geometry regulates long bone regeneration
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Honghyun Park, Yuxuan Cheng, Joel D. Boerckel, Samuel Herberg, Jung-Youn Shin, Eben Alsberg, Daniel Varghai, Phuong N. Dang, Anna D. Dikina, Daniel S. Alt, and Marsha W. Rolle
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0301 basic medicine ,Scaffold ,Bone Regeneration ,QH301-705.5 ,Long bone ,Medicine (miscellaneous) ,Bone Morphogenetic Protein 2 ,Geometry ,Biocompatible Materials ,02 engineering and technology ,Bone morphogenetic protein ,Bone morphogenetic protein 2 ,General Biochemistry, Genetics and Molecular Biology ,Bone and Bones ,Article ,Transforming Growth Factor beta1 ,03 medical and health sciences ,Tissue engineering ,Osteogenesis ,medicine ,Humans ,Biology (General) ,Progenitor cell ,Bone regeneration ,Endochondral ossification ,Cells, Cultured ,030304 developmental biology ,Uncategorized ,0303 health sciences ,Wound Healing ,Tissue Engineering ,Chemistry ,Cartilage ,Mesenchymal stem cell ,Bone development ,Cell Differentiation ,Mesenchymal Stem Cells ,021001 nanoscience & nanotechnology ,Chondrogenesis ,equipment and supplies ,Stem-cell research ,030104 developmental biology ,medicine.anatomical_structure ,Regenerative medicine ,Collagen ,General Agricultural and Biological Sciences ,0210 nano-technology ,Morphogen - Abstract
Biomimetic bone tissue engineering strategies partially recapitulate development. We recently showed functional restoration of femoral defects using scaffold-free human mesenchymal stem cell (hMSC) condensates featuring localized morphogen presentation with delayed in vivo mechanical loading. Possible effects of construct geometry on healing outcome remain unclear. Here, we hypothesized that localized presentation of transforming growth factor (TGF)-β1 and bone morphogenetic protein (BMP)-2 to engineered hMSC tubes mimicking femoral diaphyses induces endochondral ossification, and that TGF-β1 + BMP-2-presenting hMSC tubes enhance defect healing with delayed in vivo loading vs. loosely packed hMSC sheets. Localized morphogen presentation stimulated chondrogenic priming/endochondral differentiation in vitro. Subcutaneously, hMSC tubes formed cartilage templates that underwent bony remodeling. Orthotopically, hMSC tubes stimulated more robust endochondral defect healing vs. hMSC sheets. Tissue resembling normal growth plate was observed with negligible ectopic bone. This study demonstrates interactions between hMSC condensation geometry, morphogen bioavailability, and mechanical cues to recapitulate development for biomimetic bone tissue engineering., Herberg et al. previously showed functional healing of femoral defects using scaffold-free human mesenchymal stem cell (hMSC) condensates with localized morphogen presentation. In this study, they report the importance of the tubular geometry of MSC condensates in long bone regeneration. Unlike loosely packed hMSC sheets, only hMSC tubes induced regenerate tissue partially resembling normal growth plate.
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- 2021
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5. Development of a 3D Bioprinted Scaffold with Spatio-temporally Defined Patterns of BMP-2 and VEGF for the Regeneration of Large Bone Defects
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Eben Alsberg, Daniel J. Kelly, Lieke H. A. van Dommelen, Jessica Nulty, Jung-Youn Shin, Fiona E. Freeman, David C. Browe, and Pierluca Pitacco
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3D bioprinting ,Scaffold ,Strategy and Management ,Mechanical Engineering ,Regeneration (biology) ,Growth factor ,medicine.medical_treatment ,Metals and Alloys ,Bone healing ,Biology ,Bone tissue ,Bone morphogenetic protein 2 ,Industrial and Manufacturing Engineering ,law.invention ,medicine.anatomical_structure ,Reconstructive and regenerative medicine Radboud Institute for Molecular Life Sciences [Radboudumc 10] ,law ,Methods Article ,medicine ,Bone regeneration ,Biomedical engineering - Abstract
The local delivery of growth factors such as BMP-2 is a well-established strategy for the repair of bone defects. The limitations of such approaches clinically are well documented and can be linked to the need for supraphysiological doses and poor spatio-temporal control of growth factor release in vivo. Using bioprinting techniques, it is possible to generate implants that can deliver cytokines or growth factors with distinct spatiotemporal release profiles and patterns to enhance bone regeneration. Specifically, for bone healing, several growth factors, including vascular endothelial growth factor (VEGF) and bone morphogenic proteins (BMPs), have been shown to be expressed at different phases of the process. This protocol aims to outline how to use bioprinting strategies to deliver growth factors, both alone or in combination, to the site of injury at physiologically relevant dosages such that repair is induced without adverse effects. Here we describe: the printing parameters to generate the polymer mechanical backbone; instructions to generate the different bioinks and allow for the temporal control of both growth factors; and the printing process to develop implants with spatially defined patterns of growth factors for bone regeneration. The novelty of this protocol is the use of multiple-tool fabrication techniques to develop an implant with spatio-temporal control of growth factor delivery for bone regeneration. While the overall aim of this protocol was to develop an implant for bone regeneration, the technique can be modified and used for a variety of regenerative purposes. Graphic abstract: [Image: see text] 3D Bioprinting Spatio-Temporally Defined Patterns of Growth Factors to Tightly Control Bone Tissue Regeneration.
- Published
- 2021
6. 3D bioprinting spatiotemporally defined patterns of growth factors to tightly control tissue regeneration
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Daniel J. Kelly, Lieke H. A. van Dommelen, Eben Alsberg, Jessica Nulty, Pierluca Pitacco, Fiona E. Freeman, Jung-Youn Shin, and David C. Browe
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Angiogenesis ,VEGF receptors ,medicine.medical_treatment ,02 engineering and technology ,law.invention ,03 medical and health sciences ,chemistry.chemical_compound ,Engineering ,In vivo ,law ,medicine ,Research Articles ,030304 developmental biology ,0303 health sciences ,3D bioprinting ,Multidisciplinary ,biology ,Chemistry ,Growth factor ,SciAdv r-articles ,Life Sciences ,Heterotopic bone ,021001 nanoscience & nanotechnology ,Bone defect ,Cell biology ,Vascular endothelial growth factor ,Reconstructive and regenerative medicine Radboud Institute for Molecular Life Sciences [Radboudumc 10] ,biology.protein ,0210 nano-technology ,Research Article - Abstract
Spatiotemporal delivery of VEGF and BMP-2 from 3D bioprinted implants enhances angiogenesis and subsequent bone regeneration., Therapeutic growth factor delivery typically requires supraphysiological dosages, which can cause undesirable off-target effects. The aim of this study was to 3D bioprint implants containing spatiotemporally defined patterns of growth factors optimized for coupled angiogenesis and osteogenesis. Using nanoparticle functionalized bioinks, it was possible to print implants with distinct growth factor patterns and release profiles spanning from days to weeks. The extent of angiogenesis in vivo depended on the spatial presentation of vascular endothelial growth factor (VEGF). Higher levels of vessel invasion were observed in implants containing a spatial gradient of VEGF compared to those homogenously loaded with the same total amount of protein. Printed implants containing a gradient of VEGF, coupled with spatially defined BMP-2 localization and release kinetics, accelerated large bone defect healing with little heterotopic bone formation. This demonstrates the potential of growth factor printing, a putative point of care therapy, for tightly controlled tissue regeneration.
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- 2020
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7. Highly Elastic and Tough Interpenetrating Polymer Network-Structured Hybrid Hydrogels for Cyclic Mechanical Loading-Enhanced Tissue Engineering
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Oju Jeon, Hong Hyun Park, Jung Youn Shin, Eben Alsberg, Robyn Marks, Mitchell Hopkins, and Tae-Hee Kim
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Reaction conditions ,Materials science ,food.ingredient ,Biocompatibility ,General Chemical Engineering ,technology, industry, and agriculture ,Nanotechnology ,02 engineering and technology ,General Chemistry ,010402 general chemistry ,021001 nanoscience & nanotechnology ,Biocompatible material ,01 natural sciences ,Gelatin ,0104 chemical sciences ,Gel strength ,food ,Tissue engineering ,Self-healing hydrogels ,Materials Chemistry ,Interpenetrating polymer network ,Composite material ,0210 nano-technology - Abstract
Although hydrogels are extensively investigated as biomaterials due to their ability to mimic cellular microenvironments, they are often limited by their poor physical properties in response to mechanical loads, including weak gel strength, brittleness, and permanent deformation. Recently, interpenetrating polymer network (IPN) hydrogels have gained substantial attention for their use in investigating changes in encapsulated cell behaviors under mechanical stimulation. However, despite recent success in developing highly elastic IPN-structured hydrogels, it remains a great technical challenge to endow them with biocompatibility and biodegradability due to use of toxic chemicals, nonbiodegradable prepolymers, and harsh reaction conditions. In this study, we report on the synthesis and formation of highly elastic and tough IPN-structured hydrogels based on alginate and gelatin, which are biocompatible and biodegradable. Mechanical stimulation enhanced the proliferation and osteogenic differentiation of enca...
- Published
- 2017
8. Correlation between Radiographic Findings, Clinical Findings and Joint Sounds of Temporomandibular Joint Osteoarthritis Patients
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Jung-Youn Shin and Jong-Mo Ahn
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Orthodontics ,Crepitus ,business.industry ,Radiography ,Anatomy ,Osteoarthritis ,medicine.disease ,Temporomandibular joint ,medicine.anatomical_structure ,medicine ,medicine.symptom ,business ,Joint (geology) ,Clinical evaluation - Published
- 2017
9. Artificial Slanted Nanocilia Array as a Mechanotransducer for Controlling Cell Polarity
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Noo Li Jeon, Pilnam Kim, Byung Soo Kim, Hoon Eui Jeong, Min Sung Kim, Daeshik Kang, Sang Moon Kim, Hong Nam Kim, Kyung-Jin Jang, Kahp-Yang Suh, Ilkyoo Koh, Segeun Jang, Yoonmi Hong, and Jung-Youn Shin
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0301 basic medicine ,Collagen type ,Matrigel ,Materials science ,biology ,business.industry ,General Engineering ,General Physics and Astronomy ,02 engineering and technology ,equipment and supplies ,021001 nanoscience & nanotechnology ,Polarization (waves) ,Fibronectin ,03 medical and health sciences ,030104 developmental biology ,Optics ,Bending stiffness ,Cell polarity ,biology.protein ,Biophysics ,Directionality ,General Materials Science ,0210 nano-technology ,business ,Anisotropy - Abstract
We present a method to induce cell directional behavior using slanted nanocilia arrays. NIH-3T3 fibroblasts demonstrated bidirectional polarization in a rectangular arrangement on vertical nanocilia arrays and exhibited a transition from a bidirectional to a unidirectional polarization pattern when the angle of the nanocilia was decreased from 90° to 30°. The slanted nanocilia guided and facilitated spreading by allowing the cells to contact the sidewalls of the nanocilia, and the directional migration of the cells opposed the direction of the slant due to the anisotropic bending stiffness of the slanted nanocilia. Although the cells recognized the underlying anisotropic geometry when the nanocilia were coated with fibronectin, collagen type I, and Matrigel, the cells lost their directionality when the nanocilia were coated with poly-d-lysine and poly-l-lysine. Furthermore, although the cells recognized geometrical anisotropy on fibronectin coatings, pharmacological perturbation of PI3K-Rac signaling hindered the directional elongation of the cells on both the slanted and vertical nanocilia. Furthermore, myosin light chain II was required for the cells to obtain polarized morphologies. These results indicated that the slanted nanocilia array provided anisotropic contact guidance cues to the interacting cells. The polarization of cells was controlled through two steps: the recognition of underlying geometrical anisotropy and the subsequent directional spreading according to the guidance cues.
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- 2017
10. Combinatorial screening of biochemical and physical signals for phenotypic regulation of stem cell-based cartilage tissue engineering
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Ming Kong, Wujin Sun, KangJu Lee, Amr A. Abdeen, Su Ryon Shin, Somali Chaterji, Yu Bin Lee, Han-Jun Kim, Ha Neul Lee, Sang Jin Lee, Praveen Bandaru, Oju Jeon, Jung-Youn Shin, Daniel S. Alt, Ali Khademhosseini, Eben Alsberg, and Junmin Lee
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Cartilage, Articular ,Materials Science ,Chondrocyte hypertrophy ,Biocompatible Materials ,02 engineering and technology ,Mechanotransduction, Cellular ,03 medical and health sciences ,medicine ,Health and Medicine ,Mechanotransduction ,Research Articles ,030304 developmental biology ,0303 health sciences ,Multidisciplinary ,Tissue Engineering ,Chemistry ,Cartilage ,Stem Cells ,Mesenchymal stem cell ,Wnt signaling pathway ,Biomaterial ,SciAdv r-articles ,Cell Differentiation ,Mesenchymal Stem Cells ,021001 nanoscience & nanotechnology ,Chondrogenesis ,Cell biology ,medicine.anatomical_structure ,Phenotype ,Stem cell ,0210 nano-technology ,Research Article - Abstract
Multicomponent biomaterials using a high-throughput system regulate hyaline or hypertrophic chondrogenesis of hMSCs., Despite great progress in biomaterial design strategies for replacing damaged articular cartilage, prevention of stem cell-derived chondrocyte hypertrophy and resulting inferior tissue formation is still a critical challenge. Here, by using engineered biomaterials and a high-throughput system for screening of combinatorial cues in cartilage microenvironments, we demonstrate that biomaterial cross-linking density that regulates matrix degradation and stiffness—together with defined presentation of growth factors, mechanical stimulation, and arginine-glycine-aspartic acid (RGD) peptides—can guide human mesenchymal stem cell (hMSC) differentiation into articular or hypertrophic cartilage phenotypes. Faster-degrading, soft matrices promoted articular cartilage tissue formation of hMSCs by inducing their proliferation and maturation, while slower-degrading, stiff matrices promoted cells to differentiate into hypertrophic chondrocytes through Yes-associated protein (YAP)–dependent mechanotransduction. in vitro and in vivo chondrogenesis studies also suggest that down-regulation of the Wingless and INT-1 (WNT) signaling pathway is required for better quality articular cartilage-like tissue production.
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- 2019
11. Combinatorial morphogenetic and mechanical cues to mimic bone development for defect repair
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Daniel S. Alt, Honghyun Park, Yuxuan Cheng, Joel D. Boerckel, P. C. Wong, Felicia He, Anna D. Dikina, Samuel Herberg, Yu Bin Lee, Phuong N. Dang, Alexandra McMillan, Rui Tang, James H. Dawahare, Eben Alsberg, Daniel Varghai, Kentaro Umemori, Anna M. McDermott, and Jung Youn Shin
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Male ,animal structures ,Long bone ,02 engineering and technology ,Bone and Bones ,Transforming Growth Factor beta1 ,03 medical and health sciences ,Tissue engineering ,Biomimetics ,Osteogenesis ,Transforming Growth Factor beta ,In vivo ,Morphogenesis ,medicine ,Animals ,Humans ,Endochondral ossification ,Cells, Cultured ,Research Articles ,030304 developmental biology ,0303 health sciences ,Bone Development ,Multidisciplinary ,Tissue Engineering ,Chemistry ,Regeneration (biology) ,Mesenchymal stem cell ,SciAdv r-articles ,Mesenchymal Stem Cells ,021001 nanoscience & nanotechnology ,Rats ,Cell biology ,medicine.anatomical_structure ,embryonic structures ,Synthetic Biology ,0210 nano-technology ,Function (biology) ,Research Article ,Morphogen - Abstract
Mesenchymal condensations promote defect repair by mimicking cellular, morphogenetic, and mechanical aspects of bone development., Endochondral ossification during long bone development and natural fracture healing initiates by mesenchymal cell condensation, directed by local morphogen signals and mechanical cues. Here, we aimed to mimic development for regeneration of large bone defects. We hypothesized that engineered human mesenchymal condensations presenting transforming growth factor–β1 (TGF-β1) and/or bone morphogenetic protein-2 (BMP-2) from encapsulated microparticles promotes endochondral defect regeneration contingent on in vivo mechanical cues. Mesenchymal condensations induced bone formation dependent on morphogen presentation, with BMP-2 + TGF-β1 fully restoring mechanical function. Delayed in vivo ambulatory loading significantly enhanced the bone formation rate in the dual morphogen group. In vitro, BMP-2 or BMP-2 + TGF-β1 initiated robust endochondral lineage commitment. In vivo, however, extensive cartilage formation was evident predominantly in the BMP-2 + TGF-β1 group, enhanced by mechanical loading. Together, this study demonstrates a biomimetic template for recapitulating developmental morphogenic and mechanical cues in vivo for tissue engineering.
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- 2019
12. Combinatorial morphogenetic and mechanical cues to mimic bone development for defect repair
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Samuel Herberg, Honghyun Park, Felicia He, Phuong N. Dang, Anna D. Dikina, Daniel Varghai, Yuxuan Cheng, Joel D. Boerckel, Alexandra McMillan, Yu Bin Lee, Daniel S. Alt, Jung Youn Shin, P. C. Wong, Anna M. McDermott, Eben Alsberg, James H. Dawahare, Kentaro Umemori, and Rui Tang
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0303 health sciences ,Chemistry ,Regeneration (biology) ,0206 medical engineering ,Mesenchymal stem cell ,Long bone ,02 engineering and technology ,Chondrogenesis ,020601 biomedical engineering ,Cell biology ,03 medical and health sciences ,medicine.anatomical_structure ,Tissue engineering ,In vivo ,medicine ,Endochondral ossification ,030304 developmental biology ,Morphogen - Abstract
Endochondral ossification during long bone development and natural fracture healing initiates by mesenchymal cell condensation and is directed by local morphogen signals and mechanical cues. Here, we aimed to mimic these developmental conditions for regeneration of large bone defects. We hypothesized that engineered human mesenchymal stem cell (hMSC) condensations with in situ presentation of transforming growth factor-β1 (TGF-β1) and/or bone morphogenetic protein-2 (BMP-2) from encapsulated microparticles would promote endochondral regeneration of critical-sized rat femoral bone defects in a manner dependent on the in vivo mechanical environment. Mesenchymal condensations induced bone formation dependent on morphogen presentation, with dual BMP-2 + TGF-β1 fully restoring mechanical bone function by week 12. In vivo ambulatory mechanical loading, initiated at week 4 by delayed unlocking of compliant fixation plates, significantly enhanced the bone formation rate in the four weeks after load initiation in the dual morphogen group. In vitro, local presentation of either BMP-2 alone or BMP-2 + TGF-β1 initiated endochondral lineage commitment of mesenchymal condensations, inducing both chondrogenic and osteogenic gene expression through SMAD3 and SMAD5 signaling. In vivo, however, endochondral cartilage formation was evident only in the BMP-2 + TGF-β1 group and was enhanced by mechanical loading. The degree of bone formation was comparable to BMP-2 soaked on collagen but without the ectopic bone formation that limits the clinical efficacy of BMP-2/collagen. In contrast, mechanical loading had no effect on autograft-mediated repair. Together, this study demonstrates a biomimetic template for recapitulating developmental morphogenic and mechanical cues in vivo for tissue engineering.One Sentence SummaryMimicking aspects of the cellular, biochemical, and mechanical environment during early limb development, chondrogenically-primed human mesenchymal stem cell condensations promoted functional healing of critical-sized femoral defects via endochondral ossification, and healing rate and extent was a function of the in vivo mechanical environment.
- Published
- 2019
13. Enhanced Bone Repair by Guided Osteoblast Recruitment Using Topographically Defined Implant
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Min Sung Kim, Hong Nam Kim, Byung-Soo Kim, Noo Li Jeon, Suk Ho Bhang, Jaesur Oh, Jin Han, Wan-Geun La, Gun-Jae Jeong, Ju-Ro Lee, Seokyung Kang, Jeong-Kee Yoon, and Jung-Youn Shin
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0301 basic medicine ,Cell signaling ,Intracellular Space ,Biomedical Engineering ,Bioengineering ,Bone healing ,Biochemistry ,Bone and Bones ,Cell Line ,Biomaterials ,03 medical and health sciences ,Coated Materials, Biocompatible ,Cell Movement ,Osteogenesis ,In vivo ,medicine ,Animals ,Cell Proliferation ,Mice, Inbred ICR ,Wound Healing ,Osteoblasts ,Cell Death ,Cell growth ,Chemistry ,Cell migration ,Osteoblast ,Prostheses and Implants ,Original Articles ,030104 developmental biology ,medicine.anatomical_structure ,Implant ,Wound healing ,Signal Transduction ,Biomedical engineering - Abstract
The rapid recruitment of osteoblasts in bone defects is an essential prerequisite for efficient bone repair. Conventionally, osteoblast recruitment to bone defects and subsequent bone repair has been achieved using growth factors. Here, we present a methodology that can guide the recruitment of osteoblasts to bone defects with topographically defined implants (TIs) for efficient in vivo bone repair. We compared circular TIs that had microgrooves in parallel or radial arrangements with nonpatterned implants for osteoblast migration and in vivo bone formation. In vitro, the microgrooves in the TIs enhanced both the migration and proliferation of osteoblasts. Especially, the microgrooves with radial arrangement demonstrated a much higher efficiency of osteoblast recruitment to the implants than did the other types of implants, which may be due to the efficient guidance of cell migration toward the cell-free area of the implants. The expression of the intracellular signaling molecules responsible for the cell migration was also upregulated in osteoblasts on the microgrooved TIs. In vivo, the TI with radially defined topography demonstrated much greater bone repair in mouse calvarial defect models than in the other types of implants. Taken together, these results indicate that implants with physical guidance can enhance tissue repair by rapid cell recruitment.
- Published
- 2016
14. Administration of tauroursodeoxycholic acid enhances osteogenic differentiation of bone marrow-derived mesenchymal stem cells and bone regeneration
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Byung-Hyun Cha, Yoon-Ji Ma, Myungkyung Noh, Yoshie Arai, Soo-Hong Lee, Byung-Soo Kim, Moon-Joo Jung, Jung-Youn Shin, Bo-Kyung Moon, and Jin-Su Kim
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Male ,0301 basic medicine ,Bone Regeneration ,Histology ,MAP Kinase Signaling System ,Physiology ,Endocrinology, Diabetes and Metabolism ,Apoptosis ,Bone Marrow Cells ,Bone tissue ,Taurochenodeoxycholic Acid ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Osteogenesis ,medicine ,Animals ,Bone regeneration ,Inflammation ,Mice, Inbred BALB C ,biology ,Regeneration (biology) ,Skull ,Mesenchymal stem cell ,Cell Differentiation ,Mesenchymal Stem Cells ,Tauroursodeoxycholic acid ,X-Ray Microtomography ,Anatomy ,Cell biology ,030104 developmental biology ,medicine.anatomical_structure ,chemistry ,Adipogenesis ,Osteocalcin ,biology.protein ,Bone marrow ,030217 neurology & neurosurgery - Abstract
It is known that osteogenic differentiation of mesenchymal stem cells (MSCs) can be promoted by suppression of adipogenesis of MSCs. We have recently found that the chemical chaperone tauroursodeoxycholic acid (TUDCA) significantly reduces adipogenesis of MSCs. In the present study, we examined whether TUDCA can promote osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BMMSCs) by regulating Integrin 5 (ITGA5) associated with activation of ERK1/2 signal pathway and thereby enhance bone tissue regeneration by reducing apoptosis and the inflammatory response. TUDCA treatment promoted in vitro osteogenic differentiation of BMMSCs and in vivo bone tissue regeneration in a calvarial defect model, as confirmed by micro-computed tomography, histological staining, and immunohistochemistry for osteocalcin. In addition, TUDCA treatment significantly decreased apoptosis and the inflammatory response in vivo and in vitro, which is important to enhance bone tissue regeneration. These results indicate that TUDCA plays a critical role in enhancing osteogenesis of BMMSCs, and is therefore a potential alternative drug for bone tissue regeneration.
- Published
- 2016
15. Enhancing Therapeutic Efficacy and Reducing Cell Dosage in Stem Cell Transplantation Therapy for Ischemic Limb Diseases by Modifying the Cell Injection Site
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Suk Ho Bhang, Jeong-Kee Yoon, Myung Kyung Noh, Jung-Youn Shin, and Byung Soo Kim
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0301 basic medicine ,Cell ,Biomedical Engineering ,Ischemia ,Mice, Nude ,Bioengineering ,Biology ,Mesenchymal Stem Cell Transplantation ,Biochemistry ,Biomaterials ,Mice ,03 medical and health sciences ,Paracrine signalling ,medicine ,Animals ,Humans ,Stem cell transplantation for articular cartilage repair ,Mesenchymal stem cell ,Mesenchymal Stem Cells ,medicine.disease ,Hindlimb ,Transplantation ,030104 developmental biology ,medicine.anatomical_structure ,Immunology ,Cancer research ,Heterografts ,Female ,Stem cell ,Adult stem cell - Abstract
In conventional stem cell transplantation therapies for ischemic limb diseases, stem cells are generally transplanted into the ischemic region (IR), and most of the transplanted cells undergo hypoxia-mediated cell death. Due to massive cell death, the therapeutic efficacy is reduced and a high dose of stem cells is necessitated for the therapies. In this study, we investigated whether the therapeutic efficacy can be improved and the cell dosage can be reduced in the therapy for limb ischemia simply by modifying the stem cell injection site to a site where cell engraftment is improved and blood vessel sprouting is efficiently stimulated. Human mesenchymal stem cells (hMSCs) cultured under hypoxic condition, which simulates cells transplanted to IR, underwent extensive cell death in vitro. Importantly, cell death was significantly attenuated when hMSCs adhered first under normoxic condition for 24 h and then were exposed to hypoxic condition, which simulates cells transplanted to the border zone (BZ) in the upper thigh and migrated to IR. hMSCs, at doses of 2 × 10(5) or 2 × 10(6) cells, were injected into the IR or BZ of 5-week-old female athymic mice after ischemic hindlimb induction. Compared with human mesenchymal stem cell (hMSC) transplantation to the IR of mouse ischemic limbs, transplantation to the BZ significantly enhanced cell engraftment and paracrine factor secretion, which effectively stimulated vessel sprouting, enhanced blood perfusion in IR, and enabled the cell dosage reduction. Therefore, modification of the stem cell transplantation site would improve the current stem cell therapies for ischemic limb diseases in terms of cell dosage reduction and therapeutic efficacy enhancement.
- Published
- 2016
16. Therapeutic angiogenesis using tumor cell-conditioned medium
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Jin Han, Byung-Soo Kim, Ju-Ro Lee, Jung-Youn Shin, Gun-Jae Jeong, Hyeon-Ki Jang, and Jeong-Kee Yoon
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0301 basic medicine ,Angiogenesis ,Mice, Nude ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Animals ,Humans ,Therapeutic angiogenesis ,Cells, Cultured ,Cell Proliferation ,Neovascularization, Pathologic ,Chemistry ,Cell growth ,Mesenchymal stem cell ,Mesenchymal Stem Cells ,Sarcoma ,030104 developmental biology ,Cell culture ,Culture Media, Conditioned ,030220 oncology & carcinogenesis ,Immunology ,Cancer research ,Female ,Human umbilical vein endothelial cell ,HT1080 ,Stem cell ,Biotechnology - Abstract
Stem cell-conditioned medium (CM), which contains angiogenic factors that are secreted by stem cells, represents a potential therapy for ischemic diseases. Along with stem cells, tumor cells also secrete various angiogenic factors. Here, tumor cells as a cell source of CM for therapeutic angiogenesis was evaluated and the therapeutic efficacy of tumor cell CM in mouse hindlimb ischemia models was demonstrated. CM obtained from a human fibrosarcoma HT1080 cell line culture was compared with CM obtained from a human bone marrow-derived mesenchymal stem cell (MSC) culture. HT1080 CM contained higher concentrations of angiogenic factors compared with MSC CM, which was attributable to the higher cell density that resulted from a much faster growth rate of HT1080 cells compared with MSCs. For use in in vitro and in vivo angiogenesis studies, HT1080 CM was diluted such that HT1080 CM and MSC CM would have the same cell number basis. The two types of CMs induced the same extent of human umbilical vein endothelial cell (HUVEC) proliferation in vitro. The injection of HT1080 CM into mouse ischemic limbs significantly improved capillary density and blood perfusion compared with the injection of fresh medium. Although the therapeutic outcome of HT1080 CM was similar to that of MSC CM, the preparation of CM by tumor cell line culture would be much more efficient due to the faster growth and unlimited life-time of the tumor cell line. These data suggest the potential application of tumor cell CM as a therapeutic modality for angiogenesis and ischemic diseases. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:456-464, 2016.
- Published
- 2016
17. Interconnectable Dynamic Compression Bioreactors for Combinatorial Screening of Cell Mechanobiology in Three Dimensions
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Su Ryon Shin, Jung Youn Shin, Ali Khademhosseini, Oju Jeon, Jungmok Seo, Hadi Hajiali, Eben Alsberg, Ayça Bal Öztürk, Jeroen Rouwkema, Yuancheng Li, Jeroen Leijten, and Developmental BioEngineering
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0301 basic medicine ,Materials science ,food.ingredient ,UT-Hybrid-D ,02 engineering and technology ,Matrix (biology) ,Gelatin ,complex mixtures ,Mechanotransduction, Cellular ,Article ,Human mesenchymal stem cells ,03 medical and health sciences ,Mechanobiology ,food ,Bioreactors ,Dynamic compression bioreactor ,Osteogenesis ,3D mechanobiology ,Bioreactor ,Humans ,General Materials Science ,Mechanotransduction ,Mechanical stimulation ,Mesenchymal stem cell ,High-throughput screening ,technology, industry, and agriculture ,Biomaterial ,Cell Differentiation ,Hydrogels ,Mesenchymal Stem Cells ,021001 nanoscience & nanotechnology ,equipment and supplies ,030104 developmental biology ,Self-healing hydrogels ,0210 nano-technology ,Biomedical engineering - Abstract
Biophysical cues can potently direct a cell's or tissue's behavior. Cells interpret their biophysical surroundings, such as matrix stiffness or dynamic mechanical stimulation, through mechanotransduction. However, our understanding of the various aspects of mechanotransduction has been limited by the lack of proper analysis platforms capable of screening three-dimensional (3D) cellular behaviors in response to biophysical cues. Here, we developed a dynamic compression bioreactor to study the combinational effects of biomaterial composition and dynamic mechanical compression on cellular behavior in 3D hydrogels. The bioreactor contained multiple actuating posts that could apply cyclic compressive strains ranging from 0 to 42% to arrays of cell-encapsulated hydrogels. The bioreactor could be interconnected with other compressive bioreactors, which enabled the combinatorial screenings of 3D cellular behaviors simultaneously. As an application of the screening platform, cell spreading, and osteogenic differentiation of human mesenchymal stem cells (hMSCs) were characterized in 3D gelatin methacryloyl (GelMA) hydrogels. Increasing hydrogel concentration from 5 to 10% restricted the cell spreading, however, dynamic compressive strain increased cell spreading. Osteogenic differentiation of hMSCs was also affected by dynamic compressive strains. hMSCs in 5% GelMA hydrogel were more sensitive to strains, and the 42% strain group showed a significant increase in osteogenic differentiation compared to other groups. The interconnectable dynamic compression bioreactor provides an efficient way to study the interactions of cells and their physical microenvironments in three dimensions.
- Published
- 2018
18. Effects of chewing pattern and condition of dentition on taste threshold in healthy adults
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Jung Youn Shin and Jong Mo Ahn
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Orthodontics ,Dentition ,business.industry ,Medicine ,Taste Threshold ,business - Published
- 2015
19. A Dual Delivery of Substance P and Bone Morphogenetic Protein-2 for Mesenchymal Stem Cell Recruitment and Bone Regeneration
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Suk Ho Bhang, Seahyoung Lee, Min Jin, Jooyeon Park, Hyeon-Ki Jang, Jung-Youn Shin, Seokyung Kang, Byung-Soo Kim, Seong-Seo Noh, Yoon-Ji Ma, and Wan-Geun La
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Bone Regeneration ,Biomedical Engineering ,Bone Morphogenetic Protein 2 ,Bioengineering ,Substance P ,Real-Time Polymerase Chain Reaction ,Biochemistry ,Bone morphogenetic protein 2 ,Fibrin ,Flow cytometry ,Biomaterials ,Mice ,Cell Movement ,Osteogenesis ,In vivo ,medicine ,Animals ,Humans ,Bone regeneration ,Inflammation ,Tissue Scaffolds ,medicine.diagnostic_test ,biology ,Heparin ,Chemistry ,Multipotent Stem Cells ,Skull ,Mesenchymal stem cell ,Cell Differentiation ,Mesenchymal Stem Cells ,Flow Cytometry ,Cell biology ,biology.protein ,Cattle ,Stem cell ,Ex vivo ,Biomedical engineering - Abstract
Implantation of ex vivo expanded and osteogenically differentiated mesenchymal stem cells (MSCs) for bone regeneration has drawbacks for clinical applications, such as poor survival of implanted cells and increased treatment expenses. As a new approach for bone regeneration that can circumvent these limitations, we propose dual delivery of substance P (SP) and bone morphogenetic protein-2 (BMP-2) to facilitate endogenous stem cell recruitment to bone defects by SP and subsequent in situ osteogenic differentiation of those cells by BMP-2. A heparin-conjugated fibrin (HCF) gel enabled dual delivery with fast release of SP and slow release of BMP-2, which would be ideal for prompt recruitment of endogenous stem cells in the first stage and time-consuming osteogenic differentiation of the recruited stem cells in the second stage. The HCF gels with SP and/or BMP-2 were implanted into mouse calvarial defects for 8 weeks. Local delivery of SP to the calvarial defects using HCF gel was more effective in recruiting MSCs to the calvarial defects than intraperitoneal or intravenous administration of SP. Many of the cells recruited by SP underwent osteogenic differentiation through local delivery of BMP-2. The efficacy of in vivo bone regeneration was significantly higher in the SP/BMP-2 dual delivery group. The dual delivery of SP and BMP-2 using the HCF gel therefore has potential as an effective bone regeneration strategy.
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- 2015
20. Transplantation of Heterospheroids of Islet Cells and Mesenchymal Stem Cells for Effective Angiogenesis and Antiapoptosis
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Myungkyung Noh, Jin Han, Jung-Youn Shin, Taslim A. Al-Hilal, Youngro Byun, Muhammad R. Haque, Byung Soo Kim, Jee-Heon Jeong, Suk Ho Bhang, and Gun-Jae Jeong
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Male ,endocrine system ,Cell Survival ,Angiogenesis ,Xenotransplantation ,medicine.medical_treatment ,Islets of Langerhans Transplantation ,Biomedical Engineering ,Neovascularization, Physiologic ,Apoptosis ,Cell Count ,Bioengineering ,Biology ,Kidney ,Mesenchymal Stem Cell Transplantation ,Biochemistry ,Rats, Sprague-Dawley ,Biomaterials ,Islets of Langerhans ,Vasculogenesis ,Spheroids, Cellular ,medicine ,Animals ,Humans ,Insulin ,RNA, Messenger ,Cells, Cultured ,Cell Aggregation ,geography ,geography.geographical_feature_category ,Portal Vein ,Pancreatic islets ,Mesenchymal stem cell ,Mesenchymal Stem Cells ,Original Articles ,Hypoxia-Inducible Factor 1, alpha Subunit ,Islet ,Cell aggregation ,Transplantation ,surgical procedures, operative ,medicine.anatomical_structure ,Liver ,Immunology ,Cancer research - Abstract
Although islet transplantation has been suggested as an alternative therapy for type 1 diabetes, there are efficiency concerns that are attributed to poor engraftment of transplanted islets. Hypoxic condition and delayed vasculogenesis induce necrosis and apoptosis of the transplanted islets. To overcome these limitations in islet transplantation, heterospheroids (HSs), which consist of rat islet cells (ICs) and human bone marrow-derived mesenchymal stem cells (hMSCs), were transplanted to the kidney and liver. The HSs cultured under the hypoxic condition system exhibited a significant increase in antiapoptotic gene expression in ICs. hMSCs in the HSs secreted angiogenic and antiapoptotic proteins. With the HS system, ICs and hMSCs were successfully located in the same area of the liver after transplantation of HSs through the portal vein, whereas the transplantation of islets and the dissociated hMSCs did not result in localization of transplanted ICs and hMSCs in the same area. HS transplantation resulted in an increase in angiogenesis at the transplantation area and a decrease in the apoptosis of transplanted ICs after transplantation into the kidney subcapsule compared with transplantation of islet cell clusters (ICCs). Insulin production levels of ICs were higher in the HS transplantation group compared with the ICC transplantation group. The HS system may be a more efficient transplantation method than the conventional methods for the treatment of type 1 diabetes.
- Published
- 2015
21. Iron Oxide Nanoparticle-Mediated Development of Cellular Gap Junction Crosstalk to Improve Mesenchymal Stem Cells’ Therapeutic Efficacy for Myocardial Infarction
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Byung-Soo Kim, Jin Sil Park, Taeghwan Hyeon, Nohyun Lee, Donghoon Choi, Myungkyung Noh, Jongsu Woo, Jung Youn Shin, Seungmi Ryu, You-Jin Lee, Bokyoung Kim, and Jin Han
- Subjects
Materials science ,Myocardial Infarction ,General Physics and Astronomy ,Priming (immunology) ,Connexin ,Cell Separation ,Mesenchymal Stem Cell Transplantation ,Ferric Compounds ,Cell Line ,Rats, Sprague-Dawley ,Paracrine signalling ,Tissue engineering ,Paracrine Communication ,Animals ,Humans ,General Materials Science ,Ventricular Remodeling ,Myocardium ,Mesenchymal stem cell ,General Engineering ,Gap junction ,Gap Junctions ,Biological Transport ,Mesenchymal Stem Cells ,Survival Analysis ,Phenotype ,Coculture Techniques ,Rats ,Cell biology ,Crosstalk (biology) ,Gene Expression Regulation ,Connexin 43 ,Immunology ,cardiovascular system ,Nanoparticles - Abstract
Electrophysiological phenotype development and paracrine action of mesenchymal stem cells (MSCs) are the critical factors that determine the therapeutic efficacy of MSCs for myocardial infarction (MI). In such respect, coculture of MSCs with cardiac cells has windowed a platform for cardiac priming of MSCs. Particularly, active gap junctional crosstalk of MSCs with cardiac cells in coculture has been known to play a major role in the MSC modification through coculture. Here, we report that iron oxide nanoparticles (IONPs) significantly augment the expression of connexin 43 (Cx43), a gap junction protein, of cardiomyoblasts (H9C2), which would be critical for gap junctional communication with MSCs in coculture for the generation of therapeutic potential-improved MSCs. MSCs cocultured with IONP-harboring H9C2 (cocultured MSCs: cMSCs) showed active cellular crosstalk with H9C2 and displayed significantly higher levels of electrophysiological cardiac biomarkers and a cardiac repair-favorable paracrine profile, both of which are responsible for MI repair. Accordingly, significantly improved animal survival and heart function were observed upon cMSC injection into rat MI models compared with the injection of unmodified MSCs. The present study highlights an application of IONPs in developing gap junctional crosstalk among the cells and generating cMSCs that exceeds the reparative potentials of conventional MSCs. On the basis of our finding, the potential application of IONPs can be extended in cell biology and stem cell-based therapies.
- Published
- 2015
22. Bone morphogenetic protein-2 for bone regeneration – Dose reduction through graphene oxide-based delivery
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Hyeon-Ki Jang, Tae-Jin Lee, Suk Ho Bhang, Hee-Hun Yoon, Moon-Joo Jung, Jung-Youn Shin, Byung-Soo Kim, Wan-Geun La, and Jeong-Kee Yoon
- Subjects
animal structures ,Materials science ,Osteolysis ,biology ,Mesenchymal stem cell ,General Chemistry ,Pharmacology ,medicine.disease ,Bone morphogenetic protein 2 ,Fibrin ,In vitro ,Immune system ,embryonic structures ,medicine ,biology.protein ,General Materials Science ,Dose reduction ,Bone regeneration - Abstract
High doses of bone morphogenetic protein-2 (BMP-2) are required for effective bone regeneration. However, these high doses often cause undesirable adverse effects, including bone overgrowth, osteolysis, and activation of the immune response, and raise treatment costs. In an effort to reduce the BMP-2 dose to avoid or diminish side effects, we investigated whether delivery of BMP-2 using graphene oxide (GO) can reduce the BMP-2 dose for bone regeneration. Delivery of BMP-2 using GO flakes suspended in fibrin gels (GO/F) resulted in significantly greater osteogenic differentiation of human bone marrow-derived mesenchymal stem cells in vitro, and at various doses of BMP-2, significantly greater amounts of bone regeneration in mouse calvarial defects occurred than when fibrin gel (F) alone was used. A half-dose of BMP-2 delivered by GO/F resulted in bone regeneration similar to that resulting from a full dose of BMP-2 delivered by F. The enhanced bone regeneration efficacy was likely due, at least in part, to the sustained release, higher structural stability, and higher bioactivity of BMP-2 delivered by GO/F compared to BMP-2 delivered by F. Therefore, GO may be an effective carrier for BMP-2 to reduce the BMP-2 dose and avoid adverse effects.
- Published
- 2014
23. High-Throughput Approaches for Screening and Analysis of Cell Behaviors
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Jung Youn Shin, Eben Alsberg, Anna D. Dikina, Gulden Camci-Unal, Ali Khademhosseini, Oju Jeon, Jeroen Leijten, Jungmok Seo, Amir M. Ghaemmaghami, and Katelyn N. Brinegar
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0301 basic medicine ,Cellular microenvironments ,Materials science ,Surface Properties ,Bioactive molecules ,Toxicological Phenomena ,Cell ,Biophysics ,Cell Culture Techniques ,Bioengineering ,Biocompatible Materials ,Computational biology ,Gene delivery ,Bioinformatics ,Article ,Cell Line ,Biomaterials ,Small Molecule Libraries ,03 medical and health sciences ,Drug Delivery Systems ,Biomaterial screening ,Drug Discovery ,medicine ,Animals ,Humans ,High-throughput biosensor ,Drug discovery ,Gene Transfer Techniques ,High-Throughput Screening Assays ,Nanostructures ,030104 developmental biology ,medicine.anatomical_structure ,Cellular Microenvironment ,Mechanics of Materials ,Cell-biomaterial interactions ,Ceramics and Composites ,High-throughput system ,Biomolecule delivery - Abstract
The rapid development of new biomaterials and techniques to modify them challenge our capability to characterize them using conventional methods. In response, numerous high-throughput (HT) strategies are being developed to analyze biomaterials and their interactions with cells using combinatorial approaches. Moreover, these systematic analyses have the power to uncover effects of delivered soluble bioactive molecules on cell responses. In this review, we describe the recent developments in HT approaches that help identify microenvironments allowing reproducible control over cellular behaviors and highlight HT screening of biochemical libraries for gene delivery, drug discovery, and toxicological studies. We also discuss HT techniques for the analyses of cell secreted biomolecules and provide perspectives on the future utility of HT approaches in biomedical engineering.
- Published
- 2017
24. Stretchable Piezoelectric Substrate Providing Pulsatile Mechanoelectric Cues for Cardiomyogenic Differentiation of Mesenchymal Stem Cells
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Byung Soo Kim, Suk Ho Bhang, Jeong-Kee Yoon, Jung Youn Shin, Jae Min Myoung, and Tae Il Lee
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0301 basic medicine ,Materials science ,Cell ,Mesenchymal stem cell ,Pulsatile flow ,Nanotechnology ,Cell Differentiation ,Mesenchymal Stem Cells ,02 engineering and technology ,021001 nanoscience & nanotechnology ,Cell biology ,03 medical and health sciences ,030104 developmental biology ,medicine.anatomical_structure ,Downregulation and upregulation ,medicine ,Humans ,General Materials Science ,Myocytes, Cardiac ,Stem cell ,0210 nano-technology ,Transcription factor ,Ex vivo ,Ion channel ,Cells, Cultured - Abstract
Ex vivo induction of cardiomyogenic differentiation of mesenchymal stem cells (MSCs) before implantation would potentiate therapeutic efficacy of stem cell therapies for ischemic heart diseases because MSCs rarely undergo cardiomyogenic differentiation following implantation. In cardiac microenvironments, electric pulse and cyclic mechanical strain are sequentially produced. However, no study has applied the pulsatile mechanoelectric cues (PMEC) to stimulate cardiomyogenic differentiation of MSCs ex vivo. In this study, we developed a stretchable piezoelectric substrate (SPS) that can provide PMEC to human MSCs (hMSCs) for cardiomyogenic differentiation ex vivo. Our data showed that hMSCs subjected to PMEC by SPS underwent promoted cardiac phenotype development: cell alignment and the expression of cardiac markers (i.e., cardiac transcription factors, structural proteins, ion channel proteins, and gap junction proteins). The enhanced cardiac phenotype development was mediated by the upregulation of cardiomyogenic differentiation-related autocrine factor expression, focal adhesion kinase, and extracellular signal-regulated kinases signaling pathways. Thus, SPS providing electrical and mechanical regulation of stem cells may be utilized to potentiate hMSC therapies for myocardial infarction and provide a tool for the study of stem cell biology.
- Published
- 2017
25. Topography-Guided Control of Local Migratory Behaviors and Protein Expression of Cancer Cells
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Byung Soo Kim, Noo Li Jeon, Jeong-Kee Yoon, Suk Ho Bhang, Hong Nam Kim, Jung-Youn Shin, and Kahp-Yang Suh
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0301 basic medicine ,Models, Molecular ,Cell ,Biomedical Engineering ,Pharmaceutical Science ,02 engineering and technology ,Biology ,Biomaterials ,Focal adhesion ,03 medical and health sciences ,In vivo ,Cell Movement ,Cell Line, Tumor ,Neoplasms ,medicine ,Extracellular ,Humans ,Neoplasm Invasiveness ,Protein kinase A ,Extracellular Signal-Regulated MAP Kinases ,Basement membrane ,rho-Associated Kinases ,Kinase ,021001 nanoscience & nanotechnology ,Vinculin ,Cell biology ,030104 developmental biology ,medicine.anatomical_structure ,Focal Adhesion Protein-Tyrosine Kinases ,Cancer cell ,0210 nano-technology - Abstract
In vivo cancer cell migration and invasion are directed by biophysical guidance mechanisms such as pre-existing microtracks and basement membrane extracellular matrices. Here, this paper reports the correlation of the local migratory behavior of cancer cells and the biochemical signal expression using the topography that can guide or inhibit cell behaviors. To this end, the local apparent migration and the protein expression level are investigated with respect to the topographical feature size (flat, nanoline, and microline) and orientation (microline, microconcentric, and microradial) with the collectively migrating (A431) and individually migrating (MDA-MB-231 and U-87-MG) cancer cells. The results show that the migration and the protein expression of focal adhesion kinase, rho-associated protein kinase, and extracellular signal-regulated kinase are localized in the periphery of cell colony. Furthermore, the inhibition of migratory behavior at the periphery recues the protein expression, while the guidance of migration enhances the aforementioned protein expression. The results may imply the employ of biophysical inhibitory factors can help to control invasiveness of cancer cells during the progression state.
- Published
- 2017
26. Efficacious and Clinically Relevant Conditioned Medium of Human Adipose-derived Stem Cells for Therapeutic Angiogenesis
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Jung-Youn Shin, Hyeon-Ki Jang, Tae-Jin Lee, Suk Ho Bhang, Seahyoung Lee, and Byung-Soo Kim
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Cell Culture Techniques ,CD34 ,Apoptosis ,Biology ,Fibroblast growth factor ,Mice ,Drug Discovery ,medicine ,Genetics ,Animals ,Humans ,Therapeutic angiogenesis ,Molecular Biology ,Pharmacology ,Stem Cells ,Endothelial stem cell ,medicine.anatomical_structure ,Adipose Tissue ,Cell culture ,Culture Media, Conditioned ,Immunology ,Cancer research ,Molecular Medicine ,Original Article ,Hepatocyte growth factor ,Bone marrow ,Stem cell ,medicine.drug - Abstract
Using stem cell-conditioned medium (CM) might be a viable alternative to stem cell transplantation, which is often hampered by low grafting efficiency and potential tumorigenesis, but the concentrations of angiogenic growth factors in CM are too low for therapeutic use and some components of the medium are not for human use. We used three-dimensional (3D) spheroid culture of human adipose-derived stem cells (ADSCs) with clinically relevant medium composed of amino acids, vitamins, glucose, and human serum to produce clinically relevant CM containing angiogenic and/or antiapoptotic factors such as vascular endothelial cell growth factor, fibroblast growth factor 2, hepatocyte growth factor, and chemokine (C-X-C motif) ligand 12. The concentrations of these factors were 23- to 27-fold higher than that in CM produced by conventional monolayer culture. Compared with injection of either monolayer culture CM or human ADSC, injection of spheroid culture CM to an ischemic region in mice significantly enhanced endothelial cell growth, CD34(+)/PTPRC(-) (endothelial progenitor) cell mobilization from bone marrow, and bone marrow cell homing to the ischemic region, resulting in improved blood vessel density, limb salvage, and blood perfusion in a mouse hindlimb ischemia model. The stem cell CM developed in this study will likely be an effective alternative to conventional stem cell transplantation therapy.
- Published
- 2014
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27. Non-invasive optical imaging of matrix metalloproteinase activity with albumin-based fluorogenic nanoprobes during angiogenesis in a mouse hindlimb ischemia model
- Author
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Kwangmeyung Kim, Jung Youn Shin, Sun Ah Kim, Ju Hee Ryu, Kuiwon Choi, Ick Chan Kwon, Byung-Soo Kim, Seokyung Kang, Kang Sun Woong, and Hyunjoon Kim
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Materials science ,Angiogenesis ,Blotting, Western ,Biophysics ,Bioengineering ,Matrix metalloproteinase ,Biomaterials ,Mice ,Western blot ,Ischemia ,medicine ,Animals ,Humans ,Zymography ,Serum Albumin ,medicine.diagnostic_test ,Optical Imaging ,Human serum albumin ,Immunohistochemistry ,Molecular biology ,Matrix Metalloproteinases ,Hindlimb ,body regions ,Blot ,Mechanics of Materials ,embryonic structures ,Ceramics and Composites ,Female ,Molecular imaging ,Preclinical imaging ,medicine.drug - Abstract
Matrix metalloproteinase (MMP)-2 and MMP-9 have been known to play the role of essential mediators in angiogenesis. Non-invasive in vivo imaging approach using imaging probes is a potential method of detecting MMP activity in living animals, wherein imaging probes must include the characteristics of non-toxicity, specific targetability, and reasonable signal intensity. Here, we developed MMP-specific and self-quenched human serum albumin (HSA)-based (MMP-HSA) nanoprobes for non-invasive optical imaging of MMP activity during angiogenesis in the mouse hindlimb ischemia model. MMP-specific fluorogenic peptide probes, which were self-quenched with a near-infrared fluorophore and a quencher, were covalently conjugated to HSA (MMP-HSA nanoprobes). MMP-HSA nanoprobes formed stable nanoparticle structures of approximately 36 nm in diameter. Strongly self-quenched MMP-HSA nanoprobes boosted intense fluorescence signals in the presence of MMP-2 and MMP-9. Furthermore, MMP-HSA nanoprobes showed no cytotoxicity in cell culture. Importantly, intravenous injection of MMP-HSA nanoprobes provided longer blood half-life and successful non-invasive optical imaging of MMP activity during angiogenesis in the mouse hindlimb ischemia model. In addition, the MMP activity visualized by MMP-HSA nanoprobes was consistent with the results of zymography, Western blot, and immunohistochemistry. MMP-HSA nanoprobes may be useful for monitoring of the initial process of angiogenesis through non-invasive MMP imaging.
- Published
- 2013
28. Development of integrated and interactive spatial planning system of assembly blocks in shipbuilding
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Ohsuk Kwon, J. M. Lee, Cheolho Ryu, and Jung-Youn Shin
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Engineering ,Material requirements planning ,business.industry ,Mechanical Engineering ,Scheduling (production processes) ,Aerospace Engineering ,Workload ,Scheduling system ,Computer Science Applications ,Shipbuilding ,Two-level scheduling ,Automated planning and scheduling ,Systems engineering ,Electrical and Electronic Engineering ,business ,Spatial planning - Abstract
As the shipbuilding industry expands, accurate and efficient planning and scheduling of the production process is becoming increasingly important and complex. The availability of space and load in workshops should thus be examined in scheduling the production process. The variety of material, facilities, and information resources makes the spatial planning difficult. In the present work, a spatial planning and scheduling system is developed to support spatial planning and scheduling in block assembly shops, and the workload balance of workshops. The requirements and functions of the system are described and functional components are designed and implemented, based on an object-oriented methodology. The integrated environment is presented in this paper. This system can be expanded to any workshop that requires spatial planning and scheduling.
- Published
- 2008
29. Graphene oxide flakes as a cellular adhesive: prevention of reactive oxygen species mediated death of implanted cells for cardiac repair
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Bokyoung Kim, Jin Han, Subeom Park, Donghoon Choi, Jaewon Oh, Seungmi Ryu, Byung Soo Kim, Jooyeon Park, Beom Seob Lee, Subin Jung, Byung Hee Hong, and Jung Youn Shin
- Subjects
Materials science ,Cell Survival ,General Physics and Astronomy ,Myocardial Reperfusion Injury ,Mesenchymal Stem Cell Transplantation ,Extracellular matrix ,Rats, Sprague-Dawley ,medicine ,Extracellular ,Cell Adhesion ,Animals ,Humans ,General Materials Science ,Anoikis ,Myocardial infarction ,chemistry.chemical_classification ,Reactive oxygen species ,Cell Death ,Myocardium ,Mesenchymal stem cell ,General Engineering ,Mesenchymal Stem Cells ,Oxides ,Adhesion ,medicine.disease ,In vitro ,Cell biology ,Rats ,chemistry ,Graphite ,Reactive Oxygen Species - Abstract
Mesenchymal stem cell (MSC) implantation has emerged as a potential therapy for myocardial infarction (MI). However, the poor survival of MSCs implanted to treat MI has significantly limited the therapeutic efficacy of this approach. This poor survival is primarily due to reactive oxygen species (ROS) generated in the ischemic myocardium after the restoration of blood flow. ROS primarily causes the death of implanted MSCs by inhibiting the adhesion of the MSCs to extracellular matrices at the lesion site (i.e., anoikis). In this study, we proposed the use of graphene oxide (GO) flakes to protect the implanted MSCs from ROS-mediated death and thereby improve the therapeutic efficacy of the MSCs. GO can adsorb extracellular matrix (ECM) proteins. The survival of MSCs, which had adhered to ECM protein-adsorbed GO flakes and were subsequently exposed to ROS in vitro or implanted into the ischemia-damaged and reperfused myocardium, significantly exceeded that of unmodified MSCs. Furthermore, the MSC engraftment improved by the adhesion of MSCs to GO flakes prior to implantation enhanced the paracrine secretion from the MSCs following MSC implantation, which in turn promoted cardiac tissue repair and cardiac function restoration. This study demonstrates that GO can effectively improve the engraftment and therapeutic efficacy of MSCs used to repair the injury of ROS-abundant ischemia and reperfusion by protecting implanted cells from anoikis.
- Published
- 2015
30. Relationship between the tertiary structures of mastoparan B and its analogs and their lytic activities studied by NMR spectroscopy
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K. Yu, Yangmee Kim, Jung-Youn Shin, Shin-Won Kang, and Nam Gyu Park
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chemistry.chemical_classification ,Alanine ,Molecular model ,Stereochemistry ,Tryptophan ,Peptide ,Biological activity ,Nuclear magnetic resonance spectroscopy ,Antimicrobial ,Biochemistry ,Amino acid ,Endocrinology ,chemistry - Abstract
Mastoparan B (MP-B), an antimicrobial cationic tetradecapeptide amide isolated from the venom of the hornet Vespa basalis, is an amphiphilic alpha-helical peptide. MP-B possesses a variety of biological activities, such as mast cells degradation histamine release, erythrocyte lysis and inhibition of the growth of gram-positive and gram-negative bacteria. In order to study the relationship between the structure and the biological activity of MP-B, we used four analogs by replacing amino acids with alanine. Tertiary structures of MP-B and its analogs in 2,2,2-trifluoroethanol (TFE)-containing aqueous solution have been determined by NMR spectroscopy and molecular modeling. The results indicate that [Ala4]MP-B and [Ala12]MP-B with higher hydrophobicity adopt a higher content of amphiphilic helical structures, and have better antimicrobial and hemolytic activities than MP-B. However, [Ala3]MP-B and [Ala9]MP-B with lower hydrophobicity have disordered structures. [Ala3]MP-B and [Ala9]MP-B have low antimicrobial activity and much less hemolytic activity relative to MP-B. It is likely that tryptophan residue in MP-B and appropriate hydrophobicity of MP-B to induce alpha-helical structure is essential for the antibacterial and hemolytic activity of MP-B. This study can aid understanding of the structure-activity relationship of MP-B and to design peptides to possess lytic activity.
- Published
- 2000
31. Mutual effect of subcutaneously transplanted human adipose-derived stem cells and pancreatic islets within fibrin gel
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Suk Ho Bhang, Min Jin Jung, Min Jun Kim, Wan-Geun La, Byung-Soo Kim, Dong Yun Lee, Jung-Youn Shin, and Yong Hwa Hwang
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Vascular Endothelial Growth Factor A ,endocrine system ,medicine.medical_specialty ,endocrine system diseases ,Biophysics ,Islets of Langerhans Transplantation ,Adipose tissue ,Neovascularization, Physiologic ,Bioengineering ,Fibrin ,Diabetes Mellitus, Experimental ,Biomaterials ,chemistry.chemical_compound ,Islets of Langerhans ,Mice ,Subcutaneous Tissue ,Internal medicine ,medicine ,Animals ,Humans ,Tissue Survival ,geography ,geography.geographical_feature_category ,biology ,Pancreatic islets ,Islet ,Coculture Techniques ,Rats ,Vascular endothelial growth factor ,Transplantation ,Endocrinology ,medicine.anatomical_structure ,chemistry ,Adipose Tissue ,Mechanics of Materials ,Rats, Inbred Lew ,Microvessels ,Ceramics and Composites ,biology.protein ,Cancer research ,Pancreatic islet transplantation ,Fibroblast Growth Factor 2 ,Stem cell ,Gels ,Biomarkers ,Stem Cell Transplantation - Abstract
While subcutaneous tissue has been proposed as a potential site for pancreatic islet transplantation, concern remains that the microvasculature of subcutaneous tissue is too poor to support transplanted islets. In an effort to overcome this limitation, we evaluated whether fibrin gel with human adipose-derived stem cells (hADSCs) and rat pancreatic islets could cure diabetes mellitus when transplanted into the subcutaneous space of diabetic mice. Subcutaneously co-transplanted islets and hADSCs showed normalization of the diabetic recipient's blood glucose levels. The result was enhanced by co-treatment of fibroblast growth factor-2 (FGF2) in the fibrin gel. The hADSCs enhanced islet viability after transplantation by secreting various growth factors that can protect islets from hypoxic damage. Afterward, hADSCs could maintain islet viability by recruiting new microvasculature nearby the transplanted islets via overexpression of vascular endothelial growth factor (VEGF). The hADSCs did not directly differentiate into endothelial cells (no detection of biomarkers of human endothelial cells), but showed evidence of differentiation toward insulin-secreting cells (detection of human insulin). Mice receiving islet transplantation alone did not become normoglycemic. Collectively, co-transplantation of fibrin gel with islets and hADSCs will expand the indications for islet transplant therapy and the potential clinical application of cell-based therapy.
- Published
- 2013
32. pH-responsive assembly of gold nanoparticles and 'spatiotemporally concerted' drug release for synergistic cancer therapy
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Wan-Geun La, Jin Han, Sekyu Hwang, Yongmin Cho, Sungjee Kim, Sungwook Jung, Jutaek Nam, Nokyoung Park, Min Jin, Nayoun Won, Eun Kyung Wang, Jeongsoo Yoo, Jung-Youn Shin, So-Hye Cho, Sang Geol Kim, Yoon-Ji Ma, Yeong Su Ha, Byung Soo Kim, and Suk Ho Bhang
- Subjects
Materials science ,Nanostructure ,General Physics and Astronomy ,Mice, Nude ,Nanotechnology ,Antineoplastic Agents ,Conjugated system ,Mice ,Nanocapsules ,Combination cancer therapy ,Cell Line, Tumor ,Animals ,General Materials Science ,Plasmon ,General Engineering ,Hyperthermia, Induced ,Neoplasms, Experimental ,Photothermal therapy ,Hydrogen-Ion Concentration ,Surface Plasmon Resonance ,Combined Modality Therapy ,Treatment Outcome ,Colloidal gold ,Doxorubicin ,Delayed-Action Preparations ,Cancer cell ,Drug delivery ,Gold - Abstract
A challenge in using plasmonic nanostructure-drug conjugates for thermo-chemo combination cancer therapy lies in the huge size discrepancy; the size difference can critically differentiate their biodistributions and hamper the synergistic effect. Properly tuning the plasmonic wavelength for photothermal therapy typically results in the nanostructure size reaching ∼100 nm. We report a new combination cancer therapy platform that consists of relatively small 10 nm pH-responsive spherical gold nanoparticles and conjugated doxorubicins. They are designed to form aggregates in mild acidic environment such as in a tumor. The aggregates serve as a photothermal agent that can selectively exploit external light by their collective plasmon modes. Simultaneously, the conjugated doxorubicins are released. The spatiotemporal concertion is confirmed at the subcellular, cellular, and organ levels. Both agents colocalize in the cell nuclei. The conjugates accumulate in cancer cells by the rapid phagocytic actions and effective blockage of exocytosis by the increased aggregate size. They also effectively accumulate in tumors up to 17 times over the control because of the enhanced permeation and retention. The conjugates exhibit a synergistic effect enhanced by nearly an order of magnitude in cellular level. The synergistic effect is demonstrated by the remarkable reductions in both the therapeutically effective drug dosage and the photothermal laser threshold. Using an animal model, effective tumor growth suppression is demonstrated. The conjugates induce apoptosis to tumors without any noticeable damage to other organs. The synergistic effect in vivo is confirmed by qRT-PCR analysis over the thermal stress and drug-induced growth arrest.
- Published
- 2013
33. Culture on a 3,4-dihydroxy-l-phenylalanine-coated surface promotes the osteogenic differentiation of human mesenchymal stem cells
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Hee Hun Yoon, Min Jin, Byung Soo Kim, Seong Seo Noh, Gun-Il Im, Jung Youn Shin, Chang-Sung Kim, Suk Ho Bhang, and Wan Geun La
- Subjects
biology ,Mesenchymal stem cell ,Osteocalcin ,Biomedical Engineering ,Bioengineering ,Bone Marrow Cells ,Cell Differentiation ,Mesenchymal Stem Cells ,Alkaline Phosphatase ,Biochemistry ,Molecular biology ,In vitro ,Dihydroxyphenylalanine ,Biomaterials ,Tissue culture ,Coated Materials, Biocompatible ,In vivo ,Osteogenesis ,biology.protein ,Alkaline phosphatase ,Humans ,Stem cell ,Cell adhesion ,Cells, Cultured - Abstract
The culture surface can affect the in vitro differentiation of stem cells. In this study, we investigated whether modifying the culture surface with 3,4-dihydroxy-l-phenylalanine (DOPA), an element of mussel adhesion protein, could enhance the in vitro osteogenic differentiation of human bone marrow-derived mesenchymal stem cells (hBMMSCs). hBMMSCs cultured on DOPA-coated plates exhibited better cell adhesion and spreading compared with noncoated conventional tissue culture plates. The DOPA coated did not affect the apoptosis or viability of the cultured hBMMSCs. Also, hBMMSCs cultured on DOPA-coated plates exhibited a higher degree of osteogenic differentiation than did hBMMSCs cultured on noncoated plates, as evaluated with alkaline phosphate (ALP) activity, calcium content, and the mRNA expression of runt-related transcription factor 2, ALP, and osteocalcin. Further, hBMMSCs cultured on DOPA-coated plates demonstrated a higher capability of ectopic bone formation in vivo following implantation in the subcutaneous space of athymic mice compared with hBMMSCs cultured on noncoated plates, as evaluated with microcomputer topography analysis and histomorphometry. These results indicate that modifying the culture surface with DOPA can enhance the in vitro osteogenic differentiation of hBMMSCs.
- Published
- 2012
34. Zinc Oxide Nanorod-Based Piezoelectric Dermal Patch for Wound Healing
- Author
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Suk Ho Bhang, Hong Koo Baik, Byung Soo Kim, Eungkyu Lee, Woo Soon Jang, Wan Geun La, Jin Han, Jung Youn Shin, Jeong-Kee Yoon, Youn Sang Kim, and Tae-Jin Lee
- Subjects
0301 basic medicine ,Cellular metabolism ,Materials science ,integumentary system ,Skin wound ,02 engineering and technology ,021001 nanoscience & nanotechnology ,Condensed Matter Physics ,Dermal patch ,Piezoelectricity ,Electronic, Optical and Magnetic Materials ,Biomaterials ,Piezoelectric potential ,03 medical and health sciences ,030104 developmental biology ,Skin cell ,Zinc oxide nanorod ,Electrochemistry ,0210 nano-technology ,Wound healing ,Biomedical engineering - Abstract
Current treatments for wound healing engage in passive healing processes and rarely participate in stimulating skin cell behaviors for active wound healing. Electric potential difference-derived electrical fields (EFs) are known to modulate skin cell behaviors. Here, a piezoelectric dermal patch is developed that can be applied on skin wound site and EF is generated to promote wound healing. The one-directionally aligned zinc oxide nanorod-based piezoelectric patch generates piezoelectric potential upon mechanical deformations induced by animal motion, and induces EF at the wound bed. In vitro and in vivo data demonstrate that the piezoelectric patch promotes the wound healing process through enhanced cellular metabolism, migration, and protein synthesis. This modality may lead to a clinically relevant piezoelectric dermal patch therapy for active wound healing.
- Published
- 2016
35. Enhanced Cartilage Formation via Three-Dimensional Cell Engineering of Human Adipose-Derived Stem Cells
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Byung Soo Kim, Jaehoon Shin, Hee Hun Yoon, Suk Ho Bhang, and Jung-Youn Shin
- Subjects
Blotting, Western ,Biomedical Engineering ,Bioengineering ,Biology ,Microscopy, Atomic Force ,Biochemistry ,Biomaterials ,Bioreactors ,Tissue engineering ,medicine ,Humans ,Autologous chondrocyte implantation ,Cell Engineering ,Tissue Engineering ,Reverse Transcriptase Polymerase Chain Reaction ,Regeneration (biology) ,Cartilage ,Stem Cells ,Spheroid ,Original Articles ,Chondrogenesis ,Immunohistochemistry ,Cell biology ,Transplantation ,medicine.anatomical_structure ,Adipose Tissue ,Stem cell ,Biomedical engineering - Abstract
Autologous chondrocyte implantation is an effective treatment for damaged articular cartilage. However, this method involves surgical procedures that may cause further cartilage degeneration, and in vitro expansion of chondrocytes can result in dedifferentiation. Adipose-derived stem cells (ADSCs) may be an alternative autologous cell source for cartilage regeneration. In this study, we developed an effective method for large-scale in vitro chondrogenic differentiation, which is the procedure that would be required for clinical applications, and the subsequent in vivo cartilage formation of human ADSCs (hADSCs). The spheroid formation and chondrogenic differentiation of hADSCs were induced on a large scale by culturing hADSCs in three-dimensional suspension bioreactors (spinner flasks). In vitro chondrogenic differentiation of hADSCs was enhanced by a spheroid culture compared with a monolayer culture. The enhanced chondrogenesis was probably attributable to hypoxia-related cascades and enhanced cell-cell interactions in hADSC spheroids. On hADSCs loading in fibrin gel and transplantation into subcutaneous space of athymic mice for 4 weeks, the in vivo cartilage formation was enhanced by the transplantation of spheroid-cultured hADSCs compared with that of monolayer-cultured hADSCs. This study shows that the spheroid culture may be an effective method for large-scale in vitro chondrogenic differentiation of hADSCs and subsequent in vivo cartilage formation.
- Published
- 2012
36. Transplantation of Cord Blood Mesenchymal Stem Cells as Spheroids Enhances Vascularization
- Author
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Byung-Soo Kim, Tae-Jin Lee, Jung-Youn Shin, Suk Ho Bhang, and Seahyoung Lee
- Subjects
Pathology ,medicine.medical_specialty ,medicine.medical_treatment ,Blotting, Western ,Biomedical Engineering ,Cell Culture Techniques ,Adipose tissue ,Bioengineering ,Biology ,Mesenchymal Stem Cell Transplantation ,Real-Time Polymerase Chain Reaction ,Biochemistry ,Biomaterials ,Ischemia ,medicine ,Animals ,Humans ,Cells, Cultured ,Stem cell transplantation for articular cartilage repair ,Reverse Transcriptase Polymerase Chain Reaction ,Mesenchymal stem cell ,Mesenchymal Stem Cells ,Stem-cell therapy ,Original Articles ,Immunohistochemistry ,Hindlimb ,Transplantation ,medicine.anatomical_structure ,Cord blood ,Bone marrow ,Stem cell - Abstract
Despite promising results from the therapeutic use of stem cells for treating ischemic diseases, the poor survival of cells transplanted into ischemic regions is one of the major problems that undermine the efficacy of stem cell therapy. Cord blood mononuclear cells (CBMNCs) are an alternative source of mesenchymal stem cells (MSCs) without disadvantages, such as the painful and invasive harvesting procedure, of MSCs derived from bone marrow or adipose tissue. In the present study, we investigated whether the angiogenic efficacy of cord blood mesenchymal stem cells (CBMSCs) can be enhanced by grafting as spheroids in a mouse hindlimb ischemia model. Human CBMSC (hCBMSC) spheroids were prepared by using the hanging-drop method. Mouse hindlimb ischemia was induced by excising the femoral artery and its branches. After surgery, the animals were divided into no-treatment, dissociated hCBMSC, and spheroid hCBMSC groups (n=8 per group) and received corresponding hCBMSC treatments. After surgery, the ischemic hindlimbs were monitored for 4 weeks, and then, the ischemic hindlimb muscles were harvested for histological analysis. Apoptotic signaling, angiogenesis-related signal pathways, and blood vessel formation were investigated in vitro and/or in vivo. The transplantation of hCBMSCs as spheroids into mouse ischemic hindlimbs significantly improved the survival of the transplanted cells by suppressing apoptotic signaling while activating antiapoptotic signaling. Furthermore, the transplantation of hCBMSCs as spheroids significantly increased the number of microvessels and smooth muscle α-actin-positive vessels in the ischemic limbs of mice, and attenuated limb loss and necrosis. Human CBMNC can be considered an alternative source of MSC, and spheroid-based hCBMSC delivery can be considered a simple and effective strategy for enhancing the therapeutic efficacy of hCBMSCs.
- Published
- 2012
37. Volume-stable adipose tissue formation by implantation of human adipose-derived stromal cells using solid free-form fabrication-based polymer scaffolds
- Author
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Sun-Hyun Kwon, Suk Ho Bhang, Hee Hun Yoon, Byung Soo Kim, Wan-Guen La, Dong-Woo Cho, Jung-Youn Shin, Tae-Jin Lee, and Heungsoo Shin
- Subjects
Genetic Markers ,Stromal cell ,Polyesters ,Subcutaneous Fat ,Adipose tissue ,chemistry.chemical_compound ,Mice ,medicine ,Animals ,Humans ,Polymer scaffold ,Cells, Cultured ,Fibrin ,Mice, Inbred BALB C ,Adipogenesis ,Tissue Scaffolds ,business.industry ,Guided Tissue Regeneration ,Reverse Transcriptase Polymerase Chain Reaction ,Lipogenesis ,Cancer ,medicine.disease ,Transplantation ,chemistry ,Polycaprolactone ,Microscopy, Electron, Scanning ,Surgery ,Free form ,Female ,Stromal Cells ,business ,Biomedical engineering - Abstract
Regeneration of volume-stable adipose tissue is required for treatment of soft-tissue loss due to cancer, trauma, burns and for correctional cosmetic surgery. In this study, we hypothesized that transplantation of human adipose-derived stromal cells (hADSCs) using polycaprolactone (PCL) scaffolds fabricated with a solid free-form fabrication method would better maintain the volume of regenerated adipose tissues, as compared with the use of fibrin gel. Six weeks after implantation into the dorsal subcutaneous pockets of athymic mice, the volumes and adipose tissue areas of hADSC-PCL scaffold implants were significantly larger than those of hADSC-fibrin implants. In addition, the mRNA expression of adipogenic genes was more extensive in the hADSC-PCL scaffold implants.
- Published
- 2012
38. 3,4-dihydroxy-L-phenylalanine as a cell adhesion molecule in serum-free cell culture
- Author
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Wan Geun La, Hee Seok Yang, Suk Ho Bhang, Jooyeon Park, Seung Ho Yu, Yung-Eun Sung, Byung-Soo Kim, Jung Youn Shin, and Hee Hun Yoon
- Subjects
Chemistry ,Cell adhesion molecule ,Cell Survival ,Cell Culture Techniques ,Apoptosis ,Fibroblasts ,Culture Media, Serum-Free ,Synthetic materials ,Dihydroxyphenylalanine ,Biochemistry ,Serum free ,Cell culture ,Cell Adhesion ,Molecule ,Humans ,Cell adhesion ,Cell Adhesion Molecules ,Biotechnology ,Dihydroxy-L-phenylalanine ,Cell Proliferation - Abstract
In this article, we examined the feasibility of using 3,4-dihydroxy-L-phenylalanine (DOPA) as a cell adhesion molecule in serum-free cultures of anchorage-dependent mammalian cells. DOPA is a critical, functional element in mussel adhesive proteins and is known to bind strongly to various natural or synthetic materials. DOPA coating on culture plates was confirmed using X-ray photoelectron spectroscopy and energy-dispersive spectroscopy. Human dermal fibroblasts (HDFs) were cultured on DOPA-coated, fibronectin-coated, or no material-coated culture plates in serum-free medium. HDFs cultured on DOPA showed the highest cell adhesion ratio, spreading, and viability but the lowest apoptotic activity. Therefore, DOPA may be a useful cell-adhesion molecule for serum-free culture.
- Published
- 2011
39. Enhancement of long-term angiogenic efficacy of adipose stem cells by delivery of FGF2
- Author
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Suk Ho Bhang, Byung Soo Kim, Hee Seok Yang, Wan-Guen La, Hee Hun Yoon, Jun Yeup Seong, Tae-Jin Lee, Jung-Youn Shin, and Heungsoo Shin
- Subjects
medicine.medical_specialty ,Cell Survival ,medicine.medical_treatment ,Transplantation, Heterologous ,Adipose tissue ,Mice, Nude ,Neovascularization, Physiologic ,Biology ,Fibroblast growth factor ,Mesenchymal Stem Cell Transplantation ,Biochemistry ,Neovascularization ,Andrology ,chemistry.chemical_compound ,Mice ,Ischemia ,medicine ,Animals ,Cells, Cultured ,Growth factor ,Muscles ,Mesenchymal Stem Cells ,Cell Biology ,Surgery ,Hindlimb ,Transplantation ,Vascular endothelial growth factor ,Fibroblast Growth Factors ,Arterioles ,chemistry ,Adipose Tissue ,Microscopy, Electron, Scanning ,Hepatocyte growth factor ,Female ,medicine.symptom ,Stem cell ,Cardiology and Cardiovascular Medicine ,Biomarkers ,medicine.drug - Abstract
Stem cell transplantation can induce neovascularization. Regenerated blood vessels should remain stable for a long-term period in order to function as new blood vessels in ischemic tissues. Here we show that local delivery of FGF2 enhances the long-term (12 weeks) angiogenic efficacy of human adipose-derived stem cells (hADSCs) implanted into mouse ischemic hindlimbs. Following transplantation of hADSCs into ischemic hindlimbs of mice, hADSC viability was significantly higher in the hADSC + FGF2 group at 4 and 12 weeks post-transplantation than in the hADSC only group. Furthermore, hADSCs produced higher levels of angiogenic growth factors ( i.e ., fibroblast growth factor 2, vascular endothelial growth factor, hepatocyte growth factor, and platelet-derived growth factor) at both time points. As a result, the density of arterioles in the ischemic hindlimb muscle was significantly higher in the hADSC + FGF2 group than in either hADSC or FGF2 only group at both time points. The number of arterioles with larger diameters was significantly greater in the hADSC + FGF2 group than in the other groups at 12 weeks, and increased in the hADSC + FGF2 group as the time period increased from 4 weeks to 12 weeks post-transplantation. This suggests that FGF2 delivery to hADSC transplantation sites enhances long-term angiogenic efficacy of hADSCs transplanted into ischemic tissues.
- Published
- 2011
40. Efficient formation of cell spheroids using polymer nanofibers
- Author
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Suk Ho Bhang, Wan-Geun La, Hyeon-Ki Jang, Tae-Jin Lee, Byung-Soo Kim, Oh Hyeong Kwon, Jooyeon Park, Jung-Youn Shin, and Il Keun Kwon
- Subjects
chemistry.chemical_classification ,Cell ,HEK 293 cells ,Spheroid ,Cell Culture Techniques ,Nanofibers ,Bioengineering ,Nanotechnology ,General Medicine ,Polymer ,Applied Microbiology and Biotechnology ,Electrospinning ,medicine.anatomical_structure ,chemistry ,Polylactic Acid-Polyglycolic Acid Copolymer ,Cell culture ,Nanofiber ,Spheroids, Cellular ,medicine ,Biophysics ,Humans ,Lactic Acid ,Cell adhesion ,Polyglycolic Acid ,Biotechnology - Abstract
Spheroid culture has been used for suspension cultures of anchorage-dependent cells. In this study, we developed a new method for the suspension cultures of anchorage-dependent animal cells using polymer nanofibers. Poly(lactic-co-glycolic acid) nanofibers (785 nm in average fiber-diameter, 88 μm in average fiber-length) fabricated by the electrospinning method were added to each suspension culture of human embryonic kidney 293 cells and human dermal fibroblasts. As compared to no addition of nanofibers to the suspension cultures, nanofibers enhanced cell spheroid formation, thereby reducing cell death resulting from a lack of cell adhesion. Efficient formation of spheroids in the presence of polymer nanofibers may be useful for the suspension cultures of anchorage-dependent cells.
- Published
- 2011
41. Enhanced skin wound healing by a sustained release of growth factors contained in platelet-rich plasma
- Author
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Hee Seok Yang, Byung-Soo Kim, Jung Youn Shin, Chang-Sung Kim, Jaehoon Shin, Suk Ho Bhang, Jooyeon Park, and Gun-Il Im
- Subjects
Vascular Endothelial Growth Factor A ,Angiogenesis ,animal diseases ,Blotting, Western ,Clinical Biochemistry ,Becaplermin ,Pharmacology ,Biology ,Real-Time Polymerase Chain Reaction ,Fibroblast growth factor ,Biochemistry ,Fibrin ,Immunoenzyme Techniques ,Mice ,chemistry.chemical_compound ,Animals ,Regeneration ,RNA, Messenger ,Molecular Biology ,Cell Proliferation ,Skin ,Mice, Inbred BALB C ,Wound Healing ,integumentary system ,Heparin ,Platelet-Rich Plasma ,Regeneration (biology) ,Dermis ,Proto-Oncogene Proteins c-sis ,nervous system diseases ,Vascular endothelial growth factor ,Vascular endothelial growth factor A ,chemistry ,Platelet-rich plasma ,Immunology ,biology.protein ,Intercellular Signaling Peptides and Proteins ,Molecular Medicine ,Female ,Fibroblast Growth Factor 2 ,Original Article ,Wound healing - Abstract
Platelet-rich plasma (PRP) contains growth factors that promote tissue regeneration. Previously, we showed that heparin-conjugated fibrin (HCF) exerts the sustained release of growth factors with affinity for heparin. Here, we hypothesize that treatment of skin wound with a mixture of PRP and HCF exerts sustained release of several growth factors contained in PRP and promotes skin wound healing. The release of fibroblast growth factor 2, platelet-derived growth factor-BB, and vascular endothelial growth factor contained in PRP from HCF was sustained for a longer period than those from PRP, calcium-activated PRP (C-PRP), or a mixture of fibrin and PRP (F-PRP). Treatment of full-thickness skin wounds in mice with HCF-PRP resulted in much faster wound closure as well as dermal and epidermal regeneration at day 12 compared to treatment with either C-PRP or F-PRP. Enhanced skin regeneration observed in HCF-PRP group may have been at least partially due to enhanced angiogenesis in the wound beds. Therefore, this method could be useful for skin wound treatment.
- Published
- 2011
42. 3D bioprinting spatiotemporally defined patterns of growth factors to tightly control tissue regeneration.
- Author
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Freeman, Fiona E., Pitacco, Pierluca, van Dommelen, Lieke H. A., Nulty, Jessica, Browe, David C., Jung-Youn Shin, Alsberg, Eben, and Kelly, Daniel J.
- Subjects
- *
BIOPRINTING , *GROWTH factors , *VASCULAR endothelial growth factors , *MEDICAL sciences , *ENDOCHONDRAL ossification , *BONE morphogenetic proteins - Abstract
The article demonstrates the potential of growth factor printing, a putative point of care therapy, for tightly controlled tissue regeneration. It mentions that therapeutic growth factor delivery typically requires supraphysiological dosages, which can cause undesirable off-target effects. It mentions the aim of this study was to 3D bioprint implants containing spatiotemporally defined patterns of growth factors optimized for coupled angiogenesis and osteogenesis.
- Published
- 2020
- Full Text
- View/download PDF
43. Combinatorial screening of biochemical and physical signals for phenotypic regulation of stem cell-based cartilage tissue engineering.
- Author
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Lee, Junmin, Jeon, Oju Jeon, Kong, Ming, Abdeen, Amr A., Jung-Youn Shin, Ha Neul Lee, Yu Bin Lee, Sun, Wujin, Bandaru, Praveen, Alt, Daniel S., Lee, KangJu, Han-Jun Kim, Sang Jin Lee, Chaterji, Somali, Su Ryon Shin, Alsberg, Eben, and Khademhosseini, Ali
- Subjects
- *
CARTILAGE cells , *CARTILAGE regeneration , *APPLIED sciences , *CHONDROITIN sulfates , *TISSUE engineering , *CARTILAGE , *BIOENGINEERING - Abstract
The article presents a study related to combinatorial screening of biochemical and physical signals for phenotypic regulation of stem cell–based cartilage tissue engineering. It mentions that faster-degrading, soft matrices promoted articular cartilage tissue formation of hMSCs by inducing their proliferation and maturation, while slower-degrading, stiff matrices promoted cells to differentiate into hypertrophic chondrocytes through Yes-associated protein (YAP)–dependent mechanotransduction.
- Published
- 2020
- Full Text
- View/download PDF
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