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Hoon Seonwoo,Won-Gyu Bae,Sunho Park,Hong-Nam Kim,Kyoung Soon Choi,Ki Taek Lim,Hoon Hyun,Jin-Woo Kim,Jangho Kim,Jong Hoon Chung IEEE 2016 IEEE transactions on nanobioscience Vol.15 No.8
<P>Living cells receive biochemical and physical information from the surrounding microenvironment and respond to this information. Multiscale hierarchical substrates with micro- and nanogrooves have been shown to mimic the native extracellular matrix (ECM) better than conventional nanopatterned substrates; therefore, substrates with hierarchical topographical cues are considered suitable for investigating the role of physical factors in tissue functions. In this study, precisely controllable, multiscale hierarchical substrates that could mimic the micro- and nanotopography of complex ECMs were fabricated and used to culture various cell types, including fibroblasts, endothelial cells, osteoblasts, and human mesenchymal stem cells. These substrates had both microscale wrinkles and nanoscale patterns and enhanced the alignment and elongation of all the cells tested. In particular, the nanotopography on the microscale wrinkles promoted not only the adhesion, but also the functions of the cells. These findings suggest that the hierarchical multiscale substrates effectively regulated cellular structure and functions and that they can be used as a platform for tissue engineering and regenerative medicine.</P>
Natural Resource-derived Biomaterials with Nanotechnology and 3D Printing Techniques
( Hoon Seonwoo ),( Ki Taek Lim ),( Jangho Kim ),( Kyongje Jang ),( Jong Hoon Chung ) 한국농업기계학회 2018 한국농업기계학회 학술발표논문집 Vol.23 No.2
There are many trials to regenerate one’s defected organs or tissues by tissue engineered techniques. To date, synthetic polymers are frequently used as base materials. However, such polymers have unexpected side effects, such as cytotoxicity and genotoxicity. To solve these problems, biomaterials derived from natural resources are addressed as alternatives. We introduce the application of natural resource-derived biomaterials, such as equine bone powder and chitosan, with nanomaterials and 3D printing techniques. At first, equine bone powder and chitosan were solely used for tissue regeneration. In this research, their biocompatibilities were evaluated well. Next, their application with nanotechnologies were investigated. The application of nanomaterials, such as graphene, and electrospun nanofiber with natural resource-derived biomaterials resulted in enhanced tissue regenerations. Finally, we tried to apply natural resources into 3D printed tissue reconstruction. Under appropriate characterization, natural resource-derived biomaterials were successfully printed. Their application is expected to fulfill the limitation of conventional synthetic polymer-based therapies.
JNK2 silencing and caspase-9 activation by hyperosmotic polymer inhibits tumor progression
Garg, Pankaj,Pandey, Shambhavi,Hoon, Seonwoo,Jang, Kyoung-Je,Lee, Myung Chul,Choung, Yun-Hoon,Choung, Pill-Hoon,Chung, Jong Hoon Elsevier 2018 International journal of biological macromolecules Vol.120 No.2
<P><B>Abstract</B></P> <P>c-Jun N-terminal kinase 2 (JNK2) is primarily responsible for the oncogenic transformation of the transcription factor c-Jun. Expression of the proto-oncogene c-Jun progresses the cell cycle from G1 to S phase, but when its expression becomes awry it leads to uncontrolled proliferation and angiogenesis. Delivering a JNK2 siRNA (siJNK2) in tumor tissue was anticipated to reverse the condition with subsequent onset of apoptosis which predominantly requires an efficient delivering system capable of penetrating through the compact tumor mass. In the present study, it was demonstrated that polymannitol-based vector (PMGT) with inherent hyperosmotic properties was able to penetrate through and deliver the siJNK2 in the subcutaneous tumor of xenograft mice. Hyperosmotic activity of polymannitol was shown to account for the enhanced therapeutic delivery both in vitro and in vivo because of the induction of cyclooxygenase-2 (COX-2) which stimulates caveolin-1 for caveolae-mediated endocytosis of the polyplexes. Further suppression of JNK2 and hence c-Jun expression led to the activation of caspase-9 to induce apoptosis and inhibition of tumor growth in xenograft mice model. The study exemplifies PMGT as an efficient vector for delivering therapeutic molecules in compact tumor tissue and suppression of JNK2 introduces a strategy to inhibit tumor progression.</P> <P><B>Graphical abstract</B></P> <P>Hyperosmotic PMGT driven siJNK2 delivery in compact cancer cells inhibits c-jun phosphorylation resulting in tumor growth arrest via caspase-9 induction and apoptosis.</P> <P>[DISPLAY OMISSION]</P>
Hyperosmotic polydixylitol for crossing the blood brain barrier and efficient nucleic acid delivery
Garg, P.,Pandey, S.,Seonwoo, Hoon,Yeom, Seungmin,Choung, Yun-Hoon,Cho, Chong-Su,Choung, Pill-Hoon,Hoon Chung, Jong The Royal Society of Chemistry 2015 Chemical communications Vol.51 No.17
<P>Here, we introduce a polydixylitol based highly osmotic polymer that not only transmigrates the BBB by intra-arterial infusion of osmotic polyol but also triggers cellular uptake <I>via</I> modulation of caveolae mediated endocytosis.</P> <P>Graphic Abstract</P><P>We report that the incorporation of a hyperosmotic molecule, dixylitol, into the backbone of a delivery vector can enhance its blood brain barrier transmigration. <IMG SRC='http://pubs.rsc.org/services/images/RSCpubs.ePlatform.Service.FreeContent.ImageService.svc/ImageService/image/GA?id=c4cc09871d'> </P>
Lee, Myung Chul,Seonwoo, Hoon,Garg, Pankaj,Jang, Kyoung Je,Pandey, Shambhavi,Park, Sang Bae,Kim, Hong Bae,Lim, Jaewoon,Choung, Yun Hoon,Chung, Jong Hoon RSC Publications 2018 Biomaterials Science Vol.6 No.2
<P>Damage to the eardrum causes acute pain and can lead to chronic otitis media if it develops into chronic tympanic membrane (TM) perforations. Chronic TM perforations are usually treated with surgical methods such as tympanoplasty and myringoplasty. However, these surgeries are not only complicated and difficult but also cost a lot of money. Our research team developed chitosan patches (E-CPs) that release epidermal growth factor (EGF) as a patch therapy to replace surgical methods. However, there was a limitation in the healing ratio of the treatment compared to the surgical methods. In this study, we developed EGF and epidermal growth factor receptor (EGFR) gene-releasing polyethyleneimine (PEI)/chitosan patches (EErP-CPs) to increase the regeneration of TM perforations. The addition of PEI increased the adhesion and migration ability of TM cells on the patches. The simultaneous release of the EGF and the EGFR gene further enhanced TM cell proliferation, adhesion and migratory ability. It was confirmed that the EGF protein and EGFR gene were released for 30 days; however, EGF was released and increased TM cell viability almost immediately after treatment and EGFR took a minimum of 3 days before showing its effect on improved cell viability. It was also shown that EErP-CPs are more hydrophilic and have more positive charge than E-CP because of added amine groups from PEI. In conclusion, the developed EErP-CPs resulted in the improved healing of TM perforations and can potentially be applied to the regeneration of both chronic and acute tympanic membrane perforations.</P>
Effects of Micro-Electrical Stimulation on Regulation of Behavior of Electro-Active Stem Cells
Im, Ae-Lee,Kim, Jangho,Lim, KiTaek,Seonwoo, Hoon,Cho, Woojae,Choung, Pill-Hoon,Chung, Jong Hoon Korean Society for Agricultural Machinery 2013 바이오시스템공학 Vol.38 No.2
Purpose: Stem cells provide new opportunities in the regenerative medicine for human or animal tissue regeneration. In this study, we report an efficient method for the modulating behaviors of electro-active stem cells by micro-electric current stimulation (mES) without using chemical agents, such as serum or induction chemicals. Methods: Dental pulp stem cells (DPSCs) were cultured on the tissue culture dish in the mES system. To find a suitable mES condition to promote the DPSC functions, the response surface analysis was used. Results: We found that a working micro-current of 38 ${\mu}A$ showed higher DPSC proliferation compared with other working conditions. The mES altered the expressions of intracellular and extracellular proteins compared to those in unstimulated cells. The mES with 38 ${\mu}A$ significantly increased osteogenesis of DPSCs compared with ones without mES. Conclusions: Our findings indicate that mES may induce DPSC proliferation and differentiation, resulting in applying to DPSCs-based human or animal tissue regeneration.
Lim, Ki-Taek,Kim, Jangho,Seonwoo, Hoon,Chang, Jung Uk,Choi, Hwajung,Hexiu, Jin,Cho, Woo Jae,Choung, Pill-Hoon,Chung, Jong Hoon Mary Ann Liebert 2013 Tissue engineering. Part C, Methods Vol.19 No.2
<P>This study instituted a simple approach to stimulate alveolar bone regeneration for tooth tissue engineering by controlling effects of low fluid dynamic shear stress (LFDSS) on growth and differentiation in vitro. Human alveolar bone-derived mesenchymal stem cells (hABMSCs) harvested from human mandibular alveolar bone were cultured with LFDSS to generate cultures containing bone-like formations. To distinguish between osteodifferentiation and bone-like formation, cells were cultured either with or without fluid shear stress. The calcium content and alkaline phosphatase (ALP) activity of hABMSCs were used as indicators of osteogenesis. Cell viability and proliferation after stimulating with LFDSS for 10-60?min/day were higher than with longer stimulations. Mineralized nodules formed when osteoblasts were cultured with an induction medium, a marker of osteogenic differentiation. ALP activity tended to increase after 10 and 60?min/day of stimulation. In addition, LFDSS conditions also increased gene expression of IBSP, RUNX2, COL-I, ALP, OCN, and OPN, as shown by reverse transcriptase-polymerase chain reaction. From the results of a proteomics array, LFDSS groups were intensely expressed with several factors (EGF, HGF, IGF, TGF, and PDGF). Furthermore, CD146 and Stro-1 expression increased in cells treated with 30?min/day and decreased in cells treated with 120?min/day, as determined by cell surface antigen analysis by fluorescence-activated cell-sorting analysis. These results strongly showed that LFDSS at the proper intensity and time enhanced the differentiation and maturation of hABMSCs. In conclusion, an appropriate level of LFDSS can potently and positively modulate proliferation and differentiation in hABMSCs.</P>