Hierarchically Micro- and Nanopatterned Topographical Cues for Modulation of Cellular Structure and Function

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.

Graphene-Incorporated Bone Cements for Bone Regeneraton

( Hoon Seonwoo ),( Kyoung Je Jang ),( Seung Jung ),( Myung Chul Lee ),( Jong Hoon Chung ) 한국농업기계학회 2015 한국농업기계학회 학술발표논문집 Vol.20 No.2

Chitosan/PEI patch releasing EGF and the EGFR gene for the regeneration of the tympanic membrane after perforation

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>

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>

Physical Stimulation-Based Osteogenesis: Effect of Secretion <i>In Vitro</i> on Fluid Dynamic Shear Stress of Human Alveolar Bone-Derived Mesenchymal Stem Cells

Lim, Ki-Taek,Jin, Hexiu,Seonwoo, Hoon,Kim, Hye-Been,Kim, Jangho,Kim, Jin-Woo,Renji, Chen,Choung, Pill-Hoon,Chung, Jong Hoon IEEE 2016 IEEE transactions on nanobioscience Vol.15 No.8

<P>Human alveolar bone-derived mesenchymal stem cells (hABMSCs) are promising candidates for bone therapies, which have the capacity to differentiate into osteoblasts. Recently, secretion of inducible cytokines and growth factors from mesenchymal stem cells (MSCs) has been discovered, and we also have reported the osteogenic effects of cell physical stimulation. In this study, we investigated the effects of hABMSCs-conditioned secretion media (B-CSM) on osteogenic differentiation of hABMSCs in vitro. Furthermore, we analyzed the B-CSM by proteomics array to identify inducible factors which facilitate osteogenic differentiation. To determine optimal concentration, B-CSM was firstly added at varying amounts (5, 10, 20, 40, and 60%) relative to culture medium. The viability and proliferation of hABMSCs were higher after treating with 5-20% B-CSM to the cells, compared to 40-60%. In addition, the expression of stem cells markers CD146 and STRO-1 was increased in the cells treated with 5-20% B-CSM, but decreased with 40-60%. We also found that B-CSM promoted osteogenic differentiation of hABMSCs such as mineralized nodules were strongly generated by 5-20%. B-CSM was most effective in increasing the expression of Vinculin and osteocalcin (OCN) in osteogenic differentiation of hABMSCs. Taken together, the results of our study ultimately indicate that B-CSM from hABMSCs induced by physical stimulation induce the proliferation and osteogenic differentiation of hABMSCs.</P>

Controlled Fibroblast Cell Shape on Positively Charged Nanomatrixes

( Jangho Kim ),( Ki Taek Lim ),( Hoon Seonwoo ),( Soo Hyun Park ),( Yun-hoon Choung ),( Jong Hoon Chung ) 한국농업기계학회 2011 한국농업기계학회 학술발표논문집 Vol.16 No.1

Development and Characterization of Horse Bone-derived Natural Calcium Phosphate Powders

Jang, Kyoung-Je,Cho, Woo Jae,Seonwoo, Hoon,Kim, Jangho,Lim, Ki Taek,Chung, Pill-Hoon,Chung, Jong Hoon Korean Society for Agricultural Machinery 2014 바이오시스템공학 Vol.39 No.2

Purpose: This study was to develop an effective process for fabricating biocompatible calcium phosphate powders (CPPs) using horse bones, and to investigate the characteristics of them. Methods: The characteristics of horse bone powders (HBPs) were investigated according to the different osseous tissue types (compact bone and cancellous bone), bone types (spine and tibia), pretreatment methods (cold water, $H_2O_2$, and hot water), sintering time (4, 8 and 12h), and sintering temperature (600, 900, 1100 and $1300^{\circ}C$). In addition, the grinding methods were compared based on the wet grinding (ball mill) and dry grinding (blade grinder) method to make it as powders. Finally, their cytotoxicity and cell viability were checked. Results: Regardless of the types of osseous tissues and bones, HBPs were well fabricated as biocompatible CPPs. It was also found that the pretreatment methods did not influence on the resultants, showing well-fabricated HBPs. Considering the processing time, the hot water method was the most suitable compared to other pretreatment methods. Further, 12h-sintering time was sufficient to remove residual organic compounds. The sintering temperatures greatly affected the properties of bone powders fabricated. The x-ray diffraction (XRD) peak of horse bone sintered at $600^{\circ}C$ was most closed to that of hydroxyapatite (HA). Our bioactivity study demonstrated that the HBPs fabricated by sintering horse bones at $1300^{\circ}C$ showed the best performance in terms of cell viability whereas the HBPs $1100^{\circ}C$ showed the cytotoxicity. Conclusions: Using various types of horse bone tissues, biocompatible CPPs were successfully developed. We conclude that the HBPs may have a great potential as biomaterials for various biological applications including bone tissue engineering.

Biological Engineering : Original Article ; Development and Characterization of Horse Bone-derived Natural Calcium Phosphate Powders

( Kyoung Je Jang ),( Woo Jae Cho ),( Hoon Seonwoo ),( Jangho Kim ),( Ki Taek Lim ),( Pill Hoon Chung ),( Jong Hoon Chung ) 한국농업기계학회 2014 바이오시스템공학 Vol.39 No.2

Purpose: This study was to develop an effective process for fabricating biocompatible calcium phosphate powders (CPPs) using horse bones, and to investigate the characteristics of them. Methods: The characteristics of horse bone powders (HBPs) were investigated according to the different osseous tissue types (compact bone and cancellous bone), bone types (spine and tibia), pretreatment methods (cold water, H2O2, and hot water), sintering time (4, 8 and 12h), and sintering temperature (600, 900, 1100 and1300°C). In addition, the grinding methods were compared based on the wet grinding (ball mill) and dry grinding (blade grinder) method to make it as powders. Finally, their cytotoxicity and cell viability were checked. Results: Regardless of the types of osseous tissues and bones, HBPs were well fabricated as biocompatible CPPs. It was also found that the pretreatment methods did not influence on the resultants, showing well-fabricated HBPs. Considering the processing time, the hot water method was the most suitable compared to other pretreatment methods. Further, 12h-sintering time was sufficient to remove residual organic compounds. The sintering temperatures greatly affected the properties of bone powders fabricated. The x-ray diffraction (XRD) peak of horse bone sintered at 600°C was most closed to that of hydroxyapatite (HA). Our bioactivity study demonstrated that the HBPs fabricated by sintering horse bones at 1300°C showed the best performance in terms of cell viability whereas the HBPs 1100°C showed the cytotoxicity. Conclusions: Using various types of horse bone tissues, biocompatible CPPs were successfully developed. We conclude that the HBPs may have a great potential as biomaterials for various biological applications including bone tissue engineering.