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Lee, Yunki,Balikov, Daniel A.,Lee, Jung Bok,Lee, Sue Hyun,Lee, Seung Hwan,Lee, Jong Hun,Park, Ki Dong,Sung, Hak-Joon MDPI 2017 INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES Vol.18 No.8
<P>Directing angiogenic differentiation of mesenchymal stem cells (MSCs) still remains challenging for successful tissue engineering. Without blood vessel formation, stem cell-based approaches are unable to fully regenerate damaged tissues due to limited support for cell viability and desired tissue/organ functionality. Herein, we report in situ cross-linkable gelatin−hydroxyphenyl propionic acid (GH) hydrogels that can induce pro-angiogenic profiles of MSCs via purely material-driven effects. This hydrogel directed endothelial differentiation of mouse and human patient-derived MSCs through integrin-mediated interactions at the cell-material interface, thereby promoting perfusable blood vessel formation in vitro and in vivo. The causative roles of specific integrin types (α<SUB>1</SUB> and α<SUB>v</SUB>β<SUB>3</SUB>) in directing endothelial differentiation were verified by blocking the integrin functions with chemical inhibitors. In addition, to verify the material-driven effect is not species-specific, we confirmed in vitro endothelial differentiation and in vivo blood vessel formation of patient-derived human MSCs by this hydrogel. These findings provide new insight into how purely material-driven effects can direct endothelial differentiation of MSCs, thereby promoting vascularization of scaffolds towards tissue engineering and regenerative medicine applications in humans.</P>
Structure and function of the N‐terminal domain of the human mitochondrial calcium uniporter
Lee, Youngjin,Min, Choon Kee,Kim, Tae Gyun,Song, Hong Ki,Lim, Yunki,Kim, Dongwook,Shin, Kahee,Kang, Moonkyung,Kang, Jung Youn,Youn, Hyung‐,Seop,Lee, Jung‐,Gyu,An, Jun Yop,Park, Kyoung Ryou John Wiley and Sons Inc. 2015 EMBO reports Vol.16 No.10
<P><B>Abstract</B></P><P>The mitochondrial calcium uniporter (MCU) is responsible for mitochondrial calcium uptake and homeostasis. It is also a target for the regulation of cellular anti‐/pro‐apoptosis and necrosis by several oncogenes and tumour suppressors. Herein, we report the crystal structure of the MCU N‐terminal domain (NTD) at a resolution of 1.50 Å in a novel fold and the S92A MCU mutant at 2.75 Å resolution; the residue S92 is a predicted CaMKII phosphorylation site. The assembly of the mitochondrial calcium uniporter complex (uniplex) and the interaction with the MCU regulators such as the mitochondrial calcium uptake‐1 and mitochondrial calcium uptake‐2 proteins (MICU1 and MICU2) are not affected by the deletion of MCU NTD. However, the expression of the S92A mutant or a NTD deletion mutant failed to restore mitochondrial Ca<SUP>2+</SUP> uptake in a stable MCU knockdown HeLa cell line and exerted dominant‐negative effects in the wild‐type MCU‐expressing cell line. These results suggest that the NTD of MCU is essential for the modulation of MCU function, although it does not affect the uniplex formation.</P>
Lee, Yunki,Choi, Kyong-Hoon,Park, Kyung Min,Lee, Jong-Min,Park, Bong Joo,Park, Ki Dong American Chemical Society 2017 ACS APPLIED MATERIALS & INTERFACES Vol.9 No.20
<P>Various types of commercialized wound dressings (e.g., films, foams, gels, and nanofiber meshes) have been clinically used as a physical barrier against bacterial invasion and as wound-healing materials. Although these dressings can protect the wounded tissue from the external environment, they cannot treat the wounds that are already infected with bacteria. Herein, we report in situ H2O2-releasing hydrogels as an active wound dressing with antibacterial properties for treatment of drug-resistant bacterial infection. In this study, H2O2 was used for two major purposes: (1) in situ gel formation via a horseradish peroxidase (HRP)/H2O2-triggered cross-linking reaction, and (2) antibacterial activity of the hydrogel via its oxidative effects. We found that there were residual H2O2 in the matrix after in situ HRP-catalyzed gelling, and varying the feed amount of H2O2 (1-10 mM; used to make hydrogels) enabled control of H2O2 release kinetics within a range of 2-509 mu M. In addition, although the gelatin-hydroxyphenyl propionic acid (GH) gel called 'GH 10' (showing the greatest H2O2 release, 509 mu M) slightly decreased cell viability (to 82-84%) of keratinocyte (HaCaT) and fibroblast (L-929) cells in in vitro assays, none of the hydrogels showed significant cytotoxicity toward tissues in in vivo skin irritation tests. When the H2O2-releasing hydrogels that promote in vivo wound healing, were applied to various bacterial strains in vitro and ex vivo, they showed strong killing efficiency toward Gram-positive bacteria including Staphylococcus aureus, S. epidermidis, and clinical isolate of methicillin-resistant S. aureus (MRSA, drug-resistant bacteria), where the antimicrobial effect was dependent on the concentration of the H2O2 released. The present study suggests that our hydrogels have great potential as an injectable/sprayable antimicrobial dressing with biocompatibility and antibacterial activity against drug-resistant bacteria including MRSA for wound and infection treatment.</P>
Lee, Yunki,Son, Joo Young,Kang, Jeon Il,Park, Kyung Min,Park, Ki Dong American Chemical Society 2018 ACS APPLIED MATERIALS & INTERFACES Vol.10 No.21
<P>Reactive oxygen species (ROS) have been implicated as a critical modulator for various therapeutic applications such as treatment of vascular disorders, wound healing, and cancer treatment. Specifically, growing evidence has recently demonstrated that transient or low levels of hydrogen peroxide (H<SUB>2</SUB>O<SUB>2</SUB>) facilitates tissue regeneration and wound repair through acute oxidative stress that can evaluate intracellular ROS levels in cells or tissues. Herein, we report a gelatin-based H<SUB>2</SUB>O<SUB>2</SUB>-releasing hydrogel formed by dual enzyme-mediated reaction using horseradish peroxidase and glucose oxidase (GO<SUB><I>x</I></SUB>). The release behavior of H<SUB>2</SUB>O<SUB>2</SUB> from the hydrogel matrices can be precisely controlled by varying the GO<SUB><I>x</I></SUB> concentrations. We demonstrate that H<SUB>2</SUB>O<SUB>2</SUB>-releasing hydrogels with the optimal condition increase transient upregulation of intracellular ROS levels in the endothelial cells (ECs), enhance proliferative activities of ECs in vitro, and facilitate neovascularization in ovo. We suggest that our H<SUB>2</SUB>O<SUB>2</SUB>-releasing hydrogels hold great potential as an injectable and dynamic matrix for the treatment of vascular disorders as well as in tissue regenerative medicine.</P> [FIG OMISSION]</BR>
Lee, Yunki,Le Thi, Phuong,Seon, Gyeung Mi,Ryu, Seung Bae,Brophy, Colleen M.,Kim, YongTae,Park, Jong-Chul,Park, Ki Dong,Cheung-Flynn, Joyce,Sung, Hak-Joon Elsevier 2017 Journal of controlled release Vol.266 No.-
<P><B>Abstract</B></P> <P>The leading cause of synthetic graft failure includes thrombotic occlusion and intimal hyperplasia at the site of vascular anastomosis. Herein, we report a co-immobilization strategy of heparin and potent anti-neointimal drug (Mitogen Activated Protein Kinase II inhibitory peptide; MK2i) by using a tyrosinase-catalyzed oxidative reaction for preventing thrombotic occlusion and neointimal formation of synthetic vascular grafts. The binding of heparin–tyramine polymer (HT) onto the polycarprolactone (PCL) surface enhanced blood compatibility with significantly reduced protein absorption (64.7% decrease) and platelet adhesion (85.6% decrease) compared to bare PCL surface. When loading MK2i, 1) the HT depot surface gained high MK2i-loading efficiency through charge-charge interaction, and 2) this depot platform enabled long-term, controlled release over 4weeks (92–272μg/mL of MK2i). The released MK2i showed significant inhibitory effects on VSMC migration through down-regulated phosphorylation of target proteins (HSP27 and CREB) associated with intimal hyperplasia. In addition, it was found that the released MK2i infiltrated into the tissue with a cumulative manner in <I>ex vivo</I> human saphenous vein (HSV) model. This present study demonstrates that enzymatically HT-coated surface modification is an effective strategy to induce long-term MK2i release as well as hemocompatibility, thereby improving anti-neointimal activity of synthetic vascular grafts.</P> <P>Graphical abstract</P> <P>[DISPLAY OMISSION]</P>
Lee, Yunki,Bae, Jin Woo,Lee, Jin Woo,Suh, Wonhee,Park, Ki Dong The Royal Society of Chemistry 2014 Journal of Materials Chemistry B Vol.2 No.44
<P>In this study, <I>in situ</I> forming gelatin hydrogels <I>via</I> horseradish peroxidase (HRP)-catalyzed cross-linking were developed to serve as bioactive wound dressings with suitable tissue adhesive properties to deliver dermal fibroblasts (DFBs). The DFB-encapsulated gelatin hydrogels with different stiffnesses, GH-soft (1.1 kPa) and GH-hard (6.2 kPa), were prepared by controlling the hydrogen peroxide (H2O2) concentrations. The GH-soft hydrogel was capable of facilitating the proliferation of DFBs and the synthesis of extracellular components, as compared to GH-hard hydrogels. In addition, the subcutaneously injected GH-soft hydrogel with bioluminescent reporter cells provided enhanced cell survival and local retention over 14 days. <I>In vivo</I> transplantation of DFB-encapsulated GH-soft hydrogels accelerated wound contraction, and promoted collagen deposition and neovascularization within the incisions performed on mice skin. Therefore, we expect that HRP-catalyzed <I>in situ</I> forming gelatin hydrogels can be useful for local delivery of cells with high viability in wounds, which holds great promise for advancing wound healing technologies and other tissue engineering applications.</P>
Lee, Yunki,Bae, Jin Woo,Hoang Thi, Thai Thanh,Park, Kyung Min,Park, Ki Dong The Royal Society of Chemistry 2015 Chemical communications Vol.51 No.42
<P>Graphene-based nanomaterials with different oxidation degrees were incorporated into Tetronic–tyramine (Tet–TA) hydrogels <I>via</I> enzymatic cross-linking. The molecular oxidation of graphene in combination with amphiphilic Tet–TA significantly improved the water dispersibility of graphene oxide (GO), resulting in a significant reinforcement of Tet–TA/GO composite hydrogels that can be used as an injectable biomaterial platform.</P> <P>Graphic Abstract</P><P>Graphene-based nanomaterials with different oxidation degrees were incorporated into Tetronic–tyramine (Tet–TA) hydrogels <I>via</I> enzymatic cross-linking. <IMG SRC='http://pubs.rsc.org/services/images/RSCpubs.ePlatform.Service.FreeContent.ImageService.svc/ImageService/image/GA?id=c5cc02511g'> </P>
차세대 위성탑재 컴퓨터의 표준 구조 설계에 관한 개념 연구
이윤기(Yunki Lee),김지훈(Jihoon Kim) 한국항공우주학회 2013 韓國航空宇宙學會誌 Vol.41 No.12
저궤도와 정지궤도 위성을 위한 위성 탑재 컴퓨터 (OBC)는 서로 유사한 기능을 가짐에도 불구하고, 지금까지 별도의 구조로 개발되어왔다. 본 논문에서는 OBC의 표준 구조에 대한 개념 연구 결과를 제시하며, 차세대 위성용 OBC를 개발하기 위한 방안을 제안한다. 제안된 구조는 가변성이 매우 높은 구조이며, 저/중/정지궤도 그리고 달 탐사선/심 우주탐사선에 모두 사용되도록 하는 것을 목표로 하고 있다. 또한 현재 개발 진행 중인 표준형 OBC의 개발 현황을 소개한다. On-Board computers (OBC) for LEO & GEO satellites have been developed with their own dedicated architecture so far even though they have many similar functionalities. In this paper, we present a conceptual study results of standard OBC architecture design and propose the domestic development plan for the next generation satellite OBC. Proposed architecture is highly flexible and can be used at LEO/MEO/GEO and Moon Explorer/Deep Space Probe. Also, we introduce current status of standard OBC which is under development.