Deok-Ho Kim

University of Washington Seattle, Seattle, Washington, United States

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Publications (111)388.63 Total impact

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    ABSTRACT: Duchenne's muscular dystrophy (DMD) is a neuromuscular disorder accompanied with muscle weakness and wasting. Since myostatin was reported to be a key regulator of muscle wasting, myostatin inhibitors have been investigated as therapeutic candidates for the treatment of muscular diseases. Here, we report an antigenic peptide of myostatin fragment (MstnF) conjugated to hyaluronate (HA) with a low molecular weight (MW, 17 kDa) for transdermal immunotherapy of DMD. Facilitating the transdermal delivery, the low MW HA showed a boosting effect on the immunization of MstnF possibly by engaging both toll-like receptors and cluster of differentiation 44 (CD44). In vivo two-photon microscopy clearly visualized the effective transdermal penetration of HA-MstnF conjugates into deep intact skin layers. The transdermal immunization of mdx mice significantly increased antibody titers against myostatin. Furthermore, the mdx mice immunized with HA-MstnF conjugates resulted in statistically significant improvement in the biochemical and pathological status of skeletal musculature as well as functional behaviors.
    No preview · Article · Mar 2016 · Biomaterials
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    ABSTRACT: Coordinated extracellular matrix spatiotemporal reorganization helps regulate cellular differentiation, maturation, and function in vivo, and is therefore vital for the correct formation, maintenance, and healing of complex anatomic structures. In order to evaluate the potential for cultured cells to respond to dynamic changes in their in vitro microenvironment, as they do in vivo, the collective behavior of primary cardiac muscle cells cultured on nanofabricated substrates with controllable anisotropic topographies was studied. A thermally induced shape memory polymer (SMP) was employed to assess the effects of a 90° transition in substrate pattern orientation on the contractile direction and structural organization of cardiomyocyte sheets. Cardiomyocyte sheets cultured on SMPs exhibited anisotropic contractions before shape transition. 48 hours after heat-induced shape transition, the direction of cardiomyocyte contraction reoriented significantly and exhibited a bimodal distribution, with peaks at ∼ 45 and -45 degrees (P < 0.001). Immunocytochemical analysis highlighted the significant structural changes that the cells underwent in response to the shift in underlying topography. The presented results demonstrate that initial anisotropic nanotopographic cues do not permanently determine the organizational fate or contractile properties of cardiomyocytes in culture. Given the importance of surface cues in regulating primary and stem cell development, investigation of such tunable nanotopographies may have important implications for advancing cellular maturation and performance in vitro, as well as improving our understanding of cellular development in response to dynamic biophysical cues.
    No preview · Article · Feb 2016 · Biomaterials
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    Deok-Ho Kim · Ali Khademhosseini · Luke P Lee
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    ABSTRACT: No abstract is available for this article.
    Full-text · Article · Jan 2016 · Advanced Healthcare Materials
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    ABSTRACT: Engineering mature and functional skeletal muscle tissue requires an ability to promote the structural organization and differentiation of cultured myoblasts. On page 137, D.-H. Kim, S.G. Im, and co-workers describe a bio-inspired electroconductive culture platform, wherein a nanopatterned substrate mimicking the extracellular matrix of native muscle tissue is covered with a thin layer of gold. Engineered tissues using this platform feature hypertrophic and uniaxially aligned myotubes with increased expression levels of myogenic markers.
    No preview · Article · Jan 2016 · Advanced Healthcare Materials
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    ABSTRACT: Bioprinting is a 3D fabrication technology used to precisely dispense cell-laden biomaterials for the construction of complex 3D functional living tissues or artificial organs. While still in its early stages, bioprinting strategies have demonstrated their potential use in regenerative medicine to generate a variety of transplantable tissues, including skin, cartilage, and bone. However, current bioprinting approaches still have technical challenges in terms of high-resolution cell deposition, controlled cell distributions, vascularization, and innervation within complex 3D tissues. While no one-size-fits-all approach to bioprinting has emerged, it remains an on-demand, versatile fabrication technique that may address the growing organ shortage as well as provide a high-throughput method for cell patterning at the micrometer scale for broad biomedical engineering applications. In this review, we introduce the basic principles, materials, integration strategies and applications of bioprinting. We also discuss the recent developments, current challenges and future prospects of 3D bioprinting for engineering complex tissues. Combined with recent advances in human pluripotent stem cell technologies, 3D-bioprinted tissue models could serve as an enabling platform for high-throughput predictive drug screening and more effective regenerative therapies.
    Full-text · Article · Dec 2015 · Biotechnology advances
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    ABSTRACT: Human induced pluripotent stem cell derived cardiomyocytes (hiPSC-CMs) offer unprecedented opportunities to study inherited heart conditions in vitro, but are phenotypically immature, limiting their ability to effectively model adult-onset diseases. Cardiomyopathy is becoming the leading cause of death in patients with Duchenne muscular dystrophy (DMD), but the pathogenesis of this disease phenotype is not fully understood. Therefore, we aimed to test whether biomimetic nanotopography could further stratify the disease phenotype of DMD hiPSC-CMs to create more translationally relevant cardiomyocytes for disease modeling applications. We found that anisotropic nanotopography was necessary to distinguish structural differences between normal and DMD hiPSC-CMs, as these differences were masked on conventional flat substrates. DMD hiPSC-CMs exhibited a diminished structural and functional response to the underlying nanotopography compared to normal cardiomyocytes at both the macroscopic and subcellular levels. This blunted response may be due to a lower level of actin cytoskeleton turnover as measured by fluorescence recovery after photobleaching. Taken together these data suggest that DMD hiPSC-CMs are less adaptable to changes in their extracellular environment, and highlight the utility of nanotopographic substrates for effectively stratifying normal and structural cardiac disease phenotypes in vitro.
    Full-text · Article · Sep 2015 · Cellular and Molecular Bioengineering
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    ABSTRACT: This book provides readers with an integrative overview of the latest research and developments in the broad field of biomedical engineering. Each of the chapters offers a timely review written by leading biomedical engineers and aims at showing how the convergence of scientific and engineering fields with medicine has created a new basis for practically solving problems concerning human health, wellbeing and disease. While some of the latest frontiers of biomedicine, such as neuroscience and regenerative medicine, are becoming increasingly dependent on new ideas and tools from other disciplines, the paradigm shift caused by technological innovations in the fields of information science, nanotechnology, and robotics is opening new opportunities in healthcare, besides dramatically changing the ways we actually practice science. At the same time, a new generation of engineers, fluent in many different scientific “languages,” is creating entirely new fields of research that approach the “old” questions from a new and holistic angle. The book reports on the scientific revolutions in the field of biomedicine by describing the latest technologies and findings developed at the interface between science and engineering. It addresses students, fellows, and faculty and industry investigators searching for new challenges in the broad biomedical engineering fields.
    Full-text · Chapter · Jul 2015
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    ABSTRACT: Articular cartilage is the load-bearing tissue found inside all articulating joints of the body. It vastly reduces friction and allows for smooth gliding between contacting surfaces. The structure of articular cartilage matrix and cellular composition is zonal and is important for its mechanical properties. When cartilage becomes injured through trauma or disease, it has poor intrinsic healing capabilities. The spectrum of cartilage injury ranges from isolated areas of the joint to diffuse breakdown and the clinical appearance of osteoarthritis. Current clinical treatment options remain limited in their ability to restore cartilage to its normal functional state. This review focuses on the evolution of biomaterial scaffolds that have been used for functional cartilage tissue engineering. In particular, we highlight recent developments in multi-scale biofabrication approaches attempting to recapitulate the complex 3D matrix of native articular cartilage tissue. Additionally, we focus on the application of these methods to engineering each zone of cartilage and engineering full thickness osteo-chondral tissues for improved clinical implantation. These methods have shown the potential to control individual cell-to-scaffold interactions and drive progenitor cell differentiation into a chondrocyte lineage. The use of these bioinspired nanoengineered scaffolds hold promise for recreation of structure and function on the whole tissue level and may represent exciting new developments for future clinical applications for cartilage injury and restoration.
    No preview · Article · Jul 2015 · Tissue Engineering Part B Reviews
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    Dan Dongeun Huh · Deok-Ho Kim

    Preview · Article · Apr 2015 · Journal of the Association for Laboratory Automation
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    Dataset: c4ib00209a

    Full-text · Dataset · Mar 2015
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    ABSTRACT: Direct intercellular transfer of cellular components is a recently described general mechanism of cell-cell communication. It is a more non-specific mode of intercellular communication that is not actively controlled by the participating cells. Though membrane bound proteins and small non-protein cytosolic components have been shown to be transferred between cells, the possibility of transfer of cytosolic proteins has not been clearly established, and its mechanism remains unexplained. Using a cell-cell pair of metastatic melanoma and endothelial cells, known to interact at various stages during cancer progression, we show that cytosolic proteins can indeed be transferred between heterotypic cells. Using precise relative cell patterning we provide evidence that this transfer depends on extent of the interface between heterotypic cell populations. This result is further supported by a mathematical model capturing various experimental conditions. We further demonstrate that cytosolic protein transfer can have important functional consequences for the tumor-stroma interactions, e.g., in heterotypic transfer of constitutively activated BRAF, a common melanoma associated mutation, leading to an enhanced activation of the downstream MAPK pathway. Our results suggest that cytosolic protein transfer can have important consequences for regulation of processes involving physical co-location of heterotypic cell types, particularly in invasive cancer growth.
    Full-text · Article · Feb 2015 · Integrative Biology
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    ABSTRACT: Endothelial physiology is regulated not only by humoral factors but also by mechanical factors such as fluid shear stress and the underlying cellular matrix microenvironment. The purpose of the present study was to examine the effects of matrix topographical cues on the endothelial secretion of cytokines/chemokines in vitro. Human endothelial cells were cultured on nanopatterned polymeric substrates with different ratios of ridge to groove widths (1:1, 1:2, and 1:5) and with different stiffnesses (6.7 MPa and 2.5 GPa) in the presence and absence of 1.0 ng/mL TNF-α. The levels of cytokines/chemokines secreted into the conditioned media were analyzed with a multiplexed bead-based sandwich immunoassay. Of the nano-patterns tested, the 1:1 and 1:2 type-patterns were found to induce the greatest degree of endothelial cell elongation and directional alignment. The 1:2 type nanopatterns lowered the secretion of inflammatory cytokines such as IL-1β, IL-3, IL-4 and MCP-1, compared to unpatterned substrates. Additionally, of the two polymers tested, it was found that the stiffer substrate resulted in significant decreases in the secretion of IL-3, IL-13, IL-4 and MCP-1. These results suggest that substrates with specific extracellular nanotopographical cues or stiffnesses may provide anti-atherogenic effects like those seen with laminar shear stresses by suppressing the endothelial secretion of cytokines and chemokines involved in vascular inflammation and remodeling.
    No preview · Article · Feb 2015 · ACS Applied Materials & Interfaces

  • No preview · Article · Jan 2015 · Biophysical Journal

  • No preview · Article · Jan 2015 · Biophysical Journal
  • [Show abstract] [Hide abstract]
    ABSTRACT: Direct intercellular transfer of cellular components is a recently described general mechanism of cell-cell communication. It is a more non-specific mode of intercellular communication that is not actively controlled by the participating cells. Though membrane bound proteins and small non-protein cytosolic components have been shown to be transferred between cells, the possibility of transfer of cytosolic proteins has not been clearly established, and its mechanism remains unexplained. Using a cell-cell pair of metastatic melanoma and endothelial cells, known to interact at various stages during cancer progression, we show that cytosolic proteins can indeed be transferred between heterotypic cells. Using precise relative cell patterning we provide evidence that this transfer depends on extent of the interface between heterotypic cell populations. This result is further supported by a mathematical model capturing various experimental conditions. We further demonstrate that cytosolic protein transfer can have important functional consequences for the tumor-stroma interactions, e.g., in heterotypic transfer of constitutively activated BRAF, a common melanoma associated mutation, leading to an enhanced activation of the downstream MAPK pathway. Our results suggest that cytosolic protein transfer can have important consequences for regulation of processes involving physical co-location of heterotypic cell types, particularly in invasive cancer growth.
    No preview · Article · Jan 2015 · Integrative Biology
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    ABSTRACT: Most current drug screening assays used to identify new drug candidates are 2D cell-based systems, even though such in vitro assays do not adequately re-create the in vivo complexity of 3D tissues. Inadequate representation of the human tissue environment during a preclinical test can result in inaccurate predictions of compound effects on overall tissue functionality. Screening for compound efficacy by focusing on a single pathway or protein target, coupled with difficulties in maintaining long-term 2D monolayers, can serve to exacerbate these issues when using such simplistic model systems for physiological drug screening applications. Numerous studies have shown that cell responses to drugs in 3D culture are improved from those in 2D, with respect to modeling in vivo tissue functionality, which highlights the advantages of using 3D-based models for preclinical drug screens. In this review, we discuss the development of microengineered 3D tissue models that accurately mimic the physiological properties of native tissue samples and highlight the advantages of using such 3D microtissue models over conventional cell-based assays for future drug screening applications. We also discuss biomimetic 3D environments, based on engineered tissues as potential preclinical models for the development of more predictive drug screening assays for specific disease models.
    Full-text · Article · Nov 2014 · Journal of the Association for Laboratory Automation
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    ABSTRACT: Background: Periostin is a secreted matricellular protein critical for epithelial-mesenchymal transition and carcinoma metastasis. In glioblastoma, it is highly upregulated compared with normal brain, and existing reports indicate potential prognostic and functional importance in glioma. However, the clinical implications of periostin expression and function related to its therapeutic potential have not been fully explored. Methods: Periostin expression levels and patterns were examined in human glioma cells and tissues by quantitative real-time PCR and immunohistochemistry and correlated with glioma grade, type, recurrence, and survival. Functional assays determined the impact of altering periostin expression and function on cell invasion, migration, adhesion, and glioma stem cell activity and tumorigenicity. The prognostic and functional relevance of periostin and its associated genes were analyzed using the TCGA and REMBRANDT databases and paired recurrent glioma samples. Results: Periostin expression levels correlated directly with tumor grade and recurrence, and inversely with survival, in all grades of adult human glioma. Stromal deposition of periostin was detected only in grade IV gliomas. Secreted periostin promoted glioma cell invasion and adhesion, and periostin knockdown markedly impaired survival of xenografted glioma stem cells. Interactions with αvβ3 and αvβ5 integrins promoted adhesion and migration, and periostin abrogated cytotoxicity of the αvβ3/β5 specific inhibitor cilengitide. Periostin-associated gene signatures, predominated by matrix and secreted proteins, corresponded to patient prognosis and functional motifs related to increased malignancy. Conclusion: Periostin is a robust marker of glioma malignancy and potential tumor recurrence. Abrogation of glioma stem cell tumorigenicity after periostin inhibition provides support for exploring the therapeutic impact of targeting periostin.
    No preview · Article · Aug 2014 · Neuro-Oncology
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    ABSTRACT: The aim of this study is to elucidate the relationship of laryngeal electromyography (LEMG) and computed tomographic (CT) parameters to improve the prognosis of recurrent laryngeal nerve injury. 22 patients clinically suspected of having recurrent laryngeal nerve injury were examined with LEMG and CT studies. Bilateral thyroarytenoid (TA) muscles were examined and findings were interpreted by a single blind technique. Laryngeal CT image analysis of the ventricle dilation symmetry determined TA muscle atrophy. Finally, a follow-up laryngoscopic examination determined improvement of vocal fold movement. Ventricle dilation symmetry and the dichotomized TA muscle atrophy parameter significantly relate to the improvement of vocal fold movement (χ2 = 4.029, P = 0.039, and χ2 = 3.912, P = 0.048, respectively). When the severity of vocal fold impairment was classified as severe TA muscle atrophy or none/discrete MUAP recruitment, it was found to significantly relate with the improvement of vocal fold movement (χ2 = 6.712, P =.010). From this study, image analysis of the ventricle dilation symmetry to determine the severity of TA muscle atrophy shows promise for the improved prognosis of vocal fold immobility.
    No preview · Article · Aug 2014 · Journal of Electromyography and Kinesiology
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    Kshitiz Kz · Junaid Afzal · Sang-Yeob Kim · Deok-Ho Kim
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    ABSTRACT: Most cells in the body secrete, or are in intimate contact with extracellular matrix (ECM), which provides structure to tissues and regulates various cellular phenotypes. Cells are well known to respond to biochemical signals from the ECM, but recent evidence has highlighted the mechanical properties of the matrix, including matrix elasticity and nanotopography, as fundamental instructive cues regulating signal transduction pathways and gene transcription. Recent observations also highlight the importance of matrix nanotopography as a regulator of cellular functions, but lack of facile experimental platforms has resulted in a continued negligence of this important microenvironmental cue in tissue culture experimentation. In this review, we present our opinion on the importance of nanotopography as a biological cue, contexts in which it plays a primary role influencing cell behavior, and detail advanced techniques to incorporate nanotopography into the design of experiments, or in cell culture environments. In addition, we highlight signal transduction pathways that are involved in conveying the extracellular matrix nanotopography information within the cells to influence cell behavior.
    Full-text · Article · Jul 2014 · Cell adhesion & migration
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    ABSTRACT: Cardiovascular disease remains the leading cause of death worldwide(1). Cardiac tissue engineering holds much promise to deliver groundbreaking medical discoveries with the aims of developing functional tissues for cardiac regeneration as well as in vitro screening assays. However, the ability to create high-fidelity models of heart tissue has proven difficult. The heart's extracellular matrix (ECM) is a complex structure consisting of both biochemical and biomechanical signals ranging from the micro- to the nanometer scale(2). Local mechanical loading conditions and cell-ECM interactions have recently been recognized as vital components in cardiac tissue engineering(3-5). A large portion of the cardiac ECM is composed of aligned collagen fibers with nano-scale diameters that significantly influences tissue architecture and electromechanical coupling(2). Unfortunately, few methods have been able to mimic the organization of ECM fibers down to the nanometer scale. Recent advancements in nanofabrication techniques, however, have enabled the design and fabrication of scalable scaffolds that mimic the in vivo structural and substrate stiffness cues of the ECM in the heart(6-9). Here we present the development of two reproducible, cost-effective, and scalable nanopatterning processes for the functional alignment of cardiac cells using the biocompatible polymer poly(lactide-co-glycolide) (PLGA)(8) and a polyurethane (PU) based polymer. These anisotropically nanofabricated substrata (ANFS) mimic the underlying ECM of well-organized, aligned tissues and can be used to investigate the role of nanotopography on cell morphology and function(10-14). Using a nanopatterned (NP) silicon master as a template, a polyurethane acrylate (PUA) mold is fabricated. This PUA mold is then used to pattern the PU or PLGA hydrogel via UV-assisted or solvent-mediated capillary force lithography (CFL), respectively(15,16). Briefly, PU or PLGA pre-polymer is drop dispensed onto a glass coverslip and the PUA mold is placed on top. For UV-assisted CFL, the PU is then exposed to UV radiation (λ = 250-400 nm) for curing. For solvent-mediated CFL, the PLGA is embossed using heat (120 °C) and pressure (100 kPa). After curing, the PUA mold is peeled off, leaving behind an ANFS for cell culture. Primary cells, such as neonatal rat ventricular myocytes, as well as human pluripotent stem cell-derived cardiomyocytes, can be maintained on the ANFS(2).
    No preview · Article · Jun 2014 · Journal of Visualized Experiments

Publication Stats

2k Citations
388.63 Total Impact Points

Institutions

  • 2011-2016
    • University of Washington Seattle
      • • Institute for Stem Cell and Regenerative Medicine
      • • Department of Bioengineering
      Seattle, Washington, United States
  • 2005-2012
    • Johns Hopkins University
      • Department of Biomedical Engineering
      Baltimore, Maryland, United States
    • Chonnam National University
      Gwangju, Gwangju, South Korea
    • Eawag: Das Wasserforschungs-Institut des ETH-Bereichs
      Duebendorf, Zurich, Switzerland
  • 2001-2006
    • Korea Institute of Science and Technology
      • Sensor System Research Center
      Sŏul, Seoul, South Korea
    • Korea University
      • Department of Electrical Engineering
      Seoul, Seoul, South Korea