Hojae Bae

Konkuk University, Sŏul, Seoul, South Korea

Are you Hojae Bae?

Claim your profile

Publications (64)365.21 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Conventional approaches for toxicity evaluation of drugs and chemicals, such as animal tests, can be impractical due to the large experimental scale and the immunological differences between species. Organ-on-a-chip models have recently been recognized as a prominent alternative to conventional toxicity tests aiming to simulate the human in vivo physiology. This review focuses on the organ-on-a-chip applications for high-throughput screening of candidate drugs against toxicity, with a particular emphasis on bone-marrow-on-a-chip. Studies in which organ-on-a-chip models have been developed and utilized to maximize the efficiency and predictability in toxicity assessment are introduced. The potential of these devices to replace tests of acute systemic toxicity in animals, and the challenges that are inherent in simulating the human immune system are also discussed. As a promising approach to overcome the limitations, we further focus on an in-depth analysis of the development of bone-marrow-on-a-chip that is capable of simulating human immune responses against external stimuli due to the key roles of marrow in immune systems with hematopoietic activities. Owing to the complex interactions between hematopoietic stem cells and marrow microenvironments, precise control of both biochemical and physical niches that are critical in maintenance of hematopoiesis remains a key challenge. Thus, recently developed bone-marrow-on-a-chip models support immunogenicity and immunotoxicity testing in long-term cultivation with repeated antigen stimulation. In this review, we provide an overview of clinical studies that have been carried out on bone marrow transplants in patients with immune-related diseases and future aspects of clinical and pharmaceutical application of bone-marrow-on-a-chip.
    Drug Safety 03/2015; 38(5). DOI:10.1007/s40264-015-0284-x · 2.62 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Embryoid bodies have a number of similarities with cells in gastrulation, which provides useful biological information about embryonic stem cell differentiation. Extensive research has been done to study the control of embryoid body-mediated embryonic stem cell differentiation in various research fields. Recently, microengineering technology has been used to control the size of embryoid bodies and to direct lineage specific differentiation of embryonic stem cells. However, the underlying biology of developmental events in the embryoid bodies of different sizes has not been well elucidated. In this study, embryoid bodies with different sizes were generated within microfabricated PEG microwell arrays, and a series of gene and molecular expressions related to early developmental events was investigated to further elucidate the size-mediated differentiation. The gene and molecular expression profile suggested preferential visceral endoderm formation in 450 μm embryoid bodies and preferential lateral plate mesoderm formation in 150 μm embryoid bodies. These aggregates resulted in higher cardiac differentiation in 450 μm embryoid bodies and higher endothelial differentiation in 150 μm embryoid bodies, respectively. Our findings may provide further insight for understanding embryoid body size-mediated developmental progress.
    Macromolecular Research 03/2015; 23(3). DOI:10.1007/s13233-015-3034-0 · 1.68 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: For the treatment of periodontitis, local delivery of antibiotics and their sustained release are preferable to enhance microbial susceptibility and to reduce possible side effects occurrence in systemic drug delivery. To address these issues, antibiotic loaded polymeric matrices implantable into periodontal pocket have been commercially used in dentistry and oral medicine. Recently, keratin has been drawing attention as a natural polymer for its ability to mediate cell behavior with minor or no immunogenicity enabling further process towards autologous implantation. In this study, human hair keratin was extracted with a cocktail of reducing agents, and antibiotic eluting keratin-based biofilms were fabricated. Physicochemical analysis and release test showed proper physical stability and sustained release of the loaded antibiotics. In addition, the released antibiotic suppressed the growth of various types of oral bacteria including porphyromonas gingivalis. Cellular interaction studies showed that human oral epithelial cell, human gingival fibroblast and periodontal ligament cells proliferated and guided well on biofilms. This study propose that antibiotic eluting keratin-based biofilms are provisional device for the treatment of chronic periodontitis offering advantages such as local controlled drug delivery and biocompatibility, and human hair keratin is able to be a good biomaterial for the potent applications to tissue engineering and regenerative medicine.
    Macromolecular Research 03/2015; 23(3). DOI:10.1007/s13233-015-3036-y · 1.68 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Engineering living tissues that simulate their natural counterparts is a dynamic area of research. Among the various models of biological tissues being developed, fiber-shaped cellular architectures, which can be used as artificial blood vessels or muscle fibers, have drawn particular attention. However, the fabrication of continuous microfiber substrates for culturing cells is still limited to a restricted number of polymers (e.g., alginate) having easy processability but poor cell–material interaction properties. Moreover, the typical smooth surface of a synthetic fiber does not replicate the micro- and nanofeatures observed in vivo, which guide and regulate cell behavior. In this study, a method to fabricate photocrosslinkable cell-responsive methacrylamide-modified gelatin (GelMA) fibers with exquisite microstructured surfaces by using a microfluidic device is developed. These hydrogel fibers with microgrooved surfaces efficiently promote cell encapsulation and adhesion. GelMA fibers significantly promote the viability of cells encapsulated in/or grown on the fibers compared with similar grooved alginate fibers used as controls. Importantly, the grooves engraved on the GelMA fibers induce cell alignment. Furthermore, the GelMA fibers exhibit excellent processability and could be wound into various shapes. These microstructured GelMA fibers have great potential as templates for the creation of fiber-shaped tissues or tissue microstructures.
    Advanced Functional Materials 02/2015; 25(15). DOI:10.1002/adfm.201404531 · 10.44 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Engineered muscle tissues demonstrate properties far from native muscle tissue. Therefore, fabrication of muscle tissues with enhanced functionalities is required to enable their use in various applications. To improve the formation of mature muscle tissues with higher functionalities, we co-cultured C2C12 myoblasts and PC12 neural cells. While alignment of the myoblasts was obtained by culturing the cells in micropatterned methacrylated gelatin (GelMA) hydrogels, we studied the effects of the neural cells (PC12) on the formation and maturation of muscle tissues. Myoblasts cultured in the presence of neural cells showed improved differentiation, with enhanced myotube formation. Myotube alignment, length and coverage area were increased. In addition, the mRNA expression of muscle differentiation markers (Myf-5, myogenin, Mefc2, MLP), muscle maturation markers (MHC-IId/x, MHC-IIa, MHC-IIb, MHC-pn, α-actinin, sarcomeric actinin) and the neuromuscular markers (AChE, AChR-ε) were also upregulated. All these observations were amplified after further muscle tissue maturation under electrical stimulation. Our data suggest a synergistic effect on the C2C12 differentiation induced by PC12 cells, which could be useful for creating improved muscle tissue. Copyright © 2014 John Wiley & Sons, Ltd.
    Journal of Tissue Engineering and Regenerative Medicine 11/2014; DOI:10.1002/term.1956 · 4.43 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Precise control of media delivery to cells in microfluidic systems in a simple and efficient manner is a challenge for a number of cell-based applications. Conventional syringe pumps can deliver culture media into microfluidic devices at precisely controlled flow rates, but they are large and require a power source. On the other hand, passive microflow-generating systems cannot maintain continuous, controllable and long-term delivery of media. We have developed an on-chip microflow control technology that combines flow rate control and passive, long-term delivery of media to microwell tissue culture chambers. Here, passive flow is initiated using siphon effects and a yarn flow resistor is used to regulate the flow rate in the microchannel. Using the yarn flow resistor, the media flow rate into the microfluidic cell culture system is adjustable to a few hundred microliters per hour. To evaluate the effects of controlled flow on microfluidic cell culture properties (feasibility test), we measured the cell alignment and cytoskeletal arrangement of endothelial cells cultured in a microwell array inside the microfluidic channel.
    Lab on a Chip 08/2014; 14(21). DOI:10.1039/C4LC00510D · 5.75 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Engineering functional muscle tissue requires the formation of densely packed, aligned, and mature myotubes. To enhance the formation of aligned myotubes with improved contractibility, we fabricated aligned electrospun gelatin multi-walled carbon nanotubes (MWNTs) hybrid fibers that were used as scaffolds for the growth of myoblasts (C2C12). The MWNTs significantly enhanced myotube formation by improving the mechanical properties of the resulting fibers and upregulated the activation of mechanotransduction related genes. In addition, the fibers enhanced the maturation of the myotubes and the amplitude of the myotube contractions under electrical stimulation (ES). Such hybrid material scaffolds may be useful to direct skeletal muscle cellular organization, improve cellular functionality and tissue formation.
    Biomaterials 05/2014; 35(24). DOI:10.1016/j.biomaterials.2014.04.021 · 8.31 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Biological scaffolds with tunable electrical and mechanical properties are of great interest in many different fields, such as regenerative medicine, biorobotics, and biosensing. In this study, dielectrophoresis (DEP) was used to vertically align carbon nanotubes (CNTs) within methacrylated gelatin (GelMA) hydrogels in a robust, simple, and rapid manner. GelMA-aligned CNT hydrogels showed anisotropic electrical conductivity and superior mechanical properties compared with pristine GelMA hydrogels and GelMA hydrogels containing randomly distributed CNTs. Skeletal muscle cells grown on vertically aligned CNTs in GelMA hydrogels yielded a higher number of functional myofibers than cells that were cultured on hydrogels with randomly distributed CNTs and horizontally aligned CNTs, as confirmed by the expression of myogenic genes and proteins. In addition, the myogenic gene and protein expression increased more profoundly after applying electrical stimulation along the direction of the aligned CNTs due to the anisotropic conductivity of the hybrid GelMA-vertically aligned CNT hydrogels. We believe that platform could attract great attention in other biomedical applications, such as biosensing, bioelectronics, and creating functional biomedical devices.
    Scientific Reports 03/2014; 4:4271. DOI:10.1038/srep04271 · 5.08 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Like a carpet for cells, micropatterned polymeric nanosheets are developed toward local cell delivery. The nanosheets directed morphogenesis of retinal pigment epithelial (RPE) cells and allowed for the injection of an engineered RPE monolayer through syringe needles without loss of cell viability. Such an ultrathin carrier has the promise of a minimally invasive delivery of cells into narrow tissue spaces.
    Advanced Materials 03/2014; 26(11). DOI:10.1002/adma.201304183 · 15.41 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Micro- and nanotechnologies have emerged as potentially effective fabrication tools for addressing the challenges faced in tissue engineering and drug delivery. The ability to control and manipulate polymeric biomaterials at the micron and nanometre scale with these fabrication techniques has allowed for the creation of controlled cellular environments, engineering of functional tissues and development of better drug delivery systems. In tissue engineering, micro- and nanotechnologies have enabled the recapitulation of the micro- and nanoscale detail of the cell's environment through controlling the surface chemistry and topography of materials, generating 3D cellular scaffolds and regulating cell-cell interactions. Furthermore, these technologies have led to advances in high-throughput screening (HTS), enabling rapid and efficient discovery of a library of materials and screening of drugs that induce cell-specific responses. In drug delivery, controlling the size and geometry of drug carriers with micro- and nanotechnologies have allowed for the modulation of parametres such as bioavailability, pharmacodynamics and cell-specific targeting. In this review, we introduce recent developments in micro- and nanoscale engineering of polymeric biomaterials, with an emphasis on lithographic techniques, and present an overview of their applications in tissue engineering, HTS and drug delivery. Copyright © 2012 John Wiley & Sons, Ltd.
    Journal of Tissue Engineering and Regenerative Medicine 01/2014; 8(1):1-14. DOI:10.1002/term.1494 · 4.43 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Tissue engineering (TE) is a multidisciplinary research area that combines medicine, biology, and material science. In recent decades, microtechnology and nanotechnology have also been gradually integrated into this field and have become essential components of TE research. Tissues and complex organs in the body depend on a branched blood vessel system. One of the main objectives for TE researchers is to replicate this vessel system and obtain functional vascularized structures within engineered tissues or organs. With the help of new nanotechnology and microtechnology, significant progress has been made. Achievements include the design of nanoscale-level scaffolds with new functionalities, development of integrated and rapid nanotechnology methods for biofabrication of vascular tissues, discovery of new composite materials to direct differentiation of stem and inducible pluripotent stem cells into the vascular phenotype. Although numerous challenges to replicating vascularized tissue for clinical uses remain, the combination of these new advances has yielded new tools for producing functional vascular tissues in the near future.
    Journal of Nanoscience and Nanotechnology 01/2014; 14(1):487-500. DOI:10.1166/jnn.2014.9051 · 1.34 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Skeletal muscle tissue engineering (SMTE) aims to repair or regenerate defective skeletal muscle tissue lost by traumatic injury, tumor ablation or muscular disease. However, two decades after the introduction of SMTE, the engineering of functional skeletal muscle in the laboratory still remains a great challenge, and numerous techniques for growing functional muscle tissues are constantly being developed. This article reviews the recent findings regarding the methodology and various technical aspects of SMTE including cell alignment and differentiation. We address the structure and organization of muscle and describe the methods for myoblasts alignment cultured in vitro. To better understand muscle formation and to enhance the engineering of skeletal muscle, we also address the molecular basics of myogenesis and describe different methods to induce myoblast differentiation into myotubes. We then provide an overview of different co-culture systems involving skeletal muscle cells, and highlight major applications of engineered skeletal muscle tissues. Finally, potential challenges and future research directions for SMTE are discussed.
    Tissue Engineering Part B Reviews 12/2013; DOI:10.1089/ten.TEB.2013.0534 · 4.64 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Since the 17th century Spica Prunella has been used as a medicinal herb. Dried and pulverized Spica Prunella samples were extracted and used in these experiments. In this study, the effects of Spica Prunella extract (SPE) on RANKL (receptor activator of nuclear factor κB ligand)-induced osteoclastogenesis were examined. Actin ring formation, a typical marker of osteoclastogenesis, was inhibited by SPE without any toxicity. There was also a marked inhibition in the formation of tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cells in bone marrow-derived monocytes (BMMs). SPE also suppressed phosphorylation of c-Jun N-terminal kinase (JNK) and extracellular signal-regulated kinases (ERK) both of which are signals of the mitogen-activated protein kinases (MAPKs) signaling pathway. Additionally, SPE inhibited IκBα (nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha) signaling pathway, which is an important factor in osteoclastogenesis. These results indicate that SPE might suppress osteoclast differentiation by inhibiting the phosphorylation of JNK and ERK in MAPK and NF-κB signaling pathways which act as messengers in the RANKL-induced osteoclast differentiation pathway. This means that SPE could potentially have great therapeutic usage in treating bone erosive diseases such as rheumatoid arthritis or in preventing metastasis associated with bone loss.
    Food science and biotechnology 12/2013; 22(6). DOI:10.1007/s10068-013-0268-5 · 0.66 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Calcium phosphate-reinforced photosensitizer-loaded polymer nanoparticles have been developed for photodynamic therapy. Chlorin e6 (Ce6)-loaded core-shell-corona polymer micelles of poly(ethylene glycol)-b-poly(L-aspartic acid)-b-poly(L-phenylalanine) (PEG-PAsp-PPhe) were employed as template nanoparticles for mineralization with calcium phosphate (CaP). CaP deposition was performed by the electrostatic localization of calcium ions at the anionic PAsp middle shells and the subsequent addition of phosphate anions. CaP-reinforced nanoparticles exhibited enhanced stability. The CaP mineral layer effectively inhibited Ce6 release from the Ce6-loaded mineralized nanoparticles (Ce6-NP-CaP) at physiological pH value. At an acidic endosomal pH value of 5.0, Ce6 release was enhanced, owing to rapid dissolution of the CaP minerals. Upon irradiation of Ce6-NP-CaP-treated MCF-7 breast-tumor cells, the cell viability dramatically decreased with increasing irradiation time. The phototoxicity of Ce6-NP-CaP was much higher than that of free Ce6. Non-invasive optical-imaging results indicated that Ce6-NP-CaP exhibited enhanced tumor specificity compared with free Ce6 and Ce6-loaded non-mineralized polymer nanoparticles (Ce6-NP).
    Chemistry - An Asian Journal 12/2013; 8(12). DOI:10.1002/asia.201300840 · 3.94 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: In this study we describe the generation and influences on in vitro and in vivo osteogenesis of photo-cured hyaluronic acid (HA) hydrogels loaded with growth and differentiation factor 5 (GDF-5). Prior to loading GDF-5, we characterized the release profiles from these hydrogels and tested their respective cell viability, differentiation and in vivo bone regeneration. The results from this testing indicated that GDF-5 was observed to release in a sustained manner from the HA hydrogels I-III. MTT and live/dead assays showed that the HA hydrogels I-III have good biocompatibility for use as scaffolds for bone tissue regeneration. In vitro cell tests showed a higher level of MC3T3-E1 cell proliferation and differentiation on HA hydrogels I-III than on HA hydrogel 0. Moreover, in vivo animal tests showed that the HA hydrogels I and III had a significant improvement on osteogenesis. Overall, our results suggest that the HA-based hydrogel is a good biomaterial to deliver osteogenic differentiation factors such as GDF-5, and GDF-5 can be useful as an effective alternative to aid new bone formation.
    Bone 11/2013; 59. DOI:10.1016/j.bone.2013.11.019 · 4.46 Impact Factor
  • Source
    Lab on a Chip 10/2013; 13(24). DOI:10.1039/c3lc90103c · 5.75 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: In this paper we report on the development of dynamically controlled three-dimensional (3D) micropatterned cellular co-cultures within photocurable and chemically degradable hydrogels. Specifically, we generated dynamic co-cultures of micropatterned murine embryonic stem (mES) cells with human hepatocellular carcinoma (HepG2) cells within 3D hydrogels. HepG2 cells were used due to their ability to direct the differentiation of mES cells through secreted paracrine factors. To generate dynamic co-cultures, mES cells were first encapsulated within micropatterned photocurable poly(ethylene glycol) (PEG) hydrogels. These micropatterned cell-laden PEG hydrogels were subsequently surrounded by calcium alginate (Ca-Alg) hydrogels containing HepG2 cells. After 4 days, the co-culture step was halted by exposing the system to sodium citrate solution, which removed the alginate gels and the encapsulated HepG2 cells. The encapsulated mES cells were then maintained in the resulting cultures for 16 days and cardiac differentiation was analysed. We observed that the mES cells that were exposed to HepG2 cells in the co-cultures generated cells with higher expression of cardiac genes and proteins, as well as increased spontaneous beating. Due to its ability to control the 3D microenvironment of cells in a spatially and temporally regulated manner, the method presented in this study is useful for a range of cell-culture applications related to tissue engineering and regenerative medicine. Copyright © 2013 John Wiley & Sons, Ltd.
    Journal of Tissue Engineering and Regenerative Medicine 10/2013; DOI:10.1002/term.1843 · 4.43 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Using DNA as programmable, sequence-specific 'glues', shape-controlled hydrogel units are self-assembled into prescribed structures. Here we report that aggregates are produced using hydrogel cubes with edge lengths ranging from 30 μm to 1 mm, demonstrating assembly across scales. In a simple one-pot agitation reaction, 25 dimers are constructed in parallel from 50 distinct hydrogel cube species, demonstrating highly multiplexed assembly. Using hydrogel cuboids displaying face-specific DNA glues, diverse structures are achieved in aqueous and in interfacial agitation systems. These include dimers, extended chains and open network structures in an aqueous system, and dimers, chains of fixed length, T-junctions and square shapes in the interfacial system, demonstrating the versatility of the assembly system.
    Nature Communications 09/2013; 4:2275. DOI:10.1038/ncomms3275 · 10.74 Impact Factor
  • Hanna Lee, Hojae Bae
    [Show abstract] [Hide abstract]
    ABSTRACT: Over the years much has been attempted to generate engineered cardiac tissue. One approach is culturing cells within engineered biodegradable scaffolds to provide temporary elastic support and to replace the necrotic cardiomyocytes. In particular, these engineered tissue construct have been of great interest as an implantable patch over a region of the myocardial infarct to stimulate the formation of micro-vessel growth and thus increase blood flow through the myocardium. For the successful revascularization after myocardial infarction, vascularization within three-dimensional engineered cardiac tissue construct has become important for stimulating the formation of a mature microvascular network. In this review, various approaches and recent advances in vascularization of engineered cardiac patch are highlighted and discussed.
    09/2013; 3(3):138-143. DOI:10.1007/s13534-013-0106-y
  • [Show abstract] [Hide abstract]
    ABSTRACT: A graphical abstract is available for this content
    Lab on a Chip 07/2013; 13(13). DOI:10.1039/c3lc90073h · 5.75 Impact Factor

Publication Stats

1k Citations
365.21 Total Impact Points

Institutions

  • 2013–2015
    • Konkuk University
      • Department of Bio-Industrial Technologies
      Sŏul, Seoul, South Korea
    • Tohoku University
      • Graduate School of Environmental Studies
      Japan
    • Kyung Hee University
      • Department of Dentistry
      Sŏul, Seoul, South Korea
  • 2014
    • Brigham and Women's Hospital
      • Department of Medicine
      Boston, Massachusetts, United States
  • 2010–2013
    • Harvard University
      Cambridge, Massachusetts, United States
  • 2009–2013
    • Harvard Medical School
      • Department of Medicine
      Boston, Massachusetts, United States
  • 2010–2012
    • Massachusetts Institute of Technology
      • Division of Health Sciences and Technology
      Cambridge, Massachusetts, United States