Stanford Advisors

All Publications

  • Secured delivery of basic fibroblast growth factor using human serum albumin-based protein nanoparticles for enhanced wound healing and regeneration. Journal of nanobiotechnology Son, B., Kim, M., Won, H., Jung, A., Kim, J., Koo, Y., Lee, N. K., Baek, S. H., Han, U., Park, C. G., Shin, H., Gweon, B., Joo, J., Park, H. H. 2023; 21 (1): 310


    Basic fibroblast growth factor (bFGF) is one of the critical components accelerating angiogenesis and tissue regeneration by promoting the migration of dermal fibroblasts and endothelial cells associated with matrix formation and remodeling in wound healing process. However, clinical applications of bFGF are substantially limited by its unstable nature due to rapid decomposition under physiological microenvironment.In this study, we present the bFGF-loaded human serum albumin nanoparticles (HSA-bFGF NPs) as a means of enhanced stability and sustained release platform during tissue regeneration. Spherical shape of the HSA-bFGF NPs with uniform size distribution (polydispersity index < 0.2) is obtained via a simple desolvation and crosslinking process. The HSA-bFGF NPs securely load and release the intact soluble bFGF proteins, thereby significantly enhancing the proliferation and migration activity of human dermal fibroblasts. Myofibroblast-related genes and proteins were also significantly down-regulated, indicating decrease in risk of scar formation. Furthermore, wound healing is accelerated while achieving a highly organized extracellular matrix and enhanced angiogenesis in vivo.Consequently, the HSA-bFGF NPs are suggested not only as a delivery vehicle but also as a protein stabilizer for effective wound healing and tissue regeneration.

    View details for DOI 10.1186/s12951-023-02053-4

    View details for PubMedID 37658367

    View details for PubMedCentralID 7463929

  • A small-data-driven model for predicting adsorption properties in polymeric thin films CHEMICAL COMMUNICATIONS Han, U., Kang, T., Im, J., Hong, J. 2022


    Artificial intelligence allowing data-driven prediction of physicochemical properties of polymers is rapidly emerging as a powerful tool for advancing material science. Here, we developed a methodology to use polymer adsorption data as predictable data by analyzing causal relationships between polymer properties and experimental results instead of using big polymer data.

    View details for DOI 10.1039/d2cc03567g

    View details for Web of Science ID 000851563300001

    View details for PubMedID 36082781

  • Potential threats of nanoplastic accumulation in human induced pluripotent stem cells CHEMICAL ENGINEERING JOURNAL Jeong, H., Kim, W., Choi, D., Heo, J., Han, U., Jung, S., Park, H., Hong, S., Park, J., Hong, J. 2022; 427
  • Nano-structure of vitronectin/heparin on cell membrane for stimulating single cell in iPSC-derived embryoid body ISCIENCE Han, U., Kim, W., Cha, H., Park, J., Hong, J. 2021; 24 (4): 102297


    Individual cell environment stimulating single cell is a suitable strategy for the generation of sophisticated multicellular aggregates with localized biochemical signaling. However, such strategy for induced pluripotent stem cell (iPSC)-derived embryoid bodies (EBs) is limited because the presence of external stimulation can inhibit spontaneous cellular communication, resulting in misdirection in the maturation and differentiation of EBs. In this study, a facile method of engineering the iPSC membrane to stimulate the inner cell of EBs while maintaining cellular activities is reported. We coated the iPSC surface with nanoscale extracellular matrix fabricated by self-assembly between vitronectin and heparin. This nano-coating allowed iPSC to retain its in vitro properties including adhesion capability, proliferation, and pluripotency during its aggregation. More importantly, the nano-coating did not induce lineage-specific differentiation but increased E-cadherin expression, resulting in promotion of development of EB. This study provides a foundation for future production of sophisticated patient-specific multicellular aggregates by modification of living cell membranes.

    View details for DOI 10.1016/j.isci.2021.102297

    View details for Web of Science ID 000642261700048

    View details for PubMedID 33851104

    View details for PubMedCentralID PMC8022842

  • 2D graphene oxide particles induce unwanted loss in pluripotency and trigger early differentiation in human pluripotent stem cells JOURNAL OF HAZARDOUS MATERIALS Heo, J., Choi, J., Kim, J., Jeong, H., Choi, D., Han, U., Park, J., Park, H., Hong, J. 2021; 414: 125472


    The potential health hazards of particulates, such as micro/nano-sized plastics and carbon materials have recently received extensive attention. However, their toxicological properties in association with stem cell differentiation is still relatively unexplored. In this study, we elucidated the cytotoxic effects of 2D graphene oxide (GO), in relation to differentiation of human induced pluripotent stem cells (hiPSCs). Supplementation of GO to hiPSCs demonstrated uptake of GO through the plasma membrane and intracellular accumulation was observed. Increasing the concentration of GO led to reduced viability and increased likelihood of hiPSC colony detachment. Moreover, treatment of GO resulted in significant loss in pluripotency markers, OCT-4 and NANOG. In particular, when hiPSCs were cultured with GO in cardiomyocyte induction medium, upregulation of cardiomyocyte marker, NKX2.5, along with observation of early triggering of differentiation were observed. Taken together, our results highlight the risk in the uptake and accumulation of GO on the stem cell development by unwanted loss in pluripotency and accelerated initiation of differentiation.

    View details for DOI 10.1016/j.jhazmat.2021.125472

    View details for Web of Science ID 000653031100004

    View details for PubMedID 33640729

  • Enhanced salt removal performance of flow electrode capacitive deionization with high cell operational potential SEPARATION AND PURIFICATION TECHNOLOGY Ha, Y., Lee, H., Yoon, H., Shin, D., Ahn, W., Cho, N., Han, U., Hong, J., Nguyen Anh Thu Tran, Yoo, C., Kang, H., Cho, Y. 2021; 254
  • Controlling physicochemical properties of graphene oxide for efficient cellular delivery JOURNAL OF INDUSTRIAL AND ENGINEERING CHEMISTRY Heo, J., Tanum, J., Park, S., Choi, D., Jeong, H., Han, U., Hong, J. 2020; 88: 312-318
  • Transmission and regulation of biochemical stimulus via a nanoshell directly adsorbed on the cell membrane to enhance chondrogenic differentiation of mesenchymal stem cell BIOTECHNOLOGY AND BIOENGINEERING Han, U., Hwang, J., Lee, J., Kim, H., Jung, H., Hong, J., Hong, J. 2020; 117 (1): 184-193


    A nanoscale artificial extracellular matrix (nanoshell) formed by layer-by-layer adsorption can enhance and modulate the function of stem cells by transferring biochemical stimulus to the cell directly. Here, the nanoshell composed of fibronectin (FN) and chondroitin sulfate (CS) is demonstrated to promote chondrogenic differentiation of mesenchymal stem cells (MSCs). The multilayer structure of nanoshell is formed by repeating self-assembly of FN and CS, and its thickness can be controlled through the number of layers. The expression of chondrogenic markers in MSCs coated with the FN/CS nanoshell was increased as the number of bilayers in the nanoshell increased until four, but when it exceeds five bilayers, the effect began to decrease. Finally, the MSCs coated with optimized four bilayers of FN/CS nanoshell have high chondrogenic differentiation efficiency and showed the potential to increase formation of cartilage tissue when it is transplanted into mouse kidney. So, the precise regulation of stem cell fate at single cell level can be possible through the cellular surface modification by self-assembled polymeric film.

    View details for DOI 10.1002/bit.27183

    View details for Web of Science ID 000540525200016

    View details for PubMedID 31560128

  • Construction of nano-scale cellular environments by coating a multilayer nanofilm on the surface of human induced pluripotent stem cells NANOSCALE Han, U., Kim, Y., Kim, W., Park, J., Hong, J. 2019; 11 (28): 13541-13551


    Interactions with peripheral environments, such as extracellular matrix (ECM) and other cells, and their balance play a crucial role in the maintenance of pluripotency and self-renewal of human pluripotent stem cells. In this study, we focused on a nano-sized artificial cellular environment that is directly attached to the cytoplasmic membrane as a facile method that can effect intercellular interactions at the single-cell level. We designed multilayered nanofilms that are self-assembled on the surface of human induced pluripotent stem cells (iPSCs), by repetitive adsorption of fibronectin and heparin or chondroitin sulfate. However, the surface modification process could also lead to the loss of cell-cell adhesion, which may result in apoptotic cell death. We investigated the proliferation and pluripotency of the iPSCs coated with the nanofilm in order to establish the suitable nanofilm structure and coating conditions. As a result, the cell viability reduced with the increase in the duration of the coating process, but the undifferentiated state and proliferation of the cells were maintained until 2 bilayers were coated. To suppress the dissociation-induced apoptosis, Y-27632, the Rho-associated kinase inhibitor (ROCKi), was added to the coating solution; this allowed the coating of up to 4 bilayers of the nanofilm onto the iPSCs. These results are expected to accelerate the pace of iPSC studies on 3-dimensional cultures and naïve pluripotency, in which the regulation of cellular interactions plays a critical role.

    View details for DOI 10.1039/c9nr02375e

    View details for Web of Science ID 000476564300033

    View details for PubMedID 31290516

  • Artificial cellular nano-environment composed of collagen-based nanofilm promotes osteogenic differentiation of mesenchymal stem cells ACTA BIOMATERIALIA Hwang, J., Han, U., Yang, M., Choi, Y., Choi, J., Lee, J., Jung, H., Hong, J., Hong, J. 2019; 86: 247-256


    In regenerative medicine, the generation of therapeutic stem cells and tissue engineering are important for replacing damaged tissues. Numerous studies have attempted to produce cellular components that mimic the native tissue for gaining optimal function. Particularly, the extracellular matrix (ECM) composition plays an important role in cellular functions including determining the fates of mesenchymal stem cells (MSCs). Here, we evaluated the osteogenic effects of a nanofilm in which oppositely charged polyelectrolytes were alternately adsorbed onto the cell surface to create an artificial ECM environment for single MSCs. Interestingly, nanofilm composed of collagen (Col) and alginate (AA) showed relatively high stiffness and MSCs coated with the Col/AA nanofilm showed increased osteogenic differentiation efficiency compared to other nanofilm-coated MSCs. Further analysis revealed that the Col/AA nanofilm coating stimulated osteogenesis by activating transcriptional coactivators with the PDZ binding motif through extracellular signal-related kinase and p38 MAPK signaling. This nano-sized cellular coating will facilitate the development of nanotechnology for controlling cellular functions and advance stem cell-based clinical applications for regenerative medicine. STATE OF SIGNIFICANCE: In this study, we developed an artificial cellular nano-environment formed by multilayer nanofilms. We demonstrated that the nanofilms introduced to mesenchymal stem cells (MSCs) stimulate osteogenic differentiation by regulating intracellular signaling. Among the various nanofilm combinations, the induction of osteogenic gene transcription in collagen (Col) and alginate (AA) film-coated MSCs was the most pronounced compared to that on other nanofilms. A minimum number of Col/AA nanofilm bilayers (n = 2) was required for effective induction of MSC osteogenic differentiation. In addition, we observed the correlation between the promoting effect of osteogenic differentiation and stiffness of the nanofilm. Our results may be useful for developing a cell coating model system widely applicable in bioengineering and regenerative medicine.

    View details for DOI 10.1016/j.actbio.2018.12.044

    View details for Web of Science ID 000459842600019

    View details for PubMedID 30594632

  • Structure of a Multilayer Nanofilm To Increase the Encapsulation Efficiency of Basic Fibroblast Growth Factor MOLECULAR PHARMACEUTICS Han, U., Hong, J. 2018; 15 (3): 1277-1283


    In this study, we established the structure of a multilayer nanofilm that more efficiently encapsulates basic fibroblast growth factor (bFGF). First, a positively charged layer material was selected from biocompatible polymers such as collagen (Col), poly(beta-amino ester) (Poly2), and chitosan (Chi), while considering the film thickness. We then investigated the change in bFGF encapsulation efficiency when the multilayer structure was changed from a tetralayer to a trilayer. As a result, we obtained a highly improved bFGF encapsulation efficiency in the nanofilm using a positively charged layer formed by a blend of Col and Poly2 and a negatively charged poly(acrylic acid) (PAA) layer within a trilayered structure. In particular, we found that a significant amount of adsorbed bFGF was desorbed again during the film fabrication process of a tetralayered nanofilm. In the conventional nanofilm, bFGF was regarded as a polycation and formed a multilayer nanofilm that was composed of a tetralayered structure and was represented as (polycation/polyanion/bFGF/polyanion) n where n = number of repeated tetralayers. Here, we suggested that bFGF should not be considered a polycation, rather it should be considered as a small quantity of molecule that exists between the polyanion and polycation layers. In this case, the nanofilm is composed of repeating units of (polycation/polyanion/bFGF/polycation/polyanion), because the amount of adsorbed bFGF is considerably lower than that of other building blocks.

    View details for DOI 10.1021/acs.molpharmaceut.7b01099

    View details for Web of Science ID 000427093600056

    View details for PubMedID 29364691

  • Preparation of multifunctional micelles from two different amphiphilic block copolymers COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS Tanum, J., Han, U., Shin, J., Hong, J. 2018; 537: 566-571
  • Layer-by-layer assembled polymeric thin films as prospective drug delivery carriers: design and applications. Biomaterials research Park, S., Han, U., Choi, D., Hong, J. 2018; 22: 29


    BACKGROUND: The main purpose of drug delivery systems is to deliver the drugs at the appropriate concentration to the precise target site. Recently, the application of a thin film in the field of drug delivery has gained increasing interest because of its ability to safely load drugs and to release the drug in a controlled manner, which improves drug efficacy. Drug loading by the thin film can be done in various ways, depending on type of the drug, the area of exposure, and the purpose of drug delivery.MAIN TEXT: This review summarizes the various methods used for preparing thin films with drugs via Layer-by-layer (LbL) assembly. Furthermore, additional functionalities of thin films using surface modification in drug delivery are briefly discussed. There are three types of methods for preparing a drug-carrying multilayered film using LbL assembly. First methods include approaches for direct loading of the drug into the pre-fabricated multilayer film. Second methods are preparing thin films using drugs as building blocks. Thirdly, the drugs are incorporated in the cargo so that the cargo itself can be used as the materials of the film.CONCLUSION: The appropriate designs of the drug-loaded film were produced in consideration of the release amounts and site of the desired drug. Furthermore, additional surface modification using the LbL technique enabled the preparation of effective drug delivery carriers with improved targeting effect. Therefore, the multilayer thin films fabricated by the LbL technique are a promising candidate for an ideal drug delivery system and the development possibilities of this technology are infinite.

    View details for DOI 10.1186/s40824-018-0139-5

    View details for PubMedID 30275972

  • Chemical and physical modification of layer-by-layer assembled nanofilms composed of block copolymer micelles and graphene oxide for controlled drug release JOURNAL OF INDUSTRIAL AND ENGINEERING CHEMISTRY Jung, S., Han, U., Hong, J. 2017; 56: 413-421
  • Immobilization of basic fibroblast growth factor on heparin/EDC-methiodide nano-aggregates to maintain its continuous signaling JOURNAL OF INDUSTRIAL AND ENGINEERING CHEMISTRY Han, U., Choi, M., Hong, J. 2017; 53: 404-410
  • Efficient Encapsulation and Sustained Release of Basic Fibroblast Growth Factor in Nanofilm: Extension of the Feeding Cycle of Human Induced Pluripotent Stem Cell Culture ACS APPLIED MATERIALS & INTERFACES Han, U., Park, H., Kim, Y., Park, T., Park, J., Hong, J. 2017; 9 (30): 25087-25097


    Basic fibroblast growth factor (bFGF) has an established pivotal function in biomedical engineering, especially for the human pluripotent stem cells (iPSCs). However, the limitation of bFGF is the ease of denaturation under normal physiological conditions, inducing loss of its activity. In this study, we designed multi-trilayered nanofilm composed of a repeating polycation/polyanion/bFGF structure, which has high loading efficiency and short buildup time. We also investigated that the loading and release of bFGF from the nanofilm with two parameters (counter-polyanion and film architectures). Then, we prepared the optimized nanofilm which maintains a sustained bFGF level in physiological condition to apply the nanofilm to human iPSCs culture. The amount of bFGF release from 12 trilayer nanofilm was 36.4 ng/cm2, and activity of bFGF encapsulated into the nanofilm was maintained (60%) until 72 h during incubation at 37 °C. As a result, the iPSCs grown in the presence of the nanofilm with tridaily replacement of growth medium maintained undifferentiated morphology and expression levels of pluripotency marker proteins.

    View details for DOI 10.1021/acsami.7b05519

    View details for Web of Science ID 000407089300005

    View details for PubMedID 28686012

  • Multilayer Nanofilms via Inkjet Printing for Stabilizing Growth Factor and Designing Desired Cell Developments ADVANCED HEALTHCARE MATERIALS Choi, M., Park, H., Choi, D., Han, U., Park, T., Lee, H., Park, J., Hong, J. 2017; 6 (14)


    Biologically versatile basic fibroblast growth factor (bFGF), well known for roles of signaling molecules between cells and regulating various cellular processes, has been proven to utilize specific functionalities. However, the remarkable functions are inclinable to dwindle with decrease of bFGFs' activity. In nanoscale, developing thin films with intrinsic characteristics of building molecules can facilitate handling various materials for desired purposes. Fabricating nanofilm and handling sensitive materials without detriment to activity via highly productive manufacturing are significant for practical uses in the field of biomedical applications. Herein, a multilayered nanofilm fabricating system is developed by inkjet printing to incorporate bFGF successfully. It is demonstrated that water mixed with glycerol as biological ink maintains stability of bFGFs through simulation and experimental study. With highly stable bFGFs, the proliferation of human dermal fibroblast is enhanced and the undifferentiated state of induced pluripotent stem cell is maintained by the controlled release of bFGF.

    View details for DOI 10.1002/adhm.201700216

    View details for Web of Science ID 000405801800008

    View details for PubMedID 28436215

  • Inkjet-based multilayered growth factor-releasing nanofilms for enhancing proliferation of mesenchymal stem cells in vitro JOURNAL OF INDUSTRIAL AND ENGINEERING CHEMISTRY Choi, M., Choi, D., Han, U., Hong, J. 2017; 50: 36-40
  • Effect of pH on the structure and drug release profiles of layer-by-layer assembled films containing polyelectrolyte, micelles, and graphene oxide SCIENTIFIC REPORTS Han, U., Seo, Y., Hong, J. 2016; 6: 24158


    Layer by layer (lbl) assembled multilayer thin films are used in drug delivery systems with attractive advantages such as unlimited selection of building blocks and free modification of the film structure. In this paper, we report the fundamental properties of lbl films constructed from different substances such as PS-b-PAA amphiphilic block copolymer micelles (BCM) as nano-sized drug vehicles, 2D-shaped graphene oxide (GO), and branched polyethylenimine (bPEI). These films were fabricated by successive lbl assembly as a result of electrostatic interactions between the carboxyl group of BCM and amine group of functionalized GO or bPEI under various pH conditions. We also compared the thickness, roughness, morphology and degree of adsorption of the (bPEI/BCM) films to those in the (GO/BCM) films. The results showed significant difference because of the distinct pH dependence of each material. In addition, drug release rates of the GO/BCM film were more rapid those of the (bPEI/BCM) film in pH 7.4 and pH 2 PBS buffer solutions. In (bPEI/BCM/GO/BCM) film, the inserted GO layers into bPEI/BCM multilayer induced rapid drug release. We believe that these materials &pH dependent film properties allow developments in the control of coating techniques for biological and biomedical applications.

    View details for DOI 10.1038/srep24158

    View details for Web of Science ID 000373574500001

    View details for PubMedID 27052827

    View details for PubMedCentralID PMC4823712