Publications by authors named "Jinkee Hong"

92 Publications

Chitosan/Cellulose-Based Porous Nanofilm Delivering C-Phycocyanin: A Novel Platform for the Production of Cost-Effective Cultured Meat.

ACS Appl Mater Interfaces 2021 Jul 29;13(27):32193-32204. Epub 2021 Jun 29.

Department of Chemical & Biomolecular Engineering, College of Engineering, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul 03722, Republic of Korea.

Cultured meat is artificial meat produced via the mass culture of cells without slaughtering livestock. In the production process of cultured meat, the mass proliferation for preparing abundant cells is a strenuous and time-consuming procedure requiring expensive and excess serum. Herein, C-phycocyanin (C-PC) extracted from blue algae was selected as a substitute for animal-derived serum and a polysaccharide film-based platform was developed to effectively deliver C-PC to myoblast while reducing the cost of cell medium. The polysaccharide platform has a sophisticated structure in which an agarose layer is capped on a porous multilayer film formed by molecular reassembly between chitosan and carboxymethylcellulose (CMC). The porous multilayer film provides an inner structure in which C-PC can be incorporated, and the agarose layer protects and stabilizes the C-PC. The completed platform was easily applied to a cell culture plate to efficiently release C-PC, thereby improving myoblast proliferation in a serum-reduced environment during long-term culture. We developed a cell sheet-based meat model using this polysaccharide platform to evaluate the improved cost-efficiency by the platform method in the mass proliferation of cells. This strategy and innovative technology can simplify the production system and secure price competitiveness to commercialize cultured meat.
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http://dx.doi.org/10.1021/acsami.1c07385DOI Listing
July 2021

Novel enzymatic cross-linking-based hydrogel nanofilm caging system on pancreatic β cell spheroid for long-term blood glucose regulation.

Sci Adv 2021 Jun 23;7(26). Epub 2021 Jun 23.

School of Chemical and Biological Engineering, Institute of Chemical Processes, Seoul National University, Seoul 08826, Republic of Korea.

Pancreatic β cell therapy for type 1 diabetes is limited by low cell survival rate owing to physical stress and aggressive host immune response. In this study, we demonstrate a multilayer hydrogel nanofilm caging strategy capable of protecting cells from high shear stress and reducing immune response by interfering cell-cell interaction. Hydrogel nanofilm is fabricated by monophenol-modified glycol chitosan and hyaluronic acid that cross-link each other to form a nanothin hydrogel film on the cell surface via tyrosinase-mediated reactions. Furthermore, hydrogel nanofilm formation was conducted on mouse β cell spheroids for the islet transplantation application. The cytoprotective effect against physical stress and the immune protective effect were evaluated. Last, caged mouse β cell spheroids were transplanted into the type 1 diabetes mouse model and successfully regulated its blood glucose level. Overall, our enzymatic cross-linking-based hydrogel nanofilm caging method will provide a new platform for clinical applications of cell-based therapies.
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http://dx.doi.org/10.1126/sciadv.abf7832DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8221614PMC
June 2021

Co-existing "spear-and-shield" air filter: Anchoring proteinaceous pathogen and self-sterilized nanocoating for combating viral pandemic.

Chem Eng J 2021 Dec 11;426:130763. Epub 2021 Jun 11.

Department of Chemical and Biomolecular Engineering, Yonsei University, Seoul 03722, Republic of Korea.

Infectious pollutants bioaerosols can threaten human public health. In particular, the indoor environment provides a unique exposure situation to induce infection through airborne transmission like SARS-CoV-2. To prevent the infection from spreading, personal protective equipment or indoor air purification is necessary. However, it has been discovered that the conventional filter can become contaminated by pathogen-containing aerosols, meaning that advanced filtering and self-sterilization systems are required. Here, we fabricate a multilayered nanocoating around the fabric using laponite (LAP) with Cu ions (LAP-Cu nanocoating) two contradictory functions in one system: trapping proteinaceous pathogens and antibacterial effect. Due to the strong LAP-protein interaction, albumin and spike protein (S-protein) are trapped into the fabric when proteins are sprayed using a nebulizer. The protein-blocking performance of the nanocoated fabric is 9.55-fold higher than bare fabric. These trapping capacities are retained after rinsing and repeated adsorption cycles, showing reproducibility for air filtration. Even though the protein-binding occurred, the LAP-Cu fabric indicates antibacterial effect. LAP-Cu fabric has an equivalent air and water transmittance rate to that of bare fabric with a stability under physiological environment. Therefore, given its excellent "Spear-and-shield" functions, the proposed LAP-Cu fabric shows great potential for use in filter and masks during the viral pandemic.
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http://dx.doi.org/10.1016/j.cej.2021.130763DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8192840PMC
December 2021

A portable device for water-sloshing-based electricity generation based on charge separation and accumulation.

iScience 2021 May 16;24(5):102442. Epub 2021 Apr 16.

School of Mechanical Engineering, Chung-ang University, 84, Heukseok-ro, Dongjak-gu, Seoul, Republic of Korea.

Hydropower generation is a well-known electricity generation technique that uses Faraday's law and hydraulic turbines. Recently, a triboelectrification-based electricity generation device, using water as the triboelectric material (W-TEG) was developed. In addition to the enhancement of the electrical output performance through the operation mechanism, the characteristics of the W-TEG must be examined at the design level to facilitate its portable application. Therefore, in this work, we developed a portable water-sloshing-based electricity generator (PS-EG) that can produce a high electric output and achieved its closed-loop circuit design and quantitative analysis for portable applications. The proposed PS-EG produced peak open-circuit voltage ( ) and closed-circuit current ( ) of up to 484 V and 4.1 mA, respectively, when subjected to vibrations of 2 Hz. The proposed PS-EG can be effectively used as an auxiliary power source for small electronics and sensors.
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http://dx.doi.org/10.1016/j.isci.2021.102442DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8111679PMC
May 2021

Nano-structure of vitronectin/heparin on cell membrane for stimulating single cell in iPSC-derived embryoid body.

iScience 2021 Apr 11;24(4):102297. Epub 2021 Mar 11.

Department of Chemical & Biomolecular Engineering, College of Engineering, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul 03722, Republic of Korea.

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 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.
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http://dx.doi.org/10.1016/j.isci.2021.102297DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8022842PMC
April 2021

Investigation of the Structural Mechanism and Film Growth on Cytoprotective Type I Collagen-Based Nanocoating of Individual Cellular Surfaces.

Langmuir 2021 04 6;37(15):4587-4598. Epub 2021 Apr 6.

Department of Chemical and Biomolecular Engineering, Yonsei University, Seoul 03722, Republic of Korea.

Cell surface coating using the layer-by-layer assembly (LbL) method has many advantages for biomedical applications. Because the cell surface is a dynamic and highly complex structure, it is hypothesized that LbL multilayer films on cells have characteristics different from those observed in traditional film characterization results. Here, to demonstrate the mechanism of LbL-film formation on cells, LbL films are prepared on HeLa cells using collagen (Col) and hyaluronic acid (HA). The growth behavior of the film and the main driving forces inducing the formation of an LbL film on the cells are investigated. Col self-assembles via electrostatic and hydrophobic interactions; therefore, the Col-based film on the cells grows laterally rather than volumetrically. For the film construction conditions, the ionic density and chain conformation of the polymers change, resulting in mainly hydrophobic interactions. Additional interactions, such as hydrophobic interactions and biological recognition between the substrate and building blocks, also exist and tightly stabilize the films on the cells. The Col/HA film shows an even distribution on the cell surface as the extracellular matrix, and it activates proliferation and the cytoprotective signaling pathway under harsh conditions, resulting in the focal adhesion kinase signaling pathway and low lactate dehydrogenase release. Therefore, information for film construction on cells is beneficial to understand the effectiveness of an LbL film for cells.
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http://dx.doi.org/10.1021/acs.langmuir.1c00276DOI Listing
April 2021

Programmed BMP-2 release from biphasic calcium phosphates for optimal bone regeneration.

Biomaterials 2021 05 29;272:120785. Epub 2021 Mar 29.

Department of Chemical and Biomolecular Engineering, Yonsei University, Seoul, 03722, Republic of Korea. Electronic address:

This study aimed to fabricate a multi-layered biphasic calcium phosphate (BCP) platform for programmed bone morphogenetic protein-2 (BMP-2) release, which means to block the initial burst release and promote releasing during the differentiation phase of osteogenic cells. And it is to confirm in vivo whether this platform has osteogenic inductivity even when extremely low doses of BMP-2 are loaded compared to the conventional soaking method. Our strategy consisted of preparing a multilayer coating on BCP to minimize the contact between BMP-2 and BCP and allow the loading of BMP-2. The multilayer, which is surface-modified on BCP, is composed of an organosilicate and a natural polymer-based layer-by-layer (LbL) film. We applied (3-Aminopropyl)triethoxysilane (APTES) as an organosilicate was used for amine-functionalized BCP and (collagen/heparin) film was used to delay and sustain BMP-2 release. The coated multilayer not only reduced the initial burst release by more than 50% but also loaded more BMP-2. For in vivo experiment, histomorphometric analysis, it was observed that the BCP platform loaded with extremely low concentration BMP-2 (0.01 mg/ml) induced a significantly larger amount of new bones at 8 weeks compared to the conventional soaking method in the rabbit calvarium onlay graft model.
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http://dx.doi.org/10.1016/j.biomaterials.2021.120785DOI Listing
May 2021

Reverse Actuation of Polyelectrolyte Effect for Antifouling.

ACS Nano 2021 04 26;15(4):6811-6828. Epub 2021 Mar 26.

Department of Chemical and Biomolecular Engineering, College of Engineering, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul 03722, Republic of Korea.

Zwitterionic polymers have extraordinary properties, that is, significant hydration and the so-called antipolyelectrolyte effect, which make them suitable for biomedical applications. The hydration induces an antifouling effect, and this has been investigated significantly. The antipolyelectrolyte effect refers to the extraordinary ion-responsive behavior of particular polymers that swell and hydrate considerably in physiological solutions. This actuation begins to attract attention to achieve antifouling that is challenging for general polyelectrolytes. In this study, we established the sophisticated cornerstone of the antipolyelectrolyte effect in detail, including (i) the essential parameters, (ii) experimental verifications, and (iii) effect of improving antifouling performance. First, we find that both osmotic force and charge screening are essential factors. Second, we identify the antipolyelectrolyte effect by visualizing the swelling and hydration dynamics. Finally, we verify that the antifouling performance can be enhanced by exploiting the antipolyelectrolyte effect and report reduction of 85% and 80% in and biofilm formation, respectively.
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http://dx.doi.org/10.1021/acsnano.0c10431DOI Listing
April 2021

Triangulated Cylinder Origami-Based Piezoelectric/Triboelectric Hybrid Generator to Harvest Coupled Axial and Rotational Motion.

Research (Wash D C) 2021 19;2021:7248579. Epub 2021 Feb 19.

School of Mechanical Engineering, Chung-Ang University, 84, Heukseok-ro, Dongjak-gu, Seoul, Republic of Korea.

Piezoelectric nanogenerators (PENGs) and triboelectric nanogenerators (TENGs) are representative technologies that can harvest mechanical energy. In general, piezoelectric/triboelectric hybrid generators can harvest considerable energy with a limited input; however, PENGs and TENGs entail different requirements for harvesting energy. Specifically, PENGs produce a large output when a large mechanical strain is applied, and TENGs require a large surface area to produce a high power. Therefore, it is necessary to develop an innovative strategy in terms of the structural design to satisfy the requirements of both PENGs and TENGs. In this study, we developed a triangulated cylinder origami-based piezoelectric/triboelectric hybrid generator (TCO-HG) with an origami structure to enable effective energy harvesting. The proposed structure consists of a vertical contact-separation TENG on the surface of the triangulated cylinder, PENG on the inner hinge, and rotational TENG on the top substrate to harvest mechanical energy from each motion. Each generator could produce a separate electrical output with a single input. The TCO-HG could charge a 22 F commercial capacitor and power 60 LEDs when operated.
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http://dx.doi.org/10.34133/2021/7248579DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7914395PMC
February 2021

Functional ferrocene polymer multilayer coatings for implantable medical devices: Biocompatible, antifouling, and ROS-sensitive controlled release of therapeutic drugs.

Acta Biomater 2021 04 28;125:242-252. Epub 2021 Feb 28.

Center for Convergence Bioceramic Materials, Korea Institute of Ceramic Engineering and Technology, 202, Osongsaengmyeong 1-ro, Osong-eup, Heungdeok-gu, Cheongju, Chungbuk 28160, South Korea. Electronic address:

Bacterial infections and the formation of biofilms on the surface of implantable medical devices are critical issues that cause device failure. Implantable medical devices, such as drug delivery technologies, offer promising benefits for targeted and prolonged drug release, but a number of common disadvantages arise that include inadequate release and side effects. Organic film coatings for antifouling and drug delivery are expected to overcome these challenges. Ferrocene polymer-based multifunctional multilayer films were prepared to control the reactive oxygen species (ROS)-responsive release of therapeutic agents while maintaining an antifouling effect and improving biocompatibility. Polymers based on ferrocene and polyethylene glycol were prepared by controlling the molar ratio of carboxylate and amine groups. Layer-by-layer deposition was optimized to achieve the linear growth and self-assembly of dense and stable films. Outstanding anti-biofilm activity (~91% decrease) could be achieved and the films were found to be blood compatible. Importantly, the films effectively incorporated hydrophobic drugs and exhibited dual-responsive drug release at low pH and under ROS conditions at physiological pH. Drug delivery to MCF-7 breast cancer cells was achieved using a Paclitaxel loaded film, which exhibited an anticancer efficacy of 62%. STATEMENT OF SIGNIFICANCE: Healthcare associated infection is caused by the formation of a biofilm by bacteria on the surface of a medical device. In order to solve this, extensive research has been conducted on many coating technologies. Also, a method of chemical treatment by releasing the drug when it enters the body by loading the drug into the coating film is being studied. However, there is still a lack of technology that can achieve both functions of preventing biofilm production and drug delivery. Therefore, in this study, a multilayer thin film that supports drug and inhibits biofilm formation was prepared through Layer-by-Layer coating of a polymer containing PEG to prevent adsorption. As such, it helps the design of multifunctional coatings for implantable medical devices.
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http://dx.doi.org/10.1016/j.actbio.2021.02.038DOI Listing
April 2021

2D graphene oxide particles induce unwanted loss in pluripotency and trigger early differentiation in human pluripotent stem cells.

J Hazard Mater 2021 07 20;414:125472. Epub 2021 Feb 20.

Department of Chemical and Biomolecular Engineering, College of Engineering, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul 03722, Republic of Korea. Electronic address:

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.
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http://dx.doi.org/10.1016/j.jhazmat.2021.125472DOI Listing
July 2021

Acceleration of Nitric Oxide Release in Multilayer Nanofilms through Cu(II) Ion Intercalation for Antibacterial Applications.

Biomacromolecules 2021 03 22;22(3):1312-1322. Epub 2021 Feb 22.

Department of Chemical and Biomolecular Engineering, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul 03722, Republic of Korea.

Implant-derived bacterial infection is a prevalent cause of diseases, and no antibacterial coating currently exists that is biocompatible and that does not induce multidrug resistance. To this end, nitric oxide (NO) has been emerging as an effective antimicrobial agent that acts on a broad range of bacteria and elicits no known resistance. Here, a method for accelerating NO release from multilayered nanofilms has been developed for facilitating antibacterial activity. A previously reported multilayered nanofilm (nbi film) was fabricated by alternative deposition of branched polyethyleneimine (BPEI) and alginate via the layer-by-layer assembly method. -Diazeniumdiolate, a chemical NO donor, was synthesized at the secondary amine moiety of BPEI within the film (nbi/NO film). Cu(II) ions can be incorporated into the film by forming chelating compounds with unreacted amines that have not been converted to NO donors. The increase of the amine protonation state in the chelate caused destabilization of the NO donor by reducing hydrogen bonding between the deprotonated amine and the NO donor. Thus, the Cu(II) ion-embedding film presented accelerated NO release and was further subjected to antibacterial testing to demonstrate the correlation between the NO release rate and the antibacterial activity. This study aimed to establish a novel paradigm for NO-releasing material design based on multilayered nanofilms by presenting the correlation between the NO release rate and the antibacterial effect.
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http://dx.doi.org/10.1021/acs.biomac.0c01821DOI Listing
March 2021

α-Tocopherol-loaded reactive oxygen species-scavenging ferrocene nanocapsules with high antioxidant efficacy for wound healing.

Int J Pharm 2021 Mar 22;596:120205. Epub 2021 Jan 22.

Center for Convergence Bioceramic Materials, Korea Institute of Ceramic Engineering and Technology, 202, Osongsaengmyeong 1-ro, Osong-eup, Heungdeok-gu, Cheongju, Chungbuk 28160, Republic of Korea. Electronic address:

The elevated production of reactive oxygen species (ROS) in wounded sites triggers a series of harmful effects, including cellular senescence, fibrotic scar formation, and inflammation. Therefore, alleviating oxidative stress in the microenvironment of wounded sites might promote regenerative wound healing. Generally, ROS-scavenging nanocapsules are effective for treating wounds owing to their anti-oxidative stress activity and targeted effects. In this study, a highly versatile ferrocene functional polymer was synthesized by one-pot radical polymerization, for formulating self-assembled ferrocene nanocapsules (FNCs), which could function as smart carriers of an antioxidant, α-tocopherol (TP), with high stability and loading efficiency. The FNCs showed ROS-sensitive properties, as demonstrated using dynamic light scattering, transmission electron microscopy, and the controlled release of a model drug in an ROS microenvironment. The antioxidant activity of TP-loaded FNCs, analyzed using 2,2-diphenyl-1-picrylhydrazyl assay, was significantly higher than that of unloaded TP. Furthermore, TP-loaded FNCs repressed oxidative damage to mouse NIH 3T3 fibroblasts and reduced intracellular ROS production according to an in vitro antioxidant assay. Most importantly, TP-loaded FNCs showed good biocompatibility and greatly facilitated the healing of infected wounds, as demonstrated using a scratch assay. Therefore, TP-loaded FNCs have potential as an ROS-mediated drug delivery system to treat various oxidative stress-associated diseases.
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http://dx.doi.org/10.1016/j.ijpharm.2021.120205DOI Listing
March 2021

Tris(2-carboxyethyl)phosphine-Mediated Nanometric Extracellular Matrix-Coating Method of Mesenchymal Stem Cells.

ACS Biomater Sci Eng 2020 02 13;6(2):813-821. Epub 2020 Jan 13.

Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Republic of Korea.

Human iPSC-derived mesenchymal stem cells (iMSCs) are an alternative to primary mesenchymal stem cells (MSCs), which have been a limited supply, and have attracted a great deal of interest as a promising cell source in cell-based therapy. However, despite their enormous therapeutic potential, it has been difficult to translate this potential into clinical applications due to the short viability duration of transplanted iMSCs. Therefore, to maximize the therapeutic effects of iMSCs, it is extremely important to extend their retention rate during and even after the transplantation. In this study, we developed a new extracellular matrix (ECM)-coating method involving the mild reduction of the cell surface. The reduction of disulfide bonds around the cell membrane enhanced the coating efficiency without a decrease in the viability and differentiation potential of iMSCs. We then induced ECM-coated single iMSCs to form three-dimensional spheroids via self-assembly of the aggregates within a physically confined microenvironment. The spheroids exhibited longer maintenance of the survival rate. Nanometric ECM coating of the cell membrane is a new approach as a key for resolving the conventional challenges of cell-based therapy.
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http://dx.doi.org/10.1021/acsbiomaterials.9b01480DOI Listing
February 2020

Structured nanofilms comprising Laponite® and bone extracellular matrix for osteogenic differentiation of skeletal progenitor cells.

Mater Sci Eng C Mater Biol Appl 2021 Jan 25;118:111440. Epub 2020 Aug 25.

Bone and Joint Research Group, Centre for Human Development, Stem Cells and Regeneration, Institute of Developmental Sciences, University of Southampton, SO16 6YD, United Kingdom. Electronic address:

Functionalized scaffolds hold promise for stem cell therapy by controlling stem cell fate and differentiation potential. Here, we have examined the potential of a 2-dimensional (2D) scaffold to stimulate bone regeneration. Solubilized extracellular matrix (ECM) from human bone tissue contains native extracellular cues for human skeletal cells that facilitate osteogenic differentiation. However, human bone ECM displays limited mechanical strength and degradation stability under physiological conditions, necessitating modification of the physical properties of ECM before it can be considered for tissue engineering applications. To increase the mechanical stability of ECM, we explored the potential of synthetic Laponite® (LAP) clay as a counter material to prepare a 2D scaffold using Layer-by-Layer (LbL) self-assembly. The LAP and ECM multilayer nanofilms (ECM/LAP film) were successfully generated through electrostatic and protein-clay interactions. Furthermore, to enhance the mechanical properties of the ECM/LAP film, application of a NaCl solution wash step, instead of deionized water following LAP deposition resulted in the generation of stable, multi-stacked LAP layers which displayed enhanced mechanical properties able to sustain human skeletal progenitor cell growth. The ECM/LAP films were not cytotoxic and, critically, showed enhanced osteogenic differentiation potential as a consequence of the synergistic effects of ECM and LAP. In summary, we demonstrate the fabrication of a novel ECM/LAP nanofilm layer material with potential application in hard tissue engineering.
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http://dx.doi.org/10.1016/j.msec.2020.111440DOI Listing
January 2021

In vitro toxicity from a physical perspective of polyethylene microplastics based on statistical curvature change analysis.

Sci Total Environ 2021 Jan 7;752:142242. Epub 2020 Sep 7.

Department of Chemical and Biomolecular Engineering, Yonsei University, Seoul 03722, Republic of Korea. Electronic address:

Microplastics which are gradually and randomly decompose into small fragment by exposure of physical and biological external stress are emerging as a significant threat to the all the environments. Here, we have demonstrated the in vitro toxicity of microplastics of two different shapes. To minimize the chemical effect, polyethylene (PE), was used. PE microplastics with two different shapes were prepared, high-density PE microbeads and irregularly ground low-density PE from bulk pellets. It is hypothesized that morphological characteristics and concentration of PE microplastics could affect cellular viability, immunity, and lysis. To quantify the randomness of the microplastic shape, the edge patterns of the generated PE microplastics were converted into numerical values and analyzed using a statistical method. A 10-fold difference in curvature value was observed between microbeads and ground microfragments. To correlate shape differences to toxicology, cells were exposed to PE microplastics on the demand of toxicology studies. We found that the higher concentration and rough structure were associated with the toxicity of plastics toward cells, pro-inflammatory cytokine release, and hemolysis, even though PE is buoyant onto medium. The PE microbeads did not exhibit severe cytotoxicity at any of the tested concentrations, but induced immune and hemolysis responses at high concentrations. When comparing the toxicity of different shapes of PE microplastics, we confirmed by statistical analysis that irregular-shape plastics with sharp edges and higher curvature differences may adversely affect cells, further having possibility to human toxicity in real environment.
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http://dx.doi.org/10.1016/j.scitotenv.2020.142242DOI Listing
January 2021

Controlled Nitric Oxide Release Using Poly(lactic-co-glycolic acid) Nanoparticles for Anti-Inflammatory Effects.

Biomacromolecules 2020 12 4;21(12):4972-4979. Epub 2020 Nov 4.

Department of Chemical & Biomolecular Engineering, College of Engineering, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul 03722, Republic of Korea.

Nitric oxide (NO) plays a key role in several physiological functions such as inflammatory responses and immune regulation. However, despite its beneficial functions, the short half-life and diffusion radius limit NO availability in biomedical applications. Hence, controlled release is important to achieve the desired therapeutic effects with exogenous NO delivery. In this study, we fabricated a poly(lactic-co-glycolic acid) (PLGA)-based NO delivery system to release NO in a sustained manner under physiological conditions. To prevent an initial burst release, branched polyethylenimine diazeniumdiolate (BPEI/NONOate), a pH-responsive NO donor, was encapsulated into the hydrophilic core of PLGA nanoparticles. Furthermore, low concentrations of NO released at a consistent level via a stabilization effect obtained as amine groups of BPEI/NONOate interacted with the nearby NONOate. Using the controlled-release profiles, we successfully regulated the inflammatory response in lipopolysaccharide-stimulated peripheral blood mononuclear cells. This work demonstrates the potential of a NO delivery carrier in the regulation of inflammation.
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http://dx.doi.org/10.1021/acs.biomac.0c01176DOI Listing
December 2020

Effects of Nonporous Silica Nanoparticles on Human Trabecular Meshwork Cells.

J Glaucoma 2021 Feb;30(2):195-202

Department of Ophthalmology, Dongguk University Ilsan Hospital, Goyang.

Precis: Silica nanoparticles (SiNPs), which are potential drug carriers for glaucoma treatment, may induce mild dose-dependent cytotoxicity but not so severe as to compromise a mammalian target of rapamycin (mTOR) pathway in immortalized trabecular meshwork (TM) cells.

Purpose: Nanoparticle-based ophthalmic drug delivery is a promising field of drug development. In this study, we evaluated the effect of nonporous SiNPs on human TM cells.

Methods: TM cells were exposed to different concentrations (0 to 100 µg/mL) of SiNPs (50, 100, and 150 nm) for up to 48 hours. Transmission electron microscopy confirmed the intracellular distribution of SiNPs. Cellular viability assay, reactive oxygen species generation, autophagy, and activation of the mTOR pathway were evaluated. Histologic analysis of the TM structure was performed after intracameral injection of SiNPs (0.05 mL of 200 µg/mL concentration) in rabbits.

Results: SiNPs were taken up by TM cells and localized in the cytoplasm. Neither nuclear entry nor mitochondrial damage was observed. SiNPs induced a mild but dose-dependent increase of lactate dehydrogenase. However, neither increase of intracellular reactive oxygen species levels nor apoptosis was observed after SiNPs exposure. Significant coactivation of autophagy and the mTOR pathway were observed with exposure to SiNPs. Aqueous plexus structure was well maintained without inflammation in rabbits after SiNPs exposure.

Conclusions: SiNPs induce mild and dose-dependent cytotoxicity in TM cells. However, the toxicity level is not enough to compromise the mTOR pathway of TM cells and histologic structure of the aqueous plexus tissue.
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http://dx.doi.org/10.1097/IJG.0000000000001709DOI Listing
February 2021

Facile Synthesis of Poly(ethylene oxide)-Based Self-Healable Dynamic Triblock Copolymer Hydrogels.

Biomacromolecules 2020 12 16;21(12):4913-4922. Epub 2020 Oct 16.

Department of Chemistry, Yonsei University, Seoul 03722, Republic of Korea.

Stimuli-responsive smart hydrogels have garnered considerable interest for their potential in biomedical applications. While widely utilized, little is known about the rheological and mechanical properties of the hydrogels with respect to the type of cross-linker in a systematic manner. In this study, we present a facile synthetic route toward ABA triblock copolymer hydrogels based on poly(ethylene oxide) (PEO). Two classes of hydrogels were prepared by employing the functional allyl glycidyl ether (AGE) monomer during the polymerization followed by the subsequent post-polymerization modification of prepared PAGE--PEO--PAGE via respective hydrogenation or thiol-ene reaction: (1) chemically cross-linked hydrogels responsive to redox stimuli and (2) physically cross-linked hydrogels responsive to temperature. A series of dynamic mechanical analyses revealed the relaxation dynamics of the associative A block. Most interestingly, the redox-responsive hydrogels demonstrated a highly tunable nature by introducing reducing and oxidizing agents, which provided the self-healing property and injectability. Together with superior biocompatibility, these smart hydrogels offer the prospect of advancing biomedical applications.
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http://dx.doi.org/10.1021/acs.biomac.0c01140DOI Listing
December 2020

Tuning the Structural Integrity and Mechanical Properties of Globular Protein Vesicles by Blending Crosslinkable and NonCrosslinkable Building Blocks.

Biomacromolecules 2020 10 1;21(10):4336-4344. Epub 2020 Oct 1.

Department of Chemical Engineering, University of Florida, 1006 Center Drive, Gainesville, Florida 32611, United States.

Vesicles made from functionally folded, globular proteins that perform specific biological activities, such as catalysis, sensing, or therapeutics, show potential applications as artificial cells, microbioreactors, or protein drug delivery vehicles. The mechanical properties of vesicle membranes, including the elastic modulus and hardness, play a critical role in dictating the stability and shape transformation of the vesicles under external stimuli triggers. Herein, we have developed a strategy to tune the mechanical properties and integrity of globular protein vesicle (GPV) membranes of which building molecules are recombinant fusion protein complexes: a mCherry fused with an acidic leucine zipper (mCherry-Z) and a basic leucine zipper fused with an elastin-like polypeptide (Z-ELP). To control the mechanical properties of GPVs, we introduced a nonstandard amino acid (para-azidophenylalanine (pAzF)) into the ELP domains (ELP-X), which enabled the creation of crosslinked vesicles under ultraviolet (UV) irradiation. Crosslinked GPVs made from mCherry-Z/Z-ELP-X complexes presented higher stability than noncrosslinked GPVs under hypotonic osmotic stress. The degree of swelling of GPVs increased as less crosslinking was achieved in the vesicle membranes, which resulted in the disassembly of GPVs into membraneless coacervates. Nanoindentation by atomic force microscopy (AFM) confirmed that the stiffness and Young's elastic modulus of GPVs increase as the blending molar ratio of Z-ELP-X to Z-ELP increases to make vesicles. The results obtained in this study suggest a rational design to make GPVs with tunable mechanical properties for target applications by simply varying the blending ratio of Z-ELP and Z-ELP-X in the vesicle self-assembly.
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http://dx.doi.org/10.1021/acs.biomac.0c01147DOI Listing
October 2020

In vitro chemical and physical toxicities of polystyrene microfragments in human-derived cells.

J Hazard Mater 2020 12 24;400:123308. Epub 2020 Jun 24.

Department of Chemical and Biomolecular Engineering, Yonsei University, Seoul 03722, Republic of Korea. Electronic address:

With the increase in plastic production, a variety of toxicological studies on microplastics have been conducted as microplastics can be accumulated in the human body and cause unknown disease. However, previous studies have mainly assessed the toxicity of sphere-type microbeads, which may differ from randomly-shaped microplastics in a real environment. Here, we conducted in vitro toxicology analysis for randomly-shaped microplastics based on the hypotheses that (1) physical cytotoxicity is affected by nano-/micro-size roughness in polystyrene (PS) microfragments and (2) chemical toxicity is caused by chemical reagents from microplastics. We confirmed that the PS microfragments increased the acute inflammation of immune cells 20 times than control, the production of reactive oxygen species, and cell death of fibroblasts and cancer cells by releasing chemical reagents. In addition, when the PS microfragments were in direct contact with fibroblasts and red blood cells, the physical stress caused by them resulted in lactose dehydrogenase and hemoglobin release, respectively, due to cell membrane damage and hemolysis. This phenomenon was amplified when the concentration and roughness of the microfragments increased. Moreover, we quantitatively analyzed roughness differences between microplastics, which revealed a strong relationship between the physical damage of cells and the roughness of microplastics.
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http://dx.doi.org/10.1016/j.jhazmat.2020.123308DOI Listing
December 2020

Potential toxicity of polystyrene microplastic particles.

Sci Rep 2020 04 30;10(1):7391. Epub 2020 Apr 30.

Department of Chemical and Biomolecular Engineering, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea.

Environmental pollution arising from plastic waste is a major global concern. Plastic macroparticles, microparticles, and nanoparticles have the potential to affect marine ecosystems and human health. It is generally accepted that microplastic particles are not harmful or at best minimal to human health. However direct contact with microplastic particles may have possible adverse effect in cellular level. Primary polystyrene (PS) particles were the focus of this study, and we investigated the potential impacts of these microplastics on human health at the cellular level. We determined that PS particles were potential immune stimulants that induced cytokine and chemokine production in a size-dependent and concentration-dependent manner.
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http://dx.doi.org/10.1038/s41598-020-64464-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7193629PMC
April 2020

Nanoclay-Polyamine Composite Hydrogel for Topical Delivery of Nitric Oxide Gas via Innate Gelation Characteristics of Laponite.

Biomacromolecules 2020 06 8;21(6):2096-2103. Epub 2020 May 8.

School of Chemical & Biomolecular Engineering, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul 03722, Republic of Korea.

Because nitric oxide (NO) gas is an endogenously produced signaling molecule related to numerous physiological functions, manystudies have been conducted to develop NO delivery systems for potential biomedical applications. However, NO is a reactive radical gas molecule that has a very short life-time and readily transforms into nitrogen oxide species via reaction with oxygen species. Therefore, it is necessary to develop an NO delivery carrier that allows local release of the NO gas at the site of application. In this study, Laponite (LP) nanoclay was used to fabricate an NO delivery carrier through the formation of Laponite-polyamine (LP-PA) composites. The Laponite clay and pentaethylenehexamine (PEHA) formed a macromolecular structure by electrostatic interaction and the nitric oxide donor, -diazeniumdiolate (NONOates), was synthesized into the LP-PA composite. We investigated the conformation of the LP-PA composite structure and the NO donor formation by ζ potential, X-ray diffraction, and UV-vis and Fourier transform infrared (FT-IR) spectroscopies and also by analyzing the NO release profile. Additionally, we confirmed the applicability in biomedical applications via a cell viability and in vitro endothelial cell tube formation assay.
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http://dx.doi.org/10.1021/acs.biomac.0c00086DOI Listing
June 2020

Studies on the Drug Loading and Release Profiles of Degradable Chitosan-Based Multilayer Films for Anticancer Treatment.

Cancers (Basel) 2020 Mar 5;12(3). Epub 2020 Mar 5.

Department of Chemical and Biomolecular Engineering, Yonsei University, Seoul 03722, Korea.

This study demonstrates the possibility of developing a rapidly degradable chitosan-based multilayer film for controlled drug release. The chitosan (CHI)-based multilayer nanofilms were prepared with three different types of anions, hyaluronic acid (HA), alginic acid (ALG) and tannic acid (TA). Taking advantage of the Layer-by-Layer (LBL) assembly, each multilayer film has different morphology, porosity and thickness depending on their ionic density, molecular structure and the polymer functionality of the building blocks. We loaded drug models such as doxorubicin hydrochloride (DOX), fluorescein isothiocyanate (FITC) and ovalbumin (Ova) into multilayer films and analyzed the drug loading and release profiles in phosphate-buffered saline (PBS) buffer with the same osmolarity and temperature as the human body. Despite the rapid degradation of the multilayer film in a high pH and salt solution, the drug release profile can be controlled by increasing the functional group density, which results in interaction with the drug. In particular, the abundant carboxylate groups in the CHI/HA film increased the loading amount of DOX and decreased rapid drug release. The TA interaction with DOX via electrostatic interaction, hydrogen bonding and hydrophobic interaction showed a sustained drug release profile. These results serve as principles for fabricating a tailored multilayer film for drug delivery application.
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http://dx.doi.org/10.3390/cancers12030593DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7140006PMC
March 2020

Quantitative Interpretation of Hydration Dynamics Enabled the Fabrication of a Zwitterionic Antifouling Surface.

ACS Appl Mater Interfaces 2020 Feb 4;12(7):7951-7965. Epub 2020 Feb 4.

Department of Chemical & Biomolecular Engineering, College of Engineering , Yonsei University , 50 Yonsei-ro, Seodaemun-gu , Seoul 03722 , Republic of Korea.

In the medical industry, zwitterionic brushes have received significant attention owing to their antifouling effect that arose from their hydration ability. However, sufficient understanding of the hydration dynamics of zwitterionic brushes is required to fabricate the precisely controlled antifouling medical devices. In this paper, we successfully show that hydration, the interaction between water molecules and zwitterionic brushes, and its dynamics can be evaluated logically and quantitatively using (i) water contact angle, (ii) molecular dynamics simulation, and (iii) Raman spectroscopy. Based on the intuitive results on hydration, we precisely optimized the antifouling property of the model medical device, a removable orthodontic retainer, with various grafting efficiencies of 2-methacryloyloxyethyl phosphate choline. As a result, the model device reduced nonspecific adsorption of proteins and bacteria, indicating an improved antifouling effect, and also inhibited the formation of a biofilm. Furthermore, the device showed excellent physical properties desirable for application in the orthodontic field, meaning the balance between the antibacterial property and mechanical strength.
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http://dx.doi.org/10.1021/acsami.9b21566DOI Listing
February 2020

Sustained Nitric Oxide-Providing Small Molecule and Precise Release Behavior Study for Glaucoma Treatment.

Mol Pharm 2020 02 22;17(2):656-665. Epub 2020 Jan 22.

Department of Chemical and Biomolecular Engineering , Yonsei University , Seoul 03722 , Republic of Korea.

Incidence ofglaucoma, a severe disease leading to irreversible loss of vision, is increasing with global aging populations. Lowering intraocular pressure (IOP) is the only proven treatment method for glaucoma. Nitric oxide (NO) is an emerging material targeting the conventional outflow pathway by relaxing the trabecular meshwork (TM). However, there is little understanding on the NO level effective in IOP lowering without toxicity. Here, we report a novel long-term NO-releasing polydiazeniumdiolate (NOP) that enables lowering IOP via the conventional outflow pathway. NOP is composed of carbon-bound polydiazeniumdiolate, a stable NO donor moiety. NO release was monitored with accurate parameters by real-time detection of gas and analysis of the accumulated release profile. Based on the NO release information, the selected safe level of NOP exhibited effective TM relaxation and a potential IOP lowering effect in vivo without side effects. This work provides new insights into nitric oxide release behavior that should be considered for glaucoma treatment.
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http://dx.doi.org/10.1021/acs.molpharmaceut.9b01137DOI Listing
February 2020

Transmission and regulation of biochemical stimulus via a nanoshell directly adsorbed on the cell membrane to enhance chondrogenic differentiation of mesenchymal stem cell.

Biotechnol Bioeng 2020 01 8;117(1):184-193. Epub 2019 Oct 8.

Department of Chemical & Biomolecular Engineering, College of Engineering, Yonsei University, Seodaemun-gu, Seoul, Republic of Korea.

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.
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http://dx.doi.org/10.1002/bit.27183DOI Listing
January 2020

Construction of nano-scale cellular environments by coating a multilayer nanofilm on the surface of human induced pluripotent stem cells.

Nanoscale 2019 Jul 10;11(28):13541-13551. Epub 2019 Jul 10.

Department of Chemical & Biomolecular Engineering, College of Engineering, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul 03722, Republic of Korea.

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.
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http://dx.doi.org/10.1039/c9nr02375eDOI Listing
July 2019

Developing regulatory property of gelatin-tannic acid multilayer films for coating-based nitric oxide gas delivery system.

Sci Rep 2019 06 5;9(1):8308. Epub 2019 Jun 5.

School of Chemical & Biomolecular Engineering, Yonsei University, 50 Yonsei Ro, Seodaemun Gu, Seoul, 03722, Republic of Korea.

To utilize potentials of nitric oxide (NO) gas in anti-bacterial, anticancer, wound healing applications, numerous studies have been conducted to develop a NO delivery system in the past few decades. Even though a coating method and film types are essential to apply in biomedical device coating from previous NO delivery systems, release control from the coating system is still challenging. In this study, we introduced a multilayered polymeric coating system to overcome the uncontrollable NO release kinetics of film systems. We used biocompatible gelatin and tannic acid to construct a rough, porous structured film based on the layer-by-layer self-assembly method. The multilayered polymeric structure facilitated the controlled amount of NO release from (Gel/TA) film and showed burst release in early period owing to their large surface area from the rough, porous structure. We synthesized the proton-responsive NO donor, N-diazeniumdiolate (NONOates), into the (Gel/TA) film through a chemical reaction under high pressure NO gas. NO release profile was analyzed by a real-time NO analysis machine (NOA 280i). Then, the NO-releasing (Gel/TA) film was tested its toxicity against human dermal fibroblast cells and bactericidal effects against Staphylococcus aureus.
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http://dx.doi.org/10.1038/s41598-019-44678-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6549184PMC
June 2019

An assessment of the toxicity of polypropylene microplastics in human derived cells.

Sci Total Environ 2019 Sep 17;684:657-669. Epub 2019 May 17.

Department of Chemical and Biomolecular Engineering, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea. Electronic address:

Environmental pollution caused by plastic waste is a growing global problem. Discarded plastic products and debris (microplastic particles) in the oceans detrimentally affect marine ecosystems and may impact human. Humans are exposed to plastic debris via the consumption of seafood and drinking water, contact with food packaging, or inhalation of particles. The accumulation of microplastic particles in humans has potential health risks such as cytotoxicity, hypersensitivity, unwanted immune response, and acute response like hemolysis. We investigated the cellular responses of secondary polypropylene microplastics (PP particles) of approximately ~20 μm and 25-200 μm in different condition and size to normal cells, immune cells, blood cells, and murine immune cells by cytokine analysis, ROS assay, polarization assay and proliferation assay. We found that PP particles showed low cytotoxicity effect in size and concentration manner, however, a high concentration, small sized, DMSO method of PP particles stimulated the immune system and enhanced potential hypersensitivity to PP particles via an increase in the levels of cytokines and histamines in PBMCs, Raw 264.7 and HMC-1 cells.
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http://dx.doi.org/10.1016/j.scitotenv.2019.05.071DOI Listing
September 2019
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