Dr. Lee is a dedicated researcher in the field of biomedical engineering, driven by a strong desire to help individuals suffering from illnesses. With a particular interest in disease treatment and regeneration, she embarked on her journey in this field. During her doctoral studies, Dr. Lee focused on developing functional biomaterials by leveraging chemical bonding at interfaces. Her expertise in this area led her to successfully create functional medical devices. Currently, as a postdoctoral researcher at Stanford University, Dr. Lee is actively involved in drug screening using a bone-mimicking 3D in vitro cancer model that utilizes biomaterials. Her research is centered around the utilization of biomaterials to develop innovative approaches for tuning the communication between cells and biomaterials. By advancing in the field of biomaterials, Dr. Lee aims to facilitate a better understanding of cell-biomaterial interactions, with the ultimate goal of improving healthcare outcomes. With her passion for cutting-edge research and her commitment to the development of biomaterials, Dr. Lee is dedicated to making significant contributions to the field and shaping the future of healthcare.
Honors & Awards
Excellent Research Award, The Korean Society of Industrial and Engineering Chemistry (KSIEC) (2020)
Dean's list, Ewha Womans University (2013)
Scholarship, Ewha Womans University (2013-2014)
Bachelor of Science, Ewha Womans University (2014)
Doctor of Philosophy, Korean Advanced Institute of Science & Technology (2021)
Ph.D., Korea Advanced Institute of Science and Technology, Medical Science and Engineering (2021)
B.S., Ewha Womans University, Life Science (2014)
Fan Yang, Postdoctoral Faculty Sponsor
Reversible tissue sticker inspired by chemistry in plant-pathogen relationship
2023; 155: 247-257
Plants release phenolic molecules to protect against invading pathogens. In plant-microorganism relationships, phenolics bind to surface oligosaccharides, inactivating microorganism activities. Inspired by phenol-saccharide interactions in plant defense systems, we designed an adhesive sealant. By screening 16 different saccharides, the O-acetyl group, rich in glucomannan (GM), exhibited rapid, robust binding with the galloyl moiety of a model phenolic molecule, tannic acid (TA). Furthermore, the interaction showed both pH and temperature (upper critical solution temperature) sensitivities. Utilizing O-acetyl-galloyl interactions, materials of all dimensions from beads (0D) to strings (1D), films (2D), and objects (3D) could be prepared, as a suitable platform for printing techniques. GMTA films are elastic, adhesive, water-resistant, and effectively sealed perforations, as demonstrated by (1) a lung incision followed by an air inflation model and (2) a thoracic diaphragm model. STATEMENT OF SIGNIFICANCE: In nature, phenolic molecules are 'nearly always' physically bound with polysaccharides, indicating that the phenolics widen the functions of polysaccharides. An example includes that phenolic-polysaccharide interactions are key defense mechanisms against microbial infection in plants whereas polysaccharide alone functions poorly. Despite the ubiquitous biochemistry of polysaccharide-phenolic interactions, efforts on understanding binding chemistry focusing on phenol/polysaccharide interactions is little. This study is important because we found for the first time that O-acetyl group is the moiety in polysaccharides to which phenolic cis-diol and/or cis-triol is spontaneously bound. The phenol-polysaccharide interaction is non-covalent yet robust, kinetically fast, and reversible. Inspired by the interaction chemistry, a simple mixture of phenolic molecules and O-acetyl group containing polysaccharides such as glucomannan opens a promising fabrication strategy toward functional polysaccharide-based material.
View details for DOI 10.1016/j.actbio.2022.09.075
View details for Web of Science ID 000923183000001
View details for PubMedID 36216125
Diatom Silica/Polysaccharide Elastomeric Hydrogels: Adhesion and Interlocking Synergy
ACS APPLIED MATERIALS & INTERFACES
2021; 13 (18): 21703-21713
The addition of particles during the sol-to-gel conversion process generally enhances the mechanical properties of the resulting hydrogels. However, the impact of the addition of porous particles during such a process remains an open question. Herein, we report hydrogel-to-elastomer conversions by natural porous particles called diatom frustule silica, namely, Melosira nummuloides. The surface pores provide mechanical interlocking points for polymers that are reinforced by gelation. The most critical aspect when choosing polymeric materials is the presence of water-resistant adhesion moieties, such as catechol, along a polymer chain, such as chitosan. Without catechol, no sol-to-gel conversion is observed; thus, no elastomeric hydrogel is produced. The resulting hybrid gel reveals reversible compressibility up to a 60% strain and high stretchability even up to ∼400% in area. Further, in vivo study demonstrates that the hybrid composite gel can be used as a therapeutic for pressure-induced ulcers. The synergy of chemical adhesion and physical chain entanglement via pores provides a way to fabricate a new class of 100% water-based elastomeric materials.
View details for DOI 10.1021/acsami.1c01279
View details for Web of Science ID 000651750000076
View details for PubMedID 33938215
Diatom Frustule Silica Exhibits Superhydrophilicity and Superhemophilicity
2020; 14 (4): 4755-4766
Special surface wettability attracts significant attention. In this study, dramatic differences in wettability are demonstrated for microparticles with the same chemical composition, SiO2. One is natural silica prepared from the diatom, Melosira nummuloides, and the other is synthetic silica. We found that surface properties of synthetic silica are hydro- and hemophobic. However, diatom frustule silica exhibits superhydrophilicity and even superhemophilicity. Interestingly, such superhydrophilicity of natural silica is not solely originated from nanoporous structures of diatoms but from the synergy of high-density silanol anions and the nanoarchitecture. Furthermore, the observation of superhemophilicity of natural silica is also an interesting finding, because not all superhydrophilic surfaces show superhemophilicity. We demonstrate that superhemowettability is a fundamental principle for developing micropowder-based hemostatic materials despite existing hemorrhaging studies using diatoms.
View details for DOI 10.1021/acsnano.0c00621
View details for Web of Science ID 000529895500093
View details for PubMedID 32207961
Distinguishing between DNA-Loaded Full and Empty Capsids of Adeno-Associated Virus with Atomic Force Microscopy Imaging
Recently, miraculous therapy approaches involving adeno-associated virus (AAV) for incurable diseases such as spinal muscular atrophy and inherited retinal dysfunction have been introduced. Nonreplicative, nonpathogenic, low rates of chromosome insertional properties and the existence of neutralizing antibodies are main safety reasons why the FDA approved its use in gene delivery. To date, AAV production always results in a mixture of nontherapeutic (empty) and therapeutic (DNA-loaded) full capsids (10-98%). Such existence of empty viral particles inevitably increases viral doses to human. Thus, the rapid monitoring of empty capsids and reducing the empty-to-full ratio are critical in AAV science. However, transmission electron microscopy (TEM) is the primary tool for distinguishing between empty and full capsids, which creates a research bottleneck because of instrument accessibility and technical difficulty. Herein, we demonstrate that atomic force microscopy (AFM) can be an alternative tool to TEM. The simple, noncontact-mode imaging of AAV particles allows the distinct height difference between full capsids (∼22 nm) and empty capsids (∼16 nm). The sphere-to-ellipsoidal morphological distortion observed for empty AAV particles clearly distinguishes them from full AAV particles. Our study indicates that AFM imaging can be an extremely useful, quality-control tool in AAV particle monitoring, which is beneficial for the future development of AAV-based gene therapy.
View details for DOI 10.1021/acs.langmuir.3c00241
View details for Web of Science ID 000984249100001
View details for PubMedID 37130261
Silk Fibroin/Tannin/ZnO Nanocomposite Hydrogel with Hemostatic Activities
2022; 8 (10)
The inevitable bleeding and infections caused by disasters and accidents are the main causes of death owing to extrinsic trauma. Hemostatic agents are often used to quickly suppress bleeding and infection, and they can solve this problem in a short time. Silk fibroin (SF) has poor processibility in water, owing to incomplete solubility therein. In this study, aiming to overcome this disadvantage, a modified silk fibroin (SF-BGE), easily soluble in water, was prepared by introducing butyl glycidyl ether (BGE) into its side chain. Subsequently, a small amount of tannic acid (TA) was introduced to prepare an SF-BGE /TA solution, and ZnO nanoparticles (NPs) were added to the solution to form the coordination bonds between the ZnO and TA, leading to an SF-based nanocomposite hydrogel. A structural characterization of the SF-BGE, SF-BGE/TA, SF-BGE/TA/ZnO, and the coordination bonds between ZnO/TA was observed by attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR), and the phase change was observed by rheological measurements. The pore formation of the SF-BGE/TA/ZnO hydrogel and dispersibility of ZnO were verified through energy-dispersive X-ray spectroscopy (EDS) and scanning electron microscopy (SEM). The cytocompatible and hemostatic performances of the SF-BGE/TA/ZnO NPs composite hydrogels were evaluated, and the hydrogels showed superior hemostatic and cytocompatible activities. Therefore, the SF-based nanocomposite hydrogel is considered as a promising material for hemostasis.
View details for DOI 10.3390/gels8100650
View details for Web of Science ID 000873039700001
View details for PubMedID 36286151
View details for PubMedCentralID PMC9601499
ZnO nanoparticle-embedded modified silk fibroin-tannin multifunctional hydrogel
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
2022; 210: 1-10
Owing to the destruction of ozone layer, the increased exposure to UV on the earth adversely affects not only skin diseases but also wound healing. Although the demand for sunscreens is increasing to protect the human skin from these adverse effects, commercially available sunscreens have some limitations in safety. In this study, silk fibroin (SF) composite with biocompatibility and blood coagulation activity was prepared for a highly safe sunscreen. However, the SF has a disadvantage in that it is difficult to dissolve in water. To improve the solubility of SF, butyl glycidyl ether (BGE) was reacted with the side chain of SF to prepare a freely water-soluble SF (mSF) derivative, and the phase behavior according to the mixing ratio of SF derivative and tannic acid (TA) was observed. In addition, ZnO nanoparticles were added to the mSF-TA solution to form a hydrogel through the coordination bonding. The UV blocking, hemostatic, antibacterial and antioxidant effects of the mSF/TA/ZnO composite hydrogel were evaluated, and the excellent skin compatibility of multifunctional hydrogel sunscreen was confirmed through a skin irritation test.
View details for DOI 10.1016/j.ijbiomac.2022.05.005
View details for Web of Science ID 000801971000001
View details for PubMedID 35526760
Antagonistically Functionalized Diatom Biosilica for Bio-Triboelectric Generators
2022; 18 (20): e2107638
Although biomaterial-based triboelectric nanogenerators (Bio-TENGs) for use in wearable electronics and implantable sensors have been developed, power generation is not suitable for satisfying the basic requirements for practical applications. Here, to greatly enhance output performances of Bio-TENG devices, an antagonistic approach of diatom frustules (DFs) with amine and fluorine chemical functionalizations is reported. The DFs are treated with piranha solution to increase the density of hydroxyl groups and tribo-positive and tribo-negative composite films are designed with antagonistically functionalized DFs. The tribo-positive composites having electron donating functionality consist of aminated DFs and cellulose nanocrystals (CNCs), while the tribo-negative composite is composed of fluorinated DFs and polydimethylsiloxane (PDMS). An antagonistically and chemically functionalized TENG (ACF TENG) with an efficient contact area of 9.6 cm2 under a force of 8 N and a frequency of 5 Hz exhibits an output voltage of 248 V, a short-circuit current of 16.4 µA, and a power density of 2.01 W m-2 , which is 16.6 times higher than a reference (CNC:PDMS) TENG. This study shows a simple antagonistic approach for chemical functionalization as an efficient method to manipulate the tribo-polarity of bio-additives for enhancing power generation of Bio-TENGs.
View details for DOI 10.1002/smll.202107638
View details for Web of Science ID 000782568300001
View details for PubMedID 35426234
Preparation of External Stimulus-Free Gelatin-Catechol Hydrogels with Injectability and Tunable Temperature Responsiveness
ACS APPLIED MATERIALS & INTERFACES
2022; 14 (1): 236-244
Gelatin is one of the most versatile biopolymers in various biomedical applications. A gelatin derivative gelatin-catechol (Gel-C) was developed in this study to further optimize its chemical and physical properties such as thermal reversibility and injectability. We found that Gel-C remains in a solution state at room temperature, and the temperature-dependent gelation capability of gelatin is well preserved in Gel-C. Its gel-forming temperature decreased to about 10 °C (about 30 °C for gelatin), and a series of gelatin derivatives with different gel-forming temperatures (10-30 °C) were formed by mixing gelatin and Gel-C in different ratios. Additionally, irreversible Gel-C hydrogels could be made without the addition of external stimuli by combining the physical cross-linking of gelatin and the chemical cross-linking of catechol. At the same time, properties of Gel-C hydrogels such as thermal reversibility and injectability could be manipulated by controlling the temperature and pH of the precursor solution. By simulating the formation of an irreversible Gel-C hydrogel in vivo, an in situ gelling system was fabricated by lowering the local temperature of the hydrogel with cold shock, thus realizing targeted and localized molecular delivery with prolonged retention time. This simple system integrated with the temperature responsiveness of gelatin and chemical cross-linking of catechol groups thus provides a promising platform to fabricate an in situ gelling system for drug delivery.
View details for DOI 10.1021/acsami.1c19151
View details for Web of Science ID 000736533500001
View details for PubMedID 34935360
- Stretchable and self-healable catechol-chitosan-diatom hydrogel for triboelectric generator and self-powered tremor sensor targeting at Parkinson disease NANO ENERGY 2021; 82
Mussel-inspired poly(gamma-gl utamic acid)/nanosilicate composite hydrogels with enhanced mechanical properties, tissue adhesive properties, and skin tissue regeneration
2021; 123: 254-262
It was demonstrated herein that the adhesive property of catechol-functionalized nanocomposite hydrogel can be enhanced by tuning the cohesive strength due to the secondary crosslinking between catechol and synthetic bioactive nanosilicate, viz. Laponite (LP). The nanocomposite hydrogel consists of the natural anionic poly(γ-glutamic acid) (γ-PGA), which was functionalized with catechol moiety, and incorporated with disk-structured LP. The dual-crosslinked hydrogel was fabricated by enzymatic chemical crosslinking of catechol in the presence of horseradish peroxidase (HRP) and H2O2, and physical crosslinking between γ-PGA-catechol conjugate and LP. The PGADA/LP nanocomposite hydrogels with catechol moieties showed strong adhesiveness to various tissue layers and demonstrated an excellent hemostatic properties. These PGADA/LP nanocomposite hydrogels are potentially applied for injectable tissue engineering hydrogels, tissue adhesives, and hemostatic materials. STATEMENT OF SIGNIFICANCE: Recently, many attempts have been performed to manufacture high-performance tissue adhesives using synthetic and natural polymer-based materials. In order to apply in various biological substrates, commercially available tissue adhesives should have an improved adhesive property in wet conditions. Here, we designed a mussel-inspired dual crosslinked tissue adhesive that meets most of conditions as an ideal tissue adhesive. The designed tissue adhesive is composed of poly(γ-glutamic acid)-dopamine conjugate (PGADA)-gluing macromer, horseradish peroxidase (HRP)/hydrogen peroxide (H2O2)-enzymatic crosslinker, and Laponite (LP)-additional physical crosslinking nanomaterial. The PGADA hydrogel has tunable physicochemical properties by controlling the LP concentration. Furthermore, this dual crosslinked hydrogel shows strong tissue adhesive property, regardless of the tissue types. Specially the PGADA hydrogel has tissue adhesive strength four times higher than commercial bioadhesive. This dual crosslinked PGADA hydrogel with improved tissue adhesion property is a promising biological tissue adhesive for various tissue type in surgical operation.
View details for DOI 10.1016/j.actbio.2021.01.014
View details for Web of Science ID 000622328000009
View details for PubMedID 33465509
Diatom Bio-Silica and Cellulose Nanofibril for Bio-Triboelectric Nanogenerators and Self-Powered Breath Monitoring Masks
ACS APPLIED MATERIALS & INTERFACES
2021; 13 (1): 219-232
The application of biodegradable and biocompatible materials to triboelectric nanogenerators (TENGs) for harvesting energy from motions of the human body has been attracting significant research interest. Herein, we report diatom bio-silica as a biomaterial additive to enhance the output performance of cellulose nanofibril (CNF)-based TENGs. Diatom frustules (DFs), which are tribopositive bio-silica having hierarchically porous three-dimensional structures and high surface area, have hydrogen bonds with CNFs, resulting in enhanced electron-donating capability and a more roughened surface of the DF-CNF composite film. Hence, DFs were applied to form a tribopositive composite film with CNFs. The DF-CNF biocomposite film is mechanically strong, electron-rich, low-cost, and frictionally rough. The DF-CNF TENG showed an output voltage of 388 V and time-averaged power of 85.5 mW/m2 in the contact-separation mode with an efficient contact area of 4.9 cm2, and the generated power was sufficient for instantaneous illumination of 102 light-emitting diodes. In addition, a cytotoxicity study and biocompatibility tests on rabbit skin suggested that the DF-CNF composite was biologically safe. Moreover, a practical application of the DF-CNF TENG was examined with a self-powered smart mask for human breathing monitoring. This study not only suggests high output performance of biomaterial-based TENGs but also presents the diverse advantages of the DFs in human body-related applications such as self-powered health monitoring masks, skin-attachable power generators, and tactile feedback systems.
View details for DOI 10.1021/acsami.0c18227
View details for Web of Science ID 000611066000017
View details for PubMedID 33375776
Localization of Phenolic Compounds at an Air-Solid Interface in Plant Seed Mucilage: A Strategy to Maximize Its Biological Function?
ACS APPLIED MATERIALS & INTERFACES
2020; 12 (38): 42531-42536
Given a low concentration of phenols in the naturally occurring aqueous lubricant (mucilage) from hydrated seeds, their biological functions should be severely limited. Here, we introduce an undisclosed natural strategy that enables maximization of phenolic functions through exposing the phenols at the air-seed solid interface. Our findings not only offer a new perspective on plant reproduction physiology but also provide insights into an innovative design of lubricating biomaterials with additional phenolic functions.
View details for DOI 10.1021/acsami.0c12357
View details for Web of Science ID 000575557800007
View details for PubMedID 32830951
- Skin-attachable and biofriendly chitosan-diatom triboelectric nanogenerator NANO ENERGY 2020; 75
A Phenol-Amine Superglue Inspired by Insect Sclerotization Process
2020; 32 (43): e2002118
Exoskeletons of insects formed by sclerotization processes exhibit superstrong properties in moduli. Here, it is demonstrated that mimicking the sclerotization process using phenol and polyamine molecules unexpectedly results in a 100% ecofriendly, biocompatible waterborne superglue. Oxygen presented in air and dissolved in water acts as an initiator producing phenolic radical/quinone for superglue curing. Despite synthesis-free uses of water, phenol, and polyamine, its adhesion strength is comparable to commercial epoxy glue showing >6 MPa in lap shear strength. The phenol-amine superglue bonds to various substrates including ceramics, woods, fabrics, plastics, metals, and importantly biological tissues. Due to strong adhesion, the superglue effectively seals wounds within a few seconds, and, due to its waterborne nature, no harmful respiratory effect is observed because of any release of volatile organic compounds. The easy, cost-effective preparation of the phenol-amine superglue can revolutionize varieties of industrial, biomedical, daily life processes.
View details for DOI 10.1002/adma.202002118
View details for Web of Science ID 000562395600001
View details for PubMedID 32844497
Enzymatically Cross-Linked Poly(gamma-glutamic acid) Hydrogel with Enhanced Tissue Adhesive Property
ACS BIOMATERIALS SCIENCE & ENGINEERING
2020; 6 (5): 3103-3113
Enzymatic cross-linking of polymer-catechol conjugates in the presence of horseradish peroxidase (HRP) and H2O2 has emerged as an important method to fabricate in situ-forming, injectable hydrogels. Subsequently, tissue adhesion studies using catechol-containing polymers were extensively reported. However, because of the presence of numerous variables such as polymer concentration, oxidizing agent/enzyme, and stoichiometry, the design of the polymer with optimized tissue adhesive property is still challenging. In this study, a poly(γ-glutamic acid) (γ-PGA)-dopamine (PGADA) conjugate was synthesized, and in situ hydrogels were fabricated via enzymatic cross-linking of a catechol moiety. To optimize the tissue adhesive property of the PGADA hydrogel, the effect of various factors, such as polymer concentration, catechol substitution degree (DS), HRP concentration, and H2O2 content, on the gelation behavior and mechanical strength was investigated. The gelation behavior of PGADA hydrogels was characterized using a rheometer and rotational viscometer. Also, the possibility of its use as a tissue adhesive was examined by evaluating the tissue adhesion strength in vitro and ex vivo.
View details for DOI 10.1021/acsbiomaterials.0c00411
View details for Web of Science ID 000535188500055
View details for PubMedID 33463298
Toxicity-Attenuated Glycol Chitosan Adhesive Inspired by Mussel Adhesion Mechanisms
ADVANCED HEALTHCARE MATERIALS
2019; 8 (14): e1900275
Chitosan-catechol, inspired from mussel-adhesive-proteins, is characterized by the formation of an adhesive membrane complex through instant bonding with serum proteins not found in chitosan. Using this intrinsic property, chitosan-catechol is widely applied for hemostatic needles, general hemostatic materials, nanoparticle composites, and 3D printing. Despite its versatility, the practical use of chitosan-catechol in the clinic is limited due to its undesired immune responses. Herein, a catechol-conjugated glycol chitosan is proposed as an alternative hemostatic hydrogel with negligible immune responses enabling the replacement of chitosan-catechol. Comparative cellular toxicity and in vivo skin irritation between chitosan-catechol and glycol chitosan-catechol are evaluated. Their immune responses are also assessed using histological analysis after subcutaneous implantation into mice. The results show that glycol chitosan-catechol significantly attenuates the immune response compared with chitosan-catechol; this finding is likely due to the antibiofouling effect of ethylene glycol groups and the reduced adhesion of immune cells. Finally, the tissue adhesion and hemostatic ability of glycol chitosan-catechol hydrogels reveal that these ethylene glycol groups do not dramatically modify the adhesiveness and hemostatic ability compared with nonglycol chitosan-catechol. This study suggests that glycol chitosan-catechol can be a promising alternative to chitosan-catechol in various biomedical fields such as hemostatic agents.
View details for DOI 10.1002/adhm.201900275
View details for Web of Science ID 000477042600008
View details for PubMedID 31091015
Phenolic condensation and facilitation of fluorescent carbon dot formation: a mechanism study
2017; 9 (43): 16596-16601
Fluorescent carbon dots have received considerable attention as a result of their accessibility and potential applications. Although several prior studies have demonstrated that nearly any organic compound can be converted into carbon dots by chemical carbonization processes, mechanisms explaining the formation of carbon dots still remain unclear. Herein, we propose a seed-growth mechanism of carbon dot formation facilitated by ferulic acid, a widespread and naturally occurring phenolic compound in the seeds of Ocimum basilicum (basil). Ferulic acid triggers the local condensation of polysaccharide chains and forms catalytic core regions resulting in nanoscale carbonization. Our study indicates that carbon dots generated from natural sources might share the similar mechanism of phenolic compound mediated nanoscale condensation followed by core carbonization.
View details for DOI 10.1039/c7nr04170e
View details for Web of Science ID 000414960900006
View details for PubMedID 29071324
View details for PubMedCentralID PMC5687888