Ji Hyun Ryu

Mussel‐Inspired Adhesive Binders for High‐Performance Silicon Nanoparticle Anodes in Lithium‐Ion Batteries

Conjugation of mussel-inspired catechol groups to various polymer backbones results in materials suitable as silicon anode binders. The unique wetness-resistant adhesion provided by the catechol groups allows the silicon nanoparticle electrodes to maintain their structure throughout the repeated volume expansion and shrinkage during lithiation cycling, thus facilitating substantially improved specific capacities and cycle lives of lithium-ion batteries.

Catechol-Functionalized Chitosan/Pluronic Hydrogels for Tissue Adhesives and Hemostatic Materials

Bioinspired from adhesion behaviors of mussels, injectable and thermosensitive chitosan/Pluronic composite hydrogels were synthesized for tissue adhesives and hemostatic materials. Chitosan conjugated with multiple catechol groups in the backbone was cross-linked with terminally thiolated Pluronic F-127 triblock copolymer to produce temperature-sensitive and adhesive sol-gel transition hydrogels. A blend mixture of the catechol-conjugated chitosan and the thiolated Pluronic F-127 was a viscous solution state at room temperature but became a cross-linked gel state with instantaneous solidification at the body temperature and physiological pH. The adhesive chitosan/Pluronic injectable hydrogels with remnant catechol groups showed strong adhesiveness to soft tissues and mucous layers and also demonstrated superior hemostatic properties. These chitosan/Pluronic hydrogels are expected to be usefully exploited for injectable drug delivery depots, tissue engineering hydrogels, tissue adhesives, and antibleeding materials.

Chitosan Oligosaccharide-Stabilized Ferrimagnetic Iron Oxide Nanocubes for Magnetically Modulated Cancer Hyperthermia

Magnetic nanoparticles have gained significant attention as a therapeutic agent for cancer treatment. Herein, we developed chitosan oligosaccharide-stabilized ferrimagnetic iron oxide nanocubes (Chito-FIONs) as an effective heat nanomediator for cancer hyperthermia. Dynamic light scattering and transmission electron microscopic analyses revealed that Chito-FIONs were composed of multiple 30-nm-sized FIONs encapsulated by a chitosan polymer shell. Multiple FIONs in an interior increased the total magnetic moments, which leads to localized accumulation under an applied magnetic field. Chito-FIONs also exhibited superior magnetic heating ability with a high specific loss power value (2614 W/g) compared with commercial superparamagnetic Feridex nanoparticles (83 W/g). The magnetically guided Chito-FIONs successfully eradicated target cancer cells through caspase-mediated apoptosis. Furthermore, Chito-FIONs showed excellent antitumor efficacy on an animal tumor model without any severe toxicity.

Bioinspired, Calcium-Free Alginate Hydrogels with Tunable Physical and Mechanical Properties and Improved Biocompatibility

Alginate hydrogels are for various biomedical applications including tissue engineering, cell therapy, and drug delivery. However, it is not easy to control swelling or viscoelastic and biophysical properties of alginate hydrogels prepared by conventional cross-linking methods (ionic interaction using divalent cations). In this study, we describe a bioinspired approach for preparing divalent ion-free alginate hydrogels that exhibit tunable physical and mechanical properties and improved biocompatibility due to the absence of cations in the gel matrices. We conjugated dopamine, a minimalized adhesive motif found in the holdfast pads of mussels, to alginate backbones (alginate-catechol) and the tethered catechols underwent oxidative cross-linking. This resulted in divalent cation-free alginate hydrogels. The swelling ratios and moduli of the alginate-catechol hydrogels are readily tunable, which is difficult to achieve in ionic bond-based alginate hydrogels. Furthermore, alginate-catechol hydrogels enhanced the survival of various human primary cells including stem cells in the three-dimensional gel matrix, indicating that intrinsic cytotoxicity caused by divalent cations becomes negligible when employing catechol oxidation for alginate cross-linking. The inflammatory response in vivo was also significantly attenuated compared to conventional alginate hydrogels with calcium cross-linking. This biomimetic approach for the preparation of alginate hydrogels may provide a novel platform technology to develop tunable, functional, biocompatible, three-dimensional scaffolds for tissue engineering and cell therapy.

Chitosan-catechol: A polymer with long-lasting mucoadhesive properties

Numerous mucoadhesive polymers have been exploited for prolonging the residence time of formulated drugs or pharmaceuticals at specific delivery sites. However, it has been difficult to achieve satisfactory mucoadhesive properties. The two major modification strategies such as thiolation or lectin functionalization have been extensively studied, but disulfide bond reversibility in the case of thiolation and the toxicity of lectins have been problems. Thus, approaches for further improvement of mucoadhesive properties need to be developed. With an overwhelming library of mucoadhesive polymers, one practical way to improve mucoadhesion is chemical modification of existing mucoadhesive polymers. In other words, the method is based on utilizing the cooperative effect that might be achieved by chemical tethering of a small adhesive moiety to an available mucoadhesive polymer. Here, we conjugated catechols derived from mussel adhesive proteins to chitosan, which is a widely known mucoadhesive polymer. We demonstrated that the gastrointestinal (GI) tract retention of chitosan-catechol was improved compared to unmodified chitosan, which is due to the formation of irreversible catechol mediated-crosslinking with mucin. The results indicate that catechol modification of mucoadhesive polymers may possibly lead to a new generation of mucoadhesive polymers for mucosal drug delivery.

Bio-inspired adhesive catechol-conjugated chitosan for biomedical applications: A mini review

The development of adhesive materials, such as cyanoacrylate derivatives, fibrin glues, and gelatin-based adhesives, has been an emerging topic in biomaterial science because of the many uses of these materials, including in wound healing patches, tissue sealants, and hemostatic materials. However, most bio-adhesives exhibit poor adhesion to tissue and related surfaces due to the presence of body fluid. For a decade, studies have aimed at addressing this issue by developing wet-resistant adhesives. Mussels demonstrate robust wet-resistant adhesion despite the ceaseless waves at seashores, and mussel adhesive proteins play a key role in this adhesion. Adhesive proteins located at the distal end (i.e., those that directly contact surfaces) are composed of nearly 60% of amino acids called 3,4-dihydroxy-l-phenylalanine (DOPA), lysine, and histidine, which contain side chains of catechol, primary amines, and secondary amines, respectively. Inspired by the abundant catecholamine in mussel adhesive proteins, researchers have developed various types of polymeric mimics, such as polyethylenimine-catechol, chitosan-catechol, and other related catecholic polymers. Among them, chitosan-catechol is a promising adhesive polymer for biomedical applications. The conjugation of catechol onto chitosan dramatically increases its solubility from zero to nearly 60mg/mL (i.e., 6% w/v) in pH 7 aqueous solutions. The enhanced solubility maximizes the ability of catecholamine to behave similar to mussel adhesive proteins. Chitosan-catechol is biocompatible and exhibits excellent hemostatic ability and tissue adhesion, and thus, chitosan-catechol will be widely used in a variety of medical settings in the future. This review focuses on the various aspects of chitosan-catechol, including its (1) preparation methods, (2) physicochemical properties, and (3) current applications.

Bio-inspired catechol conjugation converts water-insoluble chitosan into a highly water-soluble, adhesive chitosan derivative for hydrogels and LbL assembly

This report describes a simple method to prepare water-soluble chitosan derivative by conjugation of an enediol group, catechol. Chitosan functionalized with a catechol-containing compound, 3,4-dihydroxyhydrocinnamic acid, by a carbodiimide coupling method resulted in chitosan-catechol conjugates. This one-step chemical modification of high-molecular-weight chitosan (approximately 100 kDa) dramatically increased the water solubility of the chitosan derivative to 60 mg mL-1 at pH 7.0. The degree of catechol conjugation was found critical in determining the solubility. The chitosan-catechol conjugates are not only water-soluble but are adhesive, due to the intrinsic adhesive properties of catechol. Also, the water-soluble chitosan derivative allows one to directly form chitosan hydrogel in neutral buffer solutions. The utility of both the water solubility and the adhesive property of the chitosan-catechol was demonstrated by the effective layer-by-layer assembly on substrates. The water-soluble chitosan-catechol is expected to be useful in many areas of surface functionalization, drug delivery, tissue engineering, and tissue adhesives.

Bioinspired templating synthesis of metal-polymer hybrid nanostructures within 3D electrospun nanofibers.

Novel metal nanostructures immobilized within three-dimensional (3D) porous polymeric scaffolds have been utilized for catalysts and biosensors. However, efficient, robust immobilization of the nanostructures both outside and inside of the 3D scaffolds is a challenging task. To address the challenge, we synthesized a redox-active polymer, catechol-grafted poly(vinyl alcohol), PVA-g-ct. The grafted catechol is inspired by the adhesion mechanism of marine mussels, which facilitates binding and reduction of noble metal ions. Electrospinning the PVA-g-ct polymer results in highly open porous, 3D nanostructures, on which catechol mediates the spontaneous reduction of silver ions to solid silver nanocubes at an ambient temperature. Yet, gold and platinum ions are partially reduced and complexed with the nanofiber template, requiring an additional thermal treatment for complete reduction into solid metal nanostructures. Furthermore, silver-gold and silver-platinum hybrid nanostructures are generated by sequential treatments with metal ion precursor solutions of each. This study suggests that catechol-grafted polymer nanofibers are an attractive reactive template for the facile synthesis and immobilization of noble metal nanostructures within a 3D porous matrix for the potential applications to sensors, catalysis, and tissue engineering.

Chitosan-g-hematin: Enzyme-mimicking polymeric catalyst for adhesive hydrogels

Phenol derivative-containing adhesive hydrogels has been widely recognized as having potential for biomedical applications, but their conventional production methods, utilizing a moderate/strong base, alkaline buffers, the addition of oxidizing agents or the use of enzymes, require alternative approaches to improve their biocompatibility. In this study, we report a polymeric, enzyme-mimetic biocatalyst, hematin-grafted chitosan (chitosan-g-hem), which results in effective gelation without the use of alkaline buffers or enzymes. Furthermore, gelation occurs under mild physiological conditions. Chitosan-g-hem biocatalyst (0.01%, w/v) has excellent catalytic properties, forming chitosan-catechol hydrogels rapidly (within 5 min). In vivo adhesive force measurement demonstrated that the hydrogel formed by the chitosan-g-hem activity showed an increase in adhesion force (33.6 ± 5.9 kPa) compared with the same hydrogel formed by pH-induced catechol oxidation (20.6 ± 5.5 kPa) in mouse subcutaneous tissue. Using the chitosan-g-hem biocatalyst, other catechol-functionalized polymers (hyaluronic acid-catechol and poly(vinyl alcohol)-catechol) also formed hydrogels, indicating that chitosan-g-hem can be used as a general polymeric catalyst for preparing catechol-containing hydrogels.

STAPLE: Stable Alginate Gel Prepared by Linkage Exchange from Ionic to Covalent Bonds

S. H. Hong, Dr. J. H. Ryu, Prof. H. Lee Department of Chemistry Korea Advanced Institute of Science and Technology (KAIST) 291 Daehak-ro , Yuseong-gu , Daejeon 305-701 , South Korea E-mail: haeshin@kaist.ac.kr M. Shin Graduate School of Nanoscience and Technology Korea Advanced Institute of Science and Technology (KAIST) 291 Daehak-ro , Yuseong-gu , Daejeon 305-701 , South Korea Dr. J. Lee, S. Lee, Dr. W. D. Kim Department of Nature-Inspired Nano Convergence Systems Korea Institute of Machinery and Materials(KIMM) 156 Gajeongbuk-Ro, Yuseong-gu , Daejeon 305-343 , South Korea Prof. J. W. Yang Department of Ophthalmology Inje University Pusan Paik Hospital Inje University College of Medicine Busan , South Korea