Tae-Il Son

Preparation of Furfuryl-Fish Gelatin (F-f.gel) Cured Using Visible-Light and Its Application as an Anti-Adhesion Agent

AbstractAdhesions occurring on a variety tissues and operation sites are a serious side effect of surgery and may require additional surgery for removal. Therefore, Furfuryl-fish gelatin (F-f.gel) was synthesized by introducing a furan ring to fish gelatin for application as an anti-adhesion agent. F-f.gel was cured by visible-light irradiation, which changed the material from a solution to a film. The prepared F-f.gel was characterized by proton nuclear magnetic resonance spectroscopy (1H NMR), substitution ratio, gel permeation chromatography (GPC), methyl thiazolyl tetrazolium (MTT) assay, and tests for measuring photo immobilization, water contact angle (WCA), and cell attachment. The results showed that F-f.gel was effective as an anti-adhesion agent.

Photocurable O-Carboxymethyl Chitosan Derivatives for Biomedical Applications: Synthesis, In vitro Biocompatibility, and Their Wound Healing Effects

AbstractIn this work, photocurable water-soluble chitosan derivatives were prepared for biomedical applications by modifying water-soluble O-carboxymethyl chitosan (O-CMC) derivatives with furfuryl glycidyl ether (O-CMC/FGE). Successful derivatization of chitosan to the final product (O-CMC/FGE) was verified by UV and 1H NMR spectral analysis. The degree of photo-crosslinking was measured by a flow distance experiment after exposure to visible light for a certain period of time. The degree of crosslinking increased linearly in proportion to exposure time. The in vitro cell viability test revealed a lack of cytotoxicity of O-CMC/FGE against mouse 3T3 fibroblasts. However, poor cell attachment was observed for the cells seeded onto the photocured O-CMC/FGE; this is likely due to the anionic nature of this material. O-CMC/FGE displayed wound healing effects in an in vivo animal experiment using a burn wound model. Due to its good biocompatibility, wound healing effect, and mild cross-linking condition, together with an inhibitory effect on cell attachment, O-CMC/FGE would be a promising candidate as an anti-adhesion material for biomedical applications.

Preparation of UV-curable gelatin derivatives for drug immobilization on polyurethane foam: Development of wound dressing foam

UV-curable azidophenyl-fish gelatin (azidophenyl-f.gel) for developing a wound-dressing foam was prepared by introducing the photo-reactive azidophenyl group of N-4-(azido)-benzoyloxysuccinimide (ABS) to fish gelatin. The structure of prepared azidophenyl-f.gel was identified by 1H NMR and FTIR. The biocompatibility of azidophenyl-f.gel was demonstrated through a cell cytotoxicity experiment. In order to demonstrate that azidophenyl-f.gel is photo-cured on polyurethane foam by UV irradiation, a patterning test was conducted, and the protein immobilization of azidophenyl-f.gel was demonstrated through fluorescence microscopy by using FITC-BSA. The protein release pattern in relation to the concentration of azidophenyl-f.gel and the number of underlying layers of polyurethane foam was observed, and the effect of the protein release pattern on cell growth was observed through cell proliferation. Water absorbency and moisture vapour transmission rate (MVTR) tests were conducted to measure the performance of the wound dressing foam, and a wound healing effect was observed through an in vivo animal experiment. These results demonstrate that UV-curable azidophenyl-f.gel is biocompatible and can immobilize protein by UV irradiation. It is a useful material that can be applied to the underlying layer of wound dressing foam to induce rapid wound healing by gradually releasing immobilized protein.

Wound healing effect of visible light-curable chitosan with encapsulated EGF

Low molecular O-carboxymethyl chitosan, a derivative of chitosan, was conjugated with a hydrophilic carboxymethyl group, following which the conjugate was modified with a furfuryl group. The chitosan derivative was cross-linked to encapsulate a model protein, bovine serum albumin (BSA), in the presence of Rose Bengal under visible light irradiation. The encapsulated BSA was slowly released from the matrix over 2 weeks. The modified chitosan exhibited antimicrobial activity and was non-cytotoxic to NIH3T3 fibroblasts. The wound healing effect of the cross-linked chitosan derivative was examined in Sprague-Dawley rats at 3, 7, and 14 days post-wounding. Cross-linked and murine epidermal growth factor (mEGF)-encapsulated chitosan derivatives healed wounds more rapidly in rats than non-encapsulated mEGF or chitosan derivative alone. Thus, visible light-curable chitosan has good potential for application as wound-healing matrix.

Preparation and in vivo evaluation of photo-cured O-carboxymethyl chitosan micro-particle for controlled drug delivery

Medical advances have prompted the research and development of biomaterials. Especially, chitosan has emerged as new generation of biomaterials because it beneficial properties as a natural polymer, such as less toxic, biodegradable, and biocompatible than synthetic ones. The prepared azidophenyl O-carboxymethyl chitosan (Az-O-CMC) was characterized by FTIR, 1H NMR and particle-size analyzer. The hardening rate and cross-linking maintenance of the Az-O-CMC were investigated with its irradiation time and concentration. A photo-mask was used for observation of photoimmobilization. 3T3-L1 cells were cultured to determine effect of cytotoxicity. Protein release test was conducted to evaluate the immobilizing effect. In addition, animal test was investigated for wound healing application. In this study, the results indicate that immobilization of protein with Az-O-CMC will be useful for medical application.

Preparation of photoreactive azidophenyl hyaluronic acid derivative: Protein immobilization for medical applications

AbstractPhotoreactive azidophenyl hyaluronic acid (Az-HA) derivative was synthesized to immobilize proteins such as epidermal growth factor (EGF) and bone morphogenetic protein (BMP). The photosensitizing group, 4-azidoaniline, was introduced to the carboxyl group of hyaluronic acid by a water soluble carbodiimide, 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC). To characterize the synthesized Az-HA, Fourier transform infrared (FTIR), proton nuclear magnetic resonance (1H NMR) and ultraviolet/visible (UV/vis) absorbance spectroscopy were performed. We demonstrated protein immobilization by using fluorescein isothiocyanate conjugated albumin (FITCBSA) on Az-HA derivative surfaces that were patterned with micro scale. Cytotoxicity and relative cell proliferation tests of the Az-HA derivative were performed on an MG-63 human osteoblast cell line for biocompatibility.

Visible and UV-curable chitosan derivatives for immobilization of biomolecules

Chitosan, which has many biocompatible properties, is used widely in medical field like wound healing, drug delivery and so on. Chitosan could be used as a biomaterial to immobilize protein-drug. There are many methods to immobilize protein-drug, but they have some drawbacks such as low efficiency and denaturation of protein. Therefore, photo-immobilization method is suggested to immobilize protein-drug. Photo-immobilization method is simple-reaction and also needs no additional crosslinking reagent. There has been some effort to modify chitosan to have an ability of photo-immobilization. Generally, visible and UV light reactive chitosan derivatives were prepared. Various types of photo-curable chitosan derivatives showed possibility for application to medical field. For example, they showed ability for protein-immobilization and some of them showed wound-healing effect, anti-adhesive effect, or property to interact directly with titanium surface. In this study, we introduce many types of photo-curable chitosan derivative and their possibility of medical application.

Enhancement effect of cell adhesion on titanium surface using phosphonated low-molecular-weight chitosan derivative

For improving cell adhesion on titanium surface, phosphonated low-molecular-weight chitosan (P-LMC) was prepared by introducing a phosphonate group of 4-phosphonobutyric acid to low-molecular-weight chitosan (3,000<MW<10,000). The phosphonate group of P-LMC was identified by 31P NMR. At about 30 ppm from external standard, there was a specific peak derived from phosphonate group. X-Ray Photoelectron Spectroscopy (XPS) and water contact angle were carried out for characterization of titanium surface treated with P-LMC. From these results, P-LMC coated on titanium surface was remained on that in spite of washing and P-LMC made titanium surface more hydrophilic. The biocompatibility of P-LMC was demonstrated through a cytotoxicity test using the C2C12 cell line because P-LMC should have no cytotoxicity for applying to dental implant materials. As a result, P-LMC was biocompatible to use as coating material of titanium. Improvement of cell adhesion on titanium surface treated with P-LMC was observed by microscopy, and the number of attached cells was counted using a hemocytometer. Titanium surface coated with P-LMC showed improved cell adhesion for 12 h. These results demonstrate that P-LMC is biocompatible and titanium surface treated with P-LMC has positive effects on cell adhesion. Therefore, P-LMC is a useful material that can be applied for titanium coating to enhance cell adhesion and osseointegration.

The immobilization of bone morphogenetic protein-2 via photo curable azidophenyl hyaluronic acid on a titanium surface and providing effect for cell differentiation

AbstractTitanium and its alloys have been used for a wide range of dental implant materials because of their biocompatible properties. Due to the osseointegration between the bone and implant surface that is required after implantation surgery, surface modification of titanium has been investigated. Even though bone morphogenetic protein-2 (BMP-2) and other growth factors have been applied to increase the efficiency of osseointegration, their short half-life has been a disadvantage. In this study, BMP-2 was photo-immobilized on a titanium surface using azidophenyl hyaluronic acid (Az-HA) as a matrix, and C2C12 cell lines were cultured on the modified surface. The photoreactive azidophenyl hyaluronic acid was prepared and characterized in a previous report. To demonstrate the osteoinductive effect of the photo-immobilized BMPs, alkaline phosphatase (ALP) activity assay, calcium detection assay, and alizarin red staining were conducted.

Injectable photoreactive azidophenyl hyaluronic acid hydrogels for tissue augmentation

AbstractA photoreactive azidophenyl hyaluronic acid (Az-HA) derivative for tissue augmentation was prepared by direct amide bond formation between the carboxyl groups of HA and the amine groups of 4-azidoaniline. 4-Azidoaniline was introduced to the carboxyl group of hyaluronic acid that was activated by 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC). The prepared Az-HA derivative was characterized by 1H NMR to measure the degree of modification. The Az-HA derivative was photo-cross-linked with varying UV irradiation times. Az-HA-20 hydrogels were formulated into injectable gels for soft tissue augmentation. The morphology, equilibrium swelling, rheological property, and in vitro degradation of hydrogels were examined. The cell cytotoxicity test of the Az-HA derivative was also examined. Az-HA-20 formed stronger hydrogels with higher storage modulus (Pa’) as UV irradiation time increased. Also, the in vitro degradation rate was lower as UV irradiation time increased. This study demonstrates that Az-HA-20 hydrogels have potential for use as injectable, biodegradable, and biocompatible hydrogels for tissue augmentation.