Jun Jae Lee

Mesoporous silica with fibrous morphology: a multifunctional core–shell platform for biomedical applications

Multifunctional mesoporous silica nanocomposites are attractive carriers for targeted drug delivery in nanomedicine. Although promising developments have been made in the fabrication of multifunctional mesoporous silica nanocomposites, the design and mass production of novel multifunctional carriers are still challenging. This paper reports the facile one-pot fabrication of a multifunctional inorganic composite composed of superparamagnetic Fe3O4 nanoparticles and coated dye-functionalized mesoporous silica with a high specific surface area. The resulting composite particles had a tunable particle size, special open pore channels with high specific surface area, which is quite favorable for drug loading and release properties, as well as luminescent and superparamagnetic properties suitable for targeted drug delivery and tracking. This composite exhibited low toxicity, suggesting potential biomedical applications.

Preventive Effects of Epigallocatechin-3-O-Gallate against Replicative Senescence Associated with p53 Acetylation in Human Dermal Fibroblasts

Considering the various pharmacological activities of epigallocatechin-3-O-gallate (EGCG) including anticancer, and anti-inflammatory, antidiabetic, and so forth, relatively less attention has been paid to the antiaging effect of EGCG on primary cells. In this study, the preventive effects of EGCG against serial passage-induced senescence were investigated in primary cells including rat vascular smooth muscle cells (RVSMCs), human dermal fibroblasts (HDFs), and human articular chondrocytes (HACs). The involvement of Sirt1 and acetylated p53 was examined as an underlying mechanism for the senescence preventive activity of EGCG in HDFs. All cells were employed with the initial passage number (PN) between 3 and 7. For inducing senescence, the cells were serially passaged at the predetermined times and intervals in the absence or presence of EGCG (50 or 100 μM). Serial passage-induced senescence in RVSMCs and HACs was able to be significantly prevented at 50 μM EGCG, while in HDFs, 100 μM EGCG could significantly prevent senescence and recover their cell cycle progression close to the normal level. Furthermore, EGCG was found to prevent serial passage- and H2O2-induced senescence in HDFs by suppressing p53 acetylation, but the Sirt1 activity was unaffected. In addition, proliferating HDFs showed similar cellular uptake of FITC-conjugated EGCG into the cytoplasm with their senescent counterparts but different nuclear translocation of it from them, which would partly account for the differential responses to EGCG in proliferating versus senescent cells. Taking these results into consideration, it is suggested that EGCG may be exploited to craft strategies for the development of an antiaging or age-delaying agent.

Hyaluronic Acid/PLGA Core/Shell Fiber Matrices Loaded with EGCG Beneficial to Diabetic Wound Healing

During the last few decades, considerable research on diabetic wound healing strategies has been performed, but complete diabetic wound healing remains an unsolved problem, which constitutes an enormous biomedical burden. Herein, hyaluronic acid (HA)/poly(lactic-co-glycolic acid, PLGA) core/shell fiber matrices loaded with epigallocatechin-3-O-gallate (EGCG) (HA/PLGA-E) are fabricated by coaxial electrospinning. HA/PLGA-E core/shell fiber matrices are composed of randomly-oriented sub-micrometer fibers and have a 3D porous network structure. EGCG is uniformly dispersed in the shell and sustainedly released from the matrices in a stepwise manner by controlled diffusion and PLGA degradation over four weeks. EGCG does not adversely affect the thermomechanical properties of HA/PLGA-E matrices. The number of human dermal fibroblasts attached on HA/PLGA-E matrices is appreciably higher than that on HA/PLGA counterparts, while their proliferation is steadily retained on HA/PLGA-E matrices. The wound healing activity of HA/PLGA-E matrices is evaluated in streptozotocin-induced diabetic rats. After two weeks of surgical treatment, the wound areas are significantly reduced by the coverage with HA/PLGA-E matrices resulting from enhanced re-epithelialization/neovascularization and increased collagen deposition, compared with no treatment or HA/PLGA. In conclusion, the HA/PLGA-E matrices can be potentially exploited to craft strategies for the acceleration of diabetic wound healing and skin regeneration.

Development of epigallocatechin gallate-eluting polymeric stent and its physicochemical, biomechanical and biological evaluations

Localized drug delivery from drug-eluting stents has been accepted as one of the most promising treatment methods for preventing restenosis after stenting. However, hypersensitivity reactions caused by their nonresorbable polymer coatings and bare-metal stents may result in serious clinical sequelae. Epigallocatechin-3-O-gallate (EGCG), the predominant catechin from tea, has been shown to exert anti-thrombotic, anti-inflammatory and anti-proliferative activities. In this study, it was hypothesized that sustainedly released EGCG from biodegradable poly(lactide-co-epsilon-caprolactone, PLCL) would suppress the proliferation of vascular smooth muscle cells (VSMCs). EGCG-releasing PLCL (E-PLCL) was prepared by blending PLCL with EGCG. The surface morphology, roughness and melting temperature of PLCL were not changed despite EGCG addition. EGCG was uniformly dispersed into E-PLCL and sustainedly released for periods up to 7 days by controlled diffusion rather than PLCL degradation. Moreover, EGCG did not affect tensile strength at break, but significantly increased the elastic modulus of PLCL. The proliferation of VSMCs onto E-PLCL was significantly suppressed although the cell attachment onto E-PLCL had been higher than that onto PLCL. On the other hand, EGCG-eluting polymeric stents were prepared with neither cracks nor webbings between struts, and their structural integrity was maintained without delamination or destruction. These results suggest that E-PLCL can be potentially applied for fabricating an EGCG-eluting vascular stent, namely an EGCG-eluting polymeric stent, or even an EGCG-releasing polymer-coated metal stent, to prevent thrombosis, inflammation and in-stent restenosis.

Cell imaging and DNA delivery in fibroblastic cells by conjugated polyelectrolytes

This study concentrates on the potential application of conjugated polyelectrolytes (CPEs) to cell imaging and DNA delivery. Four different types of polyfluorene copolymers, namely, PAHFP‐Br, PAEFP‐Br, PAHFbT‐Br, and PSBFP‐Na, which have the same π‐conjugated backbone but different side chains, were synthesized. For cytotoxicity testing, L‐929 fibroblastic cells were treated with increasing concentrations (0–50 µM) of each CPE and then cell viability was determined by WST‐8 assay. Cellular uptake of CPEs into cultured L‐929 cells was observed by fluorescence microscopy. To examine DNA delivery by CPEs, the cells were incubated for 1 H with PAHFP‐Br/fluorescein (Fl)‐labeled single‐stranded DNA (ssDNA‐Fl) complex and then visualized by fluorescence microscopy. Cytotoxicity of CPEs was increased in a dose‐dependent manner but at lower than 10 µM, PAHFP‐Br, PAEFP‐Br, and PSBFP‐Na did not show any cytotoxic effects on the cells. When added to cell cultures at 1 µM, PAHFP‐Br/ssDNA‐Fl complex was delivered and then dissociated into PAHFP‐Br and ssDNA‐Fl within the cells. This result implies that PAHFP‐Br can enable cell imaging and DNA delivery into fibroblastic cells. Therefore, it is suggested that PAHFP‐Br with various advantages such as low cytotoxicity and high fluorescence efficiency can be extensively used as a potential agent for cell imaging and gene delivery.

Vascular Smooth Muscle Cell Behaviors onto Epigallocatechin- 3-O-Gallate-Blended L-Lactide/ε-Caprolactone Copolymers

In this study, such behaviors of vascular smooth muscle cells (VSMCs), as proliferation and migration, with serum stimulation were investigated onto (−)-epigallocatechin-3-O-gallate (EGCG)-blended poly(L-lactide-co-ε-caprolactone, PLCL) copolymers (EGCG-b PLCL). VSMCs were primarily cultured from rat aorta, and EGCG-b PLCL films were fabricated by mixing PLCL with EGCG. The proliferation of VSMCs cultured onto EGCG-b PLCL film was significantly suppressed in spite of serum induction. Moreover, recovery of denuded area by VSMCs receiving conditioned media obtained from EGCG-b films was completely inhibited, whereas VSMCs onto intact films migrated into denuded area in response to serum showing essentially complete recovery. These results suggest that inhibition in the behaviors of serum-stimulated VSMCs may be mediated through the anti-proliferative effects of EGCG released from polymer films, and EGCG-b polymers can be applied for fabricating an EGCG-eluting vascular stent.