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The hydrogel synthesized from biocompatible polyaspartamide, and oxidized dextran had stronger adhesion properties when tested on porcine skin than the commercially available fibrin glue.

Various methods based on gold nanoparticles (AuNPs) have been applied to enhance the photothermal effect. Among these methods, combining gold nanoparticles and stem cells has been suggested as a new technique for elevating the efficiency of photothermal therapy (PT) in terms of enhancing tumor targeting effect. However, to elicit the efficiency of PT using gold nanoparticles and stem cells, delivering large amounts of AuNPs into stem cells without loss should be considered.AuNPs, AuNPs-decorated silica nanoparticles, and silica-capped and AuNPs-decorated silica nanoparticles (SGSs) were synthesized and used to treat human mesenchymal stem cells (hMSCs). After evaluating physical properties of each nanoparticle, the concentration of each nanoparticle was estimated based on its cytotoxicity to hMSCs. The amount of AuNPs loss from each nanoparticle by exogenous physical stress was evaluated after exposing particles to a gentle shaking. After these experiments, in vitro and in vivo photothermal effects were then evaluated.SGS showed no cytotoxicity when it was used to treat hMSCs at concentration up to 20 μg/mL. After intravenous injection to tumor-bearing mice, SGS-laden hMSCs group showed significantly higher heat generation than other groups following laser irradiation. Furthermore, in vivo photothermal effect in the hMSC-SGS group was significantly enhanced than those in other groups in terms of tumor volume decrement and histological outcome.Our results suggest that additional silica layer in SGSs could protect AuNPs from physical stress induced AuNPs loss. The strategy applied in SGS may offer a prospective method to improve PT.

Efficient and long-term stable triplet-triplet annihilation upconversion (TTA-UC) can be achieved by effectively protecting the excited organic triplet ensembles from photoinduced oxygen quenching, and discovery of a new material platform that promotes TTA-UC in ambient conditions is of paramount importance for practical applications. In this study, we present the first demonstration of an organic nonparaffin phase-change material (PCM) as an air-tolerant medium for TTA-UC with a unique solid-liquid phase transition in response to temperature variation. For the proposed concept, 2,4-hexadien-1-ol is used and extensively characterized with several key features, including good solvation capacity, mild melting point (30.5 °C), and exclusive antioxidant property, enabling a high-efficiency, low-threshold, and photostable TTA-UC system without energy-intensive degassing processes. In-depth characterization reveals that the triplet diffusion among the transient species, i.e.

An exosome-mimicking nanovesicle (ENV) system, in which a cell-binding lipid detergent, PEGylated mannosylerythritol lipid effectively deforms the plasma membrane without disrupting the lipid bilayer structure, is proposed.

Achilles tendon regeneration using current tissue engineering techniques requires morphometrically mimetic tendon biomaterials to attain the required microstructural tendon tissue and to achieve the necessary mechanical properties. In this study, we used nano- (400 nm) and micro-groove (5000 nm) patterned polycaprolactone patches (PCL-400, PCL-5000), which offer adequate elastic modulus and biocompatibility. The PCL patches were fabricated via capillary force lithography and were surface modified with 3,4-dihydroxy- l -phenylalanine (DOPA) for increased hydrophilicity. We hypothesized that the resulting biologically surface-modified elastic groove patterned patches would enhance the cell behaviors in vitro and the rat Achilles tendon regeneration in vivo. The micro-groove patterned PCL patches with DOPA coating (DOPA-PCL-5000) exhibited excellent cell elongation, tenogenic differentiation and YAP expression of the mesenchymal stem cells in our in vitro study and these results were further confirmed by application to the rat Achilles tendon rupture model in our in vivo study. DOPA-PCL-5000 induced dramatic regeneration of rat Achilles tendon compared to the other groups, which was further confirmed by the Achilles functional index and histological analysis at 8 weeks. In conclusion, DOPA-PCL-5000 can be used not only for damaged Achilles tendon, but also for various functional tendon regeneration techniques such as rotator cuff, patellar tendon, and flexor tendon.

At clinical transplantation of human adipose derived stem cells (hADSCs), a proteolytic enzyme treatment for harvesting hADSCs must be used but usually causes the disruption of extracellular matrices (ECMs) interconnection. As ECMs-poor hADSCs partially receive the cellular signals, hADSCs deactivated or undergo cell death. Herein, we have proposed a method for delivering ECMs-enriched hADSCs encapsulated with a new polymer for transplanting into ischemic wound sites to enhance the therapeutic angiogenic efficacy. Enzyme free pH-sensitive polymer (EFP) was synthesized and coated on tissue culture plate for hADSCs culture. When the hADSCs were cultured on EFP-coated surfaces, they were easily detached with pH 6.0 buffer solution and dissolved EFP wrapped hADSCs with more ECMs for 48 h. When ECMs enriched-hADSCs were re-adhered, the cells secreted more angiogenic factors under serum free and hypoxic cell culture condition. When injecting ECMs-enriched hADSCs to mouse hindlimb ischemia models, the blood perfusion and blood vessel regeneration rate were significantly higher. Our method for delivering ECMs-enriched stem cells using EFP significantly improved the therapeutic angiogenesis with hADSCs compared to proteolytic enzymatic application.

Light has attracted significant attention as a promising tool in the biomedical and cosmetic industries. However, little is known about the cytotoxic effects of conventional light sources based on their physical effects such as temperature and luminance. Here, the cytotoxic effects of representative light sources, a light-emitting diode (LED) and an organic light-emitting diode (OLED), were studied with human adipose-derived stem cells (hADSCs). Regardless of the identical light energy conditions, LED group induced a higher apoptotic activity in hADSCs than the OLED group due to its significant heat generation compared to OLED as further demonstrated with heat shock protein family gene expression. Additionally, we further confirmed the effect of luminance by irradiating light from LED and OLED under the same temperature and energy conditions. Increased cell proliferation was confirmed in the OLED group, and a significant expression of intracellular reactive oxygen species was observed in the LED group without showing heat shock protein upregulation. Taken together, the differences in cytotoxicity and cellular response after LED irradiation compared with OLED irradiation can be varied with temperature and luminance control. This study suggests that OLED based device could be an alternative and promising light source for future biomedical and cosmetic applications.

Control of the size and shape of nanoparticles significantly impacts the ability to control their physical and chemical properties. In this paper, we introduce a technique to split large nanoparticles into smaller ones. After the addition of ascorbic acid (AA), 50 nm-sized gold (Au) nanoparticles in the form of polycrystals were split into nanoparticles with sizes of 10 nm. We believe that AA plays a critical role in breaking down the Au particles. Additionally, this technique can be used to synthesize small AuPt bimetallic nanoparticles with a small amount of Pt on their surface showing that this reaction could help in the formation of a variety of small Au-based bimetallic nanoparticles.

Ice accumulation on vessels, airplanes, or on the off-shore plants surfaces causes major accidents and difficulties in operation. Therefore, highly efficient and environmentally friendly materials for use as deicing surfaces are in continuous demand. Accordingly, photothermal materials have gained enormous attention owing to their outstanding performance in the removal of ice. Herein, a gold nano-aggregate yolk-shell structure (GNA-YS) was introduced as a deicing material. GNA-YS was homogeneously dispersed in photocurable polyurethane acrylate and used to fabricate a highly efficient and sunlight-responsive GNA-YS film. Upon irradiation with an 810 nm light-emitting diode (LED) (135 mW cm−2), the temperature of the GNA-YS film increased by approximately 70 °C within 2 min, which rapidly (within 6 min) melted the accumulated ice. Moreover, the GNA-YS film exhibited a temperature increase of 15 °C in a refrigerator under LED illumination for 1 min. Additionally excellent stability was confirmed through repeated experiments. The newly developed deicing GNA-YS film has prospective applicability in vessels or airplanes.

Curcumin is a polyphenol extracted from the roots of Curcuma plants that exerts potential anticancer effects. However, owing to its low toxicity, curcumin is known to be effective only at high doses. Here, we report the highly sensitive assessment of curcumin toxicity in human liver cancer cells, which was facilitated using a fabricated conductive platform and an electrochemical detection method. To identify the best platform for assessing cell viability, both electrochemical deposition time (0–150 s) and RGD peptide concentrations (0–0.1 mg/mL) were varied. Unlike other cell types, liver cancer cells showed the highest electrical signals without the modification of cell adhesion peptides. With 120 s of gold deposition under peptide-free conditions, 10,000 cells/chip were detectable within a linear range of 10,000–500,000 cells. Notably, even at low concentrations (e.g., 20 µM), curcumin could inhibit liver cancer cell-specific electrical signals by 45%, which would be undetectable in conventional colorimetric assay (CCK-8). The half-maximal inhibitory concentration (IC50) of curcumin for HepG2 cells was 23.63 µM, which indicates 3.71-fold higher sensitivity than that determined in the CCK-8 assay (IC50 = 87.88 µM). Hence, the developed conductive cell culture platform, in combination with the electrochemical detection method, could serve as a promising tool for detecting toxicity and/or anticancer activity of food-derived compounds in cancer/normal cells.

Transplantation of stem cell spheroids to ischemic tissues has been suggested as an effective method for treating ischemic disease, but its therapeutic efficacy varies according to the preparation methods for spheroids. We hypothesized that increasing cell compaction while preparing spheroids could improve the angiogenic efficacy of spheroids. Optimized human adipose derived stem cell (hADSC) spheroids were shown to upregulate cell adhesion molecule, and angiogenic paracrine factors expression with downregulated senescence and apoptotic markers expression. We noted that the low seeding density (1 × 104 cells (10KS)) had a far lower probability of forming spheroids than higher seeding densities (3 × 104 cells (30KS) and 1 × 105 cells (100KS)). The 30KS spheroids demonstrated higher cell density and expression levels of the angiogenic paracrine factor expression compared to those of 100 KS spheroids. 30KS spheroids with additional incubation (A30KS) showed significantly increased angiogenic paracrine factors and cell adhesion molecule expressions with decreased senescence expression compared to those in 30KS spheroids. Transplanting A30KS spheroids showed significantly enhanced therapeutic angiogenesis in mouse hindlimb ischemia model compared to conventional spheroid transplantation. This study successfully defined a set of novel criteria for spheroid culture, which may contribute to future stem cell therapies.

To maintain the cellular functions of a stem cells for therapeutic tissue engineering, an advanced cell culture method for safe cell dissociation is necessary. We developed a novel cell dissociation method by applying pH-responsive bioreducible polymer on the surface of tissue culture plates (TCPs). We applied acid-responsive bioreducible poly (amino ester) (PAE) as a new candidate for surface coating method to develop alternative cell dissociation method against conventional enzyme (trypsin-ethylene diamine tetra acetic acid (EDTA)) treatment. Human adipose derived stem cells (hADSCs) were cultured on and dissociated from PAE-coated TCPs to compare cell adhesion, cell proliferation, cell viability, and functionality to those of the cells cultured on and dissociated with trypsin-EDTA from normal TCPs without PAE coating. To confirm the in vivo therapeutic efficacy of the hADSCs retrieved from PAE-coated TCPs compared to that of the cells retrieved from normal TCPs with trypsin-EDTA, we induced skin defects at the dorsal area of mice and injected the cells collected from both conditions. With the PAE coating method, cell adhesion, cell proliferation, cell viability, and functionality, especially the angiogenic efficacy, were well preserved when compared to those of the cells treated with trypsin-EDTA. In addition to in vitro results, injecting hADSCs retrieved from PAE-coated TCPs showed similar in vivo angiogenesis and wound closing efficiency compared to those of injecting hADSCs retrieved from normal TCPs with trypsin-EDTA treatment at 2 weeks after the transplantation into mouse skin wound models. We proposed the alternative method for the cell dissociation with pH-responsive bioreducible polymer, PAE. This PAE coating method may lead to the development of alternative cell dissociation method without using enzyme for future regenerative medicine and stem cell therapy.

Despite the advantages of stem cell injection to the skin wound site, this technique is limited in terms of the delivery of therapeutically functional stem cells to the wound site. Considering the abnormal microenvironment of a wound site, even a small damage or loss of cell function induced by severe trypsin treatment might lead to decrement of the therapeutic efficacy of stem cells. In this study, we have synthesized pH-responsive polymer mixed poly(amino ester) (mPAE), which can provide the appropriate cell culture condition for cell growth without cytotoxicity along with the maintenance of extracellular matrix after detachment using low pH (6.0) PBS. Human adipose derive stem cells (hADSCs) cultured on and detached from mPAE-coated tissue culture plates (TCPs) showed similar cell adhesion and angiogenic paracrine factor secretion, compared to hADSCs cultured on and detached from TCPs with trypsin. As a result, hADSCs detached with pH 6.0 PBS from mPAE-coated TCPs showed similar therapeutic angiogenesis and wound regeneration, compared to the hADSCs detached with trypsin from TCPs. In conclusion, our pH-responsive polymer, mPAE, might be utilized as an enzyme-free cell detachment system for future tissue engineering.

This study investigated a selective and sensitive theragnosis system for the specific targeting of the membrane and nuclei based on visible-light and pH-responsive TiO2-integrated cross-linked carbon dot (C-CD/TiO2) for tumor detection and controllable photothermal therapy. The cross-linking system was formed by boronate ester linkages between the TiO2-immobilized Dopa-decyl (D-CD) and zwitterionic-formed CD (Z-CD) for nuclear targeting, which showed fluorescence "off" at physiological pH. The fluorescence recovered to the "on" state in acidic cancer cells owing to cleavages of the boronate ester bonds, resulting in the disruption of the Forster resonance energy transfer that generated different CDs useful for tumor-selective biosensors and therapy. D-CD, which is hydrophobic, can penetrate the hydrophobic sites of the cell membrane; it caused a loss in the hydrophobicity of these sites after visible-light irradiation. This was achieved by the photocatalytic activity of the TiO2 modulating energy bandgap, whereas the Z-CD targeted the nucleus, as confirmed by merged confocal microscopy images. D-CD augmented by photothermal heat also exhibited selective anticancer activity in the acidic tumor condition but showed only minimal effects at a normal site at pH 7.4. After C-CD/TiO2 injection to an in vivo tumor model, C-CD/TiO2 efficiently ablated tumors under NIR light irradiation. The C-CD/TiO2 group showed up-regulation of the pro-apoptotic markers such as P53 and BAX in tumor. This material exhibited its potential as a theragnostic sensor with excellent biocompatibility, high sensitivity, selective imaging, and direct anticancer activity via photothermal therapy.

Curcumin, which is produced by the medicinal herbaceous plant Curcuma longa, has been widely investigated for use as a potential anticancer drug. In this study, the potential toxicity of curcumin-carrying nanoliposomes (curcumin-NLC) toward human stomach cancer cells (MKN-28) was investigated using a new cell-based electrochemical sensing platform. To satisfy both biocompatibility and electroconductivity of the electrodes, the density of the gold nanostructure and the coating conditions of extracellular matrix proteins (fibronectin and collagen) were optimized. The developed platform enabled the successful adhesion and long-term growth of stomach cancer cells on the chip surface, allowing label-free and real-time monitoring of cell viability in a quantitative manner. According to the electrochemical results, both bare curcumin and curcumin-NLC showed toxicity toward MKN-28 cells in the concentration range of 10-100 μM, which was consistent with the results obtained from a conventional colorimetric method (CCK-8). Remarkably, at a low concentration range (

Engineering an endothelium-mimetic surface has been one of long-lasting topics to develop ideal cardiovascular devices. The aim of the study was to investigate the potential use of a model of lipid bilayers that not only come from membranes extracted from endothelial cells (ECs) but also embedded with a type of organoselenium lipid enabling it to catalyze the generation of nitric oxide (NO). Herein, the titanium-cloaking in lipid bilayers extracted from ECs was prepared to propose a promising idea for the development of endovascular implants. For this purpose, we synthesized and characterized a lipidic molecule containing selenium and verified enough catalytic activity for the NO generation in the presence of S-nitrosothiols (RSNO) as endogenous NO precursors. We demonstrated the fabrication process of tethered lipid bilayers, from membrane extraction to vesicle fusion, and validated the successful formation of the layer and the catalyst insertion. The resulting bilayer presented endothelium-similar properties including the NO generation and cellular interactions. The catalyst inserted into the bilayer provided an unexampled result in the release period and kinetics of NO, likely similar to the native endothelial system. Using three different cells including EC, smooth muscle cell (SMC), and macrophage, it was demonstrated that the membrane responds selectively to each cell in the manner of promotive, suppressive, and nonimmunoreactive, respectively. Taken together, the fundamental study on obtained results not only provides understanding of the kinetics of designed NO catalyst and cellular interactions of reassembled membranes but also suggests very useful data on rational design and development of many vascular implantable devices, even expandable toward to nonvascular biointerfacing devices.

In Korea, when replacing or discarding parts of a medical linear accelerator (linac), self-disposal is required in the consideration of the activity, but there is no standard regulation to manage radioactive waste. The aim of this study is to check the activity of each part to determine the disposal time according to the clearance level for self-disposal. The results of measuring the components of the linac head parts of the disposed Varian, Elekta, and Siemens equipment were reflected in the Monte Carlo simulation to confirm the radionuclide change according to the presence or absence of impurities. To confirm the degree of activation of the linac, the main radionuclides according to the time after the linac shutdown, considering the workloads of 40/80 Gy/day of 10/15 MV linac irradiated with beams for 10 years in the results of the simulation of the linac parts, and the radionuclide concentration was confirmed. As a result of applying the clearance level for self-disposal in the notice of the Korean Nuclear Safety (KINS) to each linac head part, most parts of the 10 MV linac could be dismantled after 1 month, and 15 MV target and primary collimators were stored after a long period of time before being dismantled. Although additional radionuclides were identified according to the presence or absence of impurities, the disposal timing for each part did not change significantly. In this study, the clearance level for self-disposal for each radionuclide was applied to activated parts by three manufacturers to confirm the self-disposal timing and predict the timing at which workers are not exposed to radiation during dismantling/disposal.

Due to their heat-generating property based on exogenous energy irradiation, reduced graphene oxide particles (RGOs) have been widely used for photothermal cancer therapy. They show high absorbance for the near-infrared wavelength that is suitable for in vivo experimentation. However, enhancing the tumor-targeting efficiency and avoiding the self-aggregation of RGO to maximize the photothermal effect remain challenging. We demonstrated here that human mesenchymal stem cells (hMSCs) can deliver poloxamer conjugated RGOs (pRGOs) to target tumors. Self-aggregation limits cellular uptake and induces treatment of high particle concentrations for the photothermal effect. However, compared to RGOs, pRGOs did not show any self-aggregation. pRGOs-laden hMSCs injected intravenously to tumor-bearing mice led to significantly enhanced tumor-targeting efficiency and higher heat generation than injections of RGOs following exogenous laser irradiation. This work shows that the tumor tropism of hMSC can be applied for increased tumor-targeting efficiency with small amounts of particles. Taken together, the results indicate that combining hMSCs with pRGOs could increase the therapeutic effect in photothermal cancer therapy in a synergistic manner.

Ag–Cu–Pt–Pd quadrometallic nanoparticles which small Pt and Pd nanoparticles were attached on the surface of AgCu Janus nanoparticles were firstly synthesized by sequential reduction of Pt and Pd precursor in the presence of Janus AgCu bimetallic nanoparticles as seeds in an aqueous solution. Even though there was a small amount of Cu2O on the surface, the synthesized nanoparticles were mainly composed of four independent metallic part, not alloy parts. By theoretical calculation and growth mechanism study, we found that different reducing rate between Ag+ and Cu2+ and sequential reduction of Pt and Pd precursors would be key roles for the formation of the quadrometallic nanoparticles.