Sticky and Strain-Gradient Artificial Epineurium for Sutureless Nerve Repair in Rodents and Nonhuman Primates.

The need for the development of soft materials capable of stably adhering to nerve tissues without any suturing followed by additional damages is at the fore at a time when success in postoperative recovery depends largely on the surgical experience and/or specialized microsuturing skills of the surgeon. Despite fully recognizing such prerequisite conditions, designing the materials with robust adhesion to wet nerves as well as acute/chronic anti-inflammation remains to be resolved. Herein, a sticky and strain-gradient artificial epineurium (SSGAE) that overcomes the most critically challenging aspect for realizing sutureless repair of severely injured nerves is presented. In this regard, the SSGAE with a skin-inspired hierarchical structure entailing strain-gradient layers, anisotropic Janus layers including hydrophobic top and hydrophilic bottom surfaces, and synergistic self-healing capabilities enables immediate and stable neurorrhaphy in both rodent and nonhuman primate models, indicating that the bioinspired materials strategy significantly contributes to translational medicine for effective peripheral nerve repair.

Pomegranate Polyphenol-Derived Injectable Therapeutic Hydrogels to Enhance Neuronal Regeneration.

Drug delivery for the treatment of neurological disorders has long been considered complex due to difficulties in ensuring the drug targeting on a specific site of the damaged neural tissues and its prolonged release. A syringe-injectable polymeric hydrogel with mechanical moduli matching those of brain tissues can provide a solution to deliver the drugs to the specific region through intracranial injections in a minimally invasive manner. In this study, an injectable therapeutic hydrogel with antioxidant pomegranate polyphenols, punicalagin, is reported for efficient neuronal repair. The hydrogels composed of tyramine-functionalized hyaluronic acid and collagen crosslinked by enzymatic reactions have great injectability with high shape fidelity and effectively encapsulate the polyphenol therapeutics. Furthermore, the punicalagin continuously released from the hydrogels over several days could enhance the growth and differentiation of the neurons. Our findings for efficacy of the polyphenol therapeutic-encapsulated injectable hydrogels on neuronal regeneration would be promising for designing a new type of antioxidative biomaterials in brain disorder therapy.

Punicalagin-Loaded Alginate/Chitosan-Gallol Hydrogels for Efficient Wound Repair and Hemostasis.

For recently devised wound-healing materials, a variety of acute application systems with sustainable therapeutic effects on wound sites have been suggested. For example, hydrogel-type healing agents with porous structures and high drug encapsulation efficiencies have been developed for wound repair. However, challenges remain about the poor mechanical and adhesive properties of hydrogels. Herein, we propose a punicalagin (PC)-containing wound-healing hydrogel in adhesive form that is mechanically stable and has sustainable wound-healing therapeutic efficiency. The APC hydrogel, composed of alginate (ALG), PC, and chitosan-gallol (CHI-G), exhibits significant mechanical and self-healing properties, thus indicating that PC increases cross-linking in ALG/CHI-G as macromolecule. The PC-containing mechanically enhanced hydrogel demonstrates high tissue adhesiveness. Sustainable PC release for 192 h, which indicates high therapeutic effect of the released PC, and great blood compatibility are evaluated based on rapid blood coagulation and minimal hemolysis. The cytocompatibility and wound-healing abilities of the PC-containing APC hydrogel are greater than those of the non-PC hydrogel, as verified by cell compatibility and wound scratch assays. These results indicate that a suitable concentration of PC-containing hydrogel with sustainable moisture condition and PC release may inspire further polyphenol-agent-containing hydrogels as wound-healing agents with structural stability and therapeutic efficiency.

Plant-inspired Pluronic-gallol micelles with low critical micelle concentration, high colloidal stability, and protein affinity.

Polymeric micelles are the most common carriers used for hydrophobic drug delivery. However, they are vulnerable to physiological barriers, such as temperature changes and enzymatic degradation, and can be easily disassembled upon dilution below the critical micelle concentration (CMC) by body fluids after an intravenous injection. Here, we report that Pluronic® micelles with octyl gallate, which is a surfactant containing gallol moieties widely found in antioxidative plant polyphenols, have a low CMC, which improves their colloidal stability without the need for covalent crosslinking. Furthermore, the incorporated gallol moieties provide enzymatic degradation resistance to the micelles owing to their protein affinity, maintaining the hydrophobic cavity of unmodified Pluronic®. Thus, plant-inspired polymeric micelles with low CMC and bioavailability are promising multifunctional vehicles for drug delivery.

Addressing the Shortcomings of Polyphenol-Derived Adhesives: Achievement of Long Shelf Life for Effective Hemostasis.

For rapid and effective hemostasis of uncontrollable bleeding, versatile hemostatic agents have been emerging. Among them, polyphenol-derived adhesives have attracted those hemostatic materials due to instantaneous formation of sticky barriers by robust interactions between the material and the serum proteins from wound. However, a critical challenge in such phenolic materials lies in long-term storage due to spontaneous oxidation under humid environments, leading to changes in hemostatic capability and adhesive strength. Here, we report a transparent hemostatic film consisting of gallol-conjugated chitosan (CHI-G) for minimizing the phenolic oxidation even for 3 months and maintaining strong tissue adhesiveness and its hemostatic ability. The film undergoes a phase transition from solid to injectable hydrogels at physiological pH for efficiently stopping internal and external hemorrhage. Interestingly, the hemostatic capability of the CHI-G hydrogels after 3 month storage depends on (i) the folded microstructure of the polymer with optimal gallol modification and (ii) an initial phase of either a solution state or a solid film. When the hydrogels are originated from the dehydrated film, their successful hemostasis is observed in a liver bleeding model. Our finding would provide an insight for design rationale of hemostatic formulations with long shelf-life.

Emergency preparedness for the accidental release of radionuclides from the Uljin Nuclear Power Plant in Korea.

Site specific radionuclide dispersion databases were archived for the emergency response to the hypothetical releases of 137Cs from the Uljin nuclear power plant in Korea. These databases were obtained with the horizontal resolution of 1.5 km in the local domain centered the power plant site by simulations of the Lagrangian Particle Dispersion Model (LPDM) with the Unified Model (UM)-Local Data Assimilation Prediction System (LDAPS). The Eulerian Dispersion Model-East Asia (EDM-EA) with the UM-Global Data Assimilation Prediction System (UM-GDAPS) meteorological models was used to get dispersion databases in the regional domain. The LPDM model was performed for a year with a 5-day interval yielding 72 synoptic time-scale cases in a year. For each case hourly mean near surface concentrations, hourly mean column integrated concentrations, hourly total depositions for 5 consecutive days were archived by the LPDM model in the local domain and by the EDM-EA model in the regional domain of Asia. Among 72 synoptic cases in a year the worst synoptic case that showed the highest mean surface concentration averaged for 5 days in the LPDM model domain was chosen to illustrate the emergency preparedness to the hypothetical accident at the site. The simulated results by the LPDM model with the 137Cs emission rate of the Fukushima nuclear power plant accident for the first 5-day period were found to be able to provide prerequisite information for the emergency response to the early phase of the accident whereas those of the EDM-EA model could provide information required for the environmental impact assessment of the accident in the regional domain. The archived site-specific database of 72 synoptic cases in a year could have a great potential to be used as a prognostic information on the emergency preparedness for the early phase of accident.

Estimation of radionuclide (137Cs) emission rates from a nuclear power plant accident using the Lagrangian Particle Dispersion Model (LPDM).

A methodology for the estimation of the emission rate of 137Cs by the Lagrangian Particle Dispersion Model (LPDM) with the use of monitored 137Cs concentrations around a nuclear power plant has been developed. This method has been employed with the MM5 meteorological model in the 600 km × 600 km model domain with the horizontal grid scale of 3 km × 3 km centered at the Fukushima nuclear power plant to estimate 137Cs emission rate for the accidental period from 00 UTC 12 March to 00 UTC 6 April 2011. The Lagrangian Particles are released continuously with the rate of one particle per minute at the first level modelled, about 15 m above the power plant site. The presently developed method was able to simulate quite reasonably the estimated 137Cs emission rate compared with other studies, suggesting the potential usefulness of the present method for the estimation of the emission rate from the accidental power plant without detailed inventories of reactors and fuel assemblies and spent fuels. The advantage of this method is not so complicated but can be applied only based on one-time forward LPDM simulation with monitored concentrations around the power plant, in contrast to other inverse models. It was also found that continuously monitored radionuclides concentrations from possibly many sites located in all directions around the power plant are required to get accurate continuous emission rates from the accident power plant. The current methodology can also be used to verify the previous version of radionuclides emissions used among other modeling groups for the cases of intermittent or discontinuous samplings.

The protective effect of daidzein on high glucose-induced oxidative stress in human umbilical vein endothelial cells.

Endothelial cell dysfunction is considered a major cause of vascular complications in diabetes. In the present study, we investigated the protective effect of daidzein, a natural isoflavonoid, against high-glucose-induced oxidative damage in human umbilical vein endothelial cells (HUVECs). Treatment with a high concentration of glucose (30 mM) induced oxidative stress in the endothelial cells, against which daidzein protected the cells as demonstrated by significantly increased cell viability. In addition, lipid peroxidation, intracellular reactive oxygen species (ROS) generation, and indirect nitric oxide levels induced by the high glucose treatment were significantly reduced in the presence of daidzein (0.02-0.1 mM) in a dose-dependent manner. High glucose levels induced the overexpression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and NF-κB proteins in HUVECs, which was suppressed by treatment with 0.04 mM daidzein. These findings indicate the potential of daidzein to reduce high glucose-induced oxidative stress.

Daidzein inhibits carbohydrate digestive enzymes in vitro and alleviates postprandial hyperglycemia in diabetic mice.

This study was designed to investigate whether daidzein inhibits α-glucosidase and α-amylase activities and alleviates postprandial hyperglycemia in streptozotocin-induced diabetic mice. Daidzein showed prominent inhibitory effects against α-glucosidase and α-amylase. The IC50 values of daidzein against α-glucosidase and α-amylase were 0.048 and 0.301 mmol, respectively, which showed that daidzein was more effective than acarbose. The increase in postprandial blood glucose levels was more significantly suppressed in the daidzein-administered group than in the water group of both streptozotocin-induced diabetic and normal mice. Moreover, the area under the curve was significantly lowered following daidzein administration (2043 versus 2475 mmol min l) in the streptozotocin-induced diabetic mice. These results indicated that daidzein may be a potent α-glucosidase inhibitor and suppress the postprandial hyperglycemia caused by starch.