Fabrication and characterization of coated microneedle patches based on PEGDA for transdermal administration of metformin.

Type 2 diabetes is one of the major challenges that the world is facing today. However, metformin (MET) as most type 2 diabetics' first-line oral hypoglycemic drug may cause serious side effects such as gastrointestinal irritation and nausea which reduce the patients' medication compliance. Therefore, the aim of the study was to design a safe and effective self-treatment device for the delivery of MET. Here, a kind of coated microneedle (MN) patches based on poly(ethylene glycol)diacrylate (PEGDA) were prepared by a two-step casting method and photopolymerization process for transdermal administration of MET. The needles wrapped with drug-loaded hyaluronic acid (HA) coating showed promising mechanical properties and drug delivery ability that allowed them to penetrate the skin barrier for rapid drug delivery, and they had no skin irritancy. The in vivo experiment of type 2 diabetic rats showed a satisfying hypoglycemic effect of the coated MN patches. The study shows that the prepared MN patches will be a potential method for the treatment of type 2 diabetes in the future.

A multi-crosslinking strategy of organic and inorganic compound bio-adhesive polysaccharide-based hydrogel for wound hemostasis.

Polysaccharides are naturally occurring polymers with exceptional biodegradable and biocompatible qualities that are used as hemostatic agents. In this study, photoinduced CC bond network and dynamic bond network binding was used to give polysaccharide-based hydrogels the requisite mechanical strength and tissue adhesion. The designed hydrogel was composed of modified carboxymethyl chitosan (CMCS-MA) and oxidized dextran (OD), and introduced hydrogen bond network through tannic acid (TA) doping. Halloysite nanotubes (HNTs) were also added, and the effects of various doping amount on the performance of the hydrogel were examined, in order to enhance the hemostatic property of hydrogel. Experiments on vitro degradation and swelling demonstrated the strong structural stability of hydrogels. The hydrogel has improved tissue adhesion strength, with a maximum adhesion strength of 157.9 kPa, and demonstrated improved compressive strength, with a maximum compressive strength of 80.9 kPa. Meanwhile, the hydrogel had a low hemolysis rate and had no inhibition on cell proliferation. The created hydrogel exhibited a significant aggregation effect on platelets and a reduced blood clotting index (BCI). Importantly, the hydrogel can quickly adhere to seal the wound and has good hemostatic effect in vivo. Our work successfully prepared a polysaccharide-based bio-adhesive hydrogel dressing with stable structure, appropriate mechanical strength, and good hemostatic properties.

In situ photo-crosslinking silk fibroin based hydrogel accelerates diabetic wound healing through antibacterial and antioxidant.

Bacterial infection and excessive reactive oxygen species (ROS) in diabetic wounds lead to a prolonged inflammatory phase, and injuries are highly susceptible to developing into chronic wounds. Improving the poor microenvironment is vital to achieving effective diabetic wound healing. In this work, methacrylated silk fibroin (SFMA) was combined with ε-polylysine (EPL) and manganese dioxide nanoparticles (BMNPs) to form an SF@(EPL-BM) hydrogel with in situ forming, antibacterial and antioxidant properties. EPL imparted high antibacterial activity (>96 %) to the hydrogel. BMNPs and EPL showed good scavenging activity against a variety of free radicals. SF@(EPL-BM) hydrogel had low cytotoxicity and could alleviate H2O2-induced oxidative stress in L929 cells. In diabetic wounds infected with Staphylococcus aureus (S. aureus), the SF@(EPL-BM) hydrogel exhibited better antibacterial properties and reduced wound ROS levels more significantly than that of the control in vivo. In this process, the pro-inflammatory factor TNF-α was down-regulated, and the vascularization marker CD31 was up-regulated. H&E and Masson staining showed a rapid transition from the inflammatory to the proliferative phase of the wounds, with significant new tissue and collagen deposition. These results confirm that this multifunctional hydrogel dressing holds well potential for chronic wound healing.

MILO: Multi-Bounce Inverse Rendering for Indoor Scene With Light-Emitting Objects.

Recently, many advances in inverse rendering are achieved by high-dimensional lighting representations and differentiable rendering. However, multi-bounce lighting effects can hardly be handled correctly in scene editing using high-dimensional lighting representations, and light source model deviation and ambiguities exist in differentiable rendering methods. These problems limit the applications of inverse rendering. In this paper, we present a multi-bounce inverse rendering method based on Monte Carlo path tracing, to enable correct complex multi-bounce lighting effects rendering in scene editing. We propose a novel light source model that is more suitable for light source editing in indoor scenes, and design a specific neural network with corresponding disambiguation constraints to alleviate ambiguities during the inverse rendering. We evaluate our method on both synthetic and real indoor scenes through virtual object insertion, material editing, relighting tasks, and so on. The results demonstrate that our method achieves better photo-realistic quality.

Impact of the dynamic vegetation on climate extremes during the wheat growing period over China.

Extreme temperature and precipitation indices have important implications for the crop growing season. Whether a coupled regional model with carbon-nitrogen cycling (CN) and vegetation dynamics (DV) can better represent these indices during the growing season compared with a model without these modules remains unknown. This study evaluates the performance of extreme indices in three wheat planting regions (including northeast spring wheat, north winter wheat and south winter wheat regions) over China in the period of 1990-2009 using the Regional Climate Model (RegCM) coupled with the Community Land Model (CLM), which include CN and DV. The results show that relative to the RegCM-CLM, both the RegCM-CLM-CN and RegCM-CLM-CN-DV perform better in simulating summer days (SU), consecutive dry days (CDD), consecutive wet days (CWD), and the interannual variability in all the extreme indices in the three regions but produce larger biases on frost days (FD). The trends of extreme indices in the high-impact risk region of wheat are also better captured by the RegCM-CLM with CN or CN-DV compared with the model without these modules. In the northeast spring wheat and southern winter wheat regions, the greater cold bias of mean daily minimum temperature between RegCM-CLM-CN-DV and RegCM-CLM is consistent with the leaf area index (LAI) difference, which may increase evaporative cooling and thus increasing FD biases. Overestimation of the LAI may have a weaker effect than the surface albedo on the mean daily maximum temperature, leading to decreased SU biases in RegCM-CLM-CN-DV relative to RegCM-CLM.

Nonlinear Mode Coupling and One-to-One Internal Resonances in a Monolayer WS2 Nanoresonator.

Nanomechanical resonators make exquisite force sensors due to their small footprint, low dissipation, and high frequencies. Because the lowest resolvable force is limited by ambient thermal noise, resonators are either operated at cryogenic temperatures or coupled to a high-finesse optical or microwave cavity to reach sub aN Hz-1/2 sensitivity. Here, we show that operating a monolayer WS2 nanoresonator in the strongly nonlinear regime can lead to comparable force sensitivities at room temperature. Cavity interferometry was used to transduce the nonlinear response of the nanoresonator, which was characterized by multiple pairs of 1:1 internal resonance. Some of the modes exhibited exotic line shapes due to the appearance of Hopf bifurcations, where the bifurcation frequency varied linearly with the driving force and forms the basis of the advanced sensing modality. The modality is less sensitive to the measurement bandwidth, limited only by the intrinsic frequency fluctuations, and therefore, advantageous in the detection of weak incoherent forces.

Directing three-dimensional multicellular morphogenesis by self-organization of vascular mesenchymal cells in hyaluronic acid hydrogels.

BACKGROUND: Physical scaffolds are useful for supporting cells to form three-dimensional (3D) tissue. However, it is non-trivial to develop a scheme that can robustly guide cells to self-organize into a tissue with the desired 3D spatial structures. To achieve this goal, the rational regulation of cellular self-organization in 3D extracellular matrix (ECM) such as hydrogel is needed. RESULTS: In this study, we integrated the Turing reaction-diffusion mechanism with the self-organization process of cells and produced multicellular 3D structures with the desired configurations in a rational manner. By optimizing the components of the hydrogel and applying exogenous morphogens, a variety of multicellular 3D architectures composed of multipotent vascular mesenchymal cells (VMCs) were formed inside hyaluronic acid (HA) hydrogels. These 3D architectures could mimic the features of trabecular bones and multicellular nodules. Based on the Turing reaction-diffusion instability of morphogens and cells, a theoretical model was proposed to predict the variations observed in 3D multicellular structures in response to exogenous factors. It enabled the feasibility to obtain diverse types of 3D multicellular structures by addition of Noggin and/or BMP2. CONCLUSIONS: The morphological consistency between the simulation prediction and experimental results probably revealed a Turing-type mechanism underlying the 3D self-organization of VMCs in HA hydrogels. Our study has provided new ways to create a variety of self-organized 3D multicellular architectures for regenerating biomaterial and tissues in a Turing mechanism-based approach.

Three dimensional tubular structure self-assembled by vascular mesenchymal cells at stiffness interfaces of hydrogels.

In this study, we report a rational and robust methodology to construct three dimensional (3D) tubular-structures solely by self-assembly of vascular mesenchymal cells (VMCs). Using the cell-laden hyaluronic acid hydrogel surrounded by cell-free gel with a higher stiffness, VMCs spontaneously migrated across the interface and assembled into 3D tubes, which composes of numerous cells. Based on turing instability which describes the reaction-diffusion processes of inhibitors and activators, this result of 3D tubular structure formation agrees with theoretical predictions from simulations of the reaction-diffusion of morphogens and cells under the initial conditions of patterned cell-laden hydrogel. We showed that this combination of theoretical prediction and experiments is able to produce multi-cellular 3D tubes with desired dimensions and determinate orientation in hydrogel mimicking the 3D features of tubular tissue. This work provides a reliable methodology for creating tubular structures with controllable sizes inside the 3D hydrogel through multi-cellular self-organization.

Compact plane illumination plugin device to enable light sheet fluorescence imaging of multi-cellular organisms on an inverted wide-field microscope.

We developed a compact plane illumination plugin (PIP) device which enabled plane illumination and light sheet fluorescence imaging on a conventional inverted microscope. The PIP device allowed the integration of microscope with tunable laser sheet profile, fast image acquisition, and 3-D scanning. The device is both compact, measuring approximately 15 by 5 by 5 cm, and cost-effective, since we employed consumer electronics and an inexpensive device molding method. We demonstrated that PIP provided significant contrast and resolution enhancement to conventional microscopy through imaging different multi-cellular fluorescent structures, including 3-D branched cells in vitro and live zebrafish embryos. Imaging with the integration of PIP greatly reduced out-of-focus contamination and generated sharper contrast in acquired 2-D plane images when compared with the stand-alone inverted microscope. As a result, the dynamic fluid domain of the beating zebrafish heart was clearly segmented and the functional monitoring of the heart was achieved. Furthermore, the enhanced axial resolution established by thin plane illumination of PIP enabled the 3-D reconstruction of the branched cellular structures, which leads to the improvement on the functionality of the wide field microscopy.