Sharmakoch4634

The microgel system supported TEC maintenance and retained their phenotype. Together, these data show that our microgel system has the capacity for TEC maintenance and induction of in vitro T lineage differentiation with potential for scalability.The ultimate purpose of this study was to develop a bioactive filler system that would allow volume restoration (passive property) and continuous release of signaling molecules to recruit soft tissues (bioactive property) and thus effectively correct facial aging. To achieve this, we prepared porous particles with a leaf-stacked structure throughout the entire particle volume (LSS particles) using a simple heating-cooling technique. LSS particles were loaded with insulin-like growth factor-1 (IGF-1) and vascular endothelial growth factor (VEGF) separately, by immersing the particles in signaling molecule-containing solutions for target tissue recruitment (adipose by IGF-1 and blood vessels by VEGF). IGF-1 and VEGF were continuously released from LSS particles for 28 and 21 days in vitro, respectively, even without additional chemical/physical modifications, because of the unique morphology of the particles. Signaling molecules preserved their bioactivity in vitro (induction of adipogenic and angiogenic differentiation) and in vivo (recruitment of fat and blood vessels) for a sufficient period. Moreover, it was observed that the LSS particles themselves have stable volume retention characteristics in the body. Thus, we suggest that the signaling molecule-loaded LSS particles can function as a bioactive filler system for volume retention and target tissue regeneration.Endogenous active substance guanosine diphosphate (GDP) is involved in the physiological process of DNA transfection and expression in the cytoplasm by binding to Ran proteins. To substantially improve the gene delivery efficiency of nanoparticles, phospholipid-coated Ca(P-GDP)/pDNA/NLS hybrid nanoparticles were prepared using GDP as a common biophosphorus source based on the biological process of exogenous gene expression in the cells. This nanoparticle has a relative uniform particle size distribution and in vitro stability. The addition of GDP in nanoparticles significantly enhanced the gene expression efficiency with good biocompatibility. Moreover, an in vivo study further verified that hybrid nanoparticles were more effective in increasing the p53 gene expression, thus significantly inhibiting the tumor growth in the heterotopic tumor model of nude mice. These results demonstrated that phospholipid-coated Ca(P-GDP) nanoparticles were a potential nonviral gene vector to promote gene expression. The experimental results confirmed the feasibility of designing a delivery system based on active substances and provided a new solution to improve the transfection efficiency of gene drugs.Health care monitoring is an extremely important aspect of human life that can be accomplished using wearable skin-patchable sensors. Upon interfacing with the skin or epidermal surface of the body, the sensing patches can monitor the movements of human parts such joints, legs, and fingers as well as tiny vibrations caused by respiration, blood flow, and heart beat. Wearable skin patches have shown improved promise in monitoring the body temperature and fever in addition to quick measurement of blood pressure and pulse rate along with breathing rate. Sensors can also analyze the sweat contents when in contact with the skin as well as other analytes such as diabetes-based volatile organic compounds (VOCs) and organophosphate nerve stimulating agents. Hence, the sensors can be of immense help in the early prediction of malfunctions of the body organs such as heart and lungs, leading to timely and effective treatment. This review covers different important aspects of skin-patchable sensors including mechanical strength and flexibility, sensitivity, transparency, self-healing, self-cleaning, and self-powering ability as well as their latest applications in medical technology.Glucose oxidase (GOx) is one of the most widely investigated enzymes in the field of bioelectrochemistry. It is mainly used for the detection of glucose in solutions and enzyme-based biofuel cells. On the basis of the combination of GOx with graphene, novel nanodevices exceeding conventional limits can be developed. To develop a hybrid enzyme-graphene nanodevice with a good performance, it is important that GOx is deposited well on the graphene surface while maintaining its structure and not impeding the oxidation activity of the GOx. In this study, we propose a method to improve the stability of GOx and secure its immobility on the graphene sheet and its glucose-binding affinity by single-point mutation of GOx using molecular dynamics simulations. We confirm that the structural stability, immobility, and substrate binding affinity of GOx can be modified by changing the hydrophobicity of a key residue. We demonstrate that biosensors or biofuel cells can be redesigned and their properties can be improved by using molecular dynamics simulation.Liver fibrosis is a critical liver disease which can lead to liver cirrhosis, cancer, and liver failure. Among various etiological factors, activated stellate cells are a major factor that can induce liver fibrosis. Several studies have presented in vitro models to identify drugs for liver fibrosis; however, there are still limitations in terms of the 2D culture conditions, random co-culture of liver cells, and lack of extracellular matrix components. Therefore, a 3D liver fibrosis-on-a-chip was developed with three liver cell types (hepatocytes, activated stellate cells, and endothelial cells) using a novel cell-printing technique with gelatin bioinks, which were used to deliver each nonparenchymal liver cell type as a multilayer construct. Liver fibrosis-specific gene expression, collagen accumulation, cell apoptosis, and reduced liver functions caused by activated stellate cells were also evaluated. Furthermore, previously reported chemicals were added to the 3D liver fibrosis-on-a-chip to examine the downregulation of activated hepatic stellate cells. In conclusion, the developed 3D liver fibrosis-on-a-chip could be used as a potential in vitro model in the research field.Biodegradable ceramic (composite) scaffolds have inspired worldwide efforts in bone regenerative medicine. However, balancing the biodegradation with the bone's natural healing time scale remains difficult; in particularl, there is a lack of strategy to control component distribution and bioactive ion release favorable for stimulating alveolar bone tissue ingrowth in situ within an expected time window. Here we aimed to develop the robocasting core-shell bioceramic scaffolds and investigate their physicochemical properties and osteostimulative capability in beagle alveolar bone defect model. The β-tircalcium phosphate (TCP) and 5% Mg-doped calcium silicate (CSi-Mg5) were used to fabricate the core-shell-typed TCP@TCP, CSi-Mg5@CSi-Mg5 and TCP@CSi-Mg5 porous scaffolds. Both in vitro and in vivo studies show that the CSi-Mg5 shell readily contributed to the initial mechanical strength and early-stage osteogenic activity of the TCP@CSi-Mg5 scaffolds, including tunable ion release, enhanced biodegradation, and outstanding osteogenesis capacity in comparison with the CSi-Mg5@CSi-Mg5 scaffolds and clinically available Bio-Oss granules in alveolar bone defects. Therefore, the presented core-shell robocasting of bioceramic technology and porous scaffold biomaterials enables an accurate preparation of highly bioactive and biodegradable scaffolds with a large freedom of design, and thereby may be beneficial for fabricating osteostimulation-tuned porous scaffolds for the challengeable alveolar bone defect reconstruction medicine.Biophysical properties of cells, such as cell mechanics, cell shape, and cell migration, are emerging hallmarks for characterizing various cell functions. Conversely, disruptions to these biophysical properties may be used as reliable indicators of disruptions to cell homeostasis, such as in the case of chemical-induced toxicity. In this study, we demonstrate that treatment of lead(II) nitrate and cadmium nitrate leads to dosage-dependent changes in a collection of biophysical properties, including cellular traction forces, focal adhesions, mechanical stiffness, cell shape, migration speed, permeability, and wound-healing efficacy in mammalian cells. As those changes appear within a few hours after the treatment with a trace amount of lead/cadmium, our results highlight the promise of using biophysical properties to screen environmental chemicals to identify potential toxicants and establish dose response curves. Our systematic and quantitative characterization of the rapid changes in cytoskeletal structure and cell functions upon heavy metal treatment may inspire new research on the mechanisms of toxicity.Acellular blood vessels possess high potential to be used as tissue-engineered vascular scaffolds. Previously, a high patency was achieved for an Arg-Glu-Asp-Val (REDV) peptide-immobilized small-diameter acellular graft in a minipig model. Results revealed the potential of the peptide to capture a circulating cell and also to suppress fibrin clot deposition. ISX-9 Here, the effect of REDV peptide density on the blood response under ex vivo blood perfusion conditions was investigated. When endothelial cells or platelets were seeded under static conditions, the number of adherent endothelial cells increased with the increase in peptide density. Platelets scarcely adhered on the surface where the peptide density was above 18.9 × 10-4 molecules per nm3. Fibrin clot deposition and circulating cell capture were evaluated in a minipig extracorporeal circulatory system. The fibrin clot did not form on the peptide-immobilized surface, in the range of peptide modification density that was evaluated, whereas the unmodified surface was covered with microthrombi. REDV-specific blood circulating cells were captured on the peptide-immobilized surface with a density above 18.9 × 10-4 molecules per nm3. These results illustrated, under ex vivo blood perfusion conditions, that the REDV-immobilized acellular surface was able to capture cells and also suppress platelet adhesion and fibrin clot deposition in a peptide density-dependent manner.The development of new nonviral vectors with high transfection efficiency and low cyto-toxicity remains a great challenge in the field of small interfering RNA delivery. To address the challenge, we developed two cationic amphiphilic carriers, octa-arginine double-substituted (R8-bibola) and octa-arginine monosubstituted (R8-monobola), based on transmembrane peptide-octa-arginine (R8) for complexing siRNA (R8-bola/siRNA). To further improve the stability of the nanocomplexes and tumor targeting, HA-R8-bola/siRNA nanocomplexes were prepared by surface modification of R8-bola/siRNA with hyaluronic acid (HA). In vitro experiments showed that R8-bibola has better biocompatibility than R8-monobola, which effectively increased the cell uptake of siRNA and improved the Bcl-2 protein silencing efficiency. In vivo antitumor experiments confirmed that the HA-modified nanocomplexes effectively inhibited tumor growth by silencing Bcl-2 protein expression. The new bola-type nanoparticles provide a new strategy to improve the delivery efficiency of siRNA for tumor treatment.