PEG-grafted Hyperbranched Polyethyleneimine-Oxidized Single Walled Carbon Nanotube Complex (PEG-PEI-SWNT) for Sustained Delivery of Doxorubicin

To take advantages of single-walled carbon nanotubes (SWNTs) for cellular delivery of chemotherapeutic agents (e.g. doxorubicin) in order to decrease doxorubicin toxicity and increase its efficacy, we aimed to develop a novel approach to aqueous disperse and stabilize SWNTs through consequent steps of oxidation (oxSWNT) and PEG-PEI complexation (PEG-PEI-SWNT). Doxorubicin was loaded onto the modified SWNTs in alkalione pH with more considerable capacity ( 900 %) than those previously reported, due to complex formation with PEI proved by UV-visible spectroscopy. The loaded carrier was stable in physiologic simulated medium. Drug release was prolonged and dilution independent, but exhibited pH-dependent burst release that makes SWNTs as suitable in vivo drug carriers in acidic tumor milieu. When you are citing the document, use the following link http://essuir.sumdu.edu.ua/handle/123456789/3492

Effect of pH on Solubilisation of Practically Insoluble Sorafenib by Classic and Stealth Polyamidoamine (PAMAM) Dendrimers and -cyclodextrin

This study is the first report of the solubilization of sorafenib (SFB), a water insoluble drug, by polyamidoamine (PAMAM) dendrimers and -cyclodextrin ( -CD). For this study whole generations (G4 and G5) of PAMAM dendrimers have been used. The aqueous solubility of sorafenib was measured in the presence of dendrimers and -cyclodextin at 30 ◦ C at pH 4, 7.4, and 10 using the Higuchi rotating bottle method. The amount of solubilized SFB was measured by HPLC-UV method. FTIR and UV-Vis spectroscopy were used to confirm complexation. From the phase solubility studies, it was found that PAMAM dendrimers increased SFB solubility most in pH 4. The maximum solubilizing effect was for G4 PAMAM dendrimers at pH 4 up to 36 folds. -CD did not or slightly increased the solubility of SFB. When you are citing the document, use the following link http://essuir.sumdu.edu.ua/handle/123456789/3494

Improving the fretting biocorrosion of Ti6Al4V alloy bone screw by decorating structure optimised TiO2 nanotubes layer

TiO2 nanotubes (NT) has been demonstrated its potential in orthopaedic applications due to its enhanced surface wettability and bio-osteointegration. However, the fretting biocorrosion is the main concern that limited its successfully application in orthopaedic application. In this study, a structure optimised thin TiO2 nanotube (SONT) layer was successfully created on Ti6Al4V bone screw, and its fretting corrosion performance was investigated and compared to the pristine Ti6Al4V bone screws and NT decorated screw in a bone-screw fretting simulation rig. The results have shown that the debonding TiO2 nanotube from the bone screw reduced significantly, as a result of structure optimisation. The SONT layer also exhibited enhanced bio-corrosion resistance compared pristine bone screw and conventionally NT modified bone screw. It is postulated that interfacial layer between TiO2 nanotube and Ti6Al4V substrate, generated during structure optimisation process, enhanced bonding of TiO2 nanotube layer to the Ti6Al4V bone screws that leading to the improvement in fretting corrosion resistance. The results highlighted the potential SONT in orthopaedic application as bone fracture fixation devices

A critical review on polydopamine surface-modified scaffolds in musculoskeletal regeneration

Increasing concern about age-related diseases, particularly musculoskeletal injuries and orthopedic conditions, highlights the need for strategies such as tissue engineering to address them. Surface modification has been developed to create pro-healing interfaces, personalize scaffolds and provide novel medicines. Polydopamine, a mussel-inspired adhesive polymer with highly reactive functional groups that adhere to nearly all substrates, has gained attention in surface modification strategies for biomaterials. Polydopamine was primarily developed to modify surfaces, but its effectiveness has opened up promising approaches for further applications in bioengineering as carriers and nanoparticles. This review focuses on the recent discoveries of the role of polydopamine as a surface coating material, with focus on the properties that make it suitable for tackling musculoskeletal disorders. We report the evolution of using it in research, and discuss papers involving the progress of this field. The current research on the role of polydopamine in bone, cartilage, muscle, nerve, and tendon regeneration is discussed, thus giving comprehensive overview about the function of polydopamine both in-vitro and in-vivo. Finally, the report concludes presenting the critical challenges that must be addressed for the clinical translation of this biomaterial while exploring future perspectives and research opportunities in this area

Cell Seeding Process Experiment and Simulation on Three-Dimensional Polyhedron and Cross-Link Design Scaffolds

Cell attachment to a scaffold is a significant step toward successful tissue engineering. Cell seeding is the first stage of cell attachment, and its efficiency and distribution can affect the final biological performance of the scaffold. One of the contributing factors to maximize cell seeding efficiency and consequently cell attachment is the design of the scaffold. In this study, we investigated the optimum scaffold structure using two designs - truncated octahedron (TO) structure and cubic structure - for cell attachment. A simulation approach, by ANSYS Fluent coupling the volume of fluid (VOF) model, discrete phase model (DPM), and cell impingement model (CIM), was developed for cell seeding process in scaffold, and the results were validated with in vitro cell culture assays. Our observations suggest that both designs showed a gradual lateral variation of attached cells, and live cell movements are extremely slow by diffusion only while dead cells cannot move without external force. The simulation approaches supply a more accurate model to simulate cell adhesion for three-dimensional structures. As the initial stages of cell attachment in vivo are hard to observe, this novel method provides an opportunity to predict cell distribution, thereby helping to optimize scaffold structures. As tissue formation is highly related to cell distribution, this model may help researchers predict the effect of applied scaffold and reduce the number of animal testing

Determination of an Initial Stage of the Bone Tissue Ingrowth Into Titanium Matrix by Cell Adhesion Model

For achieving early intervention treatment to help patients delay or avoid joint replacement surgery, a personalized scaffold should be designed coupling the effects of mechanical, fluid mechanical, chemical, and biological factors on tissue regeneration, which results in time- and cost-consuming trial-and-error analyses to investigate the in vivo test and related experimental tests. To optimize the fluid mechanical and material properties to predict osteogenesis and cartilage regeneration for the in vivo and clinical trial, a simulation approach is developed for scaffold design, which is composed of a volume of a fluid model for simulating the bone marrow filling process of the bone marrow and air, as well as a discrete phase model and a cell impingement model for tracking cell movement during bone marrow fillings. The bone marrow is treated as a non-Newtonian fluid, rather than a Newtonian fluid, because of its viscoelastic property. The simulation results indicated that the biofunctional bionic scaffold with a dense layer to prevent the bone marrow flow to the cartilage layer and synovia to flow into the trabecular bone area guarantee good osteogenesis and cartilage regeneration, which leads to high-accuracy in vivo tests in sheep . This approach not only predicts the final bioperformance of the scaffold but also could optimize the scaffold structure and materials by their biochemical, biological, and biomechanical properties

Simultaneous regulation of miR-451 and miR-191 led to erythroid fate decision of mouse embryonic stem cell

Objective(s): Various microRNAs (miRNAs) are expressed during development of mammalian cells, when they aid in modulating gene expression by mediating mRNA transcript cleavage and/or regulation of translation rate. miR-191 and miR-451 have been shown to be critical regulators of hematopoiesis and have important roles in the induction of erythroid fate decision. So, the aim of this study is investigation of the miR-191 and miR-451 roles in the controlling mouse embryonic stem cell (mESC) differentiation toward the erythroid lineage. Materials and Methods: mESCs were infected with either pCDH-miR-Off-191 viruses in pCDH-miR-Off-191 group or simultaneously with pCDH-miR-Off-191 and pCDH-miR-451 lentiviruses in simultaneous group. Then, the expression profiles of erythroid specific transcription factors and globin genes were analyzed using QRT-PCR on day 14 and 21 of differentiation. Flow cytometry analysis was used to evaluate of TER119 and CD235a erythroid specific surface markers. Results: Gata-1, Klf-1, Epor and globin chains were found to be expressed in pCDH-miR-Off-191 and in simultaneous groups. The majority of globin chains showed changes in their expression levels with progression of differentiation from day 14 to day 21. Flow cytometry results showed that miR-451 upregulation and miR-191 down-regulation is associated with the expression of TER119 and CD235a. Of these two groups analyzed, simultaneous group was most significantly potent in stimulation of erythroid fate decision of mESCs. Conclusion: Together, present data demonstrate that down-regulation of miR-191 alone can enhance the differentiation of mESCs. However, the simultaneous effect of miR-451up-regulation and miR-191 down-regulation is much stronger and can have more practical use in artificial blood production

miR-455-5p downregulation promotes inflammation pathways in the relapse phase of relapsing-remitting multiple sclerosis disease

MicroRNA-455-5p (miR-455-5p) seems to have an anti-inflammatory role in the immune system since its expression is induced by IL-10 cytokine. Multiple sclerosis (MS) is a chronic demyelinating neurodegenerative disease of the central nervous system that is caused by an autoimmune inflammatory attack against the myelin insulation of neurons. The expression level of miR-455-5p and its role in MS pathogenesis has yet to be elucidated. We found that miR-455-5p expression was highly correlated with disease severity in MS patients. miR-455-5p expression inversely correlates with its inflammatory-predicted targets (MyD88 and REL) in relapse- and remitting-phase patients. Luciferase assays confirm that MyD88 and REL are direct targets of miR-455-5p. This study represents the first report of the miR-455-5p acts as an anti-inflammatory role in MS, at least partially through targeting MyD88 and REL. This study may provide important information for the use of miR-455-5p as a novel strategy to improve the severity of disease and control inflammation and attack in MS patients. © 2018, Springer-Verlag GmbH Germany, part of Springer Nature

Hyperbolic contraction measuring systems for extensional flow

In this paper an experimental method for extensional measurements on medium viscosity fluids in contraction flow is evaluated through numerical simulations and experimental measurements. This measuring technique measures the pressure drop over a hyperbolic contraction, caused by fluid extension and fluid shear, where the extensional component is assumed to dominate. The present evaluative work advances our previous studies on this experimental method by introducing several contraction ratios and addressing different constitutive models of varying shear and extensional response. The constitutive models included are those of the constant viscosity Oldroyd-B and FENE-CR models, and the shear-thinning LPTT model. Examining the results, the impact of shear and first normal stress difference on the measured pressure drop are studied through numerical pressure drop predictions. In addition, stream function patterns are investigated to detect vortex development and influence of contraction ratio. The numerical predictions are further related to experimental measurements for the flow through a 15:1 contraction ratio with three different test fluids. The measured pressure drops are observed to exhibit the same trends as predicted in the numerical simulations, offering close correlation and tight predictive windows for experimental data capture. This result has demonstrated that the hyperbolic contraction flow is well able to detect such elastic fluid properties and that this is matched by numerical predictions in evaluation of their flow response. The hyperbolical contraction flow technique is commended for its distinct benefits: it is straightforward and simple to perform, the Hencky strain can be set by changing contraction ratio, non-homogeneous fluids can be tested, and one can directly determine the degree of elastic fluid behaviour. Based on matching of viscometric extensional viscosity response for FENE-CR and LPTT models, a decline is predicted in pressure drop for the shear-thinning LPTT model. This would indicate a modest impact of shear in the flow since such a pressure drop decline is relatively small. It is particularly noteworthy that the increase in pressure drop gathered from the experimental measurements is relatively high despite the low Deborah number range explored

The App-Runx1 Region Is Critical for Birth Defects and Electrocardiographic Dysfunctions Observed in a Down Syndrome Mouse Model

Down syndrome (DS) leads to complex phenotypes and is the main genetic cause of birth defects and heart diseases. The Ts65Dn DS mouse model is trisomic for the distal part of mouse chromosome 16 and displays similar features with post-natal lethality and cardiovascular defects. In order to better understand these defects, we defined electrocardiogram (ECG) with a precordial set-up, and we found conduction defects and modifications in wave shape, amplitudes, and durations in Ts65Dn mice. By using a genetic approach consisting of crossing Ts65Dn mice with Ms5Yah mice monosomic for the App-Runx1 genetic interval, we showed that the Ts65Dn viability and ECG were improved by this reduction of gene copy number. Whole-genome expression studies confirmed gene dosage effect in Ts65Dn, Ms5Yah, and Ts65Dn/Ms5Yah hearts and showed an overall perturbation of pathways connected to post-natal lethality (Coq7, Dyrk1a, F5, Gabpa, Hmgn1, Pde10a, Morc3, Slc5a3, and Vwf) and heart function (Tfb1m, Adam19, Slc8a1/Ncx1, and Rcan1). In addition cardiac connexins (Cx40, Cx43) and sodium channel sub-units (Scn5a, Scn1b, Scn10a) were found down-regulated in Ts65Dn atria with additional down-regulation of Cx40 in Ts65Dn ventricles and were likely contributing to conduction defects. All these data pinpoint new cardiac phenotypes in the Ts65Dn, mimicking aspects of human DS features and pathways altered in the mouse model. In addition they highlight the role of the App-Runx1 interval, including Sod1 and Tiam1, in the induction of post-natal lethality and of the cardiac conduction defects in Ts65Dn. These results might lead to new therapeutic strategies to improve the care of DS people