Ahmedjustesen9745

Considering the substantive potential benefits of thermally stable dry powder vaccines to public health, causes for inactivation of their sensitive viral vectors during preparation require intensive study. The focus of this work was atomization of suspensions containing encapsulating excipients and a human type 5 adenovirus, involving a detailed investigation of shear stresses in the nozzle of a spray dryer. Samples were sprayed at 25 °C into falcon tubes and immediately evaluated for viral activity by in vitro testing, minimizing the confounding of thermal effects on the deactivation of the virus, although interfacial stresses could not be decoupled from shear stresses. Selleck SEL120 Despite the expectations of only virus deactivation with ever-increasing shear stresses in the spray nozzle, some conditions were found to show better activity than the positive control, leading to investigations of viral aggregation. It was found that the adenovirus experienced minor aggregation when mixed with the excipient solutions, which was reversed by subjecting samples to moderate shear conditions in the spray nozzle. At very high shear rates, the activity diminished again because of damage to the viral capsid fibers, which also led to the production of new aggregates after atomization. Despite these findings, activity losses caused by shear were small compared to the overall spray drying process loss. However, formulation composition, solution viscosity, and process conditions should be considered carefully for optimization because of their impact on aggregation. This is the first known report comparing shear, aggregation, and biological activity loss during the atomization step of spray drying viral vaccines.Photothermal agents with good biocompatibility, high tumor accumulation efficiency, large-scale production ability, and low cost are crucial for potential photothermal treatment in clinic. Herein, we proposed a green and highly efficient strategy to fabricate a kilogram-scale alginate-Ca2+-Fe powder hydrogel (ALG-Ca2+-Fe) by turning commercial Fe powder into hydrogel for enhanced photothermal therapy. The ALG-Ca2+-Fe was formed by simply dispersing commercial Fe powder into the preformed alginate-Ca2+ hydrogel in a green and energy-/time-saving way. The hydrogel exhibited the advantages of ultrahigh loading capacity of Fe powder (>100 mg mL-1), excellent large-scale production capacity (>1 kg in lab synthesis), low cost ( less then 1.7 $/kg), and good injectability. More importantly, large size and hydrophobicity endowed Fe powder with excellent tumor retention effect and minimal diffusion to surrounding tissues, greatly benefiting improving treatment efficiency and reducing side effects. link2 In vivo and in vitro studies both proved that the large-scale produced ALG-Ca2+-Fe can be used for highly efficient and biosafe tumor treatment in vivo by simple noninvasive injection. The developed ALG-Ca2+-Fe with multiple superiors opens up a novel green way to develop efficient and safe photothermal therapeutic agents with great clinic transformation potential.Obtaining a comprehensive understanding of the bactericidal mechanisms of natural nanotextured surfaces is crucial for the development of fabricated nanotextured surfaces with efficient bactericidal activity. However, the scale, nature, and speed of bacteria-nanotextured surface interactions make the characterization of the interaction a challenging task. There are currently several different opinions regarding the possible mechanisms by which bacterial membrane damage occurs upon interacting with nanotextured surfaces. Advanced imaging methods could clarify this by enabling visualization of the interaction. Charged particle microscopes can achieve the required nanoscale resolution but are limited to dry samples. In contrast, light-based methods enable the characterization of living (hydrated) samples but are limited by the resolution achievable. Here we utilized both helium ion microscopy (HIM) and 3D structured illumination microscopy (3D-SIM) techniques to understand the interaction of Gram-negative bacterextured surfaces can be designed and fabricated, and their bacteria-nanotopography interactions can be assessed in situ.Hydrogels that allow for the successful long-term in vitro culture of cell-biomaterial systems to enable the maturation of tissue engineering constructs are highly relevant in regenerative medicine. Naturally derived polysaccharide-based hydrogels promise to be one material group with enough versatility and chemical functionalization capability to tackle the challenges associated with long-term cell culture. We report a marine derived oxidized alginate, alginate dialdehyde (ADA), and gelatin (GEL) system (ADA-GEL), which is cross-linked via ionic (Ca2+) and enzymatic (microbial transglutaminase, mTG) interaction to form dually cross-linked hydrogels. The cross-linking approach allowed us to tailor the stiffness of the hydrogels in a wide range (from 30 days) degradation kinetics. The cytocompatibility of mTG cross-linked ADA-GEL was assessed using NIH-3T3 fibroblasts and ATDC-5 mouse teratocarcinoma cells. Both cell types showed highly increased cellular attachment on mTG cross-linked ADA-GEL in comparison to Ca2+ cross-linked hydrogels. In addition, ATDC-5 cells showed a higher proliferation on mTG cross-linked ADA-GEL hydrogels in comparison to tissue culture polystyrene control substrates. link3 Further, the attachment of human umbilical vein endothelial cells (HUVEC) on ADA-GEL (+) mTG was confirmed, proving the suitability of mTG+Ca2+ cross-linked ADA-GEL for several cell types. Summarizing, a promising platform to control the properties of ADA-GEL hydrogels is presented, with the potential to be applied in long-term cell culture investigations such as cartilage, bone, and blood-vessel engineering, as well as for biofabrication.Glioblastoma (GBM) is the most common primary brain tumor and has a poor prognosis; as such, there is an urgent need to develop innovative new therapies. Tumoricidal stem cells are an emerging therapy that has the potential to combat limitations of traditional local and systemic chemotherapeutic strategies for GBM by providing a source for high, sustained concentrations of tumoricidal agents locally to the tumor. One major roadblock for tumoricidal stem cell therapy is that the persistence of tumoricidal stem cells injected as a cell suspension into the GBM surgical resection cavity is limited. Polymeric biomaterial scaffolds have been utilized to enhance the delivery of tumoricidal stem cells in the surgical resection cavity and extend their persistence in the brain, ultimately increasing their therapeutic efficacy against GBM. In this review, we examine three main scaffold categories explored for tumoricidal stem cell therapy microcapsules, hydrogels, and electrospun scaffolds. Furthermore, considering the significant impact of surgery on the brain and recurrent GBM, we survey a brief history of orthotopic models of GBM surgical resection.Biomaterials engineered with specific cell binding sites, tunable mechanical properties, and complex architectures are essential to control cell adhesion and proliferation. The influence of the local properties, such as the local hardness and stability on the interaction with cells, has not been yet fully understood and exploited. This is particularly relevant for hydrogels, very promising materials with, unfortunately, poor cell adhesion properties, attributed mostly to their softness. Here, we propose a new approach for producing hybrid hydrogels by functionalizing them with particles and performing a thermal treatment. Exploring the interaction of cells with these materials we introduce a new concept, cells-grabbing-onto-particles, a facilitation of the cell adhesion through modulation of local properties. The approach is implemented on alginate hydrogels typically unsuitable for cell growth by turning them into a very effective cell culture growth platform. Specifically, alginate hydrogels are bio-mineralized with calcium carbonate (CaCO3) particles, where an additional thermal annealing (T-A) process has been applied. The local Young's modulus of new T-A treated hybrid hydrogels has increased to over 3 MPa on areas of hydrogels containing particles and to around 1 MPa on areas without particles, which is drastically different from 130 to 180 kPa values for unmodified hydrogels. Intriguingly, our results show that enhancement of local mechanical properties alone is a necessary, but insufficient, condition; the particles must be stably fixed in gels for cell growth and proliferation. Extended for hydrogels functionalized with silica particles too, the cells-grab-on-particles concept is shown applicable to different materials and cells for cell biology and tissue engineering.Controlled cell assembly is essential for fabricating in vitro 3D models that mimic the physiology of in vivo cellular architectures. Whereas tissue engineering techniques often rely on intrusive magnetic nanoparticles placed in cells and hydrogel encapsulation of cells to produce multilayered cellular constructs, we describe a high-throughput, label-free, and scaffold-free magnetic field-guided technique that assembles cells into a layered aggregate. An inhomogeneous magnetic field influences the diamagnetic cells suspended in a paramagnetic culture medium. Driven by the magnetic susceptibility difference and the field gradient, the cells are displaced toward the region of lowest field strength. Two cell lines are used to demonstrate the sequential assembly of layer-on-layer aggregates in microwells within 6 h. The effect of magnet size on the assembly dynamics is characterized and a microwell size criterion for the highest cell aggregation provided. Label-free magnetic-field-assisted assembly is relevant for on-demand scalable biofabrication of complex layered structures. Potential applications include drug discovery, developmental biology, lab-on-chip devices, and cancer research.It is extremely important to develop a minimally invasive and efficient approach for treatment of superficial skin tumors (SSTs). In this work, a near-infrared (NIR)-triggered transdermal therapeutic system based on two-stage separable microneedles (MNs) has been proposed for synergistic chemo-photothermal therapy against SSTs. Lauric acid and polycaprolactone as phase-change materials have been used to prepare the arrowheads of the two-stage separable MNs in which an anticancer drug (doxorubicin, DOX) and photothermal agent (indocyanine green, ICG) were embedded. The arrowheads are capped on the dissolvable support bases that consisted of poly(vinyl alcohol)/polyvinyl pyrrolidone (PVA/PVP). After inserting into skin tissue, the PVA/PVP support bases can be dissolved quickly owing to the absorption of the interstitial fluid, leading the arrowheads to be left in the skin tissue. Under NIR irradiation, the arrowheads embedded in the skin can be ablated because of the photothermal conversion of the ICG, resulting in liberation and penetration of the DOX from the MNs into the tumor tissue. A mouse model of melanoma tumor has been established to evaluate the synergistic effect of two-stage separable MN phototherapy and chemotherapy in the treatment of skin cancer.