Micron Size Range Research Articles

A DNA Origami Bubble Blower for Liposome Production.

While liposomes are commonly produced on the industrial scale with diameters in the hundreds of nanometers to micrometer size range, the variation from the mean diameter can be significant. In nature, functional liposome-like systems can be as small as tens of nanometers in diameter but reproducible synthetic production at this size scale is not easily achievable. Here we outline the development of a DNA origami "bubble blower"-a nanoscale ring able to seed and constrain liposome formation. The bubble blower has the potential to be employed in a reusable fashion for production of nanometric liposomes. It improves currently available DNA origami liposome seeding techniques by expanding the range of compatible detergents and introducing solid support integration with potential for semiautomated laboratory scale production.

Microfluidic Stress Device to Decouple the Synergistic Effect of Shear and Interfaces on Antibody Aggregation

Protein denaturation and aggregation resulting from the effects of interfacial stress, often enhanced by flow and shear stress, pose significant challenges in the production of therapeutic proteins and monoclonal antibodies. The influence of flow on protein stability is closely intertwined with interfacial effects. In this study, we have developed a microfluidic device capable of exposing low volume (< 320 µL) protein solutions to highly uniform shear. To disentangle the synergistic impact of flow and interfaces on protein aggregation, we fabricated two devices composed of different materials, namely poly(methyl methacrylate) (PMMA) and stainless steel. Upon application of shear, we observed formation of protein particles in the micron-size range. Notably, The number of particles generated in the steel devices was ∼ 3.5 fold lower than in the PMMA device, hinting at an interface-mediated effect. With increasing the protein concentration from 1 to 50 mg/mL we observed a saturation in the amount of aggregates, further confirming the key role of solid-liquid interfaces in inducing particle formation. Introduction of non-ionic surfactants prevented protein aggregation, even at the highest tested protein concentration and low surfactant concentrations of 0.05 mg/mL. Overall, our findings corroborate the synergistic impact of shear and interface effects on protein aggregation. The device developed in this study offers a small-scale platform for assessing the stability of antibody formulations throughout various stages of the development and manufacturing process.

BSA Binding and Aggregate Formation of a Synthetic Amino Acid with Potential for Promoting Fibroblast Proliferation: An In Silico, CD Spectroscopic, DLS, and Cellular Study.

This study presents the chemical synthesis, purification, and characterization of a novel non-natural synthetic amino acid. The compound was synthesized in solution, purified, and characterized using NMR spectroscopy, polarimetry, and melting point determination. Dynamic Light Scattering (DLS) analysis demonstrated its ability to form aggregates with an average size of 391 nm, extending to the low micrometric size range. Furthermore, cellular biological assays revealed its ability to enhance fibroblast cell growth, highlighting its potential for tissue regenerative applications. Circular dichroism (CD) spectroscopy showed the ability of the synthetic amino acid to bind serum albumins (using bovine serum albumin (BSA) as a model), and CD deconvolution provided insights into the changes in the secondary structures of BSA upon interaction with the amino acid ligand. Additionally, molecular docking using HDOCK software elucidated the most likely binding mode of the ligand inside the BSA structure. We also performed in silico oligomerization of the synthetic compound in order to obtain a model of aggregate to investigate computationally. In more detail, the dimer formation achieved by molecular self-docking showed two distinct poses, corresponding to the lowest and comparable energies, with one pose exhibiting a quasi-coplanar arrangement characterized by a close alignment of two aromatic rings from the synthetic amino acids within the dimer, suggesting the presence of π-π stacking interactions. In contrast, the second pose displayed a non-coplanar configuration, with the aromatic rings oriented in a staggered arrangement, indicating distinct modes of interaction. Both poses were further utilized in the self-docking procedure. Notably, iterative molecular docking of amino acid structures resulted in the formation of higher-order aggregates, with a model of a 512-mer aggregate obtained through self-docking procedures. This model of aggregate presented a cavity capable of hosting therapeutic cargoes and biomolecules, rendering it a potential scaffold for cell adhesion and growth in tissue regenerative applications. Overall, our findings highlight the potential of this synthetic amino acid for tissue regenerative therapeutics and provide valuable insights into its molecular interactions and aggregation behavior.

Squeezing the Threshold of Metal‐Halide Perovskite Micro‐Crystal Lasers Grown by Solution Epitaxy

AbstractMetal halide perovskite semiconductors have demonstrated remarkable progress not only in photovoltaics and X‐ray detection but also in laser technologies. Particularly appealing is the simplicity with which micro‐crystallites can be epitaxially grown, thereby forming micro‐resonators suitable for lasing. Here, the laser threshold is optimized by selecting excitation laser parameters and by improving material quality. The latter process is conducted for formamidinium lead tribromide, emitting in the green spectral range. Depending on the growth method and parameters, the sizes of the micro‐resonators can be tuned between ≈3 and 23 micrometers. Under laser excitation systematically lower thresholds are observed for micro‐resonators in the 4–7 micrometer size range, than for larger ones, irrespective of growth method. Among three optimized growth methods, epitaxial growth via antisolvent vapor‐assisted crystallization exhibits the smallest threshold powers, indicating the highest material quality. This conclusion is supported by hyperspectral microscopic luminescence imaging and by transient photoluminescence. The best laser structures exhibit record threshold powers for epitaxially grown perovskites, indicating that the selected antisolvent vapor epitaxial growth holds great promises also for other perovskite materials.

A comprehensive characterization of indoor ambient microplastics in households during the COVID-19 pandemic

AbstractAirborne microplastics (MPs) can be easily inhaled by humans, impacting their health as they spend more than 80% of their time indoors, especially during the pandemic. Only a few research studies have examined indoor MPs in the micrometer size range using active sampling, and studies have mainly concentrated on MPs that are millimeters in size. This study investigated the composition of indoor airborne MPs by active sampling in seven houses in the city center of northwestern Turkey (Eskişehir) during the COVID-19 pandemic. The visual identification showed the presence of different colored MPs, white, red, orange, green, and yellow, with different shapes (fibers, fragments, films, lines, foam, and pellets). The size of the identified MPs was between 2.5 and 327.36 μm. The polymeric composition analysis showed the presence of 123 MPs in all the samples with 22 different polymeric compositions. Residents in these houses are exposed to airborne MPs, with inhalation estimates ranging from 12.03 to 18.51 MPs/m3. However, it was also estimated that humans inhale 156–240 MPs daily in these houses. The dominant MPs were polyamide 6, polyvinyl chloride, polypropylene, ethylene propylene, polystyrene, and high-density polyethylene. Scanning electron microscopy energy dispersive x-ray elemental analysis revealed the presence of common structural elements, additives, or vectors that are added or adsorbed to MPs like carbon, oxygen, fluorine, magnesium, silicon, chlorine, nitrogen, and aluminum. These indoor environments are prone to MP pollution. Still, the MP level varies due to different characteristics of indoor environments, like activities and the number of occupants/people in the space, etc. The smaller MPs in all the samples highlight the necessity for standardized techniques of MP collection.

Abstract 5745: Electrosprayed minocycline and temozolomide-loaded PLGA microparticles for the treatment of glioblastoma

Abstract Glioblastoma multiforme (GBM), the most common and aggressive form of malignant brain tumor, leads to poor prognoses with high rates of reoccurrence and low survival rates, therefore, it is vital to explore alternative treatments for GBM. Minocycline, a commonly used antibiotic and tetracycline derivative, has proven anti-angiogenic effects and the ability to inhibit tumor growth, making it an effective GBM treatment. Temozolomide is an alkylating antineoplastic agent and the current first-choice chemotherapy agent for GBM. Poly(lactic-co-glycolic acid) (PLGA) is widely used as a biomaterial for drug delivery due to its inert properties, great biocompatibility and versatility and has been approved by the FDA. Therefore, the objective of this project is to fabricate electrosprayed minocycline- and temozolomide-loaded PLGA microparticles with optimal morphology, drug loading, loading efficiency, and drug release kinetics for the treatment of GBM. The microparticles were fabricated by electrospraying vertically with a 2ml/hr flow rate, 14kV voltage, 20 cm distance for minocycline and a 10ml/hr flow rate, 10kV voltage, 10 cm distance for temozolomide with both collected on a copper/glass plate. The parameters that were investigated were the chamber humidity, duration of spraying, and the addition of polyethylene glycol (PEG), a hydrophilic polymer. To determine the microparticles’ morphology, bright-field microscopy and scanning electron microscopy (SEM) were used. The absorbance measurements at 350 and 327 nm were used to determine drug loading, loading efficiency, and release kinetics for minocycline and temozolomide, respectively. Microparticles with low chamber humidity and duration of spraying were more spherical, less aggregated and easier to collect for both drugs. The addition of PEG to minocycline-loaded microparticles led to higher drug loading and loading efficiency (4.02% ± 0.34, 64.30% ± 5.47 vs. 3.23% ± 0.29, 49.40% ± 4.49) as the PEG helps the solubilization of minocycline. Using acetonitrile instead of dichloromethane as the solvent, increased drug loading and loading efficiency (4.72% ± 0.76, 70.77 ± 11.43 vs. 2.37% ± 0.27, 35.62% ± 4.09) for temozolomide-loaded microparticles as more temozolomide can be solubilized in acetonitrile. Drug release kinetics demonstrated a burst release of minocycline in the first hour (65.46%). To decrease the burst release, the microparticles can be incorporated into a scaffold or depot. Overall, electrospraying is a promising method to fabricate drug loaded PLGA microparticles with high drug loading, loading efficiency, and right morphology and we determined optimal parameters to successfully fabricate electrosprayed drug loaded PLGA microparticles in the micron size range with high drug loading and loading efficiency compared to the often-used emulsion solvent extraction/evaporation for microparticle fabrication. Citation Format: Alma Rodriguez, Jaqueline Quintanilla, Juan Amieva, Marco A. Arriaga, Sean Nievera, Ivan Davila, Karen S. Martirosyan, Sue Anne Chew. Electrosprayed minocycline and temozolomide-loaded PLGA microparticles for the treatment of glioblastoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5745.

The friction of surface textured cylinder liner segments modified by Direct Laser Writing and Direct Laser Interference Patterning processes

Direct Laser Writing (DLW) using ultrashort pulsed lasers and galvanometer scanning, has become an established process for surface texturing, allowing an extensive variety of feature geometries and texture designs to be produced. The minimum feature sizes that can be generated are however limited by factors such as the laser output power, beam diameter, beam wavelength and associated optics. To address the need to produce even smaller texture features, Direct Laser Interference Patterning (DLIP) has been developed, which utilises bespoke beam splitting and converging optics to produce periodic interference fringing and enabling surface textures in the micrometric size range to be produced.In this study, the texturing of cast iron cylinder liner segments using DLW and DLIP processes is explored, to assess their tribological performance in high efficiency internal combustion engines, such as for hybrid applications. To facilitate the designs of textures and to capture high resolution data on surface interactions at specific points in the combustion cycle, the segmentation of cylinder lines and piston rings is undertaken. The results of tribology tests covering combinations of high and low speeds and contact pressures, have shown that the mechanical honing of cylinder liners could potentially be replaced with the cleaner DLIP texturing as an alternative.Optimised texture designs using the DLW process achieved up to a 54 % reduction in kinematic friction between the piston ring and textured cylinder liner surfaces, compared with mechanically honed cylinder liner segments. These results have indicated that DLW texturing offers the best improvement in friction performance in the boundary and mixed lubrication regimes at higher contact pressures, at both lower and higher sliding speeds. The results also provide useful comparative data on the performance of meso and micrometric scale textures and how they can be best applied to cylinder liners.

Switching Separation Migration Order by Switching Electrokinetic Regime in Electrokinetic Microsystems.

Analyte migration order is a major aspect in all migration-based analytical separations methods. Presented here is the manipulation of the migration order of microparticles in an insulator-based electrokinetic separation. Three distinct particle mixtures were studied: a binary mixture of particles with similar electrical charge and different sizes, and two tertiary mixtures of particles of distinct sizes. Each one of the particle mixtures was separated twice, the first separation was performed under low voltage (linear electrokinetic regime) and the second separation was performed under high voltage (nonlinear electrokinetic regime). Linear electrophoresis, which discriminates particles by charge, is the dominant electrokinetic effect in the linear regime; while nonlinear electrophoresis, which discriminates particles by size and shape, is the dominant electrokinetic effect in the nonlinear regime. The separation results obtained with the three particle mixtures illustrated that particle elution order can be changed by switching from the linear electrokinetic regime to the nonlinear electrokinetic regime. Also, in all cases, better separation performances in terms of separation resolution (Rs) were obtained by employing the nonlinear electrokinetic regime allowing nonlinear electrophoresis to be the discriminatory electrokinetic mechanism. These findings could be applied to analyze complex samples containing bioparticles of interest within the micron size range. This is the first report where particle elution order is altered in an iEK system.

A study on melting characteristics of micron aluminum particles by lattice Boltzmann method

In this article, a two-dimensional lattice Boltzmann model, utilizing enthalpy as a basis, has been constructed to explore the melting behavior of aluminum particles in the micron size range. The study investigates the impacts of several key factors such as particle size, Rayleigh number, Stefan number, and porosity on temperature distribution, liquid fraction, solid-liquid interface, and melting end time. The findings demonstrate that an increase in particle size stimulates the melting process, with a weakened effect observed as particle size continues to increase. Rayleigh number has a significant effect on natural convection and heat transfer, promoting the development of these processes. Additionally, Stefan number presents a noticeable impact on the melting process, with a more apparent effect in the range of low Stefan numbers. Finally, the increase of porosity proves to be a compelling factor in the promotion of the melting process.

Degradation behavior and ageing mechanism of E-glass fiber reinforced epoxy resin composite pipes under accelerated thermal ageing conditions

In this work, accelerated ageing experiments with circulating air and simulated oilfield water were carried out at 95 °C on aromatic amine-cured GFRP pipes used in oilfield environments, with effective ageing times of 5000 h and 3000 h respectively. The differences in ageing behavior and ageing mechanisms of the GFRP tubes at different times under the two conditions were then analyzed and discussed. The changes in the apparent morphology and microstructure of the samples after thermal ageing were first observed using optical microscopy and scanning electron microscopy, and the results demonstrated that the thermal oxygen environment triggered more drastic color changes and obvious oxidation layers. The resin matrix manifests a large number of nano-scale micropores and modest matrix shrinkage pores in the micron size range, this is accompanied by damage to the fiber cross-section. Hydrothermal ageing causes further dissolution of the surface resin and dissolution of the exposed fibers. ATR-FTIR analysis verifies the increase in CO bonding of the ester group during thermal oxidation and the decreasing strength of the C–O–C and C–H bonds, while the behavior of ageing water absorption and glass fiber hydrolysis is illustrated by changes in the intensity of the –OH and Si–O characteristic bands. NMR hydrogen spectroscopy verified the formation of amides, methyl ethers and carboxylic acids in the thermal oxidation products of epoxy resins. Furthermore, the decay pattern of the circumferential tensile strength indicates that the hydrothermal environment has a more significant effect on the mechanical properties of GFRP pipes, which is attributed to the physical dissolution of the surface resin, significant hydrolytic damage to the surface exposed fibers, and the combined damage to the resin-fiber interfacial bonding by chloride ions in simulated oilfield water.

Abstract 17854: Imaging Intravascular Macrophages Using Micro-Sized Superparamagnetic Decoys

Introduction: During inflammatory processes, intravascular macrophages are capable of phagocytizing circulating debris in the circulation. Hypothesis: Intravenous injection of contrast-loaded decoys could be used to label intravascular macrophages and map their distribution by non-invasive imaging. Methods: We synthetized superparamagnetic decoys with hydrodynamic diameters from 20 nm to 4.5 μm. Experimental models of neuroinflammation (intrastriatal injection of LPS or TNF) and ischemic stroke (thrombin model and ferric chloride model) were performed in mice. High resolution 3D T2*-weighted MRI sequences were performed after intravenous injection of the superparamagnetic decoys. Results: In experimental models of neuroinflammation, intravenous injection of superparamagnetic decoys with a diameter of 1 μm (but neither smaller nor larger particles) reveals intravascular phagocytic cells in the cerebral circulation, in a dose dependent manner. In ischemic stroke, we found that intravenous injection of the decoys leads to numerous signal voids in the vessels in and around the infarct core at 48 hours (Figure 1a-b). Interestingly, the intravascular phagocytic activity appears much higher in permanent rather than transient models of ischemic stroke. Pre-treatment with anti-CD11a blocking antibodies significantly reduced the number of intravascular macrophages in stroke. Histological studies confirmed that injected decoys are phagocytized by intravascular cells which express typical markers of the monocyte/macrophage lineage including CX3CR1 dependent GFP expression and CD68 (Figure 1c). Conclusions: Intravenous injection of superparamagnetic decoys in the micrometer size range allows to image intravascular macrophages. This new method allows to study the pathophysiological roles of intravascular macrophages in experimental models and could be easily translated to humans.

Characterization of Sprays Generated by the Expansion of Emulsions with Liquid Carbon Dioxide

AbstractExpanding emulsions with liquid CO2 facilitates the creation of aerosols with an average droplet diameter in the low micrometer size range, which is challenging with conventional atomizers. The droplet formation process of the expansion of high‐pressure emulsions was investigated using a plain‐orifice atomizer and different swirl nozzles. The local droplet size and droplet velocities were measured and used to estimate the local Weber number and thus infer the droplet size reduction. Measurements of the local mass concentration in the aerosol showed that, for the swirl nozzle, the highest concentration was found outside of the central axis, indicating radial momentum generated by the swirl nozzle. Furthermore, it was shown that the type of expansion nozzle used has an influence on the resulting median droplet size in the aerosol. For a water mass load of 0.01, the median droplet diameter was reduced from 8 to 3 μm by increasing the swirl number from 0.01 to 0.1.

The application of electrosprayed minocycline-loaded PLGA microparticles for the treatment of glioblastoma.

The survival of patients with glioblastoma multiforme (GBM), the most common and invasive form of malignant brain tumors, remains poor despite advances in current treatment methods including surgery, radiotherapy, and chemotherapy. Minocycline is a semi-synthetic tetracycline derivative that has been widely used as an antibiotic and more recently, it has been utilized as an antiangiogenic factor to inhibit tumorigenesis. The objective of this study was to investigate the utilization of electrospraying process to fabricate minocycline-loaded poly(lactic-co-glycolic acid) (PLGA) microparticles with high drug loading and loading efficiency and to evaluate their ability to induce cell toxicity in human glioblastoma (i.e., U87-MG) cells. The results from this study demonstrated that solvent mixture of dicholoromethane (DCM) and methanol is the optimal solvent combination for minocycline and larger amount of methanol (i.e., 70:30) resulted in a higher drug loading. All three solvent ratios of DCM:methanol tested produced microparticles that were both spherical and smooth, all in the micron size range. The electrosprayed microparticles were able to elicit a cytotoxic response in U87-MG glioblastoma cells at a lower concentration of drug compared to the free drug. This work provides proof of concept to the hypothesis that electrosprayed minocycline-loaded PLGA microparticles can be a promising agent for the treatment of GBM and could have potential application for cancer therapies.

Encapsulation of Carbon Nanotubes by Styrene and Butyl Acrylate Particles via Suspension Polymerization for Polymerized Toner Applications.

Electrophotographic printing and copying processes primarily use toner, which is a mixture of colorant, polymer, and additives. Toner can be made using traditional mechanical milling techniques or more contemporary chemical polymerization techniques. Suspension polymerization provides spherical particles with less stabilizer adsorption, homogeneous monomers, higher purity, and easier control of the reaction temperature. In contrast to these advantages, however, the particle size resulting from suspension polymerization is too large for toner. To overcome this disadvantage, devices such as high-speed stirrers and homogenizers can be used to reduce the size of the droplets. This research investigated the use of carbon nanotubes (CNTs) instead of carbon black as the pigment in toner development. We succeeded in achieving a good dispersion of four different types of CNT, specifically modified with NH2 and Boron or unmodified with long or short chains in water rather than chloroform, using sodium n-dodecyl sulfate as a stabilizer. We then performed polymerization of the monomers styrene and butyl acrylate in the presence of the different CNT types and found that the best monomer conversion and largest particles (in the micron range) occurred with CNTs modified with boron. The insertion of a charge control agent into the polymerized particles was achieved. Monomer conversion of over 90% was realized with all concentrations of MEP-51, whereas conversion was under 70% with all concentrations of MEC-88. Furthermore, analysis with dynamic light scattering and scanning electron microscopy (SEM) indicated that all polymerized particles were in the micron size range, suggesting that our newly developed toner particles were less harmful and environmentally friendly products than those typically and commercially available. The SEM micrographs clearly showed good dispersion and attachment of the CNTs on the polymerized particles (no CNT aggregation was found), which has never been published before.

Formulation and Evaluation of Sustained Release Tablet of Metformin by Ionic Gelation Technique using Sida acuta Gum as Release Retardant

This research was done to formulate and assess the sustained release property of metformin tablets prepared from metformin microcapsules produced by ionic gelation technique using Sida acuta gum or sodium carboxymethylcellulose as release retardant. Sida acuta gum was produced by isopropyl alcohol precipitation of the filtrate obtained from distilled water maceration of powdered dried Sida acuta leaves. Metformin and Sida acuta gum compatibility was determined using FTIR. Metformin microcapsules were prepared by ionic gelation technique using sodium alginate alone or with either Sida acuta gum or sodium carboxymethylcellulose as release retardant. The microcapsules were evaluated for % yield and flow properties. The size and surface morphology of the microcapsules were determined using scanning electron microscopy. Metformin tablets were prepared from the microcapsules using direct compression technique. The tablets were evaluated for hardness, friability and in vitro dissolution. There was no major incompatibility between metformin and Sida acuta gum. The microcapsules have excellent flow property and were of micrometer size range. They have rough surfaces. The friability of the tablets ranged from 0.4-1.6% while the hardness was from 3.82-11.17 Kgf. The tablets from formulations M2 failed both friability and hardness test. About 44.5-47.1% of metformin was released from the tablet formulations after 6 h while 86.0-100% was released after 10 h. All the tablet formulations showed sustained release ability.&#x0D; Keywords: Microcapsules, metformin, Sida acuta gum, sustained release, ionic gelation

148 Development of a test Method to Determine Inhalation Exposure of Microplastic Particles when Reusable Disposable Masks in Place

Abstract Situation/broad aims The SARS-CoV-2 pandemic has swept the globe since late 2019 and has driven explosive growth in the use of masks that has arisen an emerging concern of inhaled microplastic particles (MPs) when reuse disposable masks. In this study, we proposed a new methodology to determine whether the inhaled particles of microplastics emitted from the disposable masks when reusable mask in place as source control. Methods All experiments were conducted using a head-form manikin with a constant inspiratory flow at a simulated chamber. One commercially available ASTM Level 1 face (or surgical) mask with three-layer material, namely polypropylene (outer and middle layers), and polyethylene (inner layer) was used as test specimen to characterize the inhalation exposure of MPs. Brand new and reusable masks with and without a hand rubbing were compared. Particle physical characterization and morphology were determined using fluorescent staining with Nile red dye and scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FTIR) as well. The multiple-path particle dosimetry model was utilized to calculate the particle deposition in the respiratory tracts of human adults for emitted MPs fallen within the micrometer size range. Outcomes of the work: In this study, we proposed a method that the incorporation of scanning electron microscopy and infrared spectroscopy into the current fluorescent staining method to enhance the detection of MPs for qualitative analysis, may be more predictive of fragment microplastics are sourced from the different layer of disposable mask with a hand rubbing when in use.

Trends and perspectives on the commercialization of bioactive glasses.

At least 25 bioactive glass (BG) medical devices have been approved for clinical use by global regulatory agencies. Diverse applications include monolithic implants, bone void fillers, dentin hypersensitivity agents, wound dressing, and cancer therapeutics. The morphology and delivery systems of bioactive glasses have evolved dramatically since the first devices based on 45S5 Bioglass®. The particle size of these devices has generally decreased with the evolution of bioactive glass technology but primarily lies in the micron size range. Morphologies have progressed from glass monoliths to granules, putties, and cements, allowing medical professionals greater flexibility and control. Compositions of these commercial materials have primarily relied on silicate-based systems with varying concentrations of sodium, calcium, and phosphorus. Furthermore, therapeutic ions have been investigated and show promise for greater control of biological stimulation of genetic processes and increased bioactivity. Some commercial products have exploited the borate and phosphate-based compositions for soft tissue repair/regeneration. Mesoporous BGs also promise anticancer therapies due to their ability to deliver drugs in combination with radiotherapy, photothermal therapy, and magnetic hyperthermia. The objective of this article is to critically discuss all clinically approved bioactive glass products. Understanding essential regulatory standards and rules for production is presented through a review of the commercialization process. The future of bioactive glasses, their promising applications, and the challenges are outlined. STATEMENT OF SIGNIFICANCE: Bioactive glasses have evolved into a wide range of products used to treat various medical conditions. They are non-equilibrium, non-crystalline materials that have been designed to induce specific biological activity. They can bond to bone and soft tissues and contribute to their regeneration. They are promising in combating pathogens and malignancies by delivering drugs, inorganic therapeutic ions, and heat for magnetic-induced hyperthermia or laser-induced phototherapy. This review addresses each bioactive glass product approved by regulatory agencies for clinical use. A review of the commercialization process is also provided with insight into critical regulatory standards and guidelines for manufacturing. Finally, a critical evaluation of the future of bioactive glass development, applications, and challenges are discussed.

Degradable, biocompatible, and antibacterial polygalacturonic acid/polyethyleneimine polyplex particles

AbstractAnionic polygalacturonic acid (PGA), a prebiotic for healthy microbiota, and cationic polyethyleneimine (PEI), a strong antimicrobial polymer against harmful infections, were ionically crosslinked to prepare biocompatible and antibacterial polygalacturonic acid/polyethyleneimine (PGA/PEI) polyplex particles. The PGA/PEI particles were spherical in shape and had a wrinkled surface with a micron size range of particles from 9 to 0.6 μm. The PGA/PEI polyplex particle was degradable under more acidic and basic conditions but was highly stable between pH 3 and 7. The prepared PGA/PEI polyplex particles are found compatible for intravenous applications with hemolysis rate of less than 1% and almost 100% blood clotting index values up to 1 mg/mL concentration. Similarly, no significant toxicity was found on L929 fibroblast cells for 24 h incubation time in the presence of 1 mg/mL concentration of the PGA/PEI polyplex particles. As an antibacterial material, the PGA/PEI polyplex particles totally prevented the growth of Gram‐negative Escherichia coli and Gram‐positive Staphylococcus aureus. Due to the antibacterial, biocompatible, blood compatibility, and degradability, the PGA/PEI polyplex particles can be utilized in wide range of application such as particularly wound dressing, cosmetic and health care products, and drug delivery applications.

An In Vitro Assay to Quantify Effects of Micro- and Nano-Plastics on Human Gene Transcription

In today’s age, plastic waste is a major problem for our environment. The decomposition of plastic waste causes widespread contamination in all types of ecosystems worldwide. Micro-plastics in the lower micrometer size range and especially nano-plastics can become internalized by cells and thus become a threat to human health. To investigate the effects of internalized micro- and nano-plastics on human gene transcription, we used an in vitro assay to quantify CREB (cAMP response element binding protein) mediated transcription. Here we show that CREB mediated gene expression was mainly but not exclusively induced by phosphorylation. In addition, the amount of CREB affected transcription was also studied. We were also able to show that the strong CREB mediated stimulation of transcription was diminished by micro- and nano-plastics in any chosen setting. This indicates a threat to human health via the deregulation of transcription induced by internalized micro- and nano-plastics. However, this established quantifiable in vitro transcription test system could help to screen for toxic substances and non-toxic alternatives.

Micro-flow imaging and flow virometry as preferred methods to monitor particulate matter for a human cytomegalovirus vaccine candidate.

The presence of particulate matter in vaccine samples is of concern as aggregates have the potential to reduce product efficacy, impact immunogenicity, or block capillaries upon injection. As a result, regulatory agencies routinely request particulate matter tests for particles in the micron size range for release. Particles may come in a variety of forms and can be intrinsic (e.g., from proteinaceous aggregates) or extrinsic (e.g., silicone oil from tubing or contamination from the manufacturing process). They may span the size range of sub-visible to visible particle sizes. In recent years, there has been a rise in requests from regulatory agencies for methods to detect and monitor aggregated particles as well as a desire to evaluate particle size and concentration of sub-micron sized particles. Typically utilized techniques include biophysical analytical methodologies that leverage light scattering or imaging. In this study, Dynamic Light Scattering (DLS), Micro-Flow Imaging (MFI) and Flow Virometry are evaluated as methods to detect and monitor sub-micron to micron sized particles, to support assessments of stability and processability, for drug substance (DS) and drug product (DP) samples of a Human Cytomegalovirus (HCMV) vaccine candidate. For this attenuated live virus vaccine candidate, MFI and flow virometry proved to be the most sensitive methods to monitor particulate matter.