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At least 361 records · Page 20

Influence of TiO{sub 2} Nanoparticles on the Crystallization Behaviour and Tensile Properties of Biodegradable PLA and PCL Nanocomposites

This paper investigated the influence of TiO{sub 2} nanoparticles on the morphologies, as well as crystallization behaviour and kinetics, of neat PLA and PCL, and of these polymers in different PLA/PCL blends. We used transmission electron microscopy to evaluate the morphologies of the systems, while the crystallization behaviour and kinetics were investigated through differential scanning calorimetry (DSC). In addition to standard and modulated (StepScan) DSC analyses, the self-nucleation temperatures of neat PCL and PCL in the different nanocomposites were determined, followed by a self-nucleation and annealing thermal fractionation analysis of PCL crystallization and an Avrami isothermal kinetic analysis of PCL crystallization and PLA cold crystallization. We found that the nanoparticles were well dispersed, but only in the PLA phase of the blends, with only a few on the interface or in the PCL phase. They did nucleate and accelerate, and influence the mechanism of, the PCL crystallization in neat PCL, but had little influence on PCL crystallization in the blends. They strongly influenced the rate of cold crystallization of PLA, but had little influence on this parameter in the blends. The tensile properties were also determined, and changes in these properties could be related to the morphologies of the systems.

77 NANOSCIENCE AND NANOTECHNOLOGY↗

High modulus biocomposites via additive manufacturing: Cellulose nanofibril networks as “microsponges”

For the successful transition of additive manufacturing (AM) from prototyping to manufacturing of structural load bearing parts, feedstock systems with improved mechanical properties are needed. In terms of sustainability and environmental impact, selection of biobased renewable alternatives instead of petroleum-based options is important. Nanocellulose, which gives plants and trees their structural integrity, can offer significant improvements in the mechanical properties of AM polymers, provided that the right fibril morphology, dispersion and adhesion are achieved. In this study, although the interfacial adhesion between the hydrophilic cellulose nanofibrils (CNFs) and the hydrophobic polylactate matrix was not strong, and the optimal dispersion in individual fibril level was not attained, dramatic improvements in mechanical properties of neat polymer were achieved (up to 80% tensile strength increase, up to 200% elastic modulus increase). An interlocking reinforcing mechanism in which CNF bundles act as “microsponges” was proposed and supported by high resolution electron microscopy images, x-ray computed chromatography scans and thermal and dynamic mechanical behavior. Additively manufactured samples showed significantly higher elastic modulus (7.12 GPa vs. 6.57 GPa at 30 wt % CNF content) and dramatically improved storage modulus (1.72 GPa vs. 0.9 GPa at 30 wt % CNF content) in the printing direction compared to compression molded samples. Finally, in conclusion, preparation and 3D-printing of a 100% biobased renewable feedstock material with substantial mechanical property improvements were successfully demonstrated, which can open up new window of opportunities in the AM industry.

42 ENGINEERING↗

An epidermal equivalent assay for identification and ranking potency of contact sensitizers

The purpose of this study was to explore the possibility of combining the epidermal equivalent (EE) potency assay with the assay which assesses release of interleukin-18 (IL-18) to provide a single test for identification and classification of skin sensitizing chemicals, including chemicals of low water solubility or stability. A protocol was developed using different 3D-epidermal models including in house VUMC model, epiCS® (previously EST1000™), MatTek EpiDerm™ and SkinEthic™ RHE and also the impact of different vehicles (acetone:olive oil 4:1, 1% DMSO, ethanol, water) was investigated. Following topical exposure for 24 h to 17 contact allergens and 13 non-sensitizers a robust increase in IL-18 release was observed only after exposure to contact allergens. A putative prediction model is proposed from data obtained from two laboratories yielding 95% accuracy. Correlating the in vitro EE sensitizer potency data, which assesses the chemical concentration which results in 50% cytotoxicity (EE-EC{sub 50}) with human and animal data showed a superior correlation with human DSA{sub 05} (μg/cm{sup 2}) data (Spearman r = 0.8500; P value (two-tailed) = 0.0061) compared to LLNA data (Spearman r = 0.5968; P value (two-tailed) = 0.0542). DSA{sub 05} = induction dose per skin area that produces a positive response in 5% of the tested population Also a good correlation was observed for release of IL-18 (SI-2) into culture supernatants with human DSA{sub 05} data (Spearman r = 0.8333; P value (two-tailed) = 0.0154). This easily transferable human in vitro assay appears to be very promising, but additional testing of a larger chemical set with the different EE models is required to fully evaluate the utility of this assay and to establish a definitive prediction model. - Highlights: • A potential epidermal equivalent assay to label and classify sensitizers • Il-18 release distinguishes sensitizers from non sensitizers • IL-18 release can rank sensitizer potency • EC50 (chemical concentration causing 50% decrease in cell viability) ranks potency • In vitro: human DSA{sub 05} correlation is better than in vitro: LLNA correlation.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

Development and assessment of countermeasure formulations for treatment of lung injury induced by chlorine inhalation

Chlorine is a commonly used, reactive compound to which humans can be exposed via accidental or intentional release resulting in acute lung injury. Formulations of rolipram (a phosphodiesterase inhibitor), triptolide (a natural plant product with anti-inflammatory properties), and budesonide (a corticosteroid), either neat or in conjunction with poly(lactic:glycolic acid) (PLGA), were developed for treatment of chlorine-induced acute lung injury by intramuscular injection. Formulations were produced by spray-drying, which generated generally spherical microparticles that were suitable for intramuscular injection. Multiple parameters were varied to produce formulations with a wide range of in vitro release kinetics. Testing of selected formulations in chlorine-exposed mice demonstrated efficacy against key aspects of acute lung injury. The results show the feasibility of developing microencapsulated formulations that could be used to treat chlorine-induced acute lung injury by intramuscular injection, which represents a preferred route of administration in a mass casualty situation. - Highlights: • Chlorine causes lung injury when inhaled and is considered a chemical threat agent. • Countermeasures for treatment of chlorine-induced acute lung injury are needed. • Formulations containing rolipram, triptolide, or budesonide were produced. • Formulations with a wide range of release properties were developed. • Countermeasure formulations inhibited chlorine-induced lung injury in mice.

60 APPLIED LIFE SCIENCES↗

MAGs from alcoholic fermentation in sugarcane biorefineries

Genome-resolved metagenomics was applied to recover microbial metagenome-assembled genomes (MAGs) from alcoholic fermentation samples collected at two sugarcane biorefineries in São Paulo state, Brazil, during the 2024 harvest season.

59 BASIC BIOLOGICAL SCIENCES↗

The importance of new processing techniques in tissue engineering

The use of polymer scaffolds in tissue engineering is reviewed and processing techniques are examined. The discussion of polymer-scaffold processing explains fiber bonding, solvent casting and particulate leaching, membrane lamination, melt molding, polymer/ceramic fiber composite-foam processing, phase separation, and high-pressure processing.

Non-NASA Center↗

Estimation of skeletal muscle interstitial adenosine during forearm dynamic exercise in humans

It has been proposed that adenosine is a metabolic signal that triggers activation of muscle afferents involved in the exercise pressor reflex. Furthermore, exogenous adenosine induces sympathetic activation that mimics the exercise pressor reflex, and blockade of adenosine receptors inhibits sympathetic activation induced by exercise. Thus, we hypothesize that adenosine is released locally by the muscle during exercise. We used microdialysis probes, placed in the flexor digitorium superficialis muscle, to estimate muscle interstitial adenosine levels in humans. We estimated resting in vivo muscle interstitial adenosine concentrations (0.292+/-0.058 micromol/L, n=4) by perfusing increasing concentrations of adenosine to determine the gradient produced in the dialysate. Muscle interstitial adenosine concentrations increased from 0.23+/-0.04 to 0.82+/-0.14 micromol/L (n=14, P<0.001) during intermittent dynamic exercise at 50% of maximal voluntary contraction. Lactate increased from 0.8+/-0.1 to 2.3+/-0.3 mmol/L (P<0.001). Lower intensity (15% maximal voluntary contraction) intermittent dynamic exercise increased adenosine concentrations from 0.104+/-0.02 to 0.42+/-0.16 micromol/L (n=7). The addition of ischemia to this low level of exercise produced a greater increase in adenosine (from 0.095+/-0.02 to 0.48+/-0.2 micromol/L) compared with nonischemic exercise (0. 095+/-0.02 to 0.25+/-0.12 micromol/L). These results indicate that microdialysis is useful in estimating adenosine concentrations and in reflecting changes in muscle interstitial adenosine during dynamic exercise in humans.

Non-NASA Center↗

Glucose absorption, hormonal release and hepatic metabolism after guar gum ingestion

Six non-anaesthetized Large White pigs (mean body weight 59 +/- 1.7 kg) were fitted with permanent catheters in the portal vein, the brachiocephalic artery and the right hepatic vein and with electromagnetic flow probes around the portal vein and the hepatic artery. The animals were provided a basal none-fibre diet (diet A) alone or together with 6% guar gum (diet B) or 15% purified cellulose (diet C). The diets were given for 1 week and according to a replicated 3 x 3 latin-square design. On the last day of each adaptation period test meals of 800 g were given prior to blood sampling. The sampling was continued for 8 h. Guar gum strongly reduced the glucose absorption as well as the insulin, gastric inhibitory polypeptide (GIP) and insulin-like growth factor-1 (IGF-1) production. However, the reduction in peripheral blood insulin levels caused by guar gum was not associated with a change in hepatic insulin extraction. IGF-1 appeared to be strongly produced by the gut. The liver had a net uptake of the peptide. Ingestion of guar gum increased the hepatic extraction coefficient of gut produced IGF-1. Guar gum ingestion also appeared to decrease pancreatic glucagon secretion. Cellulose at the level consumed had very little effect on the parameters considered. It is suggested that the modulation of intestinal mechanisms by guar gum was sufficient to mediate the latter internal metabolic effects.

Glucose/metabolism↗

Bone formation by three-dimensional stromal osteoblast culture in biodegradable polymer scaffolds

Bone formation was investigated in vitro by culturing stromal osteoblasts in three-dimensional (3-D), biodegradable poly(DL-lactic-co-glycolic acid) foams. Three polymer foam pore sizes, ranging from 150-300, 300-500, and 500-710 microns, and two different cell seeding densities, 6.83 x 10(5) cells/cm2 and 22.1 x 10(5) cells/cm2, were examined over a 56-day culture period. The polymer foams supported the proliferation of seeded osteoblasts as well as their differentiated function, as demonstrated by high alkaline phosphatase activity and deposition of a mineralized matrix by the cells. Cell number, alkaline phosphatase activity, and mineral deposition increased significantly over time for all the polymer foams. Osteoblast foam constructs created by seeding 6.83 x 10(5) cells/cm2 on foams with 300-500 microns pores resulted in a cell density of 4.63 x 10(5) cells/cm2 after 1 day in culture; they had alkaline phosphatase activities of 4.28 x 10(-7) and 2.91 x 10(-6) mumol/cell/min on Days 7 and 28, respectively; and they had a cell density that increased to 18.7 x 10(5) cells/cm2 by Day 56. For the same constructs, the mineralized matrix reached a maximum penetration depth of 240 microns from the top surface of the foam and a value of 0.083 mm for mineralized tissue volume per unit of cross sectional area. Seeding density was an important parameter for the constructs, but pore size over the range tested did not affect cell proliferation or function. This study suggests the feasibility of using poly(alpha-hydroxy ester) foams as scaffolding materials for the transplantation of autogenous osteoblasts to regenerate bone tissue.

Non-NASA Center↗

Biological toxicity and environmental hazards associated with PLGA nanoparticles

There have been tremendous advances in nanotechnology. More recently, the use of nanoparticles has expanded to applications including materials, packaging, energy, and medical uses such as drug delivery, diagnostics, and therapeutics. The American Society for Testing and Materials (ASTM) and the International Organization for Standardization (ISO) define nanoparticles as particles with at least one dimension measuring between 1 and 100 nm (2), but this view is generally too limited, and recommendations have been made to consider all materials with a dimension measuring under 1,000 nm as nanoparticles. The biomedical uses of nanoparticles are particularly promising because of their ability to reach and target various sites and organs. However, some nanoparticles can be composed of toxic materials or are limited by issues of biodistribution and bioaccumulation, which have hampered their use in biomedicine. The copolymer poly lactic-co-glycolic acid (PLGA) has gained use in biomedical applications as a delivery system because it is considered biocompatible and can be formulated with controlled degradation in physiological environments. PLGA has a history in biomedicine that dates to the 1970s when biodegradable sutures were developed using PLGA. In addition, the United States (US) Food and Drug Administration (FDA) and the European Medicine Agency (EMA) have approved various PLGA particle formulations as therapeutic delivery vehicles. Interest in biocompatible materials to deliver a range of therapeutic drugs, proteins, nucleic acids, and other molecules has risen recently. In addition to drug delivery, sustained drug release can be achieved by tuning the physical properties of PLGA, such as the molecular weight, ratio of lactic to glycolic acid, drug concentration, stabilizing molecules, and particle size. Given the rise of nanoparticles, human and environmental exposure to them is inevitable as more applications use free, unbound, and highly mobile particles. Although PLGA is generally considered safe, a detailed understanding of how PLGA and the other components used to help formulate this copolymer into a nanoparticle delivery vehicle is useful for assessing potential harmful effects. Despite recent advances in PLGA nanoparticle formulations, residual stabilizing molecules, inconsistent preparations, and batch-to-batch variations can lead to toxicity. Poor preparations of PLGA can lead to common mechanisms of toxicity observed with nanoparticles, such as inflammation and oxidative stress. Consistency in PLGA formulations and accurate methods to evaluate nanoparticle toxicity are needed to ensure safety. In order to better assess PLGA nanoparticles as non-toxic delivery systems, it is critical to understand their physical and chemical properties and the formulation protocols that may introduce toxic components into particles.

Biology, nanoparticle, toxicity↗

Development of 225Ac-doped biocompatible nanoparticles for targeted alpha therapy

Abstract Targeted alpha therapy (TAT) relies on chemical affinity or active targeting using radioimmunoconjugates as strategies to deliver α-emitting radionuclides to cancerous tissue. These strategies can be affected by transmetalation of the parent radionuclide by competing ions in vivo and the bond-breaking recoil energy of decay daughters. The retention of α-emitting radionuclides and the dose delivered to cancer cells are influenced by these processes. Encapsulating α-emitting radionuclides within nanoparticles can help overcome many of these challenges. Poly(lactic- co -glycolic acid) (PLGA) nanoparticles are a biodegradable and biocompatible delivery platform that has been used for drug delivery. In this study, PLGA nanoparticles are utilized for encapsulation and retention of actinium-225 ([ 225 Ac]Ac 3+ ). Encapsulation of [ 225 Ac]Ac 3+ within PLGA nanoparticles (Z ave = 155.3 nm) was achieved by adapting a double-emulsion solvent evaporation method. The encapsulation efficiency was affected by both the solvent conditions and the chelation of [ 225 Ac]Ac 3+ . Chelation of [ 225 Ac]Ac 3+ to a lipophilic 2,9-bis-lactam-1,10-phenanthroline ligand ([ 225 Ac]AcBLPhen) significantly decreased its release (< 2%) and that of its decay daughters (< 50%) from PLGA nanoparticles. PLGA nanoparticles encapsulating [ 225 Ac]AcBLPhen significantly increased the delivery of [ 225 Ac]Ac 3+ to murine (E0771) and human (MCF-7 and MDA-MB-231) breast cancer cells with a concomitant increase in cell death over free [ 225 Ac]Ac 3+ in solution. These results demonstrate that PLGA nanoparticles have potential as radionuclide delivery platforms for TAT to advance precision radiotherapy for cancer. In addition, this technology offers an alternative use for ligands with poor aqueous solubility, low stability, or low affinity, allowing them to be repurposed for TAT by encapsulation within PLGA nanoparticles. Graphical Abstract

60 APPLIED LIFE SCIENCES↗

COMBINING NEUTRAL AND ACIDIC EXTRACTANTS FOR RECOVERING TRANSURANIC ELEMENTS FROM NUCLEAR FUEL

We have been investigating a solvent extraction system that combines a neutral extractant--octyl(phenyl)-N,N-diisobutyl-carbamoylmethylphosphine oxide (CMPO)--with an acidic extractant--bis(2-ethylhexyl)phosphoric acid (HDEHP)--to form a single process solvent for separating Am and Cm from the other components of irradiated nuclear fuel. It was originally hypothesized that the extraction chemistry of CMPO would dominate under conditions of high acidity (> 1 M HNO3), resulting in co-extraction of the transuranic and lanthanide elements into the organic phase. Contacting the loaded solvent with a solution of diethylenetriaminepentaacetate (DTPA) buffered with lactic or citric acid at pH {approx}3 to 4 would result in a condition in which the HDEHP chemistry dominates. Although the data somewhat support this hypothesis, it is clear that there are interactions between the two extractants such that they do not act independently in the extraction and stripping regimes. We report here studies directed at determining the nature and extent of interaction between CMPO and HDEHP, the synergistic behavior of CMPO and HDEHP in the extraction of americium and neodymium, and progress towards determining the thermodynamics of this extraction system. Neodymium and americium behave similarly in the combined solvent system, with a significant synergy between CMPO and HDEHP in the extraction of both of these trivalent elements from lactate-buffered DTPA solutions. In contrast, a much weaker synergistic behaviour is observed for europium. Thus, investigations into the fundamental chemistry involved in this system have focused on the neodymium extraction. The extraction of neodymium has been systematically investigated, individually varying the HDEHP concentration, the CMPO concentration, or the aqueous phase composition. Thermodynamic modeling of the neodymium extraction system has been initiated. Interactions between CMPO and HDEHP in the organic phase must be taken into account in the thermodynamic modeling; such interactions have been quantified by nuclear magnetic resonance measurements.

11 NUCLEAR FUEL CYCLE AND FUEL MATERIALS↗

Hydroxyapatite fiber reinforced poly(alpha-hydroxy ester) foams for bone regeneration

A process has been developed to manufacture biodegradable composite foams of poly(DL-lactic-co-glycolic acid) (PLGA) and hydroxyapatite short fibers for use in bone regeneration. The processing technique allows the manufacture of three-dimensional foam scaffolds and involves the formation of a composite material consisting of a porogen material (either gelatin microspheres or salt particles) and hydroxyapatite short fibers embedded in a PLGA matrix. After the porogen is leached out, an open-cell composite foam remains which has a pore size and morphology defined by the porogen. By changing the weight fraction of the leachable component it was possible to produce composite foams with controlled porosities ranging from 0.47 +/- 0.02 to 0.85 +/- 0.01 (n = 3). Up to a polymer:fiber ratio of 7:6, short hydroxyapatite fibers served to reinforce low-porosity PLGA foams manufactured using gelatin microspheres as a porogen. Foams with a compressive yield strength up to 2.82 +/- 0.63 MPa (n = 3) and a porosity of 0.47 +/- 0.02 (n = 3) were manufactured using a polymer:fiber weight ratio of 7:6. In contrast, high-porosity composite foams (up to 0.81 +/- 0.02, n = 3) suitable for cell seeding were not reinforced by the introduction of increasing quantities of hydroxyapatite short fibers. We were therefore able to manufacture high-porosity foams which may be seeded with cells but which have minimal compressive yield strength, or low porosity foams with enhanced osteoconductivity and compressive yield strength.

NASA Discipline Cell Biology↗