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At least 595 records · Page 33

Effects of helium cavity size and morphology on the strength of pure titanium

In this study, high-purity α-titanium was implanted with helium to observe cavity morphology – size, number density, and form (i.e., bubbles vs. voids) – effects on materials strength. Increasing implantation temperatures lead to an Arrhenius-type (i.e., exponential) increase in cavity size, a transition from spherical bubbles to faceted voids, and a marked increase in strength (~20–50%). Implanted samples deformed uniformly in contrast to nano-compression of unimplanted or alloyed titanium, but pillars with the largest faceted voids developed a type of bulging localized deformation. Affected voids were repeatedly sheared, becoming rough and shrunken. Dislocation-cavity interactions and the role of helium content within cavities are considered.

36 MATERIALS SCIENCE↗

Exosomes secreted from mesenchymal stem cells mediate the regeneration of endothelial cells treated with rapamycin by delivering pro-angiogenic microRNAs

Highlights: • MSC-derived exosomes play an important role in promoting endothelial regeneration treated with rapamycin in vitro. • A distinct class of exosomal miRNAs is identified to be tightly related to endothelial regeneration. • The therapeutic effects of MSC-exosomes may be ascribed to the delivery of pro-angiogenic miRNAs to endothelial cells. • MSC-exosomes may serve as a cell-free therapy for clinical treatment of delayed endothelial healing after DES implantation. Delayed endothelial healing after drug eluting stent (DES) implantation is a critical clinical problem in treatment of coronary artery diseases. Exosomes exhibit proangiogenic potential in a variety of ischemic diseases. However, the association of exosomes with endothelial regeneration after DES implantation has been rarely reported. In this study, we aimed to investigate the therapeutic effects of mesenchymal stem cell (MSC)-derived exosomes on endothelial cells treated with rapamycin and explore the potential mechanisms of MSC-derived exosomes in promoting endothelial regeneration. Exosomes were isolated from MSCs by ultracentrifugation and identified by transmission electron microscopy, nanoparticle tracking analysis, and Western blot assay. The in vitro effects of MSC-derived exosomes on the proliferation and migration of endothelial cells treated with rapamycin were evaluated by integrated experiment, cell counting kit-8, scratch, tube formation, and transwell assays. And the apoptosis of rapamycin-induced endothelial cells loaded with MSC-derived exosomes was detected using TUNEL and Annexin-V FITC and PI double-staining assays. The microRNA (miRNA) cargo of MSC-derived exosomes was identified by high-throughput RNA sequencing. Pro-angiogenic miRNAs and key pathways were further characterized. Our results indicated that MSC-derived exosomes could be ingested into umbilical vein endothelial cells (HUVECs) and significantly enhanced cell proliferation rate, migratory and tube-forming capabilities in vitro. MSC-derived exosomes also inhibited the apoptosis of HUVECs induced by rapamycin. A distinct class of exosomal miRNAs was further identified, including six miRNAs tightly related to neovasculogenesis. Silencing the expression of exosomal miRNA-21–5p and let-7c-5p attenuated the pro-proliferative and pro-migratory capacity of MSC-derived exosomes. Moreover, functional enrichment analysis indicated that metabolic pathways might contribute to reendothelialization. This study highlights a proregenerative effect of MSC-derived exosomes in vitro, which may be partly explained by the delivery of pro-angiogenic miRNAs to endothelial cells.

60 APPLIED LIFE SCIENCES↗

Radiation Damage Mechanisms in Oxide-Based Solid Electrolytes

Ion implantation is a promising approach to mitigate dendrite formation in metal anode solid-state batteries by modifying the chemical and mechanical properties of oxide-based electrolyte surfaces such as Li 7 La 3 Zr 2 O 12 (LLZO). Yet, the detailed atomistic mechanisms and potentially adverse side effects of ion implantation remain poorly understood. In this study, we used molecular dynamics simulations to elucidate the evolution of radiation-induced damage in LLZO. The results reveal that radiation damage is primarily driven by recoils from heavy ions in the lattice, producing antisite defect clusters whose density decreases as recoil energy increases, a counterintuitive finding that highlights complex cascade fragmentation. Radiation-induced disruption to the crystal sublattice connectivity, especially in the La–O network critical for Li-ion transport, leads to degradation in ionic pathways at low energies, while higher energy cascades can form new conduction pathways via enhanced Zr–O network connectivity. These findings provide a mechanistic foundation for optimizing ion implantation strategies that balance disruption of the lattice for surface modification for dendrite resistance with preservation of essential ionic conductivity.

Defects↗

Laser activation of single group-IV colour centres in diamond

Abstract Spin-photon interfaces based on group-IV colour centres in diamond offer a promising platform for quantum networks. A key challenge in the field is realising precise single-defect positioning and activation, which is crucial for scalable device fabrication. Here we address this problem by demonstrating a two-step fabrication method for tin vacancy (SnV − ) centres that uses site-controlled ion implantation followed by local femtosecond laser annealing with in-situ spectral monitoring. The ion implantation is performed with sub-50 nm resolution and a dosage that is controlled from hundreds of ions down to single ions per site, limited by Poissonian statistics. Using this approach, we successfully demonstrate site-selective creation and modification of single SnV − centres. Our in-situ spectral monitoring opens a window onto materials tuning at the single defect level, and provides new insight into defect structures and dynamics during the annealing process. While demonstrated for SnV − centres, this versatile approach can be readily generalised to other implanted colour centres in diamond and wide-bandgap materials.

Science & Technology - Other Topics↗

Edge termination in vertical GaN diodes: Electric field distribution probed by second harmonic generation

We characterized the electric field distribution of GaN-on-GaN p–n diodes with partially compensated ion-implanted edge termination (ET) using an electric field induced second harmonic generation technique (EFISHG). The distributed electric field from the anode to the outer edge of the ET demonstrates the effectiveness of the ET structure. However, EFISHG also shows that its effectiveness is strongly dependent on the acceptor charge distribution in the ET's partially compensated layer (PC). A generally lower amount of acceptor charge can be inferred from the measured electric field distribution resulting from excessive ion implantation energy or dose during ET fabrication and causing lower than optimal breakdown voltage. Localized field crowding can be observed when the remaining acceptors uncompensated by the implant in the PC layer are nonuniformly distributed around the periphery of the devices. Important information can be obtained from these direct electric field measurements and used for optimizing the device design and fabrication process.

Cao, Yuke↗

Depth-dependent recovery of thermal conductivity after recrystallization of amorphous silicon

The depth-dependent recovery of silicon thermal conductivity was achieved after the recrystallization of silicon that had been partially amorphized due to ion implantation. Transmission electron microscopy revealed nanoscale amorphous pockets throughout a structurally distorted band of crystalline material. The minimum thermal conductivity of as-implanted composite material was 2.46 W m −1 K −1 and was found to be uniform through the partially amorphized region. X-ray diffraction measurements reveal 60% strain recovery of the crystalline regions after annealing at 450 °C for 30 min and almost full strain recovery and complete recrystallization after annealing at 700 °C for 30 min. In addition to strain recovery, the amorphous band thickness reduced from 240 to 180 nm after the 450 °C step with nanoscale recrystallization within the amorphous band. A novel depth-dependent thermal conductivity measurement technique correlated thermal conductivity with the structural changes, where, upon annealing, the low thermal conductivity region decreases with the distorted layer thickness reduction and the transformed material shows bulk-like thermal conductivity. Full recovery of bulk-like thermal conductivity in silicon was achieved after annealing at 700 °C for 30 min. After the 700 °C anneal, extended defects remain at the implant projected range, but not elsewhere in the layer. Previous results showed that high point-defect density led to reduced thermal conductivity, but here, we show that point defects can either reform into the lattice or evolve into extended defects, such as dislocation loops, and these very localized, low-density defects do not have a significant deleterious impact on thermal conductivity in silicon.

Huynh, Kenny↗

High conductivity in Ge-doped AlN achieved by a non-equilibrium process

Highly conductive Ge-doped AlN with conductivity of 0.3 (Ω cm) −1 and electron concentration of 2 × 10 18 cm −3 was realized via a non-equilibrium process comprising ion implantation and annealing at a moderate thermal budget. Similar to a previously demonstrated shallow donor state in Si-implanted AlN, Ge implantation also showed a shallow donor behavior in AlN with an ionization energy ∼80 meV. Ge showed a 3× higher conductivity than its Si counterpart for a similar doping level. Photoluminescence spectroscopy indicated that higher conductivity for Ge-doped AlN was achieved primarily due to lower compensation. This is the highest n-type conductivity reported for AlN doped with Ge to date and demonstration of technologically useful conductivity in Ge-doped AlN.

Bagheri, Pegah↗

Positron stopping in multilayer materials

Positron annihilation spectroscopy provides a sensitive toolset for defect characterization. In beam based studies of single-layer targets, the form of implantation profiles is well established, depending on the kinetic energy and angle of incident positrons relative to the target surface and the density and average atomic number of the target. For multilayer systems, the difference in density and across the layers makes derivation of an analytical form difficult. To date, the determination of positron stopping profiles in multilayer targets has primarily involved Monte Carlo simulations. We present here an alternative approach that estimates the energy distribution dN/dE of those positrons transmitted past each layer boundary, by fitting the remaining tail of the stopping profile after each layer with a basis set comprised of calculated stopping profiles in the same material they are transmitted through. The stopping profile in the next layer is then found by summing a series of stopping profiles in the new medium in proportion to the determined distribution dN/dE. The results of our model are compared with simulation results in a system of alternating layers of Al and Au and find reasonable agreement in the predicted profile and excellent agreement in the predicted mean implantation depth. Finally, we derived a simple formula-based approach for the calculation of the mean implantation depth in two-layer systems that provides results in excellent agreement with the full model.

Jones, A. C. L. [Arizona State University, Tempe, ↗

Optimization of a Lethal, Combat-Relevant Model of Sterile Inflammation in Mice for Drug Candidate Screening

ABSTRACT Introduction Extensive trauma, commonly seen in wounded military Service Members, often leads to a severe sterile inflammation termed systemic inflammatory response syndrome (SIRS), which can progress to multiple organ dysfunction syndrome (MODS) and death. MODS is a serious threat to wounded Service Members, historically causing 10% of all deaths in trauma admissions at a forward deployed combat hospital. The importance of this problem will be exacerbated in large-scale combat operations, in which evacuation will be delayed and care of complex injuries at lower echelons of care may be prolonged. The main goal of this study was to optimize an existing mouse model of lethal SIRS/MODS as a therapeutic screening platform for the evaluation of immunomodulatory drugs. Materials and Methods Male C57BL/6 mice were euthanized, and the bones and muscles were collected and blended into a paste termed tissue–bone matrix (TBX). The TBX at 12.5%–20% relative to body weight of each recipient mouse was implanted into subcutaneous pouches created on the dorsum of anesthetized animals. Mice were observed for clinical scores for up to 48 hours postimplantation and euthanized at the preset point of moribundity. To test effects of anesthetics on TBX-induced mortality, animals received isoflurane or ketamine/xylazine (K/X). In a separate set of studies, mice received TBX followed by intraperitoneal injection with 20 mg/kg or 40 mg/kg Eritoran or a placebo carrier. All Eritoran studies were performed in a blinded fashion. Results We observed that K/X anesthesia significantly increased the lethality of the implanted TBX in comparison to inhaled anesthetics. Although all the mice anesthetized with isoflurane and implanted with 12.5% TBX survived for 24 hours, 60% of mice anesthetized with K/X were moribund by 24 hours postimplantation. To mimic more closely the timing of lethal SIRS/MODS following polytrauma in human patients, we extended observation to 48 hours. We performed TBX dose–response studies and found that as low as 15%, 17.5%, and 20% TBX caused moribundity/mortality in 50%, 80%, and 100% mice, respectively, over a 48-hour time period. With 17.5% TBX, we tested if moribundity/mortality could be rescued by anti-inflammatory drug Eritoran, a toll-like receptor 4 antagonist. Neither 20 mg/kg nor 40 mg/kg doses of Eritoran were found to be effective in this model. Conclusions We optimized a TBX mouse model of SIRS/MODS for the purpose of evaluating novel therapeutic interventions to prevent trauma-related pathophysiologies in wounded Service Members. Negative effects of K/X on lethality of TBX should be further evaluated, particularly in the light of widespread use of ketamine in treatment of pain. By mimicking muscle crush, bone fracture, and necrosis, the TBX model has pleiotropic effects on physiology and immunology that make it uniquely valuable as a screening tool for the evaluation of novel therapeutics against trauma-induced SIRS/MODS.

General & Internal Medicine↗

Compliant Intramedullary Stems for Joint Reconstruction

The longevity of current joint replacements is limited by aseptic loosening, which is the primary cause of non-infectious failure for hip, knee, and ankle arthroplasty. Aseptic loosening is typically caused either by osteolysis from particulate wear, or by high shear stresses at the bone-implant interface from over-constraint. Our objective was to demonstrate feasibility of a compliant intramedullary stem that eliminates over-constraint without generating particulate wear. The compliant stem is built around a compliant mechanism that permits rotation about a single axis. We first established several models to understand the relationship between mechanism geometry and implant performance under a given angular displacement and compressive load. We then used a neural network to identify a design space of geometries that would support an expected 100-year fatigue life inside the body. We additively manufactured one representative mechanism for each of three anatomic locations, and evaluated these prototypes on a KR-210 robot. The neural network predicts maximum stress and torsional stiffness with 2.69% and 4.08% error respectively, relative to finite element analysis data. We identified feasible design spaces for all three of the anatomic locations. Simulated peak stresses for the three stem prototypes were below the fatigue limit. Benchtop performance of all three prototypes was within design specifications. Our results demonstrate the feasibility of designing patient- and joint-specific compliant stems that address the root causes of aseptic loosening. Guided by these results, we expect the use of compliant intramedullary stems in joint reconstruction technology to increase implant lifetime.

60 APPLIED LIFE SCIENCES↗

Osteogenic preconditioning in perfusion bioreactors improves vascularization and bone formation by human bone marrow aspirates

Cell-derived extracellular matrix (ECM) provides a niche to promote osteogenic differentiation, cell adhesion, survival, and trophic factor secretion. To determine whether osteogenic preconditioning would improve the bone-forming potential of unfractionated bone marrow aspirate (BMA), we perfused cells on ECM-coated scaffolds to generate naïve and preconditioned constructs, respectively. The composition of cells selected from BMA was distinct on each scaffold. Naïve constructs exhibited robust proangiogenic potential in vitro, while preconditioned scaffolds contained more mesenchymal stem/stromal cells (MSCs) and endothelial cells (ECs) and exhibited an osteogenic phenotype. Upon implantation into an orthotopic calvarial defect, BMA-derived ECs were present in vessels in preconditioned implants, resulting in robust perfusion and greater vessel density over the first 14 days compared to naïve implants. After 10 weeks, human ECs and differentiated MSCs were detected in de novo tissues derived from naïve and preconditioned scaffolds. These results demonstrate that bioreactor-based preconditioning augments the bone-forming potential of BMA.

59 BASIC BIOLOGICAL SCIENCES↗

Development of Single Photon Sources in GaN

The recent discovery of bright, room-temperature, single photon emitters in GaN leads to an appealing alternative to diamond best single photon emitters given the widespread use and technological maturity of III-nitrides for optoelectronics (e.g. blue LEDs, lasers) and high-speed, high-power electronics. This discovery opens the door to on-chip and on-demand single photon sources integrated with detectors and electronics. Currently, little is known about the underlying defect structure nor is there a sense of how such an emitter might be controllably created. A detailed understanding of the origin of the SPEs in GaN and a path to deterministically introduce them is required. In this project, we develop new experimental capabilities to then investigate single photon emission from GaN nanowires and both GAN and AlN wafers. We ion implant our wafers with the ion implanted with our focused ion beam nanoimplantation capabilities at Sandia, to go beyond typical broad beam implantation and create single photon emitting defects with nanometer precision. We've created light emitting sources using Li + and He + , but single photon emission has yet to be demonstrated. In parallel, we calculate the energy levels of defects and transition metal substitutions in GaN to gain a better understanding of the sources of single photon emission in GaN and AlN. The combined experimental and theoretical capabilities developed throughout this project will enable further investigation into the origins of single photon emission from defects in GaN, AlN, and other wide bandgap semiconductors.

36 MATERIALS SCIENCE↗

Waveguides for neurostimulation in the cochlea

Introduction Optical stimulation has been suggested for neural stimulation to improve cochlear implants. Light allows for more spatially selective activation of neuron populations than electrical current, offering more independent frequency bands along the spiral ganglion. These bands are available to encode acoustic information with anticipated better frequency resolution, improving cochlear implant user performance in noisy listening environments, tonal languages, and music perception. Methods Optical cochlear implants (oCIs) can deliver light either directly via small emitters within the cochlea or via waveguides from external optical sources. We investigated three waveguide designs made from OrmoComp ® , a polymer that cures through ultraviolet (UV) radiation. Waveguides were fabricated via injection molding and coated using dip-coating or thermal reflow, or through aspiration of OrmoComp ® into polyimide tubing that served as the cladding of the waveguide. The choice of fabrication technique directly determined the waveguides' total diameter: thermal reflow yielded ≈940 μm, dip-coating produced ≈306 μm, and aspiration resulted in ≈132 μm core diameter waveguides. Given the human cochlea's small size, we focused on analyzing the 306-μm and 132-μm waveguides, evaluating their optical performance (propagation and bending losses) and mechanical properties (bending stiffness and insertion forces). Furthermore, we evaluated some of these designs in in-vivo guinea pigs experiments. Results For the 100-μm core diameter waveguides, the propagation losses were 12.34 ± 1.26, 1.18 ± 0.88, 1.49 ± 0.58, and 3.43 ± 0.68 dB/cm at 534, 1,375, 1,460, and 1,550 nm, respectively. The respective bending losses at a 2 mm radius of curvature were 5.50 ± 1.32, 0.56 ± 0.26, 0.79 ± 0.18, and 0.64 ± 0.23 dB, and at 1 mm 8.54 ± 1.30, 2.05 ± 0.84, 2.11 ± 0.50, and 1.44 ± 0.37 dB. The bending stiffness of a 1 mm segment of the 100-μm-diameter waveguides was 18.9 ± 2.2 N/m. Insertion forces for the 100-μm-diameter waveguides into an acrylic human-size scala tympani model were < 25 mN. For the waveguides with 306 and 940 μm total diameter, the propagation losses ranged between 0.43 and 2.40 dB/cm at 534, 680, 1,375, and 1,550 nm, between 2.19 and 3.78 dB/cm at 450 and 1,460 nm. Bending losses for 360 degrees at 1,375 nm were 5.0, 2.4, and 0.46 for a bending radius of 2.5-, 3-, and 4-mm. Discussion Our study demonstrated that the polymer OrmoComp ® is suitable for fabricating waveguides to transmit near-infrared radiation. In-vivo experiments showed optically evoked auditory responses originating from optical stimulation in the guinea pigs' first cochlear turn while radiation was delivered. Incoming experiments will focus on evaluating long-term performance of these waveguides in guinea pigs and cats. This study will be designed to provide insights into the waveguides' performance and biocompatibility over extended periods, essential for their potential clinical application in future oCIs.

Kim, Matthew↗

Melt-Pool Dynamics and Microstructure of Mg Alloy WE43 under Laser Powder Bed Fusion Additive Manufacturing Conditions

Magnesium-based alloy WE43 is a state-of-the-art bioresorbable metallic implant material. There is a need for implants with both complex geometries to match the mechanical properties of bone and refined microstructure for controlled resorption. Additive manufacturing (AM) using laser powder bed fusion (LPBF) presents a viable fabrication method for implant applications, as it offers near-net-shape geometrical control, allows for geometry customization based on an individual patient, and fast cooling rates to achieve a refined microstructure. In this study, the laser–alloy interaction is investigated over a range of LPBF-relevant processing conditions to reveal melt-pool dynamics, pore formation, and the microstructure of laser-melted WE43. In situ X-ray imaging reveals distinct laser-induced vapor depression morphology regimes, with minimal pore formation at laser-scan speeds greater than 500 mm/s. Optical and electron microscopy of cross-sectioned laser tracks reveal three distinct microstructural regimes that can be controlled by adjusting laser-scan parameters: columnar, dendritic, and banded microstructures. These regimes are consistent with those predicted by the analytic solidification theory for conduction-mode welding, but not for keyhole-mode tracks. The results provide insight into the fundamental laser–material interactions of the WE43 alloy under AM-processing conditions and are critical for the successful implementation of LPBF-produced WE43 parts in biomedical applications.

36 MATERIALS SCIENCE↗

Methods for Determining Blood Flow Through Intact Vessels of Experimental Animals Under Conditions of Gravitational Stress and in Extraterrestrial Space Capsules

Work during the initial six months of this program has proceeded along three lines: (1) technical development of blood flowmeter instrumentation: (2) surgical considerations related to special problems of chronic implantation of flowmeter probes: (3) study of the relationship between levels of blood flow and organ activity. Principal engineering effort has been focused on the fundamental phenomena operative in the flowmeter probe and on probe design. Two probes have been constructed and a third is nearing completion. A previously unrecognized source of zero drift has been discovered and corrected. has been designed, assembled, tested and successfully employed in work on the several probes. A significant innovation which has been introduced is the use of a transformer coupled input for suppression of unwanted common mode signals. New low noise transistor amplifiers with characteristics suitable for space vehicle packaging are being developed. Linearity of the present apparatus has been found to extend at least into the near turbulent flow region. Attention has been directed to the two vascular beds of physiologic interest that present particular problems with regard to chronic implantation of flowmeter probes, the myocardium and the liver. Surgical techniques have been perfected that will permit myocardial and liver blood flow measurement. Two groups of animals have successfully undergone surgery and await the implantation of probes. Studies of the relationship between organ blood flow and levels of physiologic activity have been initiated. The first organ system studied was the heart, For the first time autoregulatory mechanisms have been demonstrated within the myocardial vascular bed which rapidly and precisely maintain coronary blood flow at a level i n keeping with the magnitude of cardiac work, Following a summary statement of the status of the program, the work performed is described, A financial review of expenditures incurred and a proposal for future funding are appended,

Shaw, R. F.↗

Percutaneous connector device

A device is reported for facilitating the passage of electrical signals from an external source through the skin of a patient to internal portions of the body such as muscles and nerves. The connector device includes a bio-compatible shell having an enlarged disk shaped portion for being implanted below the skin of the patient. The shell has a first and second electrically conductive post carried therein upon which a plug can be readily connected and disconnected. A modified form of the invention utilizes a unipolar connector that is adapted to be plugged into a shell implanted below the skin of a patient. Both of the connector devices are designed to be separated when a predetermined force is applied. This prevents excessive force from being applied to the implanted bio-compatible shell.

Parsons, W. E.↗

An inductively powered telemetry system for temperature, EKG, and activity monitoring

An implant telemetry system for the simultaneous monitoring of temperature, activity, and EKG from small animals, such as rats, was designed with the feature that instead of a battery the system is energized by an inductive field. A 250 kHz resonant coil surrounds the cage (30 x 30 x 20 cm) and provides the approximately 100 microns of power required to operate the implant transmitter while allowing the animal unrestrained movement in the cage. The implant can also be battery operated if desired. RF transmission is in the 8-10 MHz band, which allows the use of a simple, essentially single IC chip, receiver.

Fryer, T. B.↗

Adaptation of ion beam technology to microfabrication of solid state devices and transducers

A number of areas were investigated to determine the potential uses of ion beam techniques in the construction of solid state devices and transducers and the packaging of implantable electronics for biomedical applications. The five areas investigated during the past year were: (1) diode-like devices fabricated on textured silicon; (2) a photolithographic technique for patterning ion beam sputtered PVC (polyvinyl chloride); (3) use of sputtered Teflon as a protective coating for implantable pressure sensors; (4) the sputtering of Macor to seal implantable hybrid circuits; and (5) the use of sputtered Teflon to immobilize enzymes.

Topich, J. A.↗