Evaluation of laser bacterial anti-fouling of transparent nanocrystalline yttria-stabilized-zirconia cranial implant.

BACKGROUND AND OBJECTIVE: The development and feasibility of a novel nanocrystalline yttria-stabilized-zirconia (nc-YSZ) cranial implant has been recently established. The purpose of what we now call "window to the brain (WttB)" implant (or platform), is to improve patient care by providing a technique for delivery and/or collection of light into/from the brain, on demand, over large areas, and on a chronically recurring basis without the need for repeated craniotomies. WttB holds the transformative potential for enhancing light-based diagnosis and treatment of a wide variety of brain pathologies including cerebral edema, traumatic brain injury, stroke, glioma, and neurodegenerative diseases. However, bacterial adhesion to the cranial implant is the leading factor for biofilm formation (fouling), infection, and treatment failure. Escherichia coli (E. coli), in particular, is the most common isolate in gram-negative bacillary meningitis after cranial surgery or trauma. The transparency of our WttB implant may provide a unique opportunity for non-invasive treatment of bacterial infection under the implant using medical lasers. STUDY DESIGN/MATERIALS AND METHODS: A drop of a diluted overnight culture of BL21-293 E. coli expressing luciferase was seeded between the nc-YSZ implant and the agar plate. This was followed by immediate irradiation with selected laser. After each laser treatment the nc-YSZ was removed, and cultures were incubated for 24 hours at 37 °C. The study examined continuous wave (CW) and pulsed wave (PW) modes of near-infrared (NIR) 810 nm laser wavelength with a power output ranging from 1 to 3 W. During irradiation, the temperature distribution of nc-YSZ surface was monitored using an infrared thermal camera. Relative luminescence unit (RLU) was used to evaluate the viability of bacteria after the NIR laser treatment. RESULTS: Analysis of RLU suggests that the viability of E. coli biofilm formation was reduced with NIR laser treatment when compared to the control group (P < 0.01) and loss of viability depends on both laser fluence and operation mode (CW or PW). The results demonstrate that while CW laser reduces the biofilm formation more than PW laser with the same power, the higher surface temperature of the implant generated by CW laser limits its medical efficacy. In contrast, with the right parameters, PW laser produces a more moderate photothermal effect which can be equally effective at controlling bacterial growth. CONCLUSIONS: Our results show that E. coli biofilm formation across the thickness of the nc-YSZ implant can be disrupted using NIR laser treatment. The results of this in vitro study suggest that using nc-YSZ as a cranial implant in vivo may also allow for locally selective, non-invasive, chronic treatment of bacterial layers (fouling) that might form under cranial implants, without causing adverse thermal damage to the underlying host tissue when appropriate laser parameters are used. Lasers Surg. Med. 48:782-789, 2016. © 2016 Wiley Periodicals, Inc.

Transparent nanocrystalline yttria-stabilized-zirconia calvarium prosthesis.

Laser-based diagnostics and therapeutics show promise for many neurological disorders. However, the poor transparency of cranial bone (calvaria) limits the spatial resolution and interaction depth that can be achieved, thus constraining opportunity in this regard. Herein, we report preliminary results from efforts seeking to address this limitation through use of novel transparent cranial implants made from nanocrystalline yttria-stabilized zirconia (nc-YSZ). Using optical coherence tomography (OCT) imaging of underlying brain in an acute murine model, we show that signal strength is improved when imaging through nc-YSZ implants relative to native cranium. As such, this provides initial evidence supporting the feasibility of nc-YSZ as a transparent cranial implant material. Furthermore, it represents a crucial first step towards realization of an innovative new concept we are developing, which seeks to eventually provide a clinically-viable means for optically accessing the brain, on-demand, over large areas, and on a chronically-recurring basis, without need for repeated craniectomies. FROM THE CLINICAL EDITOR: In this study, transparent nanocrystalline yttria-stabilized-zirconia is used as an experimental "cranium prosthesis" material, enabling the replacement of segments of cranial bone with a material that allows for optical access to the brain on a recurrent basis using optical imaging methods such as OCT.

Thermal conductivity of nanocrystalline silicon: importance of grain size and frequency-dependent mean free paths.

The thermal conductivity reduction due to grain boundary scattering is widely interpreted using a scattering length assumed equal to the grain size and independent of the phonon frequency (gray). To assess these assumptions and decouple the contributions of porosity and grain size, five samples of undoped nanocrystalline silicon have been measured with average grain sizes ranging from 550 to 64 nm and porosities from 17% to less than 1%, at temperatures from 310 to 16 K. The samples were prepared using current activated, pressure assisted densification (CAPAD). At low temperature the thermal conductivities of all samples show a T(2) dependence which cannot be explained by any traditional gray model. The measurements are explained over the entire temperature range by a new frequency-dependent model in which the mean free path for grain boundary scattering is inversely proportional to the phonon frequency, which is shown to be consistent with asymptotic analysis of atomistic simulations from the literature. In all cases the recommended boundary scattering length is smaller than the average grain size. These results should prove useful for the integration of nanocrystalline materials in devices such as advanced thermoelectrics.

Nanocrystalline Yttria-Stabilized Zirconia Ceramics for Cranial Window Applications.

Transparent yttria-stabilized zirconia (YSZ) ceramics are promising for cranial window applications because of their good mechanical and optical properties as well as biocompatibility. YSZ discs with different yttria concentrations were either processed via current-activated pressure-assisted densification (CAPAD) using commercial nanoparticles or densified via spark plasma sintering (SPS) using pyrolysis-synthesized nanoparticles in-house. This study provided critical results to screen composition, processing, microstructure, and cytocompatibility of transparent YSZ discs for cranial window applications. CAPAD-processed YSZ discs with 6 or 8 mol % yttria (6YSZ and 8YSZ) and SPS-densified YSZ discs with 4 mol % yttria (4YSZ_P) showed 200-350 nm polycrystalline grains containing 20-30 nm crystallite domains. SPS-densified YSZ discs with 8 mol % yttria (8YSZ_P) showed larger polycrystalline grains of 819 ± 155 nm with 29 ± 5 nm crystallite domains. CAPAD-processed YSZ discs with 3 mol % yttria (3YSZ) showed 39 ± 9 nm grains. Bone-marrow-derived stem cells (BMSCs) on the polished YSZ discs showed statistically higher spreading areas than those on the unpolished YSZ discs of the same compositions. Generally, polished 8YSZ, 4YSZ_P, and 8YSZ_P discs and unpolished 8YSZ_R, 4YSZ_PR, and 8YSZ_PR discs had lower average cell adhesion densities than other YSZ discs under direct contact conditions. Under indirect contact conditions, all the YSZ disc groups showed similar average cell adhesion densities to the Cell-only control. The groups of polished 4YSZ_P and 8YSZ_P discs, unpolished 4YSZ_PR and 8YSZ_PR discs, and particle control of 8YSZ_Pnp showed higher Y3+ ion concentrations than other groups. No mineral deposition was detected on the polished YSZ discs after cell culture. Considering multiple factors such as cytocompatibility, cell adhesion density, Y3+ ion release, mineral deposition, and optical transparency collectively, 8YSZ may be the best candidate for the cranial window applications. Further studies are needed to evaluate the long-term transparency and biocompatibility of YSZ discs.

Processing and Thermal Conductivity of Bulk Nanocrystalline Aluminum Nitride.

Producing bulk AlN with grain sizes in the nano regime and measuring its thermal conductivity is an important milestone in the development of materials for high energy optical applications. We present the synthesis and subsequent densification of nano-AlN powder to produce bulk nanocrystalline AlN. The nanopowder is synthesized by converting transition alumina (δ-Al2O3) with <40 nm grain size to AlN using a carbon free reduction/nitridation process. We consolidated the nano-AlN powder using current activated pressure assisted densification (CAPAD) and achieved a relative density of 98% at 1300 °C with average grain size, d¯~125 nm. By contrast, high quality commercially available AlN powder yields densities ~75% under the same CAPAD conditions. We used the 3-ω method to measure the thermal conductivity, κ of two nanocrystalline samples, 91% dense, d¯ = 110 nm and 99% dense, d¯ = 220 nm, respectively. The dense sample with 220 nm grains has a measured κ = 43 W/(m·K) at room temperature, which is relatively high for a nanocrystalline ceramic, but still low compared to single crystal and large grain sized polycrystalline AlN which can exceed 300 W/(m·K). The reduction in κ in both samples is understood as a combination of grain boundary scattering and porosity effects. We believe that these are finest d¯ reported in bulk dense AlN and is the first report of thermal conductivity for AlN with ≤220 nm grain size. The obtained κ values are higher than the vast majority of conventional optical materials, demonstrating the advantage of AlN for high-energy optical applications.

Characterization of ageing resistant transparent nanocrystalline yttria-stabilized zirconia implants.

The "Window to the Brain" is a transparent cranial implant under development, based on nanocrystalline yttria-stabilized zirconia (nc-YSZ) transparent ceramic material. Previous work has demonstrated the feasibility of this material to facilitate brain imaging over time, but the long-term stability of the material over decades in the body is unknown. In this study, the low-temperature degradation (LTD) of nc-YSZ of 3, 6, and 8 mol % yttria is compared before and after accelerated ageing treatments following ISO standards for assessing the ageing resistance of zirconia ceramics. After 100 hr of accelerated ageing (equivalent to many decades of ageing in the body), the samples do not show any signs of phase transformation to monoclinic by X-ray diffraction and micro-Raman spectroscopy. Moreover, the mechanical hardness of the samples did not decrease, and changes in optical transmittance from 500 to 1000 nm due to ageing treatments was minimal (below 3% for all samples), and unlikely to be due to phase transformation of surface crystals to monoclinic. These results indicate the nc-YSZ has excellent ageing resistance and can withstand long-term implantation conditions without exhibiting LTD.

Iron oxide-based nanostructured ceramics with tailored magnetic and mechanical properties: development of mechanically robust, bulk superparamagnetic materials.

Nanostructured iron-oxide based materials with tailored mechanical and magnetic behavior are produced in bulk form. By applying ultra-fast heating routines via spark plasma sintering (SPS) to supercrystalline pellets, materials with an enhanced combination of elastic modulus, hardness and saturation magnetization are achieved. Supercrystallinity - namely the arrangement of the constituent nanoparticles into periodic structures - is achieved through self-assembly of the organically-functionalized iron oxide nanoparticles. The optimization of the following SPS regime allows the control of organics' removal, necking, iron oxide phase transformations and nano-grain size retention, and thus the fine-tuning of both mechanical properties and magnetic response, up until the production of bulk mm-size superparamagnetic materials.

Gain in polycrystalline Nd-doped alumina: leveraging length scales to create a new class of high-energy, short pulse, tunable laser materials.

Traditionally accepted design paradigms dictate that only optically isotropic (cubic) crystal structures with high equilibrium solubilities of optically active ions are suitable for polycrystalline laser gain media. The restriction of symmetry is due to light scattering caused by randomly oriented anisotropic crystals, whereas the solubility problem arises from the need for sufficient active dopants in the media. These criteria limit material choices and exclude materials that have superior thermo-mechanical properties than state-of-the-art laser materials. Alumina (Al2O3) is an ideal example; it has a higher fracture strength and thermal conductivity than today's gain materials, which could lead to revolutionary laser performance. However, alumina has uniaxial optical proprieties, and the solubility of rare earths (REs) is two-to-three orders of magnitude lower than the dopant concentrations in typical RE-based gain media. We present new strategies to overcome these obstacles and demonstrate gain in a RE-doped alumina (Nd:Al2O3) for the first time. The key insight relies on tailoring the crystallite size to other important length scales-the wavelength of light and interatomic dopant distances, which minimize optical losses and allow successful Nd doping. The result is a laser gain medium with a thermo-mechanical figure of merit of R s~19,500 Wm-1 a 24-fold and 19,500-fold improvements over the high-energy-laser leaders Nd:YAG (R s~800 Wm-1) and Nd:Glass (R s~1 Wm-1), respectively. Moreover, the emission bandwidth of Nd:Al2O3 is broad: ~13 THz. The successful demonstration of gain and high bandwidth in a medium with superior R s can lead to the development of lasers with previously unobtainable high-peak powers, short pulses, tunability, and high-duty cycles.

Novel Cranial Implants of Yttria-Stabilized Zirconia as Acoustic Windows for Ultrasonic Brain Therapy.

Therapeutic ultrasound can induce changes in tissues by means of thermal and nonthermal effects. It is proposed for treatment of some brain pathologies such as Alzheimer's, Parkinson's, Huntington's diseases, and cancer. However, cranium highly absorbs ultrasound reducing transmission efficiency. There are clinical applications of transcranial focused ultrasound and implantable ultrasound transducers proposed to address this problem. In this paper, biocompatible materials are proposed for replacing part of the cranium (cranial implants) based on low porosity polycrystalline 8 mol% yttria-stabilized-zirconia (8YSZ) ceramics as acoustic windows for brain therapy. In order to assess the viability of 8YSZ implants to effectively transmit ultrasound, various 8YSZ ceramics with different porosity are tested; their acoustic properties are measured; and the results are validated using finite element models simulating wave propagation to brain tissue through 8YSZ windows. The ultrasound attenuation is found to be linearly dependent on ceramics' porosity. Results for the nearly pore-free case indicate that 8YSZ is highly effective in transmitting ultrasound, with overall maximum transmission efficiency of ≈81%, compared to near total absorption of cranial bone. These results suggest that 8YSZ polycrystals could be suitable acoustic windows for ultrasound brain therapy at 1 MHz.

Retraction: A photon thermal diode.

This corrects the article DOI: 10.1038/ncomms6446.

Unprecedented Electro-Optic Performance in Lead-Free Transparent Ceramics.

A high-performance lead-free electro-optic (EO) transparent material is introduced and used in an EO device operating up to 10 kHz. The BZT-BCT ceramic, named as BXT, has an effective DC EO coefficient, rc = 530 pm V-1 , which is higher than state-of-the-art materials such as LiNbO3 . The high EO response can be leveraged for miniaturization and/or reduction of the operating voltage of EO devices.

A 3 omega method to measure an arbitrary anisotropic thermal conductivity tensor.

Previous use of the 3 omega method has been limited to materials with thermal conductivity tensors that are either isotropic or have their principal axes aligned with the natural cartesian coordinate system defined by the heater line and sample surface. Here, we consider the more general case of an anisotropic thermal conductivity tensor with finite off-diagonal terms in this coordinate system. An exact closed form solution for surface temperature has been found for the case of an ideal 3 omega heater line of finite width and infinite length, and verified numerically. We find that the common slope method of data processing yields the determinant of the thermal conductivity tensor, which is invariant upon rotation about the heater line's axis. Following this analytic result, an experimental scheme is proposed to isolate the thermal conductivity tensor elements. Using two heater lines and a known volumetric heat capacity, the arbitrary 2-dimensional anisotropic thermal conductivity tensor can be measured with a low frequency sweep. Four heater lines would be required to extend this method to measure all 6 unknown tensor elements in 3 dimensions. Experiments with anisotropic layered mica are carried out to demonstrate the analytical results.

A photon thermal diode.

A thermal diode is a two-terminal nonlinear device that rectifies energy carriers (for example, photons, phonons and electrons) in the thermal domain, the heat transfer analogue to the familiar electrical diode. Effective thermal rectifiers could have an impact on diverse applications ranging from heat engines to refrigeration, thermal regulation of buildings and thermal logic. However, experimental demonstrations have lagged far behind theoretical proposals. Here we present the first experimental results for a photon thermal diode. The device is based on asymmetric scattering of ballistic energy carriers by pyramidal reflectors. Recent theoretical work has predicted that this ballistic mechanism also requires a nonlinearity in order to yield asymmetric thermal transport, a requirement of all thermal diodes arising from the second Law of Thermodynamics, and realized here using an 'inelastic thermal collimator' element. Experiments confirm both effects: with pyramids and collimator the thermal rectification is 10.9 ± 0.8%, while without the collimator no rectification is detectable (<0.3%).

Ultralow-temperature superplasticity in nanoceramic composites.

We report the successful demonstration for low-temperature and high-strain-rate superplastic forming of nanoceramic composites for the first time. Porous preforms of nanoceramic composites that were partially densified at low temperatures were superplastically deformed by SPS at the record low temperatures of approximately 1000 to 1050 degrees C, which are comparable to those of Ni-based superalloys. The maximum strain rate achieved is over 10(-2) s(-1), and a compressive strain over 200% can be obtained without cracking. The final products have nanosized grains with excellent optical properties. The present findings present a new strategy for nanoceramic superplasticity, demonstrating that a more practical application of nanoceramic superplasticity is not in the shaping of already-dense materials but in the near-net-shape forming of partially dense parts.