Microglia-derived extracellular vesicles trigger age-related neurodegeneration upon DNA damage.

DNA damage and neurodegenerative disorders are intimately linked but the underlying mechanism remains elusive. Here, we show that persistent DNA lesions in tissue-resident macrophages carrying an XPF-ERCC1 DNA repair defect trigger neuroinflammation and neuronal cell death in mice. We find that microglia accumulate dsDNAs and chromatin fragments in the cytosol, which are sensed thereby stimulating a viral-like immune response in Er1Cx/- and naturally aged murine brain. Cytosolic DNAs are packaged into extracellular vesicles (EVs) that are released from microglia and discharge their dsDNA cargo into IFN-responsive neurons triggering cell death. To remove cytosolic dsDNAs and prevent inflammation, we developed targeting EVs to deliver recombinant DNase I to Er1Cx/- brain microglia in vivo. We show that EV-mediated elimination of cytosolic dsDNAs is sufficient to prevent neuroinflammation, reduce neuronal apoptosis, and delay the onset of neurodegenerative symptoms in Er1Cx/- mice. Together, our findings unveil a causal mechanism leading to neuroinflammation and provide a rationalized therapeutic strategy against age-related neurodegeneration.

Influence of antireflection Si coatings on the damage threshold of fused silica upon irradiation with mid-IR femtosecond laser pulses.

Recent progress in the development of high-power mid-IR laser sources and the exciting laser driven physical phenomena associated with the irradiation of solids via ultrashort laser pulses in that spectral region are aimed to potentially create novel capabilities for material processing. In particular, the investigation of the underlying physical processes and the evaluation of the optical breakdown threshold (OBT) following irradiation of bulk dielectric materials with mid-IR femtosecond (fs) pulses have been recently presented. In this Letter, we will explore the conditions that generate sufficient carrier excitation levels which lead to damage upon irradiation of a dielectric material (SiO2) coated with antireflection (AR) semiconducting films (Si) of variable thickness with fs pulses. Simulation results demonstrate that the reflectivity and transmissivity of the Si/SiO2 are thickness dependent which can be employed to modulate the damage threshold of the substrate. The study is to provide innovative routes for selecting material sizes that can be used for antireflection coatings and applications in the mid-IR region.

Upside-Down Preference in the Forskolin-Induced In Vitro Differentiation of 50B11 Sensory Neurons: A Morphological Investigation by Label-Free Non-Linear Microscopy.

In this study, we revealed a peculiar morphological feature of 50B11 nociceptive sensory neurons in in vitro culture related to the forskolin-induced differentiation of these cells growing upside-down on cover glass supports. Multi-photon non-linear microscopy was applied to monitor increased neurite arborization and elongation. Under live and unstained conditions, second harmonic generation (SHG) microscopy could monitor microtubule organization inside the cells while also correlating with the detection of cellular multi-photon autofluorescence, probably derived from mitochondria metabolites. Although the differentiated cells of each compartment did not differ significantly in tubulin or multi-photon autofluorescence contents, the upturned neurons were more elongated, presenting a higher length/width cellular ratio and longer neurites, indicative of differentiated cells. SHG originating from the axons' microtubules represented a proper tool to study neurons' inverted culture in live conditions without exogenous staining. This work represents the first instance of examining neuronal cell lines growing and differentiated in an upside-down orientation, allowing a possible improvement of 50B11 as a model in physiology studies of sensory neurons in peripheric nervous system disease (e.g., Fabry disease, Friedreich ataxia, Charcot-Marie-Tooth, porphyria, type 1 diabetes, Guillain-Barré syndrome in children) and analgesic drug screening.

The Role of Ligands in the Chemical Synthesis and Applications of Inorganic Nanoparticles.

The design of nanoparticles is critical for their efficient use in many applications ranging from biomedicine to sensing and energy. While shape and size are responsible for the properties of the inorganic nanoparticle core, the choice of ligands is of utmost importance for the colloidal stability and function of the nanoparticles. Moreover, the selection of ligands employed in nanoparticle synthesis can determine their final size and shape. Ligands added after nanoparticle synthesis infer both new properties as well as provide enhanced colloidal stability. In this article, we provide a comprehensive review on the role of the ligands with respect to the nanoparticle morphology, stability, and function. We analyze the interaction of nanoparticle surface and ligands with different chemical groups, the types of bonding, the final dispersibility of ligand-coated nanoparticles in complex media, their reactivity, and their performance in biomedicine, photodetectors, photovoltaic devices, light-emitting devices, sensors, memory devices, thermoelectric applications, and catalysis.

Impact of Pre-Patterned Structures on Features of Laser-Induced Periodic Surface Structures.

The efficiency of light coupling to surface plasmon polariton (SPP) represents a very important issue in plasmonics and laser fabrication of topographies in various solids. To illustrate the role of pre-patterned surfaces and impact of laser polarisation in the excitation of electromagnetic modes and periodic pattern formation, Nickel surfaces are irradiated with femtosecond laser pulses of polarisation perpendicular or parallel to the orientation of the pre-pattern ridges. Experimental results indicate that for polarisation parallel to the ridges, laser induced periodic surface structures (LIPSS) are formed perpendicularly to the pre-pattern with a frequency that is independent of the distance between the ridges and periodicities close to the wavelength of the excited SPP. By contrast, for polarisation perpendicular to the pre-pattern, the periodicities of the LIPSS are closely correlated to the distance between the ridges for pre-pattern distance larger than the laser wavelength. The experimental observations are interpreted through a multi-scale physical model in which the impact of the interference of the electromagnetic modes is revealed.

Nanomedicines and Nanosimilars: Looking for a New and Dynamic Regulatory "Astrolabe" Inspired System.

The application of the nanotechnology in medicine and pharmaceutics opens new horizons in therapeutics. Several nanomedicines are in the market and an increasing number is in clinical trials. But which is the advantage of the medicines in nanoscale? The scientists and the regulatory authorities agree that the size and consequently the physiochemical/biological properties of nanomaterials play a key role in their safety and effectiveness. Additionally, all of them agree that a new scientific-based regulatory landscape is required for the establishment of nanomedicines in the market. The aim of this review is to investigate the parameters that the scientists and the regulatory authorities should take into account in order to build up a dynamic regulatory landscape for nanomedicines. For this reason, we propose an "astrolabe-like system" as the guide for establishing the regulatory approval process. Its function is based on the different physicochemical/biological properties in comparison to low molecular weight drugs.

Efficient and environmental-friendly perovskite solar cells via embedding plasmonic nanoparticles: an optical simulation study on realistic device architectures.

Solution-processed, lead halide-based perovskite solar cells have recently overcome important challenges, offering low-cost and high solar power conversion efficiencies. However, they still undergo unoptimized light collection due mainly to the thin (∼350 nm) polycrystalline absorber layers. Moreover, their high toxicity (due to the presence of lead in perovskite crystalline structures) makes it necessary that the thickness of the absorber layers to be further reduced. Here we address these issues via embedding spherical plasmonic nanoparticles of various sizes, composition, concentrations, and vertical positions, in realistic halide-based perovskite solar cells. We theoretically show that plasmon-enhanced near-field effects and scattering leads to a device photocurrent enhancement up to ∼7.3% when silver spheres are embedded inside the perovskite layer. An even further enhancement, up to ∼12%, is achieved with the combination of silver spheres in perovskite and aluminum spheres inside the hole transporting layer (PEDOT:PSS). The proper involvement of nanoparticles allows the employment of much thinner perovskite layers (up to 150 nm), reducing thus significantly the toxicity. Providing the requirements related to the design parameters of nanoparticles, our study establishes guidelines for a future development of highly-efficient, environmentally friendly and low-cost plasmonic perovskite solar cells.

Controlling the Outgrowth and Functions of Neural Stem Cells: The Effect of Surface Topography.

Neural stem cells (NSCs) are self-renewing cells that generate the major cell types of the central nervous system, namely neurons, astrocytes and oligodendrocytes, during embryonic development and in the adult brain. NSCs reside in a complex niche where they are exposed to a plethora of signals, including both soluble and physical signals such as compressive and shear stresses, but also discontinuities and differences in morphology of the extracellular environment, termed as topographical features. Different approaches that incorporate artificial micro- and nano-scale surface topographical features have been developed aiming to recapitulate the in vivo NSC niche discontinuities and features, particularly for in vitro studies. The present review article aims at reviewing the existing body of literature on the use of artificial micro- and nano-topographical features to control NSCs orientation and differentiation into neuronal and/or neuroglial lineage. The different approaches on the study of the underlying mechanism of the topography-guided NSC responses are additionally revised and discussed.

Novel Biomaterials for Tissue Engineering 2018.

The concept of regenerating tissues, with properties and functions that mimic natural tissues, has attracted significant attention in recent years. [...].

Engineering Cell Adhesion and Orientation via Ultrafast Laser Fabricated Microstructured Substrates.

Cell responses depend on the stimuli received by the surrounding extracellular environment, which provides the cues required for adhesion, orientation, proliferation, and differentiation at the micro and the nano scales. In this study, discontinuous microcones on silicon (Si) and continuous microgrooves on polyethylene terephthalate (PET) substrates were fabricated via ultrashort pulsed laser irradiation at various fluences, resulting in microstructures with different magnitudes of roughness and varying geometrical characteristics. The topographical models attained were specifically developed to imitate the guidance and alignment of Schwann cells for the oriented axonal regrowth that occurs in nerve regeneration. At the same time, positive replicas of the silicon microstructures were successfully reproduced via soft lithography on the biodegradable polymer poly(lactide-co-glycolide) (PLGA). The anisotropic continuous (PET) and discontinuous (PLGA replicas) microstructured polymeric substrates were assessed in terms of their influence on Schwann cell responses. It is shown that the micropatterned substrates enable control over cellular adhesion, proliferation, and orientation, and are thus useful to engineer cell alignment in vitro. This property is potentially useful in the fields of neural tissue engineering and for dynamic microenvironment systems that simulate in vivo conditions.

Ripple formation on nickel irradiated with radially polarized femtosecond beams.

We report on the morphological effects induced by the inhomogeneous absorption of radially polarized femtosecond laser irradiation of nickel (Ni) in sub-ablation conditions. A theoretical prediction of the morphology profile is performed, and the role of surface plasmon excitation in the production of self-formed periodic ripple structures is evaluated. Results indicate a smaller periodicity of the ripples profile compared to that attained under linearly polarized irradiation conditions. A combined hydrodynamical and thermoelastic model is presented in laser beam conditions that lead to material melting. The simulation results are presented to be in good agreement with the experimental findings. The ability to control the size of the morphological changes via modulating the beam polarization may provide an additional route for controlling and optimizing the outcome of laser micro-processing.

Phosphate Glass Microspheres with Silver Nanoparticles for Whispering Gallery Mode Resonators.

Glass microspheres have gained significant attention over the years in the field of photonics due to their application in whispering gallery mode (WGM) microresonator platforms. However, the synthesis of glass spheres in the micro regime remains challenging, while it relies mostly on complicated synthetic methods or sol-gel chemistry. Herein, we demonstrate the controlled formation of phosphate glass microspheres by means of a simple, fast, low-temperature, post-glass melting thermal treatment of previously quenched glass. Moreover, we report on the simultaneous formation of silver nanoparticles (AgNPs) on the surface of glass spheres upon the same treatment. The formation of metal nanoparticles onto the glass spheres induces attractive optical and plasmonic properties, believed to be suitable for WGM resonator-based applications, as well as a wide range of optoelectronic, photonic, and sensing applications.

Harnessing laser technology to create stable metal halide perovskite-rGO conjugates as promising electrodes for Zn-ion capacitors.

We report that the direct conjugation of metal halide perovskite nanocrystals on rGO sheets can provide high performance and stable electrodes for Zn-ion capacitors. It is the first time that metal halide nanocrystals have been used to enhance the energy storage of 2D materials in capacitors by introducing an additional pseudocapacitance mechanism. In particular, we present a simple, rapid and room temperature laser-induced method to anchor CsPbBr3 nanocrystals on rGO sheets without affecting the initial morphology and crystal structure of the two components. The flexible and high surface area of the rGO sheets enables the conjugation of individual metal halide perovskite nanocrystals, giving rise to new synergetic functionalities. As a result, the specific capacitance of the perovskite-rGO conjugated electrodes can be enhanced by 178- and 152-times compared to those of the plain rGO and perovskite electrodes respectively.

Postmelting Encapsulation of Glass Microwires for Multipath Light Waveguiding within Phosphate Glasses.

Glass waveguides are the fundamental component of advanced photonic circuits and play a pivotal role in diverse applications, including quantum information processing, light generation, imaging, data storage, and sensing platforms. Up to date, the fabrication of glass waveguides relies mainly on demanding chemical processes or on the employment of expensive ultrafast laser equipment. In this work, we demonstrate an advanced, simple, low-temperature, postmelting encapsulation procedure for the development of glass waveguides. Specifically, silver iodide phosphate glass microwires (MWs) are drawn from splat-quenched glasses. These MWs are then incorporated in a controlled manner within transparent silver phosphate glass matrices. The judicious selection of glass compositions ensures that the refractive index of the host phosphate glass is lower than that of the embedded MWs. This facilitates the propagation of light inside the encapsulated higher refractive index MWs, leading to the facile development of waveguides. Importantly, we substantially enhance the light transmission within the MWs by leveraging the plasmon resonance effects due to the presence of silver nanoparticles spontaneously generated owing to the silver iodide phosphate glass composition. Employing this innovative approach, we have successfully engineered waveguide devices incorporating either one or two MWs. Remarkably, the dual MW devices are capable of transmitting light of different colors and in multipath direction, rendering the developed waveguides outstanding candidates for extending the functionalities of diverse photonic and optoelectronic circuits, as well as in intelligent signaling applications in smart glass technologies.

Comparative analysis of aligned and random amniotic membrane-derived cryogels for neural tissue repair.

The ordered arrangement of cells and extracellular matrix facilitates the seamless transmission of electrical signals along axons in the spinal cord and peripheral nerves. Therefore, restoring tissue geometry is crucial for neural regeneration. This study presents a novel method using proteins derived from the human amniotic membrane, which is modified with photoresponsive groups, to produce cryogels with aligned porosity. Freeze-casting was used to produce cryogels with longitudinally aligned pores, while cryogels with randomly distributed porosity were used as the control. The cryogels exhibited remarkable injectability and shape-recovery properties, essential for minimally invasive applications. Different tendencies in proliferation and differentiation were evident between aligned and random cryogels, underscoring the significance of the scaffold's microstructure in directing the behaviour of neural stem cells (NSC). Remarkably, aligned cryogels facilitated extensive cellular infiltration and migration, contrasting with NSC cultured on isotropic cryogels, which predominantly remained on the scaffold's surface throughout the proliferation experiment. Significantly, the proliferation assay demonstrated that on day 7, the aligned cryogels contained eight times more cells compared to the random cryogels. Consistent with the proliferation experiments, NSC exhibited the ability to differentiate into neurons within the aligned scaffolds and extend neurites longitudinally. In addition, differentiation assays showed a four-fold increase in the expression of neural markers in the cross-sections of the aligned cryogels. Conversely, the random cryogels exhibited minimal presence of cell bodies and extensions. The presence of synaptic vesicles on the anisotropic cryogels indicates the formation of functional synaptic connections, emphasizing the importance of the scaffold's microstructure in guiding neuronal reconnection.

Texture-Induced Strain in a WS2 Single Layer to Monitor Spin-Valley Polarization.

Nanoscale-engineered surfaces induce regulated strain in atomic layers of 2D materials that could be useful for unprecedented photonics applications and for storing and processing quantum information. Nevertheless, these strained structures need to be investigated extensively. Here, we present texture-induced strain distribution in single-layer WS2 (1L-WS2) transferred over Si/SiO2 (285 nm) substrate. The detailed nanoscale landscapes and their optical detection are carried out through Atomic Force Microscopy, Scanning Electron Microscopy, and optical spectroscopy. Remarkable differences have been observed in the WS2 sheet localized in the confined well and at the periphery of the cylindrical geometry of the capped engineered surface. Raman spectroscopy independently maps the whole landscape of the samples, and temperature-dependent helicity-resolved photoluminescence (PL) experiments (off-resonance excitation) show that suspended areas sustain circular polarization from 150 K up to 300 K, in contrast to supported (on un-patterned area of Si/SiO2) and strained 1L-WS2. Our study highlights the impact of the dielectric environment on the optical properties of two-dimensional (2D) materials, providing valuable insights into the selection of appropriate substrates for implementing atomically thin materials in advanced optoelectronic devices.

Nanoliposomes Permeability in a Microfluidic Drug Delivery Platform across a 3D Hydrogel.

Nanoliposomes are nano-sized vesicles that can be used as drug delivery carriers with the ability to encapsulate both hydrophobic and hydrophilic compounds. Moreover, their lipid compositions facilitate their internalization by cells. However, the interaction between nanoliposomes and the membrane barrier of the human body is not well-known. If cellular tests and animal testing offer a solution, their lack of physiological relevance and ethical concerns make them unsuitable to properly mimic human body complexity. Microfluidics, which allows the environment of the human body to be imitated in a controlled way, can fulfil this role. However, existing models are missing the presence of something that would mimic a basal membrane, often consisting of a simple cell layer on a polymer membrane. In this study, we investigated the diffusion of nanoliposomes in a microfluidic system and found the optimal parameters to maximize their diffusion. Then, we incorporated a custom made GelMA with a controlled degree of substitution and studied the passage of fluorescently labeled nanoliposomes through this barrier. Our results show that highly substituted GelMA was more porous than lower substitution GelMA. Overall, our work lays the foundation for the incorporation of a hydrogel mimicking a basal membrane on a drug delivery microfluidic platform.

Strain distribution in WS2 monolayers detected through polarization-resolved second harmonic generation.

Two-dimensional (2D) graphene and graphene-related materials (GRMs) show great promise for future electronic devices. GRMs exhibit distinct properties under the influence of the substrate that serves as support through uneven compression/ elongation of GRMs surface atoms. Strain in GRM monolayers is the most common feature that alters the interatomic distances and band structure, providing a new degree of freedom that allows regulation of their electronic properties and introducing the field of straintronics. Having an all-optical and minimally invasive detection tool that rapidly probes strain in large areas of GRM monolayers, would be of great importance in the research and development of novel 2D devices. Here, we use Polarization-resolved Second Harmonic Generation (P-SHG) optical imaging to identify strain distribution, induced in a single layer of WS2 placed on a pre-patterned Si/SiO2 substrate with cylindrical wells. By fitting the P-SHG data pixel-by-pixel, we produce spatially resolved images of the crystal armchair direction. In regions where the WS2 monolayer conforms to the pattern topography, a distinct cross-shaped pattern is evident in the armchair image owing to strain. The presence of strain in these regions is independently confirmed using a combination of atomic force microscopy and Raman mapping.

Amniotic Membrane-Derived Multichannel Hydrogels for Neural Tissue Repair.

In the pursuit of advancing neural tissue regeneration, biomaterial scaffolds have emerged as promising candidates, offering potential solutions for nerve disruptions. Among these scaffolds, multichannel hydrogels, characterized by meticulously designed micrometer-scale channels, stand out as instrumental tools for guiding axonal growth and facilitating cellular interactions. This study explores the innovative application of human amniotic membranes modified with methacryloyl domains (AMMA) in neural stem cell (NSC) culture. AMMA hydrogels, possessing a tailored softness resembling the physiological environment, are prepared in the format of multichannel scaffolds to simulate native-like microarchitecture of nerve tracts. Preliminary experiments on AMMA hydrogel films showcase their potential for neural applications, demonstrating robust adhesion, proliferation, and differentiation of NSCs without the need for additional coatings. Transitioning into the 3D realm, the multichannel architecture fosters intricate neuronal networks guiding neurite extension longitudinally. Furthermore, the presence of synaptic vesicles within the cellular arrays suggests the establishment of functional synaptic connections, underscoring the physiological relevance of the developed neuronal networks. This work contributes to the ongoing efforts to find ethical, clinically translatable, and functionally relevant approaches for regenerative neuroscience.

Organic solar cells with plasmonic layers formed by laser nanofabrication.

A method for the synthesis of metal nanoparticle coatings for plasmonic solar cells which can meet large scale industrial demands is demonstrated. A UV pulsed laser is utilized to fabricate Au and Ag nanoparticles on the surface of polymer materials which form the substrates for plasmonic organic photovoltaic devices to enhance their performance. Control of the particles' size and density is demonstrated. The optical and electrical effects of these embedded particles on the power conversion efficiency are examined rigorously using both experimental and computer simulation. Gold nanoparticles of particular size and spatial distribution enhance the device efficiency. Based on our findings, we propose design considerations for utilizing the entire AM1.5 spectrum using plasmonic structures towards enhancing the efficiency of polymer solar cells using broad spectrum plasmonics.