Fatigue-resistant hydrogel optical fibers enable peripheral nerve optogenetics during locomotion.

We develop soft and stretchable fatigue-resistant hydrogel optical fibers that enable optogenetic modulation of peripheral nerves in naturally behaving animals during persistent locomotion. The formation of polymeric nanocrystalline domains within the hydrogels yields fibers with low optical losses of 1.07 dB cm-1, Young's modulus of 1.6 MPa, stretchability of 200% and fatigue strength of 1.4 MPa against 30,000 stretch cycles. The hydrogel fibers permitted light delivery to the sciatic nerve, optogenetically activating hindlimb muscles in Thy1::ChR2 mice during 6-week voluntary wheel running assays while experiencing repeated deformation. The fibers additionally enabled optical inhibition of pain hypersensitivity in an inflammatory model in TRPV1::NpHR mice over an 8-week period. Our hydrogel fibers offer a motion-adaptable and robust solution to peripheral nerve optogenetics, facilitating the investigation of somatosensation.

Self-removal of condensed water on the legs of water striders.

The ability to control drops and their movements on phobic surfaces is important in printing or patterning, microfluidic devices, and water-repellent materials. These materials are always micro-/nanotextured, and a natural limitation of repellency occurs when drops are small enough (as in a dew) to get trapped in the texture. This leads to sticky Wenzel states and destroys the superhydrophobicity of the material. Here, we show that droplets of volume ranging from femtoliter (fL) to microliter (µL) can be self-removed from the legs of water striders. These legs consist of arrays of inclined tapered setae decorated by quasi-helical nanogrooves. The different characteristics of this unique texture are successively exploited as water condenses, starting from self-penetration and sweeping effect along individual cones, to elastic expulsion between flexible setae, followed by removal at the anisotropic leg surface. We envision that this antifogging effect at a very small scale could inspire the design of novel applicable robust water-repellent materials for many practical applications.

Highly Boosted Oxygen Reduction Reaction Activity by Tuning the Underwater Wetting State of the Superhydrophobic Electrode.

By rationally designing superhydrophobic electrodes with different underwater wetting states, it is revealed that only the underwater Wenzel-Cassie coexistent state shows the clearly enhanced ability in catalyzing the oxygen reduction reaction, a typical underwater gas-consuming reaction at electrode. It is proposed that the maximizing and stabilizing the liquid/gas/solid triphase interface, endowed by the underwater Wenzel-Cassie coexistent state, plays a rather crucial role.

Near-infrared activated liposomes for neuroprotection in glaucoma.

Neurodegenerative diseases have a profound impact on vision, leading to conditions such as glaucoma, optic neuropathy, and diabetic retinopathy, affecting millions worldwide. These diseases are characterized by the degeneration of retinal ganglion cells (RGCs), resulting in a progressive loss of visual acuity and field, with the threat of irreversible blindness. However, existing treatments, such as eye drops, direct injections, and laser surgeries face significant challenges due to limited efficacy and potential infection. The inefficiency of traditional corneal drug delivery methods is a major obstacle in treating vision neurodegenerative diseases. To address these challenges, we developed a remotely triggered on-demand liposomal delivery system to treat glaucomatous neurodegeneration in mice. We utilized the localized surface plasmon resonance (LSPR) effect of gold nanorods (AuNRs) under near-infrared (NIR) light (808 nm) to control the release of cyclodextrin-encapsulated melatonin from thermally responsive liposomal nanocarriers in the vitreous humor. Due to the transparency of the eye's cornea, NIR light can penetrate deep tissues, enabling on-demand drug delivery to the retina. By enhancing the drug's solubility and stability through cyclodextrin encapsulation, this remotely activated melatonin/HPßCD AuNRs liposomes delivery system can decrease intraocular pressure (IOP) elevation by (24 ± 7)%, enhance the survival rate of RGCs by (77 ± 6)%, and decrease glial fibrillary acidic protein (GFAP) activation by (75 ± 6)% at depth in an acute experimental glaucoma model. This NIR-triggered drug delivery system presents the potential of a promising minimally photo-triggered therapeutic option for glaucoma treatment.

Biologically Driven In Vivo Occlusion Design Provides a Reliable Experimental Glaucoma Model.

Fluid flow transport through the trabecular meshwork tissues is a major regulator of intraocular pressure (IOP) modulation in healthy and glaucomatous individuals. Microbead occlusion models of ocular hypertension regulate aqueous humor drainage to induce high IOP to allow for in vivo study of pressure-related glaucomatous pathology. However, the reliability and application of current injectable microbeads are hindered by inadequate design of the beads-tissue interfaces to maintain a stable IOP elevation over the long term. Considering the graded, porous architecture and fluid transport of the trabecular meshwork, we developed a tailored, injectable "viscobeads" technique, which induced a sustained elevation of IOP for at least 8 weeks. These composite viscobeads contain a non-degradable polystyrene (PS) core for structural support and a biodegradable polylactic-co-glycolic acid (PLGA) viscoelastic surface. This approach enhances the obstruction of aqueous humor drainage through heterogeneous sizes of trabecular meshwork fenestrations and reliably modulates the magnitude and duration of ocular hypertension. In a mouse model, a single viscobeads injection resulted in sustained IOP elevation (average 21.4±1.39 mm Hg), leading to a 34% retinal ganglion cell (RGC) loss by 56 days. In an earlier stage of glaucoma progression, we conducted non-invasive electroretinography (ERG) recording and revealed glaucomatous progression by analyzing high-frequency oscillatory potentials. To further explore the application of the viscobeads glaucoma models, we assayed a series of genes through adeno-associated virus (AAV)-mediated screening in mice and assessed the impact of genetic manipulation on RGC survivals. CRISPR mediated disruption of the genes, PTEN, ATF3 and CHOP enhanced RGC survival while LIN 28 disruption negatively impacted RGC survival. This biologically driven viscobeads design provides an accessible approach to investigate chronic intraocular hypertension and glaucoma-like neurodegeneration and ultimately tenders the opportunity to evaluate genetic and pharmacological therapeutics.

Control of polymers' amorphous-crystalline transition enables miniaturization and multifunctional integration for hydrogel bioelectronics.

Soft bioelectronic devices exhibit motion-adaptive properties for neural interfaces to investigate complex neural circuits. Here, we develop a fabrication approach through the control of metamorphic polymers' amorphous-crystalline transition to miniaturize and integrate multiple components into hydrogel bioelectronics. We attain an about 80% diameter reduction in chemically cross-linked polyvinyl alcohol hydrogel fibers in a fully hydrated state. This strategy allows regulation of hydrogel properties, including refractive index (1.37-1.40 at 480 nm), light transmission (>96%), stretchability (139-169%), bending stiffness (4.6 ± 1.4 N/m), and elastic modulus (2.8-9.3 MPa). To exploit the applications, we apply step-index hydrogel optical probes in the mouse ventral tegmental area, coupled with fiber photometry recordings and social behavioral assays. Additionally, we fabricate carbon nanotubes-PVA hydrogel microelectrodes by incorporating conductive nanomaterials in hydrogel for spontaneous neural activities recording. We enable simultaneous optogenetic stimulation and electrophysiological recordings of light-triggered neural activities in Channelrhodopsin-2 transgenic mice.

Anisotropic Hydrogel Microelectrodes for Intraspinal Neural Recordings in vivo.

Creating durable, motion-compliant neural interfaces is crucial for accessing dynamic tissues under in vivo conditions and linking neural activity with behaviors. Utilizing the self-alignment of nano-fillers in a polymeric matrix under repetitive tension, here, we introduce conductive carbon nanotubes with high aspect ratios into semi-crystalline polyvinyl alcohol hydrogels and create electrically anisotropic percolation pathways through cyclic stretching. The resulting anisotropic hydrogel fibers (diameter of 187 ± 13 µm) exhibit fatigue resistance (20,000 cycles at 20% strain) with a stretchability of 64.5 ± 7.9%, and low electrochemical impedance (900 ± 149 kΩ @ 1kHz). We observe the re-constructed nanofillers' axial alignment and a corresponding anisotropic impedance decrease along the direction of cyclic stretching. We fabricate fiber-shaped hydrogels into bioelectronic devices and implant them into wild-type and transgenic Thy1-ChR2-EYFP mice to record electromyographic signals from muscles in anesthetized and freely moving conditions. These hydrogel fibers effectively enable the simultaneous recording of electrical signals from ventral spinal cord neurons and the tibialis anterior muscles during optogenetic stimulation. Importantly, the devices maintain functionality with repeatable recording results over eight months after implantation, demonstrating their durability and potential for long-term monitoring in neurophysiological studies.

A nanoscale inorganic coating strategy for stabilizing hydrogel neural probes in vivo.

Hydrogels with adaptable optical and mechanical characteristics show considerable promise for light delivery in vivo with neuroengineering applications. However, the unlinked amorphous polymer chains within hydrogels can cause volumetric swelling after water absorption under physiological conditions over time. Chemically cross-linked poly(vinyl alcohol) (PVA) hydrogels showcase fatigue-resistant attributes and promising biocompatibility for the manufacture of soft neural probes. However, possible swelling of the PVA hydrogel matrix could impact the structural stability of hydrogel-based bioelectronics and their long-term in vivo functionality. In this study, we utilized an atomic layer deposition (ALD) technique to generate an inorganic, silicon dioxide (SiO2) coating layer on chemically cross-linked PVA hydrogel fibers. To evaluate the stability of SiO2-coated PVA hydrogel fibers mimicking the in vivo environment, we conducted accelerated stability tests. SiO2-coated PVA hydrogel fibers showed improved stability over a one-week incubation period under a harsh environment, preventing swelling and preserving their mechanical and optical properties compared to uncoated fibers. These SiO2-coated PVA hydrogel fibers demonstrated nanoscale polymeric crystalline domains (6.5 ± 0.1 nm), an elastic modulus of 73.7 ± 31.7 MPa, a maximum elongation of 113.6 ± 24.2%, and minimal light transmission loss (1.9 ± 0.2 dB cm-1). Lastly, we applied these SiO2-coated PVA hydrogel fibers in vivo to optically activate the motor cortex of transgenic Thy1::ChR2 mice during locomotor behavioral tests. This mouse cohort was genetically modified to express the light-sensitive ion channel, channelrhodopsin-2 (ChR2), and implanted with hydrogel fibers to deliver light to the motor cortex area (M2). Light stimulation via hydrogel fibers resulted in optogenetically modulated mouse locomotor behaviors, including increased contralateral rotation, mobility speeds, and travel distances.

Control of Polymers' Amorphous-crystalline Transition for Hydrogel Bioelectronics Miniaturization and Multifunctional Integration.

Bioelectronic devices made of soft elastic materials exhibit motion-adaptive properties suitable for brain-machine interfaces and for investigating complex neural circuits. While two-dimensional microfabrication strategies enable miniaturizing devices to access delicate nerve structures, creating 3D architecture for expansive implementation requires more accessible and scalable manufacturing approaches. Here we present a fabrication strategy through the control of metamorphic polymers' amorphous-crystalline transition (COMPACT), for hydrogel bioelectronics with miniaturized fiber shape and multifunctional interrogation of neural circuits. By introducing multiple cross-linkers, acidification treatment, and oriented polymeric crystalline growth under deformation, we observed about an 80% diameter decrease in chemically cross-linked polyvinyl alcohol (PVA) hydrogel fibers, stably maintained in a fully hydrated state. We revealed that the addition of cross-linkers and acidification facilitated the oriented polymetric crystalline growth under mechanical stretching, which contributed to the desired hydrogel fiber diameter decrease. Our approach enabled the control of hydrogels' properties, including refractive index (RI 1.37-1.40 at 480 nm), light transmission (> 96%), stretchability (95% - 111%), and elastic modulus (10-63 MPa). To exploit these properties, we fabricated step-index hydrogel optical probes with contrasting RIs and applied them in optogenetics and photometric recordings in the mouse brain region of the ventral tegmental area (VTA) with concurrent social behavioral assessment. To extend COMPACT hydrogel multifunctional scaffolds to assimilate conductive nanomaterials and integrate multiple components of optical waveguide and electrodes, we developed carbon nanotubes (CNTs)-PVA hydrogel microelectrodes for hindlimb muscle electromyographic and brain electrophysiological recordings of light-triggered neural activities in transgenic mice expressing Channelrhodopsin-2 (ChR2).

Application of K/Sr co-doped calcium polyphosphate bioceramic as scaffolds for bone substitutes.

Ion doping is one of the most important methods to modify the properties of bioceramics for better biodegrade abilities, biomechanical properties, and biocompatibilities. This paper presents a novel ion doping method applied in calcium polyphosphate (CPP)-based bioceramic scaffolds substituted by potassium and strontium ions (K/Sr) to form (K/Sr-CPP) scaffolds for bone tissue regeneration. The microstructure and crystallization of the scaffolds were detected by scanning electron microscopy and X-ray diffraction. Compressive strength and degradation tests were assessed to evaluate the mechanical and chemical stabilities of K/Sr-CPP in vitro. The cell biocompatibility was measured with respect to the cytotoxicity of the extractions of scaffolds. Muscle pouches and bone implantation were performed to evaluate the biodegradability and osteoconductivity of the scaffolds. The results indicated that the obtained K/Sr-CPP scaffolds had a single beta-CPP phase. The unit cell volume and average grain size increased but the crystallization decreased after the ions were doped into the CPP structure. The K/Sr-CPP scaffolds yielded a higher compressive strength and a better degradation property than the pure CPP scaffold. The MTT assay and in vivo results reveal that the K/Sr-CPP scaffolds exhibited a better cell biocompatibility and a tissue biocompatibility than CPP and hydroxyapatite scaffolds. This study proves the potential applications of K/Sr-CPP scaffolds in bone repair.

Preparation and evaluation of a biomimetic scaffold with porosity gradients in vitro.

A novel biodegradable scaffold based on mimetic a natural bone tissue morphology with a porosity gradient structure was prepared in this paper. The result of surface morphology indicated that a graded porous structure was formed in the fabricated scaffold, where the dense layer (0%) was connected with the most porous layer (60%) by a middling porous layer (30%). To evaluate the degradability, graded porous scaffolds compared with homogeneous scaffolds were placed into a Tris-HCl buffer solution (pH = 7.4) for 28 days. It was found that both scaffolds presented the same degradation trend, and the graded porous structure did not change the original degradability of the scaffold. Moreover, the compressive strength of the graded porous scaffold was better than that of conventional homogeneous scaffold with the increase of degradation time, and the graded porous structure can enhanced the mechanical property of the scaffold. These findings suggest that this biodegradable and porosity-graded scaffold may be a new promising scaffold for loaded bone implant.

Non-Invasive Electroretinogram Recording with Simultaneous Optogenetics to Dissect Retinal Ganglion Cells Electrophysiological Dynamics.

Electroretinography (ERG) is a non-invasive electrophysiological recording technique that detects the electrical signaling of neuronal cells in the visual system. In conventional ERG recordings, the signals are considered a collective electrical response from various neuronal cell populations, including rods, cones, bipolar cells, and retinal ganglion cells (RGCs). However, due to the limited ability to control electrophysiological responses from different types of cells, the detailed information underlying ERG signals has not been analyzed and interpreted. Linking the features of ERG signals to the specific neuronal response will advance the understanding of neuronal electrophysiological dynamics and provide more evidence to elucidate pathological mechanisms, such as RGC loss during the progression of glaucoma. Herein, we developed an advanced ERG recording system integrated with a programmable, non-invasive optogenetic stimulation method in mice. In this system, we applied an automatic and unbiased ERG data analysis approach to differentiate a, b wave, negative response, and oscillatory potentials. To differentiate the electrophysiological response of RGCs in ERG recordings, we sensitized mouse RGCs with red-light opsin, ChRmine, through adeno-associated virus (AAV) intravitreal injection. Features of RGC dynamics under red-light stimulation were identified in the ERG readout. This non-invasive ERG recording system, associated with the programmable optogenetics stimulation method, provides a new methodology to dissect neural dynamics under variable physiological and pathological conditions in vivo. With the merits of non-invasiveness, improved sensitivity, and specificity, we envision this system can be further applied for early-stage detection of RGC degeneration and functional progression in neural degenerative diseases, such as glaucoma.

Microbial composition and nitrogen removal pathways in a novel sequencing batch reactor integrated with semi-fixed biofilm carrier: evidence from a pilot study for low- and high-strength sewage treatment.

The sequencing batch reactor (SBR) activated sludge process is a well-established technology for sewage treatment. One of the drawbacks of SBRs, however, total nitrogen (TN) removals is insufficient. By means of introducing four improvements, including semi-fixed biofilm carrier, sludge elevation mixing and change for the mode of influent and effluent, compliant standard for TN discharge was obtained in this novel SBR configuration during low- and high-strength sewage load. To illustrate the microbial compositions and functions of the attached biofilm on semi-fixed carrier and the suspended aggregates, as well as the nitrogen removal pathway, high throughput 16S rRNA gene amplicon sequencing, PICRUSt2 algorithm, and KEGG database were applied. The results revealed that (i) the microbial communities from suspended aggregates and biofilm samples were significantly different from each other; (ii) during low-strength sewage loads, TN removal was mainly by nitrification-denitrification. The suspended aggregates was responsible for denitrification, while the biofilm was focused on ammonium oxidation; (iii) during high-strength sewage loads, function of nitrate reductase from suspended aggregates was faded, and anammox and N assimilation by biofilm became dominant. Meanwhile, TN removal referring to the formation of L-glutamine via assimilation was the main pathway.

Core transcription programs controlling injury-induced neurodegeneration of retinal ganglion cells.

Regulatory programs governing neuronal death and axon regeneration in neurodegenerative diseases remain poorly understood. In adult mice, optic nerve crush (ONC) injury by severing retinal ganglion cell (RGC) axons results in massive RGC death and regenerative failure. We performed an in vivo CRISPR-Cas9-based genome-wide screen of 1,893 transcription factors (TFs) to seek repressors of RGC survival and axon regeneration following ONC. In parallel, we profiled the epigenetic and transcriptional landscapes of injured RGCs by ATAC-seq and RNA-seq to identify injury-responsive TFs and their targets. These analyses converged on four TFs as critical survival regulators, of which ATF3/CHOP preferentially regulate pathways activated by cytokines and innate immunity and ATF4/C/EBPγ regulate pathways engaged by intrinsic neuronal stressors. Manipulation of these TFs protects RGCs in a glaucoma model. Our results reveal core transcription programs that transform an initial axonal insult into a degenerative process and suggest novel strategies for treating neurodegenerative diseases.

In situ reversible underwater superwetting transition by electrochemical atomic alternation.

Materials with in situ reversible wettability have attractive properties but remain a challenge to use since the inverse process of liquid spreading is normally energetically unfavorable. Here, we propose a general electrochemical strategy that enables the in situ reversible superwetting transition between underwater superoleophilicity and superoleophobicity by constructing a binary textured surface. Taking the copper/tin system as an example, the surface energy of the copper electrode can be lowered significantly by electrodeposited tin, and be brought back to the initial high-energy state as a result of dissolving tin by removing the potential. Tin atoms with the water depletion layer inhibit the formation of a hydrogen-bonding network, causing oil droplets to spread over the surface, while copper atoms, with a high affinity for hydroxyl groups, facilitate replacing the oil layer with the aqueous electrolyte. The concept is applicable to other systems, such as copper/lead, copper/antimony, gold/tin, gold/lead and gold/antimony, for both polar and nonpolar oils, representing a potentially useful class of switchable surfaces.

Energy-Mediated Machinery Drives Cellular Mechanical Allostasis.

Allostasis is a fundamental biological process through which living organisms achieve stability via physiological or behavioral changes to protect against internal and external stresses, and ultimately better adapt to the local environment. However, an full understanding of cellular-level allostasis is far from developed. By employing an integrated micromechanical tool capable of applying controlled mechanical stress on an individual cell and simultaneously reporting dynamic information of subcellular mechanics, individual cell allostasis is observed to occur through a biphasic process; cellular mechanics tends to restore to a stable state through a mechanoadaptative process with excitative biophysical activity followed by a decaying adaptive phase. Based on these observations, it is found that cellular allostasis occurs through a complex balance of subcellular energy and cellular mechanics; upon a transient and local physical stimulation, cells trigger an allostatic state that maximizes energy and overcomes a mechanical "energy barrier" followed by a relaxation state that reaches its mechanobiological stabilization and energy minimization. Discoveries of energy-driven cellular machinery and conserved mechanotransductive pathways underscore the critical role of force-sensitive cytoskeleton equilibrium in cellular allostasis. This highlight the biophysical origin of cellular mechanical allostasis, providing subcellular methods to understand the etiology and progression of certain diseases or aging.

In Situ Characterization of the Triphase Contact Line in a Brush-Coating Process: Toward the Enhanced Efficiency of Polymer Solar Cells.

Solution processes have been widely used for making polymer films in organic photoelectric devices but suffer from difficulties in controlling the film formation. Here, by in situ characterization triphase contact lines (TCLs) in a brush-coating process, we clarify how TCLs affect the quality of as-prepared films. By fine-tuning the dewetting of a binary polymer solution (P3HT:PCBM) via different directions, TCLs with different patterns lead to films with different morphologies. High-quality nanothin films with larger crystallized sizes and higher orientations were enabled when TCLs were parallel to the brush edge, based on which the polymer solar cell shows higher power conversion efficiency (2.665%) compared with that of the spin-coated film.

Electrospun γ-Fe2O3 nanofibers as bioelectrochemical sensors for simultaneous determination of small biomolecules.

Nanofibers of α-Fe2O3 and γ-Fe2O3 have been obtained after the controlled calcination of precursor nanofibers synthesized by electrospinning. α-Fe2O3 nanofibers showed an irregular toruloid structure due to the decomposition of poly (4-vinyl) pyridine in air while γ-Fe2O3 nanoparticles decorated nanofibers were observed after the calcination under N2 atmosphere. Electrochemical measurements showed that different electrochemical behaviors were observed on the glassy carbon electrodes modified by α-Fe2O3 and γ-Fe2O3 nanofibers. The electrode modified by γ-Fe2O3 nanofibers exhibited high electrocatalytic activities toward oxidation of dopamine, uric acid and ascorbic acid while α-Fe2O3 nanofibers cannot. Furthermore, the γ-Fe2O3 modified electrode can realize the selective detection of biomolecules in ternary electrolyte solutions. The synthesis of nanofibers of α-Fe2O3 and γ-Fe2O3 and their electrochemical sensing properties relationship have been discussed and analyzed based on the experimental results.