Recent progresses in neural tissue engineering using topographic scaffolds.

Neural tissue engineering as alternatives to recover damaged tissues and organs is getting more and more attention due to the lack of regeneration ability of natural tissue nervous system after injury. Particularly, topographic scaffolds are one of the critical elements to guide nerve orientation and reconnection with characteristics of mimic the natural extracellular matrix. This review focuses on scaffolds preparation technologies, topographical features, scaffolds-based encapsulations delivery strategies for neural tissue regeneration, biological functions on nerve cell guidance and regeneration, and applications of topographic scaffolds in vivo and in vitro. Here, the recent developments in topographic scaffolds for neural tissue engineering by simulating neural cell topographic orientation and differentiation are presented. We also explore the challenges and future perspectives of topographical scaffolds in clinical trials and practical applications.

Characterization of the microRNA transcriptomes and proteomics of cochlear tissue-derived small extracellular vesicles from mice of different ages after birth.

The cochlea is an important sensory organ for both balance and sound perception, and the formation of the cochlea is a complex developmental process. The development of the mouse cochlea begins on embryonic day (E)9 and continues until postnatal day (P)21 when the hearing system is considered mature. Small extracellular vesicles (sEVs), with a diameter ranging from 30 to 200 nm, have been considered a significant medium for information communication in both physiological and pathological processes. However, there are no studies exploring the role of sEVs in the development of the cochlea. Here, we isolated tissue-derived sEVs from the cochleae of FVB mice at P3, P7, P14, and P21 by ultracentrifugation. These sEVs were first characterized by transmission electron microscopy, nanoparticle tracking analysis, and western blotting. Next, we used small RNA-seq and mass spectrometry to characterize the microRNA transcriptomes and proteomes of cochlear sEVs from mice at different ages. Many microRNAs and proteins were discovered to be related to inner ear development, anatomical structure development, and auditory nervous system development. These results all suggest that sEVs exist in the cochlea and are likely to be essential for the normal development of the auditory system. Our findings provide many sEV microRNA and protein targets for future studies of the roles of cochlear sEVs.

Synergistically Bifunctional Paramagnetic Separation Enables Efficient Isolation of Urine Extracellular Vesicles and Downstream Phosphoproteomic Analysis.

Extracellular vesicles (EVs) have emerged as important carriers for intercellular communication and biological sources for diagnosis and therapeutics. Low efficiency in EV isolation from biofluids, however, severely restricts their downstream characterization and analysis. Here, we introduced a novel strategy for EV isolation from urine for prostate cancer diagnosis using bifunctionalized magnetic beads through high affinity Ti(IV) ions and the insertion of a phospholipid derivative, 1,2-distearoyl-sn-glycero-3-phosphoethanolamine, into the EV membrane synergistically. We demonstrated its efficient isolation of EVs from urine samples with low contamination, high recovery (>80%), and short separation time (within 1 h), resulting in the identification of 36,262 unique EV peptides corresponding to 3302 unique proteins and 3233 unique phosphopeptides representing 1098 unique phosphoproteins using only 100 µL and 5 mL urine samples, respectively. Coupled with trapped ion mobility spectrometry and parallel accumulation-serial fragmentation for phosphosite-specific resolution, quantitative phosphoproteomics of urine samples from prostate cancer patients and healthy individuals revealed 121 upregulated phosphoproteins in cancer patients in contrast to the healthy group. These particular advantages indicate that the novel bifunctional material enables sensitive EV phosphoproteomic analysis for noninvasive biomarker screening and early cancer diagnosis.

Isolation and analysis of extracellular vesicles in a Morpho butterfly wing-integrated microvortex biochip.

With the function of mediating intercellular communication between cells, extracellular vesicles (EVs) have been intently studied for their physiopathology and clinical application values. However, efficient EV isolation from biological fluids remains a significant challenge. To address this, this work constructs a new microvortex chip that can isolate EVs efficiently by integrating the lipid nanoprobe modified Morpho Menelaus (M. Menelaus) butterfly wing into microfluidic chip. M. Menelaus wing is well known for its orderly arranged periodic nanostructures and can generate microvortex when liquid passes through it, leading to increased interaction between EVs and M. Menelaus wing. In addition, the nanoprobe containing lipid tails can be inserted into EVs through their lipid bilayer membrane structure. Based on the described properties, high-throughput enrichment of EVs with over 70% isolation efficiency was realized. Moreover, it was demonstrated that the nanoprobe system based on M. Menelaus wing enabled downstream biological analysis of nucleic acids and proteins in EVs. Microvortex chips showed potential application value in efficient EV isolation for biomedical research and cancer diagnosis.

The application of graphene-based biomaterials in biomedicine.

Graphene-based nanocomposites have attracted more and more attention recently in the field of biology and biomedicine. Graphene and its derivatives have been integrated with drugs, nucleic acids, antibodies, and other molecules. And these materials could be use as nanocomposite carriers or scaffold materials taking advantages of their enormous specific surface area, good elasticity and ductility, excellent biocompatibility, and outstanding mechanical strength. In addition, these composites have strong near-infrared absorbance and can act as photothermal agents to kill target cells through physical or chemical mechanisms. Along with significant advances in cell and organ transplantation, many of these materials have been explored in recent years for use in tissue engineering and regenerative medicine. Tissue engineering includes bone, nerve, heart, and muscle tissue engineering based on two-dimensional and three-dimensional graphene-based matrices or scaffolds possessing certain mechanical strengths and electrical conductivities, and the aim is to produce bioactive tissues to replace or repair natural tissue by promoting osteogenic, neuronal, and myogenic differentiation and myocardial cell growth. In this review, the basic properties of graphene-based complexes are systematically described and the biomedical applications of graphene-based materials in vivo and in vitro are summarized. This review first discusses the safety of graphene-based materials in terms of their biocompatibility and toxicity, and then it discusses these materials' applications in biosensing, photothermal therapy, stem cell culture, and tissue engineering. This review therefore provides a comprehensive understanding of graphene and its derivatives and their present and future applications.

In Vivo Biosynthesized Zinc and Iron Oxide Nanoclusters for High Spatiotemporal Dual-Modality Bioimaging of Alzheimer's Disease.

Alzheimer's disease is still incurable and neurodegenerative, and there is a lack of detection methods with high sensitivity and specificity. In this study, by taking different month old Alzheimer's mice as models, we have explored the possibility of the target bioimaging of diseased sites through the initial injection of zinc gluconate solution into Alzheimer's model mice post-tail vein and then the combination of another injection of ferrous chloride (FeCl2) solution into the same Alzheimer's model mice post-stomach. Our observations indicate that both zinc gluconate solution and FeCl2 solution could cross the blood-brain barrier (BBB) to biosynthesize the fluorescent zinc oxide nanoclusters and magnetic iron oxide nanoclusters, respectively, in the lesion areas of the AD model mice, thus enabling high spatiotemporal dual-modality bioimaging (i.e., including fluorescence bioimaging (FL) and magnetic resonance imaging (MRI)) of Alzheimer's disease for the first time. The result presents a novel promising strategy for the rapid and early diagnosis of Alzheimer's disease.

Synergistic effect of pyrroloquinoline quinone and graphene nano-interface for facile fabrication of sensitive NADH biosensor.

A self-assembly composite of graphene-pyrroloquinoline quinone (PQQ) was fabricated and modified on glassy carbon electrode (GCE) for sensitive detection of nicotinamide adenine dinucleotide (NADH). Chitosan (CTS) was applied to disperse graphene to form a stable robust film on GCE. A synergistic effect between PQQ and graphene was observed during the electrocatalytic oxidation of NADH, with about 260mV reduction in the oxidation potential and 2.5-fold increase in the oxidation current compared with those on the bare GCE. The electrochemical sensors based on the modified electrodes allowed the detection of NADH with a good linear dependence from 0.32 to 220µM with a high sensitivity of 0.421µAµM-1cm-2 and a low detection limit of 0.16µM (S/N=3). It could also eliminate the interference of electroactive substances like ascorbic acid (AA), uric acid, and dopamine and its derivatives. The outstanding performances of graphene-PQQ/CTS composite capable of improving the electrical conductivity and accelerating the electron transport suggested its promising applications for design of different graphene based composites used in electrochemical sensing and energy fields.