Chiral nanomaterials in tissue engineering.

Addressing significant medical challenges arising from tissue damage and organ failure, the field of tissue engineering has evolved to provide revolutionary approaches for regenerating functional tissues and organs. This involves employing various techniques, including the development and application of novel nanomaterials. Among them, chiral nanomaterials comprising non-superimposable nanostructures with their mirror images have recently emerged as innovative biomaterial candidates to guide tissue regeneration due to their unique characteristics. Chiral nanomaterials including chiral fibre supramolecular hydrogels, polymer-based chiral materials, self-assembling peptides, chiral-patterned surfaces, and the recently developed intrinsically chiroptical nanoparticles have demonstrated remarkable ability to regulate biological processes through routes such as enantioselective catalysis and enhanced antibacterial activity. Despite several recent reviews on chiral nanomaterials, limited attention has been given to the specific potential of these materials in facilitating tissue regeneration processes. Thus, this timely review aims to fill this gap by exploring the fundamental characteristics of chiral nanomaterials, including their chiroptical activities and analytical techniques. Also, the recent advancements in incorporating these materials in tissue engineering applications are highlighted. The review concludes by critically discussing the outlook of utilizing chiral nanomaterials in guiding future strategies for tissue engineering design.

Building a Better Silver Bullet: Current Status and Perspectives of Non-Viral Vectors for mRNA Vaccines.

In recent years, messenger RNA (mRNA) vaccines have exhibited great potential to replace conventional vaccines owing to their low risk of insertional mutagenesis, safety and efficacy, rapid and scalable production, and low-cost manufacturing. With the great achievements of chemical modification and sequence optimization methods of mRNA, the key to the success of mRNA vaccines is strictly dependent on safe and efficient gene vectors. Among various delivery platforms, non-viral mRNA vectors could represent perfect choices for future clinical translation regarding their safety, sufficient packaging capability, low immunogenicity, and versatility. In this review, the recent progress in the development of non-viral mRNA vectors is focused on. Various organic vectors including lipid nanoparticles (LNPs), polymers, peptides, and exosomes for efficient mRNA delivery are presented and summarized. Furthermore, the latest advances in clinical trials of mRNA vaccines are described. Finally, the current challenges and future possibilities for the clinical translation of these promising mRNA vectors are also discussed.

Recent Advances in Engineering Carriers for siRNA Delivery.

RNA interference (RNAi) technology has been a promising treatment strategy for combating intractable diseases. However, the applications of RNAi in clinical are hampered by extracellular and intracellular barriers. To overcome these barriers, various siRNA delivery systems have been developed in the past two decades. The first approved RNAi therapeutic, Patisiran (ONPATTRO) using lipids as the carrier, for the treatment of amyloidosis is one of the most important milestones. This has greatly encouraged researchers to work on creating new functional siRNA carriers. In this review, the recent advances in siRNA carriers consisting of lipids, polymers, and polymer-modified inorganic particles for cancer therapy are summarized. Representative examples are presented to show the structural design of the carriers in order to overcome the delivery hurdles associated with RNAi therapies. Finally, the existing challenges and future perspective for developing RNAi as a clinical modality will be discussed and proposed. It is believed that the addressed contributions in this review will promote the development of siRNA delivery systems for future clinical applications.

Creation of Chitosan-Based Nanocapsule-in-Nanofiber Structures for Hydrophobic/Hydrophilic Drug Co-Delivery and Their Dressing Applications in Diabetic Wounds.

Nanofiber meshes (NFMs) loaded with therapeutic agents are very often employed to treat hard-to-heal wounds such as diabetic wounds. However, most of the NFMs have limited capability to load multiple or hydrophilicity distinctive-therapeutic agents. The therapy strategy is therefore significantly hampered. To tackle the innate drawback associated with the drug loading versatility, a chitosan-based nanocapsule-in-nanofiber (NC-in-NF) structural NFM system is developed for simultaneous loading of hydrophobic and hydrophilic drugs. Oleic acid-modified chitosan is first converted into NCs by the developed mini-emulsion interfacial cross-linking procedure, followed by loading a hydrophobic anti-inflammatory agent Curcumin (Cur) into the NCs. Sequentially, the Cur-loaded NCs are successfully introduced into reductant-responsive maleoyl functional chitosan/polyvinyl alcohol NFMs containing a hydrophilic antibiotic Tetracycline hydrochloride. Having a co-loading capability for hydrophilicity distinctive agents, biocompatibility, and a controlled release property, the resulting NFMs have demonstrated the efficacy on promoting wound healing either in normal or diabetic rats.

Micro/Nano-Fabrication of Flexible Poly(3,4-Ethylenedioxythiophene)-Based Conductive Films for High-Performance Microdevices.

With the increasing demands for novel flexible organic electronic devices, conductive polymers are now becoming the rising star for reaching such targets, which has witnessed significant breakthroughs in the fields of thermoelectric devices, solar cells, sensors, and hydrogels during the past decade due to their outstanding conductivity, solution-processing ability, as well as tailorability. However, the commercialization of those devices still lags markedly behind the corresponding research advances, arising from the not high enough performance and limited manufacturing techniques. The conductivity and micro/nano-structure of conductive polymer films are two critical factors for achieving high-performance microdevices. In this review, the state-of-the-art technologies for developing organic devices by using conductive polymers are comprehensively summarized, which will begin with a description of the commonly used synthesis methods and mechanisms for conductive polymers. Next, the current techniques for the fabrication of conductive polymer films will be proffered and discussed. Subsequently, approaches for tailoring the nanostructures and microstructures of conductive polymer films are summarized and discussed. Then, the applications of micro/nano-fabricated conductive films-based devices in various fields are given and the role of the micro/nano-structures on the device performances is highlighted. Finally, the perspectives on future directions in this exciting field are presented.

Machine-learning screening of luminogens with aggregation-induced emission characteristics for fluorescence imaging.

Due to the excellent biocompatible physicochemical performance, luminogens with aggregation-induced emission (AIEgens) characteristics have played a significant role in biomedical fluorescence imaging recently. However, screening AIEgens for special applications takes a lot of time and efforts by using conventional chemical synthesis route. Fortunately, artificial intelligence techniques that could predict the properties of AIEgen molecules would be helpful and valuable for novel AIEgens design and synthesis. In this work, we applied machine learning (ML) techniques to screen AIEgens with expected excitation and emission wavelength for biomedical deep fluorescence imaging. First, a database of various AIEgens collected from the literature was established. Then, by extracting key features using molecular descriptors and training various state-of-the-art ML models, a multi-modal molecular descriptors strategy has been proposed to extract the structure-property relationships of AIEgens and predict molecular absorption and emission wavelength peaks. Compared to the first principles calculations, the proposed strategy provided greater accuracy at a lower computational cost. Finally, three newly predicted AIEgens with desired absorption and emission wavelength peaks were synthesized successfully and applied for cellular fluorescence imaging and deep penetration imaging. All the results were consistent successfully with our expectations, which demonstrated the above ML has a great potential for screening AIEgens with suitable wavelengths, which could boost the design and development of novel organic fluorescent materials.

Semiconducting electrodes for neural interfacing: a review.

In the past 50 years, the advent of electronic technology to directly interface with neural tissue has transformed the fields of medicine and biology. Devices that restore or even replace impaired bodily functions, such as deep brain stimulators and cochlear implants, have ushered in a new treatment era for previously intractable conditions. Meanwhile, electrodes for recording and stimulating neural activity have allowed researchers to unravel the vast complexities of the human nervous system. Recent advances in semiconducting materials have allowed effective interfaces between electrodes and neuronal tissue through novel devices and structures. Often these are unattainable using conventional metallic electrodes. These have translated into advances in research and treatment. The development of semiconducting materials opens new avenues in neural interfacing. This review considers this emerging class of electrodes and how it can facilitate electrical, optical, and chemical sensing and modulation with high spatial and temporal precision. Semiconducting electrodes have advanced electrically based neural interfacing technologies owing to their unique electrochemical and photo-electrochemical attributes. Key operation modalities, namely sensing and stimulation in electrical, biochemical, and optical domains, are discussed, highlighting their contrast to metallic electrodes from the application and characterization perspective.

Silk fibroin fibers-based shape memory membrane with Janus wettability for multitiered wearable protection.

Realizing breathable shape memory fiber-based material with antibacterial and waterproof performances is important for multitiered wearable protection to address the increasing concerns of air pollution. Herein, using an alternating electrospinning-electrospraying technology, we develop a fiber-based membrane with Janus wettability based on a silk fibroin nanofibers-substrate (SFNFs), a polyurethane nanospheres-top layer (PUNSs), and a middle layer of PU nanofibers-mat with in-situ grown silver nanoparticles (PUNFs-AgNPs), which serves separately for skin contact, a self-cleaning physical barrier to resist external aerosol/bacteria (PM2.5 filtration efficiency ~ 98.1%), and a bio-barrier that can sterilize harmful particles and inhibit bacteria proliferation (> 95%). This breathable Janus film (SFNFs/PUNFs-AgNPs/PUNSs, SPAP) with an antibacterial filter shows shape memory stretchability enabled by the thermoplastic PU component, which is mechanically adaptive to human body for wearable protection. This work presents a breathable wearable material for air-filtration and anti-bacteria, promising for applications such as wound dressings, medical masks, protection suits, and multifunctional filters. Graphical abstract: An alternating electrospinning-electrospraying technology was proposed to achieve a silk fibroin-based antibacterial membrane with Janus wettability, as well as good skin affinity and breathability, which serves well as physical and bio-barriers for water resistance, PM2.5 filtration (~98.1%) and bacteria inhibition (efficiency of 95%). This shape memory Janus membrane can adapt mechanically to human body curvatures for functional wearable protections. Supplementary Information: The online version contains supplementary material available at 10.1557/s43578-022-00805-w.

Numerical Analysis of Three-dimensional Nanodisk Array-based Surface Plasmon Resonance Biosensors for SARS-CoV-2 Detection.

With continuous mutations of SARS-CoV-2 virus, new highly contagious and fast-spreading variants have emerged, including Delta and Omicron. The popular label-free immunosensor based on surface plasmon resonance (SPR) technique can be used for real-time monitoring of the ligand-analyte or antibody-antigen interactions occurring on the sensor surface. In this work, an SPR-based biosensor combined with a nanodisk array was presented to enhance the sensitivity toward virus detection. The nanodisk arrays were employed to enhance the adsorption of molecules for better detection by increasing the SPR field. Four optimal sensing configurations of silver or gold nanodisks on gold thin films with different aspect ratios were achieved through systematic optimization of all parameters to yield the best sensor performance. The resonance angle can be modulated simply by the aspect ratio of nanodisk array. The sensitivity of the optimized sensors has been improved, and the detection limit is smaller than that of bare gold-based sensor. The multi-jump resonance angle curves at tiny refractive index can clearly distinguish the difference of trace concentrations, which is very important for the accurate detection of trace substances. Supplementary Information: The online version contains supplementary material available at 10.1007/s11468-023-01802-3.

Label-free plasmonic-based biosensing using a gold nanohole array chip coated with a wafer-scale deposited WS2 monolayer.

This paper reports the fabrication, testing and obtained performance of a plasmonic sensor employing a gold (Au) nanohole array chip coated with tungsten disulphide (WS2), which is then functionalized for the detection of protein-protein interactions. A key novelty is that the WS2 was deposited as a monoatomic layer using a wafer-scale synthesis method that successfully provided a film of both high quality and uniform thickness. The deposited WS2 film was transferred onto a Au nanohole array chip using a novel method and was subsequently functionalized with biotin. The final sensor was tested and it demonstrated efficient real-time and label-free plasmonic detection of biotin-streptavidin coupling. Specifically, compared to a standard (i.e. uncoated) Au nanohole-based sensor, our WS2-coated Au nanohole array boosted the spectral shift of the resonance wavelength by ∼190%, resulting in a 7.64-fold improvement of the limit of detection (LOD).

Membrane-intercalating conjugated oligoelectrolytes.

By acting as effective biomimetics of the lipid bilayers, membrane-intercalating conjugated oligoelectrolytes (MICOEs) can spontaneously insert themselves into both synthetic lipid bilayers and biological membranes. The modular and intentional molecular design of MICOEs enable a range of applications, such as bioproduction, biocatalysis, biosensing, and therapeutics. This tutorial review provides a structural evolution of MICOEs, which originated from the broader class of conjugated molecules, and analyses the drivers behind this evolutionary process. Various representative applications of MICOEs, accompanied by insights into their molecular design principles, will be reviewed separately. Perspectives on the current challenges and opportunities in research on MICOEs will be discussed at the end of the review to highlight their potential as unconventional and value-added materials for biological systems.

Plasmonic Biosensing with Nano-Engineered Van der Waals Interfaces.

Observing a Goos-Hänchen (GH) shift of the incident light beam provides a simple and convenient method of detecting fast phase variations without the need for cumbersome direct phase measurements. Here, we show that few-monolayers-thick van der Waals structures (WS2 , MoSe2 and graphene) nano-engineered onto a plasmonic surface can enhance the phase variation sensitivity to analyte presence, leading to more than 3 orders of magnitude increase in the Goos-Hänchen shift (ca. 886 mm/RIU for a WS2 /graphene/Au multilayer). The detection limit is evaluated to be as low as 0.1 aM (6.7 pg/mL) for bovine serum albumin protein with molecular weight of 67 kDa and 1 fM (24.4 ng/mL) for biotin (244 Da) molecules.

Liver-on-a-chip: Considerations, advances, and beyond.

The liver is the largest internal organ in the human body with largest mass of glandular tissue. Modeling the liver has been challenging due to its variety of major functions, including processing nutrients and vitamins, detoxification, and regulating body metabolism. The intrinsic shortfalls of conventional two-dimensional (2D) cell culture methods for studying pharmacokinetics in parenchymal cells (hepatocytes) have contributed to suboptimal outcomes in clinical trials and drug development. This prompts the development of highly automated, biomimetic liver-on-a-chip (LOC) devices to simulate native liver structure and function, with the aid of recent progress in microfluidics. LOC offers a cost-effective and accurate model for pharmacokinetics, pharmacodynamics, and toxicity studies. This review provides a critical update on recent developments in designing LOCs and fabrication strategies. We highlight biomimetic design approaches for LOCs, including mimicking liver structure and function, and their diverse applications in areas such as drug screening, toxicity assessment, and real-time biosensing. We capture the newest ideas in the field to advance the field of LOCs and address current challenges.

Recent advances in nanotechnology approaches for non-viral gene therapy.

Gene therapy has shown great potential in the treatment of many diseases by downregulating the expression of certain genes. The development of gene vectors as a vehicle for gene therapy has greatly facilitated the widespread clinical application of nucleic acid materials (DNA, mRNA, siRNA, and miRNA). Currently, both viral and non-viral vectors are used as delivery systems of nucleic acid materials for gene therapy. However, viral vector-based gene therapy has several limitations, including immunogenicity and carcinogenesis caused by the exogenous viral vectors. To address these issues, non-viral nanocarrier-based gene therapy has been explored for superior performance with enhanced gene stability, high treatment efficiency, improved tumor-targeting, and better biocompatibility. In this review, we discuss various non-viral vector-mediated gene therapy approaches using multifunctional biodegradable or non-biodegradable nanocarriers, including polymer-based nanoparticles, lipid-based nanoparticles, carbon nanotubes, gold nanoparticles (AuNPs), quantum dots (QDs), silica nanoparticles, metal-based nanoparticles and two-dimensional nanocarriers. Various strategies to construct non-viral nanocarriers based on their delivery efficiency of targeted genes will be introduced. Subsequently, we discuss the cellular uptake pathways of non-viral nanocarriers. In addition, multifunctional gene therapy based on non-viral nanocarriers is summarized, in which the gene therapy can be combined with other treatments, such as photothermal therapy (PTT), photodynamic therapy (PDT), immunotherapy and chemotherapy. We also provide a comprehensive discussion of the biological toxicity and safety of non-viral vector-based gene therapy. Finally, the present limitations and challenges of non-viral nanocarriers for gene therapy in future clinical research are discussed, to promote wider clinical applications of non-viral vector-based gene therapy.

Elastic Fibers/Fabrics for Wearables and Bioelectronics.

Wearables and bioelectronics rely on breathable interface devices with bioaffinity, biocompatibility, and smart functionality for interactions between beings and things and the surrounding environment. Elastic fibers/fabrics with mechanical adaptivity to various deformations and complex substrates, are promising to act as fillers, carriers, substrates, dressings, and scaffolds in the construction of biointerfaces for the human body, skins, organs, and plants, realizing functions such as energy exchange, sensing, perception, augmented virtuality, health monitoring, disease diagnosis, and intervention therapy. This review summarizes and highlights the latest breakthroughs of elastic fibers/fabrics for wearables and bioelectronics, aiming to offer insights into elasticity mechanisms, production methods, and electrical components integration strategies with fibers/fabrics, presenting a profile of elastic fibers/fabrics for energy management, sensors, e-skins, thermal management, personal protection, wound healing, biosensing, and drug delivery. The trans-disciplinary application of elastic fibers/fabrics from wearables to biomedicine provides important inspiration for technology transplantation and function integration to adapt different application systems. As a discussion platform, here the main challenges and possible solutions in the field are proposed, hopefully can provide guidance for promoting the development of elastic e-textiles in consideration of the trade-off between mechanical/electrical performance, industrial-scale production, diverse environmental adaptivity, and multiscenario on-spot applications.

Dual-network self-healing hydrogels composed of graphene oxide@nanocellulose and poly(AAm-co-AAc).

A nature-inspired strategy is developed to build dual-network hydrogels made up of rigid graphene oxide-functionalized nanocellulose (GO@NC) network and flexible poly[acrylamide-co-(acrylic acid)] (poly(AAm-co-AAc)) network. A pre-stretching method is used to form a muscle-shape anisotropic architecture. The penetration of poly(AAm-co-AAc) flexible network relieves the stiffness of NC network, thus improving the average elongation at break from 86.2 % to 748.0 %. Compared with the poly(AAm-co-AAc), the average rupture tensile strength rises remarkably by 228.6 %. The dual-crosslinked strategy endows the GO@NC-poly(AAm-co-AAc) hydrogels with a fast, stable and repeatable self-healing ability, which can achieve 85.0 % of healing efficiency after only 600 s of self-healing and maintain 76.2 % of initial strength after 10 cycles of breaking-self-healing. The superb self-healing ability is similar to the muscle function. For potential applications, the hydrogels can achieve real-time, stable, and long-term sensing as smart wearable strain sensors (high gauge factor: 5.13), and can effectively purify Sudan IV wastewater as green recyclable adsorbents.

Diagnostic plasmonic sensors: opportunities and challenges.

The medical fraternity is currently burgeoned and stressed with a huge rush of patients who have inflammatory conditions, metabolite diseases, and cardiovascular diseases. In these circumstances, advanced sensing technologies could have a huge impact on the quality of life of patients. Given plasmonic resonance effects significantly improve the ability to rapidly and accurately detect biological markers, plasmonic technology is harnessed to develop a fast and accurate diagnosis that can provide timely intervention with the diseases and can also aid the recovery process by complementing the therapy stage. In this short review, we provide an overlook of how the field of plasmonic sensing has revolutionized the field of medical diagnostics. This article reviews the fundamentals and development of plasmonics. In addition, we highlight the sensitivity of various SPR and LSPR sensors. The chemistry for functionalizing plasmonic sensors is also discussed. This review also outlines some general suggestions for future directions that we feel might be useful to advance our understanding of the universe or speed up the development of plasmonic sensors in the future.

A biocompatible ratiometric fluorescent nanoprobe for intracellular hydrogen sulfide accurate detection based on rare earth nanoparticle.

Hydrogen sulfide (H2S) is an important signal molecule involved in intracellular activities. To understand the role of H2S in cellular physiological and pathological process, the development of sensitive and selective methods, especially biocompatible assays, for efficient monitoring the level of H2S is necessary. Herein, we modified novel rare earth element europium (EU) based fluorescent nanospheres with azide (-N3) based sensor to construct an ingenious ratiometric fluorescent nanoprobe EU-N3. This nanoprobe showed excellent water solubility and high biocompatibility for intracellular H2S accurate detection. Nanoprobe EU-N3 had two obvious emission peaks, the green fluorescence peak at 540 nm increased according to the increasing of H2S concentration and the red fluorescence peak at 616 nm was stable as ratiometric reference. The fluorescence intensity ratio (I540/I616) displayed good linear response (R = 0.99136) in H2S range of 0.5 âˆ¼ 30 µM. The analytes response assay demonstrated that the nanoprobe EU-N3 possessed a better specificity for H2S, compared with other 9 anions and 3 cations. The cell viability assay indicated the nanoprobe EU-N3 had an excellent biocompatibility. The cell imaging showed that the proposed nanoprobe could be applied for detecting the intracellular H2S changes accurately in live cells. Such nanoprobe provided a safe and accurate strategy for intracellular H2S detection, which is helpful for the real-time H2S visualization in the live cell activities.

Role of microfluidics in accelerating new space missions.

Numerous revolutionary space missions have been initiated and planned for the following decades, including plans for novel spacecraft, exploration of the deep universe, and long duration manned space trips. Compared with space missions conducted over the past 50 years, current missions have features of spacecraft miniaturization, a faster task cycle, farther destinations, braver goals, and higher levels of precision. Tasks are becoming technically more complex and challenging, but also more accessible via commercial space activities. Remarkably, microfluidics has proven impactful in newly conceived space missions. In this review, we focus on recent advances in space microfluidic technologies and their impact on the state-of-the-art space missions. We discuss how micro-sized fluid and microfluidic instruments behave in space conditions, based on hydrodynamic theories. We draw on analyses outlining the reasons why microfluidic components and operations have become crucial in recent missions by categorically investigating a series of successful space missions integrated with microfluidic technologies. We present a comprehensive technical analysis on the recently developed in-space microfluidic applications such as the lab-on-a-CubeSat, healthcare for manned space missions, evaluation and reconstruction of the environment on celestial bodies, in-space manufacturing of microfluidic devices, and development of fluid-based micro-thrusters. The discussions in this review provide insights on microfluidic technologies that hold considerable promise for the upcoming space missions, and also outline how in-space conditions present a new perspective to the microfluidics field.

Silk Fabric Decorated with Thermo-Sensitive Hydrogel for Sustained Release of Paracetamol.

Paracetamol is a safe and widely used antipyretic and analgesic drug, however, with the drawbacks of gastrointestinal first-pass effect and short intervals of administration. Transdermal drug delivery system can effectively avoid the liver metabolism caused by excess oral ingestion of paracetamol. Herein, a silk fabric-based medical dressing decorated by a thermo-responsive hydrogel for sustained release of paracetamol is proposed. Genipin as a bio-safe cross-linker is applied to assist gelation of a thermo-responsive hydrogel system coupled with chitosan and glycerol-phosphate disodium salt around body temperature (37 °C), as well as densifying the microporous gel to improve mechanical strength. The in situ sol-gel transition enabled hydrogel well penetrate and coat the silk fabric, forming a hierarchical hydrogel structure capable of prolonging the sustained release of drug to 12 h, twice as long as a blank fabric. The silk fabric with a thin gel coating maintains a good water vapor transmission rate, compatible for skin contact application. The drug release properties can be tuned by regulating the genipin content and fabric braiding structure. The silk fabric dressing exhibits temperature-dependent instant release behavior within the first 2 h. The sustained release mechanism of paracetamol well matches with the Korsmeyer-Peppas model in a non-Fickian diffusion.