Latent stem cell-stimulating radially aligned electrospun nanofibrous patches for chronic tympanic membrane perforation therapy.

Chronic tympanic membrane (TM) perforation is a tubotympanic disease caused by either traumatic injury or inflammation. A recent study demonstrated significant progress in promoting the regeneration of chronic TM perforations through the application of nanofibers with radially aligned nanostructures and controlled release of growth factors. However, radially aligned nanostructures with stem cell-stimulating factors have never been used. In this study, insulin-like growth factor binding factor 2 (IGFBP2)-incorporated radially aligned nanofibrous patches (IRA-NFPs) were developed and applied to regenerate chronic TM perforations. The IRA-NFPs were prepared by electrospinning 8 wt% polycaprolactone in trifluoroethanol and acetic acid (9:1). Random nanofibers (RFs) and aligned nanofibers (AFs) were successfully fabricated using a flat plate and a custom-designed circular collector, respectively. The presence of IGFBP2 was confirmed via Fourier transform infrared spectroscopy and the release of IGFBP2 was sustained for up to 20 days. In vitro studies revealed enhanced cellular proliferation and migration on AFs compared to RFs, and the incorporation of IGFBP2 further promoted these effects. Quantitative real-time PCR revealed mRNA downregulation, correlating with accelerated migration and increased cell confluency. In vivo studies showed IGFBP2-loaded RF and AF patches increased regeneration success rates by 1.59-fold and 2.23-fold, respectively, while also reducing healing time by 2.5-fold compared to the control. Furthermore, IGFBP2-incorporated AFs demonstrated superior efficacy in healing larger perforations with enhanced histological similarity to native TMs. This study, combining stem cell stimulating factors and aligned nanostructures, proposes a novel approach potentially replacing conventional surgical methods for chronic TM perforation regeneration. STATEMENT OF SIGNIFICANCE: Chronic otitis media (COM) affects approximately 200 million people worldwide due to inflammation, inadequate blood supply, and lack of growth factors. Current surgical treatments have limitations like high costs and anesthetic risks. Recent research explored the use of nanofibers with radially aligned nanostructures and controlled release of growth factors to treat chronic tympanic membrane (TM) perforations. In this study, insulin-like growth factor binding protein 2 (IGFBP2)-incorporated radially aligned nanofibrous patches (IRA-NFPs) were developed and applied to regenerate chronic TM perforations. We assessed their properties and efficacy through in vitro and in vivo studies. IRA-NFPs showed promising healing capabilities with chronic TM perforation models. This innovative approach has the potential to improve COM management, reduce surgery costs, and enhance patient safety.

Gelatin Nanoparticles can Improve Pesticide Delivery Performance to Plants.

Nanomaterials associated with plant growth and crop cultivation revolutionize traditional concepts of agriculture. However, the poor reiterability of these materials in agricultural applications necessitates the development of environmentally-friendly approaches. To address this, biocompatible gelatin nanoparticles (GNPs) as nanofertilizers with a small size (≈150 nm) and a positively charged surface (≈30 mV) that serve as a versatile tool in agricultural practices is designed. GNPs load agrochemical agents to improve maintenance and delivery. The biocompatible nature and small size of GNPs ensure unrestricted nutrient absorption on root surfaces. Furthermore, when combined with pesticides, GNPs demonstrate remarkable enhancements in insecticidal (≈15%) and weed-killing effects (≈20%) while preserving the efficacy of the pesticide. That GNPs have great potential for use in sustainable agriculture, particularly in inducing plant growth, specifically plant root growth, without fertilization and in enhancing the functions of agrochemical agents is proposed. It is suggested conceptual applications of GNPs in real-world agricultural practices.

Wet tissue adhesive polymeric powder hydrogels for skeletal muscle regeneration.

Volumetric muscle loss (VML) frequently results from traumatic incidents and can lead to severe functional disabilities. Hydrogels have been widely employed for VML tissue regeneration, which are unfortunately ineffective because of the lack of intimate contact with injured tissue for structural and mechanical support. Adhesive hydrogels allow for strong tissue connections for wound closure. Nevertheless, conventional adhesive hydrogels exhibit poor tissue adhesion in moist, bleeding wounds due to the hydration layer at the tissue-hydrogel interfaces, resulting in insufficient performance. In this study, we developed a novel, biocompatible, wet tissue adhesive powder hydrogel consisting of dextran-aldehyde (dex-ald) and gelatin for the regeneration of VML. This powder absorbs the interfacial tissue fluid and buffer solution on the tissue, spontaneously forms a hydrogel, and strongly adheres to the tissue via various molecular interactions, including the Schiff base reaction. In particular, the powder composition with a 1:4 ratio of dex-ald to gelatin exhibited optimal characteristics with an appropriate gelation time (258 s), strong tissue adhesion (14.5 kPa), and stability. Dex-ald/gelatin powder hydrogels presented strong adhesion to various organs and excellent hemostasis compared to other wet hydrogels and fibrin glue. A mouse VML injury model revealed that the dex-ald/gelatin powder hydrogel significantly improved muscle regeneration, reduced fibrosis, enhanced vascularization, and decreased inflammation. Consequently, our wet-adhesive powder hydrogel can serve as an effective platform for repairing various tissues, including the heart, muscle, and nerve tissues.

Effect of Carbon Nanotubes on Chloride Diffusion, Strength, and Microstructure of Ultra-High Performance Concrete.

This study delved into the integration of carbon nanotubes (CNTs) in Ultra-High Performance Concrete (UHPC), exploring aspects such as mechanical properties, microstructure analysis, accelerated chloride penetration, and life service prediction. A dispersed CNT solution (0.025 to 0.075 wt%) was employed, along with a superplasticizer, to ensure high flowability in the UHPC slurry. In addition, the combination of high-strength functional artificial lightweight aggregate (ALA) and micro hollow spheres (MHS) was utilized as a replacement for fine aggregate to not only reduce the weight of the concrete but also to increase its mechanical performance. Experimental findings unveiled that an increased concentration of CNT in CNT1 (0.025%) and CNT2 (0.05%) blends led to a marginal improvement in compressive strength compared to the control mix. Conversely, the CNT3 (0.075%) mixture exhibited a reduction in compressive strength with a rising CNT content as an admixture. SEM analysis depicted that the heightened concentration of CNTs as an admixture induced the formation of nanoscale bridges within the concrete matrix. Ponding test results indicated that, for all samples, the effective chloride transport coefficient remained below the standard limitation of 1.00 × 10-12 m2/s, signifying acceptable performance in the ponding test for all samples. The life service prediction outcomes affirmed that, across various environmental scenarios, CNT1 and CNT2 mixtures consistently demonstrated superior performance compared to all other mixtures.

Graphene Hybrid Tough Hydrogels with Nanostructures for Tissue Regeneration.

Over the past few decades, hydrogels have attracted considerable attention as promising biomedical materials. However, conventional hydrogels require improved mechanical properties, such as brittleness, which significantly limits their widespread use. Recently, hydrogels with remarkably improved toughness have been developed; however, their low biocompatibility must be addressed. In this study, we developed a tough graphene hybrid hydrogel with nanostructures. The resultant hydrogel exhibited remarkable mechanical properties while representing an aligned nanostructure that resembled the extracellular matrix of soft tissue. Owing to the synergistic effect of the topographical properties, and the enhanced biochemical properties, the graphene hybrid hydrogel had excellent stretchability, resilience, toughness, and biocompatibility. Furthermore, the hydrogel displayed outstanding tissue regeneration capabilities (e.g., skin and tendons). Overall, the proposed graphene hybrid tough hydrogel may provide significant insights into the application of tough hydrogels in tissue regeneration.

Micro/nanoengineered agricultural by-products for biomedical and environmental applications.

Agriculturally derived by-products generated during the growth cycles of living organisms as secondary products have attracted increasing interest due to their wide range of biomedical and environmental applications. These by-products are considered promising candidates because of their unique characteristics including chemical stability, profound biocompatibility and offering a green approach by producing the least impact on the environment. Recently, micro/nanoengineering based techniques play a significant role in upgrading their utility, by controlling their structural integrity and promoting their functions at a micro and nano scale. Specifically, they can be used for biomedical applications such as tissue regeneration, drug delivery, disease diagnosis, as well as environmental applications such as filtration, bioenergy production, and the detection of environmental pollutants. This review highlights the diverse role of micro/nano-engineering techniques when applied on agricultural by-products with intriguing properties and upscaling their wide range of applications across the biomedical and environmental fields. Finally, we outline the future prospects and remarkable potential that these agricultural by-products hold in establishing a new era in the realms of biomedical science and environmental research.

Glycine-Rich RNA-Binding Protein AtGRP7 Functions in Nickel and Lead Tolerance in Arabidopsis.

Plant glycine-rich RNA-binding proteins (GRPs) play crucial roles in the response to environmental stresses. However, the functions of AtGRP7 in plants under heavy metal stress remain unclear. In the present study, in Arabidopsis, the transcript level of AtGRP7 was markedly increased by Ni but was decreased by Pb. AtGRP7-overexpressing plants improved Ni tolerance, whereas the knockout mutant (grp7) was more susceptible than the wild type to Ni. In addition, grp7 showed greatly enhanced Pb tolerance, whereas overexpression lines showed high Pb sensitivity. Ni accumulation was reduced in overexpression lines but increased in grp7, whereas Pb accumulation in grp7 was lower than that in overexpression lines. Ni induced glutathione synthase genes GS1 and GS2 in overexpression lines, whereas Pb increased metallothionein genes MT4a and MT4b and phytochelatin synthase genes PCS1 and PCS2 in grp7. Furthermore, Ni increased CuSOD1 and GR1 in grp7, whereas Pb significantly induced FeSOD1 and FeSOD2 in overexpression lines. The mRNA stability of GS2 and PCS1 was directly regulated by AtGRP7 under Ni and Pb, respectively. Collectively, these results indicate that AtGRP7 plays a crucial role in Ni and Pb tolerance by reducing Ni and Pb accumulation and the direct or indirect post-transcriptional regulation of genes related to heavy metal chelators and antioxidant enzymes.

Piezoelectrically and Topographically Engineered Scaffolds for Accelerating Bone Regeneration.

Bone regeneration remains a critical concern across diverse medical disciplines, because it is a complex process that requires a combinatorial approach involving the integration of mechanical, electrical, and biological stimuli to emulate the native cellular microenvironment. In this context, piezoelectric scaffolds have attracted considerable interest owing to their remarkable ability to generate electric fields in response to dynamic forces. Nonetheless, the application of such scaffolds in bone tissue engineering has been limited by the lack of a scaffold that can simultaneously provide both the intricate electromechanical environment and the biocompatibility of the native bone tissue. Here, we present a pioneering biomimetic scaffold that combines the unique properties of piezoelectric and topographical enhancement with the inherent osteogenic abilities of hydroxyapatite (HAp). Notably, the novelty of this work lies in the incorporation of HAp into polyvinylidene fluoride-co-trifluoro ethylene in a freestanding form, leveraging its natural osteogenic potential within a piezoelectric framework. Through comprehensive in vitro and in vivo investigations, we demonstrate the remarkable potential of these scaffolds to accelerate bone regeneration. Moreover, we demonstrate and propose three pivotal mechanisms─(i) electrical, (ii) topographical, and (iii) paracrine─that collectively contribute to the facilitated bone healing process. Our findings present a synergistically derived biomimetic scaffold design with wide-ranging prospects for bone regeneration as well as various regenerative medicine applications.

Engineering Considerations on Large-Scale Cultured Meat Production.

In recent decades, cultured meat has received considerable interest as a sustainable alternative to traditional meat products, showing promise for addressing the inherent problems associated with conventional meat production. However, current limitations on the scalability of production and extremely high production costs have prevented their widespread adoption. Therefore, it is important to develop novel engineering strategies to overcome the current limitations in large-scale cultured meat production. Such engineering considerations have the potential for advancements in cultured meat production by providing innovative and effective solutions to the prevailing challenges. In this review, we discuss how engineering strategies have been utilized to advance cultured meat technology by categorizing the production processes of cultured meat into three distinct steps: (1) cell preparation; (2) cultured meat fabrication; and (3) cultured meat maturation. For each step, we provide a comprehensive discussion of the recent progress and its implications. In particular, we focused on the engineering considerations involved in each step of cultured meat production, with specific emphasis on large-scale production.

Bioinspired magnetic cilia: from materials to applications.

Microscale and nanoscale cilia are ubiquitous in natural systems where they serve diverse biological functions. Bioinspired artificial magnetic cilia have emerged as a highly promising technology with vast potential applications, ranging from soft robotics to highly precise sensors. In this review, we comprehensively discuss the roles of cilia in nature and the various types of magnetic particles utilized in magnetic cilia; additionally, we explore the top-down and bottom-up fabrication techniques employed for their production. Furthermore, we examine the various applications of magnetic cilia, including their use in soft robotics, droplet and particle control systems, fluidics, optical devices, and sensors. Finally, we present our conclusions and the future outlook for magnetic cilia research and development, including the challenges that need to be overcome and the potential for further integration with emerging technologies.

Graphene-encapsulated yeast cells in harsh conditions.

Yeast, as a versatile microorganism, holds significant importance in various industries and research fields due to its remarkable characteristics. In the pursuit of biotechnological applications, cell-surface engineering including encapsulation has been proposed as a new strategy to interface with individual living yeast cells. While previous researches of yeast encapsulation with materials have shown promise, it often involves complex processes and lacks confirmation of condition-dependent yeast viability under harsh conditions. To address these issues, we present a rational and facile design for graphene-encapsulated yeast cells. Through a straightforward blending technique, yeast cells are encapsulated with graphene layers, demonstrating the unique properties of yeast cells in structural and functional aspects with graphene. We show graphene layer-dependent functions of yeast cells under various conditions, including pH and temperature-dependent conditions. The layer of graphene can induce the delayed lag time without the transfer of graphene-layered membrane. Our findings highlight the high potential of graphene-encapsulated yeast cells for various industrial applications, offering new avenues for exploration in biotechnology.

Rapid acoustofluidic mixing by ultrasonic surface acoustic wave-induced acoustic streaming flow.

Ultrasonic surface acoustic wave (SAW)-induced acoustic streaming flow (ASF) has been utilized for microfluidic flow control, patterning, and mixing. Most previous research employed cross-type SAW acousto-microfluidic mixers, in which the SAWs propagated perpendicular to the flow direction. In this configuration, the flow mixing was induced predominantly by the horizontal component of the acoustic force, which was usually much smaller than the vertical component, leading to energy inefficiency and limited controllability. Here, we propose a vertical-type ultrasonic SAW acousto-microfluidic mixer to achieve rapid flow mixing with improved efficiency and controllability. We conducted in-depth numerical and experimental investigations of the vertical-type SAW-induced ASF to elucidate the acousto-hydrodynamic phenomenon under varying conditions of total flow rate, acoustic wave amplitude, and fluid viscosity conditions. We conducted computational fluid dynamics simulations for numerical flow visualization and utilized micro-prism-embedded microchannels for experimental flow visualization for the vertical SAW-induced ASF. We found that the SAW-induced vortices served as a hydrodynamic barrier for the co-flow streams for controlled flow mixing in the proposed device. For proof-of-concept application, we performed chemical additive-free rapid red blood cell lysis and achieved rapid cell lysis with high lysis efficiency based on the physical interactions of the suspended cells with the SAW-induced acoustic vortical flows. We believe that the proposed vertical-type ultrasonic SAW-based mixer can be broadly utilized for various microfluidic applications that require rapid, controlled flow mixing.

Transplantable stem cell nanobridge scaffolds for accelerating articular cartilage regeneration.

Microfracture technique for treating articular cartilage defects usually has poor clinical outcomes due to critical heterogeneity and extremely limited in quality. To improve the effects of current surgical technique (i.e., microfracture technique), we propose the transplantable stem cell nanobridge scaffold, acting as a protective bridge between host tissue and defected cartilage as well as microfracture-derived cells. Nanobridge scaffolds have a sophisticated nanoaligned structure with freestanding and flexible shapes for imposing direct structural guidance to cells including transplanted stem cells and host cells, and it can induce not only chondrocyte migration but also stem cell differentiation, maturation, and growth factor secretion. The transplantable stem cell nanobridge scaffold is capable of reconstructing the defected cartilage with homogeneous architecture and highly enhanced adhesive stress similar with native cartilage tissue by the synergistic effects of stem cells-based chondro-induction and nanotopography-based chondro-conduction. Our findings demonstrate a significant advancement in the traditional treatment technique by using a nanoengineered tool for achieving successful cartilage regeneration.

Bioprinting Methods for Fabricating In Vitro Tubular Blood Vessel Models.

Dysfunctional blood vessels are implicated in various diseases, including cardiovascular diseases, neurodegenerative diseases, and cancer. Several studies have attempted to prevent and treat vascular diseases and understand interactions between these diseases and blood vessels across different organs and tissues. Initial studies were conducted using 2-dimensional (2D) in vitro and animal models. However, these models have difficulties in mimicking the 3D microenvironment in human, simulating kinetics related to cell activities, and replicating human pathophysiology; in addition, 3D models involve remarkably high costs. Thus, in vitro bioengineered models (BMs) have recently gained attention. BMs created through biofabrication based on tissue engineering and regenerative medicine are breakthrough models that can overcome limitations of 2D and animal models. They can also simulate the natural microenvironment in a patient- and target-specific manner. In this review, we will introduce 3D bioprinting methods for fabricating bioengineered blood vessel models, which can serve as the basis for treating and preventing various vascular diseases. Additionally, we will describe possible advancements from tubular to vascular models. Last, we will discuss specific applications, limitations, and future perspectives of fabricated BMs.

Engineering considerations of iPSC-based personalized medicine.

Personalized medicine aims to provide tailored medical treatment that considers the clinical, genetic, and environmental characteristics of patients. iPSCs have attracted considerable attention in the field of personalized medicine; however, the inherent limitations of iPSCs prevent their widespread use in clinical applications. That is, it would be important to develop notable engineering strategies to overcome the current limitations of iPSCs. Such engineering approaches could lead to significant advances in iPSC-based personalized therapy by offering innovative solutions to existing challenges, from iPSC preparation to clinical applications. In this review, we summarize how engineering strategies have been used to advance iPSC-based personalized medicine by categorizing the development process into three distinctive steps: 1) the production of therapeutic iPSCs; 2) engineering of therapeutic iPSCs; and 3) clinical applications of engineered iPSCs. Specifically, we focus on engineering strategies and their implications for each step in the development of iPSC-based personalized medicine.

Probing the Ion Transport Properties of Ultrashort Carbon Nanotubes Integrated with Supported Lipid Bilayers via Electrochemical Analysis.

Supported lipid bilayers (SLBs) are commonly used to investigate interactions between cell membranes and their environment. These model platforms can be formed on electrode surfaces and analyzed using electrochemical methods for bioapplications. Carbon nanotube porins (CNTPs) integrated with SLBs have emerged as promising artificial ion channel platforms. In this study, we present the integration and ion transport characterization of CNTPs in in vivo environments. We combine experimental and simulation data obtained from electrochemical analysis to analyze the membrane resistance of the equivalent circuits. Our results show that carrying CNTPs on a gold electrode results in high conductance for monovalent cations (K+ and Na+) and low conductance for divalent cations (Ca2+).

Graphene Hybrid Inner Ear Organoid with Enhanced Maturity.

Inner ear organoids (IEOs) are 3D structures grown in vitro, which can mimic the complex cellular structure and function of the inner ear. IEOs are potential solutions to problems related to inner ear development, disease modeling, and drug delivery. However, current approaches in generating IEOs using chemical factors have a few limitations, resulting in unpredictable outcomes. In this study, we propose the use of nanomaterial-based approaches, specifically by using graphene oxide (GO). GO's unique properties promote cell-extracellular matrix interactions and cell-cell gap junctions, thereby enhancing hair cell formation, which is an essential part of IEO development. We also investigated the potential applications for drug testing. Our findings suggest that GO is a promising candidate for enhancing the functionality of IEOs and advancing our understanding of the problems underlying inner ear development. The use of nanomaterial-based approaches may provide a more reliable and effective method for building better IEOs in the future.

Nanomaterial-Based Scaffolds for Tissue Engineering Applications: A Review on Graphene, Carbon Nanotubes and Nanocellulose.

Nanoscale biomaterials have garnered immense interest in the scientific community in the recent decade. This review specifically focuses on the application of three nanomaterials, i.e., graphene and its derivatives (graphene oxide, reduced graphene oxide), carbon nanotubes (CNTs) and nanocellulose (cellulose nanocrystals or CNCs and cellulose nanofibers or CNFs), in regenerating different types of tissues, including skin, cartilage, nerve, muscle and bone. Their excellent inherent (and tunable) physical, chemical, mechanical, electrical, thermal and optical properties make them suitable for a wide range of biomedical applications, including but not limited to diagnostics, therapeutics, biosensing, bioimaging, drug and gene delivery, tissue engineering and regenerative medicine. A state-of-the-art literature review of composite tissue scaffolds fabricated using these nanomaterials is provided, including the unique physicochemical properties and mechanisms that induce cell adhesion, growth, and differentiation into specific tissues. In addition, in vitro and in vivo cytotoxic effects and biodegradation behavior of these nanomaterials are presented. We also discuss challenges and gaps that still exist and need to be addressed in future research before clinical translation of these promising nanomaterials can be realized in a safe, efficacious, and economical manner.

Tissue-engineered tendon nano-constructs for repair of chronic rotator cuff tears in large animal models.

Chronic rotator cuff tears (RCTs) are one of the most common injuries of shoulder pain. Despite the recent advances in surgical techniques and improved clinical outcomes of arthroscopically repaired rotator cuffs (RCs), complete functional recovery-without retear-of the RC tendon through tendon-to-bone interface (TBI) regeneration remains a key clinical goal to be achieved. Inspired by the highly organized nanostructured extracellular matrix in RC tendon tissue, we propose herein a tissue-engineered tendon nano-construct (TNC) for RC tendon regeneration. When compared with two currently used strategies (i.e., transosseous sutures and stem cell injections), our nano-construct facilitated more significant healing of all parts of the TBI (i.e., tendon, fibrocartilages, and bone) in both rabbit and pig RCT models owing to its enhancements in cell proliferation and differentiation, protein expression, and growth factor secretion. Overall, our findings demonstrate the high potential of this transplantable tendon nano-construct for clinical repair of chronic RCTs.

Investigation of genetic variants and causal biomarkers associated with brain aging.

Delta age is a biomarker of brain aging that captures differences between the chronological age and the predicted biological brain age. Using multimodal data of brain MRI, genomics, and blood-based biomarkers and metabolomics in UK Biobank, this study investigates an explainable and causal basis of high delta age. A visual saliency map of brain regions showed that lower volumes in the fornix and the lower part of the thalamus are key predictors of high delta age. Genome-wide association analysis of the delta age using the SNP array data identified associated variants in gene regions such as KLF3-AS1 and STX1. GWAS was also performed on the volumes in the fornix and the lower part of the thalamus, showing a high genetic correlation with delta age, indicating that they share a genetic basis. Mendelian randomization (MR) for all metabolomic biomarkers and blood-related phenotypes showed that immune-related phenotypes have a causal impact on increasing delta age. Our analysis revealed regions in the brain that are susceptible to the aging process and provided evidence of the causal and genetic connections between immune responses and brain aging.