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.

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.

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.

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.

Novel Latent Heat Storage Systems Based on Liquid Metal Matrices with Suspended Phase Change Material Microparticles.

Phase change materials (PCMs) are considered useful tools for efficient thermal management and thermal energy utilization in various application fields. In this study, a colloidal PCM-in-liquid metal (LM) system is demonstrated as a novel platform composite with excellent latent heat storage capability, high thermal and electrical conductivities, and unique viscoelastic properties. In the proposed formulation, eutectic Ga-In is utilized as a high-thermal-conductivity and high-fluidity liquid matrix in which paraffinic PCM microparticles with various solid-liquid phase transition temperatures are suspended as fillers. Good compatibility between the fillers and matrix is achieved by the nanosized inorganic oxides (titania) adsorbed at the filler-matrix interface; thus, the composite is produced via simple vortex mixing without tedious pre- or post-processing. The composite shows unique trade-off effects among various properties, i.e., elastic modulus, yield stress, density, thermal conductivity, and melting or crystallization enthalpy, which can be easily controlled by varying the contents of the suspended fillers. A Joule heating device incorporating the composite exhibits improved electrothermal performance owing to the synergy between the high electrical conductivity and latent heat storage capability of the composite. The proposed platform may be exploited for the rational design and facile manufacture of high-performance form-factor-free latent heat storage systems for various potential applications such as battery thermal management and flexible heaters.

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.

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.

Eggshell membrane-incorporated cell friendly tough hydrogels with ultra-adhesive property.

Adhesive and tough hydrogels have received increased attention for their potential biomedical applications. However, traditional hydrogels have limited utility in tissue engineering because they tend to exhibit low biocompatibility, low adhesiveness, and poor mechanical properties. Herein, the use of the eggshell membrane (ESM) for developing tough, cell-friendly, and ultra-adhesive hydrogels is described. The ESM enhances the performance of the hydrogel network in three ways. First, its covalent cross-linking with the polyacrylamide and alginate chains strengthens the hydrogel network. Second, it provides functional groups, such as amine and carboxyl moieties, which are well known for enhancing the surface adhesion of biomaterials, thereby increasing the adhesiveness of the hydrogel. Third, it is a bioactive agent and improves cell adhesion and proliferation on the constructed scaffold. In conclusion, this study proposes the unique design of ESM-incorporated hydrogels with high toughness, cell-friendly, and ultra-adhesive properties for various biomedical engineering applications.

Therapeutic strategies of three-dimensional stem cell spheroids and organoids for tissue repair and regeneration.

Three-dimensional (3D) stem cell culture systems have attracted considerable attention as a way to better mimic the complex interactions between individual cells and the extracellular matrix (ECM) that occur in vivo. Moreover, 3D cell culture systems have unique properties that help guide specific functions, growth, and processes of stem cells (e.g., embryogenesis, morphogenesis, and organogenesis). Thus, 3D stem cell culture systems that mimic in vivo environments enable basic research about various tissues and organs. In this review, we focus on the advanced therapeutic applications of stem cell-based 3D culture systems generated using different engineering techniques. Specifically, we summarize the historical advancements of 3D cell culture systems and discuss the therapeutic applications of stem cell-based spheroids and organoids, including engineering techniques for tissue repair and regeneration.

Therapeutic Strategies and Enhanced Production of Stem Cell-Derived Exosomes for Tissue Regeneration.

Exosomes are nanovesicles surrounded by a plasma membrane and carry bioactive molecules (e.g., proteins, lipids, and nucleic acids) of the origin cell type. The bioactive molecules delivered by exosomes to the recipient cells have attracted considerable attention, as they play an important role in intercellular communication. Moreover, exosomes have unique properties, including the ability to penetrate the biological barrier with minimal immunogenicity and side effects, which can influence various physiological and pathological processes. Thus, exosomes are a promising therapeutic platform for various diseases (e.g., malignancies and allergies), as well as for the regeneration of damaged tissues. However, challenges of obtaining exosomes, such as complex extraction procedures, low yield, and difficulty in quantification are yet to be overcome, which limits the use of exosomes in clinical settings. In this review, we describe the state-of-the-art engineering techniques and strategies for highly efficient mass production of exosomes. Moreover, we discuss the functional aspects and potential therapeutic applications of stem cell-derived exosomes, and deliberate upon various engineering techniques and platform combinations for improved tissue regeneration by exosomes.

Engineering plants with carbon nanotubes: a sustainable agriculture approach.

Sustainable agriculture is an important conception to meet the growing food demand of the global population. The increased need for adequate and safe food, as well as the ongoing ecological destruction associated with conventional agriculture practices are key global challenges. Nanomaterials are being developed in the agriculture sector to improve the growth and protection of crops. Among the various engineered nanomaterials, carbon nanotubes (CNTs) are one of the most promising carbon-based nanomaterials owing to their attractive physiochemical properties such as small size, high surface area, and superior mechanical and thermal strength, offering better opportunities for agriculture sector applications. This review provides basic information about CNTs, including their history; classification; and electrical, thermal, and mechanical properties, with a focus on their applications in the agriculture field. Furthermore, the mechanisms of the uptake and translocation of CNTs in plants and their defense mechanisms against environmental stresses are discussed. Finally, the major shortcomings, threats, and challenges of CNTs are assessed to provide a broad and clear view of the potential and future directions for CNT-based agriculture applications to achieve the goal of sustainability.

Discovery of indirubin-3'-aminooxy-acetamide derivatives as potent and selective FLT3/D835Y mutant kinase inhibitors for acute myeloid leukemia.

Mutations in Fms-like tyrosine kinase 3 (FLT3) have been implicated in the pathogenesis of acute myeloid leukemia (AML) by affecting the proliferation and differentiation of hematopoietic stem and progenitor cells. Although several FLT3 inhibitors have been developed, the occurrence of secondary TKD mutations of FLT3 such FLT3/D835Y and FLT3/F691L lead to drug resistance and has become a key area of unmet medical needs. To overcome the obstacle of secondary TKD mutations, a new series of indirubin-3'-aminooxy-acetamide derivatives was discovered as potent and selective FLT3 and FLT3/D835Y inhibitors that were predicted to bind at the DFG-in active conformation of FLT3 in molecular docking studies. Through structure-activity relationship studies, the most optimized compound 13a was developed as a potent inhibitor at FLT3 and FLT3/D835Y with IC50 values of 0.26 nM and 0.18 nM, respectively, which also displayed remarkably strong in vitro anticancer activities, with single-digit nanomolar GI50 values for several AML (MV4-11 and MOLM14) and Ba/F3 cell lines expressed with secondary TKD mutated FLT3 kinases as well as FLT3-ITD. The selectivity profiles of compound 13a in the oncology kinase panel and various human cancer cell lines were prominent, demonstrating that its inhibitory activities were mainly focused on a few members of the receptor tyrosine kinase family and AML versus solid tumor cell lines. Furthermore, significant in vivo anticancer efficacy of compound 13a was confirmed in a xenograft animal model implanted with FLT3-ITD/D835Y-expressing MOLM-14 cells related to secondary TKD mutation.

Biodegradable and Flexible Nanoporous Films for Design and Fabrication of Active Food Packaging Systems.

Nanotechnology has facilitated the development of active food packaging systems with functions that could not be achieved by their traditional counterparts. Such smart and active systems can improve the shelf life of perishable products and overcome major bottlenecks associated with the fabrication of safe and environmentally friendly food packaging systems. Herein, we used a plasma-enabled surface modification strategy to fabricate biodegradable and flexible nanoporous polycaprolactone-based (FNP) films for food packaging systems. Their capacity for preserving tomatoes, tangerines, and bananas at room and refrigeration temperatures was tested by analyzing various fruit parameters (mold generation, appearance changes, freshness, weight loss, firmness, and total soluble solids contents). Compared with commonly used polyethylene terephthalate-based containers, the proposed system enhanced the fruit storage quality (i.e., retained appearance, reduced weight loss, better firmness, and sugar contents) by controlling moisture evaporation and inhibiting mold generation. Thus, the FNP film represents a new active food packaging strategy.

A Freezing and Thawing Method for Fabrication of Small Gelatin Nanoparticles with Stable Size Distributions for Biomedical Applications.

BACKGROUND: Gelatin, a natural polymer, has a number of advantages as a material for fabricating nanoparticles, such as its hydrophilicity, biodegradability, nontoxicity, and biocompatibility, as well as low cost. Despite these various advantages, gelatin-based nanoparticles still have critical limitation for biomedical applications due to their relatively larger size than those of other materials. METHODS: In this study, a new strategy to design and fabricate small gelatin nanoparticles (GNPs) was proposed. The technique was based on the natural phenomenon where with decreasing temperature, the compression between the molecules of substances increases and the volume shrinks. RESULTS: The average size of the fabricated small GNPs was less than 100 nm and their gelatin properties (including non-cytotoxicity) were well maintained. The drug release profiles of the GNPs were confirmed, for which a simple mathematical model based on the conventional diffusion equation was proposed. There was a burst of drug release in the first 3 days, with different release profiles according to the concentration of model drugs loaded onto the GNPs. It was also demonstrated that the drug release profiles of the proposed mathematical model were consistent with the experimental results. CONCLUSION: Our work proposes that these small GNPs could be used as efficient drug and gene delivery and tissue engineering platforms for various biomedical applications.

Synthesis and structure-activity relationship studies of 1,5-isomers of triazole-pyrrolopyrimidine as selective Janus kinase 1 (JAK1) inhibitors.

JAK inhibitors have been considered as useful targets for the treatment of related diseases. However, first-generation JAK inhibitors have side effects such as anemia, thrombocytopenia, neutropenia and headaches which have been suggested to result from high JAK2 inhibition. Second-generation JAK inhibitors with more specific JAK isozyme inhibition have been studied to eliminate these adverse effects. In this study, novel 4-(1,5- or 2,5-triazole)-pyrrolopyrimidine derivatives with aromatic moieties were synthesized as JAK1 inhibitors, and an in vitro enzyme assay was used to evaluate the JAK inhibitory effects. Among these JAK1 inhibitors, the compound 23a showed an IC50 level of 72 nM, as well as being selective against other JAKs by 12 times or more: the results of molecular docking studies suggested that the high JAK1 selectivity resulted from a key interaction between the iodine atom of compound 23a and His-885 of hJAK1.

An Indexing Method of Continuous Spatiotemporal Queries for Stream Data Processing Rules of Detected Target Objects.

Real-time performance is important in rule-based continuous spatiotemporal query processing for risk analysis and decision making of target objects collected by sensors of combat vessels. The existing Rete algorithm, which creates a compiled node link structure for executing rules, is known to be the best. However, when a large number of rules are to be processed and the stream data to be performed are large, the Rete technique has an overhead of searching for rules to be bound. This paper proposes a hashing indexing technique for Rete nodes to the overhead of searching for spatiotemporal condition rules that must be bound when rules are expressed in a node link structure. A performance comparison evaluation experiment was conducted with Drool, which implemented the Rete method, and the method that implemented the hash index method presented in this paper. For performance measurement, processing time was measured for the change in the number of rules, the change in the number of objects, and the distribution of objects. The hash index method presented in this paper improved performance by at least 18% compared to Drool.

Observability Study on Passive Target Localization by Conic-Angle Measurements.

Information from a passive linear array sensor is related to the conic angle formed by a target and the sensor in three-dimensional (3D) space so that the target localization system using the sensor should be also designed in 3D space. This paper presents an observability study of a passive target localization system created using conic angle information. The study includes the analysis of the sensor maneuver requirement needed to achieve system observability and simulations to demonstrate the results of the analytic scheme. The proposed sensor maneuver requirements satisfy the system observability conditions by using the local linearization approach of the Fisher information matrix. It is also shown that this requirement can be mitigated for special cases in which the depth difference between the sensor and the target is given. Using the simulation, it is shown that sensors following the proposed scheme are able to obtain meaningful information that can be used to estimate 3D target states.

Plasma-assisted multiscale topographic scaffolds for soft and hard tissue regeneration.

The design of transplantable scaffolds for tissue regeneration requires gaining precise control of topographical properties. Here, we propose a methodology to fabricate hierarchical multiscale scaffolds with controlled hydrophilic and hydrophobic properties by employing capillary force lithography in combination with plasma modification. Using our method, we fabricated biodegradable biomaterial (i.e., polycaprolactone (PCL))-based nitrogen gas (N-FN) and oxygen gas plasma-assisted flexible multiscale nanotopographic (O-FMN) patches with natural extracellular matrix-like hierarchical structures along with flexible and controlled hydrophilic properties. In response to multiscale nanotopographic and chemically modified surface cues, the proliferation and osteogenic mineralization of cells were significantly promoted. Furthermore, the O-FMN patch enhanced regeneration of the mineralized fibrocartilage tissue of the tendon-bone interface and the calvarial bone tissue in vivo in rat models. Overall, the PCL-based O-FMN patches could accelerate soft- and hard-tissue regeneration. Thus, our proposed methodology was confirmed as an efficient approach for the design and manipulation of scaffolds having a multiscale topography with controlled hydrophilic property.

Rebirth of the Eggshell Membrane as a Bioactive Nanoscaffold for Tissue Engineering.

Eggshell membrane (ESM)-based biomaterials have generated significant interest for their potential biomedical applications, including those in tissue engineering and regenerative medicine. Herein, the development of a bioactive ESM-based nanopatterned scaffold for enhancing the adhesion and functions of cells has been described. To control the shape of the raw ESM with entangled protein fibers, a two-step dissolution technique is used. Subsequently, nanoimprint lithography is applied to the ESM solution to fabricate scaffolds with a nanotopographic surface inspired by the fiber alignment of the extracellular matrix. In this way, the morphology and proliferation of attached osteoblasts are sensitively controlled through their response to the nanopatterned topography of the prepared scaffold, allowing significant improvements in their osteogenic differentiation and growth factor secretion. This study demonstrates the potential use of this bioactive ESM-based nanopatterned substrate as an effective cell and tissue engineering scaffold.