The surface topography of substrates is a crucial factor that determines the interaction with biological materials in bioengineering research. Therefore, it is important to appropriately modify the surface topography according to the research purpose. Surface topography can be fabricated in various forms, such as wrinkles, creases, and ridges using surface deformation techniques, which can contribute to the performance enhancement of cell chips, organ chips, and biosensors. This review provides a comprehensive overview of the characteristics of soft, hard, and hybrid substrates used in the bioengineering field and the surface deformation techniques applied to the substrates. Furthermore, this review summarizes the cases of cell-based research and other applications, such as biosensor research, that utilize surface deformation techniques. In cell-based research, various studies have reported optimized cell behavior and differentiation through surface deformation, while, in the biosensor and biofilm fields, performance improvement cases due to surface deformation have been reported. Through these studies, we confirm the contribution of surface deformation techniques to the advancement of the bioengineering field. In the future, it is expected that the application of surface deformation techniques to the real-time interaction analysis between biological materials and dynamically deformable substrates will increase the utilization and importance of these techniques in various fields, including cell research and biosensors.

In this study, we created a 3D Artificial Skin Platform that can be used for the treatment of pigmentation by artificially realizing the skin of pregnant women. For the stable realization of 3D artificial skin, a bilayer hydrogel composed of collagen type I and fibrin was designed and applied to the study to reduce the tension-induced contraction of collagen type I, the extracellular matrix (ECM) of artificial skin, by dynamic culture. Oxygen concentration and 17β-Estradiol (E2) concentration, which are highly related to melanin production, were selected as parameters of the pregnancy environment and applied to cell culture. Oxygen concentration, which is locally reduced in the first trimester (2.5–3%), and E2, which is upregulated in the third trimester, were applied to the cell culture process. We analyzed whether the 3D artificial skin implemented in the 3D Artificial Skin Platform could better represent the tendency of melanin expression in pregnant women than cells cultured under the same conditions in 2D. The expression levels of melanin and melanin-related genes in the 2D cell culture did not show a significant trend that was similar to the melanin expression trend in pregnant women. However, the 3D artificial skin platform showed a significant trend towards a 2-6-fold increase in melanin expression in response to low oxygen concentrations (2.5%) and E2 concentrations (17 ng/mL), which was similar to the trend in pregnant women in vivo. These results suggest that 3D artificial skin cultured on the Artificial Skin Platform has the potential to be used as a substitute for human pregnant skin in various research fields related to the treatment of pigmentation.

The development of therapeutic interventions for diseases necessitates a crucial step known as drug screening, wherein potential substances with medicinal properties are rigorously evaluated. This process has undergone a transformative evolution, driven by the imperative need for more efficient, rapid, and high-throughput screening platforms. Among these, microfluidic systems have emerged as the epitome of efficiency, enabling the screening of drug candidates with unprecedented speed and minimal sample consumption. This review paper explores the cutting-edge landscape of microfluidic-based drug screening platforms, with a specific emphasis on two pioneering approaches: organ-on-a-chip and C. elegans-based chips. Organ-on-a-chip technology harnesses human-derived cells to recreate the physiological functions of human organs, offering an invaluable tool for assessing drug efficacy and toxicity. In parallel, C. elegans-based chips, boasting up to 60% genetic homology with humans and a remarkable affinity for microfluidic systems, have proven to be robust models for drug screening. Our comprehensive review endeavors to provide readers with a profound understanding of the fundamental principles, advantages, and challenges associated with these innovative drug screening platforms. We delve into the latest breakthroughs and practical applications in this burgeoning field, illuminating the pivotal role these platforms play in expediting drug discovery and development. Furthermore, we engage in a forward-looking discussion to delineate the future directions and untapped potential inherent in these transformative technologies. Through this review, we aim to contribute to the collective knowledge base in the realm of drug screening, providing valuable insights to researchers, clinicians, and stakeholders alike. We invite readers to embark on a journey into the realm of microfluidic-based drug screening platforms, fostering a deeper appreciation for their significance and promising avenues yet to be explored.

Placental trophoblast invasion is critical for establishing the maternal–fetal interface, yet the mechanisms driving trophoblast-induced maternal arterial remodeling remain elusive. To address this gap, we developed a three-dimensional microfluidic placenta-on-chip model that mimics early pregnancy placentation in a hypoxic environment. By studying human umbilical vein endothelial cells (HUVECs) under oxygen-deprived conditions upon trophoblast invasion, we observed significant HUVEC artery remodeling, suggesting the critical role of hypoxia in placentation. In particular, we found that trophoblasts secrete matrix metalloproteinase (MMP) proteins under hypoxic conditions, which contribute to arterial remodeling by the degradation of extracellular matrix components. This MMP-mediated remodeling is critical for facilitating trophoblast invasion and proper establishment of the maternal–fetal interface. In addition, our platform allows real-time monitoring of HUVEC vessel contraction during trophoblast interaction, providing valuable insights into the dynamic interplay between trophoblasts and maternal vasculature. Collectively, our findings highlight the importance of MMP-mediated arterial remodeling in placental development and underscore the potential of our platform to study pregnancy-related complications and evaluate therapeutic interventions.

Liposomeshave been extensively adopted in drug delivery systemswith clinically approved formulations. However, hurdles remain interms of loading multiple components and precisely controlling theirrelease. Herein, we report a vesosomal carrier composed of liposomesencapsulated inside the core of another liposome for the controlledand sustained release of multiple contents. The inner liposomes aremade of lipids with different compositions and are co-encapsulatedwith a photosensitizer. Upon induction of reactive oxygen species(ROS), the contents of the liposomes are released, with each typeof liposome displaying distinct kinetics due to the variance in lipidperoxidation for differential structural deformation. In vitro experimentsdemonstrated immediate content release from ROS-vulnerable liposomes,followed by sustained release from ROS-nonvulnerable liposomes. Moreover,the release trigger was validated at the organismal level using Caenorhabditis elegans. This study demonstrates apromising platform for more precisely controlling the release of multiplecomponents.

AbstractMiniaturized untethered soft robots are recently exploited to imitate multi‐modal curvilinear locomotion of living creatures that perceive change of surrounding environments. Herein, the use of Caenorhabditis elegans (C. elegans) is proposed as a microscale model capable of curvilinear locomotion with mechanosensing, controlled by magnetically reconfigured 3D microtopography. Static entropic microbarriers prevent C. elegans from randomly swimming with the omega turns and provide linear translational locomotion with velocity of ≈0.14 BL s−1. This velocity varies from ≈0.09 (for circumventing movement) to ≈0.46 (for climbing) BL s−1, depending on magnetic bending and twisting actuation coupled with assembly of microbarriers. Furthermore, different types of neuronal mutants prevent C. elegans from implementing certain locomotion modes, indicating the potential for investigating the correlation between neurons and mechanosensing functions. This strategy promotes a platform for the contactless manipulation of miniaturized biobots and initiates interdisciplinary research for investigating sensory neurons and human diseases.

Caenorhabditis elegans Caenorhabditis elegans selectively performs multi-modal locomotion modes including linear translation, navigating movement, circumventing movement, and climbing determined by magnetically twisted, bent, and assembled three-dimensional microtopography. More details can be found in article number 2203396 by Seung Goo Lee, Sun Min Kim, Jeong Jae Wie, and co-workers.

C. elegans is an attractive model organism, especially for neural system studies as it is the simplest organism with a nervous system. Moreover, the worm has interesting behavioral responses to various external physical and chemical stimuli. In the past few decades, numerous studies have been performed on the behavioral response of C. elegans using a micro system platform. Hence, the results of these studies found several applications such as drug screening. In this chapter, we describe various micro systems for the analysis of the behavioral responses of C. elegans to various external stimuli. However, we mainly focus on thermotaxis in micro systems. We divided this chapter into two major parts. In the first part, we briefly discuss the behavioral responses of C. elegans to various physical and chemical stimuli. In the second part, we summarize the microfluidic platform used for the behavioral response analysis of C. elegans.

Mechanical vibration is a key external stimulus of living organisms. In previous studies, mechanical vibration has been found to affect the proliferation and differentiation of cells. However, there have been few reports of similar effects at the organismal scale. In this study, we demonstrated the effect of mechanical vibration on the growth and activity of Caenorhabditis elegans in the embryonic stage. The group of worms that were exposed to mechanical vibration during the embryonic period grew faster than the control group of worms. The growth of all groups was compared by measuring body length. Furthermore, we investigated the mechanical vibration effects in two types of mutants: body wall mechanosensory-abnormal mutants (mec-4(e1339)) and head mechanosensory-defective mutants (trp-4(sy695)). The mec-4(e1339) mutant was not affected by mechanical vibration during growth. On the other hand, the trp-4(sy695) mutant exposed to mechanical vibration showed a difference in growth compared with the control group, similar to wild-type worms. Therefore, mechanical vibration during the early developmental period of C. elegans affects the growth and activity of worms. Additionally, we observed a relationship between the gastrulation period and the mechanosensory system development of the worms. This study will serve as the basis for analyzing the effects of mechanical vibration on the developmental stages of C. elegans.

In biological cells, membrane proteins are the most crucial component for the maintenance of cell physiology and processes, including ion transportation, cell signaling, cell adhesion, and recognition of signal molecules. Therefore, researchers have proposed a number of membrane platforms to mimic the biological cell environment for transmembrane protein incorporation. The performance and selectivity of these transmembrane proteins based biomimetic platforms are far superior to those of traditional material platforms, but their lack of stability and scalability rule out their commercial presence. This review highlights the development of transmembrane protein-based biomimetic platforms for four major applications, which are biosensors, molecular interaction studies, energy harvesting, and water purification. We summarize the fundamental principles and recent progress in transmembrane protein biomimetic platforms for each application, discuss their limitations, and present future outlooks for industrial implementation.

Vibration is an important physical stimulus to living organisms. Previous studies have focused on the mechanical vibration effects on cells, as either a factor of promotion or inhibition. However, there have been few studies on this effect at the organism scale. Some studies have shown only the behavior response of a model organism, such as C. elegans, to vibration. In this study, we demonstrate the vibration effect on the embryonic period of C. elegans. Vibration was found to affect growth promotion and gene expression. Furthermore, we obtained results for the wild-type (N2) and sur-5::gfp mutant of C. elegans. We expect this investigation to provide a foundation for various future vibration effect studies on C. elegans.

C. elegans is a popular model organism with a well-developed neural network. Approximately 60% of the genes in C. elegans have genomic counterparts in humans, including those involved in building neural circuits. Therefore, we can extend the study of human neural network mechanisms to C. elegans which is easy to genetically manipulate. C. elegans shows behavioural responses to various external physical and chemical stimuli. Electrotaxis is one of its distinct behavioural responses, which is defined as movement towards the cathode in an electric field. In this study, we developed an effective microfluidic trap system for analysing electrotaxis in C. elegans. In addition, two mutant strains (unc-54(s74) and unc-6(e78)) from wild-type (N2) worms were screened using the system. Wild-type (N2) worms and the two mutant strains clearly showed different behavioural responses to the applied electric field, thus enabling the effective screening of the mutant worms from the wild type (N2). This microfluidic system can be utilized as a platform for the study of behavioural responses, and for the sorting and mutant screening of C. elegans.

Caenorhabditis elegans ( C. elegans ), which shares a considerable amount of characteristics with human genes is one of the important model organisms for the study of behavioral responses. Thermotaxis is a representative behavior response of C. elegans; C. elegans stores the cultivation temperature in thermosensory neurons and moves to the cultivation temperature region in a temperature variation. In this study, we developed a microfluidic system for effective thermotaxis analysis of C. elegans . The microfluidic channel was fabricated using polydimethylsiloxane (PDMS) by soft lithography process. The temperature gradient (15–20°C) was generated in the microchannel and controlled by Peltier modules attached to the bottom of the channel. The thermotaxis of wild type (N2), tax-4(p678) and ttx-7(nj50) mutants were effectively analyzed using this microfluidic system. We believe that this system can be employed as a basic platform for studying the neural circuit of C. elegans responding to external stimuli.

An artificial lipid bilayer, or black lipid membrane (BLM), is a powerful tool for studying ion channels and protein interactions, as well as for biosensor applications. However, conventional BLM formation techniques have several drawbacks and they often require specific expertise and laborious processes. In particular, conventional BLMs suffer from low formation success rates and inconsistent membrane formation time. Here, we demonstrate a storable and transportable BLM formation system with controlled thinning-out time and enhanced BLM formation rate by replacing conventionally used films (polytetrafluoroethylene, polyoxymethylene, polystyrene) to polydimethylsiloxane (PDMS). In this experiment, a porous-structured polymer such as PDMS thin film is used. In addition, as opposed to conventionally used solvents with low viscosity, the use of squalene permitted a controlled thinning-out time via slow solvent absorption by PDMS, prolonging membrane lifetime. In addition, by using a mixture of squalene and hexadecane, the freezing point of the lipid solution was increased (~16 °C), in addition, membrane precursors were produced that can be indefinitely stored and readily transported. These membrane precursors have reduced BLM formation time of < 1 hr and achieved a BLM formation rate of ~80%. Moreover, ion channel experiments with gramicidin A demonstrated the feasibility of the membrane system.

Caenorhabditis elegans (C.elegans) is a significant model organism due to its various behavioral properties, such as electrotaxis, thermotaxis, and chemotaxis. C.elegans can detect various physical and chemical stimuli through special neurons and transform sensory detections as behavioral responses. In addition, as C.elegans share over 60% of genes with human, including neural circuit genes, elucidating C.elegans behavioral property can provide clues for understanding human neural circuit. In this research, we propose a microfluidic system with electric field as stimulus to analyze behavioral response of C.elegans. To test our system, we compared electrotaxis response of wild type worm (N2) and two mutant worms (BC347, CB78) and showed feasibility of our system for analyzing behavioral response of C.elegans. We believe that our stimulus system provide gold standards for studying human neural circuit through C.elegans.