Search Results (57)

Breast cancers can appear and progress rapidly, necessitating more frequent monitoring outside of hospital settings to significantly reduce mortality rates. Recently, there has been considerable interest in developing techniques for portable, user-friendly, and low-cost breast tumor monitoring applications, enabling frequent and cost-efficient examinations. Microwave technique-based breast cancer detection, which is based on differential dielectric properties of malignant and healthy tissues, is regarded as a promising solution for cost-effective breast tumor monitoring. This paper presents the development process of the first proof-of-concept of a breast tumor monitoring vest which is based on the microwave technique. Two unique vests are designed and evaluated on realistic 3D human tissue phantoms having different breast density types. Additionally, the measured results are verified using simulations carried out on anatomically realistic voxel models of the electromagnetic simulations. The radio channel characteristics are evaluated and analyzed between the antennas embedded in the vest in tumor cases and reference cases. Both measurements and simulation results show that the proposed vest can detect tumors even if only 1 cm in diameter. Additionally, simulation results show detectability with 0.5 cm tumors. It is observed that the detectability of breast tumors depends on the frequency, antenna selection, size of the tumors, and breast types, causing differences of 0.5–30 dB in channel responses between the tumorous and reference cases. Due to simplicity and cost-efficiency, the proposed channel analysis-based breast monitoring vests can be used for breast health checks in smaller healthcare centers and for user-friendly home monitoring which can prove beneficial in rural areas and developing countries. Full article

Three-dimensional cell culture spheroids are commonly used for drug evaluation studies because they can produce large quantities of homogeneous cell aggregates. As the spheroids grow, nutrients supplied from outer spheroid regions render the inner spheroid areas hypoxic and hyponutrient, which makes them unobservable through confocal microscopy. In this study, we fabricated a cancer cell aggregate culture device that facilitates the observation of nutrient and oxygen gradients. An alginate gel fiber was created in the cell culture chamber to ensure a flow path for supplying the culture medium. A gradient of nutrients and oxygen was generated by positioning the flow channel close to the edge of the chamber. We devised a fabrication method that uses calcium carbonate as a source of Ca²⁺ for the gelation of sodium alginate, which has a slow reaction rate. We then cultured a spheroid of HCT116 cells, which were derived from human colorectal carcinoma using a fluorescent ubiquitination-based cell cycle indicator. Fluorescence observation suggested the formation of a hypoxic and hyponutrient region within an area approximately 500 µm away from the alginate gel fiber. This indicates the development of a cancer cell aggregate culture device that enables the observation of different nutrition and oxygen states. Full article

The development of biomaterials for protein delivery is an emerging field that spans materials science, bioengineering, and medicine. In this review, we highlight the immense potential of protein-delivering biomaterials as therapeutic options and discuss the multifaceted challenges inherent to the field. We address current advancements and approaches in protein delivery that leverage stimuli-responsive materials, harness advanced fabrication techniques like 3D printing, and integrate nanotechnologies for greater targeting and improved stability, efficacy, and tolerability profiles. We also discuss the demand for highly complex delivery systems to maintain structural integrity and functionality of the protein payload. Finally, we discuss barriers to clinical translation, such as biocompatibility, immunogenicity, achieving reliable controlled release, efficient and targeted delivery, stability issues, scalability of production, and navigating the regulatory landscape for such materials. Overall, this review summarizes insights from a survey of the current literature and sheds light on the interplay between innovation and the practical implementation of biomaterials for protein delivery. Full article

Creating model systems that replicate in vivo tissues is crucial for understanding complex biological pathways like drug response and disease progression. Three-dimensional (3D) in vitro models, especially multicellular spheroids (MCSs), offer valuable insights into physiological processes. However, generating MCSs at scale with consistent properties and efficiently recovering them pose challenges. We introduce a workflow that automates large-scale spheroid production and enables parallel harvesting into individual wells of a microtiter plate. Our method, based on the hanging-drop technique, utilizes a non-contact dispenser for dispensing nanoliter droplets of a uniformly mixed-cell suspension. The setup allows for extended processing times of up to 45 min without compromising spheroid quality. As a proof of concept, we achieved a 99.3% spheroid generation efficiency and maintained highly consistent spheroid sizes, with a coefficient of variance below 8% for MCF7 spheroids. Our centrifugation-based drop transfer for spheroid harvesting achieved a sample recovery of 100%. We successfully transferred HT29 spheroids from hanging drops to individual wells preloaded with collagen matrices, where they continued to proliferate. This high-throughput workflow opens new possibilities for prolonged spheroid cultivation, advanced downstream assays, and increased hands-off time in complex 3D cell culture protocols. Full article

Three-dimensionally printed phantoms are increasingly used in medical imaging and research due to their cost-effectiveness and customizability, offering valuable alternatives to commercial phantoms. The purpose of this study was to assess the computed tomography (CT) attenuation characteristics of 27 resin materials from Formlabs, a 3D printing equipment and materials manufacturer. Cube phantoms (both solid and hollow constructions) produced with each resin were subjected to CT scanning under varying tube current–time products with attenuation measurements recorded in Hounsfield units (HU). The resins exhibited a wide range of attenuation values (−3.33 to 2666.27 HU), closely mimicking a range of human tissues, from fluids to dense bone structures. The resins also demonstrated consistent attenuation regardless of changes in the tube current. The CT attenuation analysis of FormLabs resins produced an archive of radiological imaging characteristics of photopolymers that can be utilized to construct more accurate tissue mimicking medical phantoms and improve the evaluation of imaging device performance. Full article

Microcontact printing (CP) is widely used to guide neurons to form 2D networks for neuroscience research. However, it is still difficult to establish 3D neuronal cultures on the CP substrate even though 3D neuronal structures are able to recapitulate critical aspects of native tissue. Here, we demonstrate that the reduced cell-substrate adhesion caused by the CP substrate could conveniently facilitate the aggregate formation of large-scale 3D neuron cluster networks. Furthermore, based on the quantitative analysis of the calcium activity of the resulting cluster networks, the effect of cell seeding density and local restriction of the CP substrate on network dynamics was investigated in detail. The results revealed that cell aggregation degree, rather than cell number, could take on the main role of the generation of synchronized network-wide calcium oscillation (network bursts) in the 3D neuron cluster networks. This finding may provide new insights for easy and cell-saving construction of in vitro 3D pathological models of epilepsy, and into deciphering the onset and evolution of network bursts in developmental nerve systems. Full article

Myocyte-driven robots, a type of biological actuator that combines myocytes with abiotic systems, have gained significant attention due to their high energy efficiency, sensitivity, biocompatibility, and self-healing capabilities. These robots have a unique advantage in simulating the structure and function of human tissues and organs. This review covers the research progress in this field, detailing the benefits of myocyte-driven robots over traditional methods, the materials used in their fabrication (including myocytes and extracellular materials), and their properties and manufacturing techniques. Additionally, the review explores various control methods, robot structures, and motion types. Lastly, the potential applications and key challenges faced by myocyte-driven robots are discussed and summarized. Full article

Cellular response to mechanical stimuli is a crucial factor for maintaining cell homeostasis. The interaction between the extracellular matrix and mechanical stress plays a significant role in organizing the cytoskeleton and aligning cells. Tools that apply mechanical forces to cells and tissues, as well as those capable of measuring the mechanical properties of biological cells, have greatly contributed to our understanding of fundamental mechanobiology. These tools have been extensively employed to unveil the substantial influence of mechanical cues on the development and progression of various diseases. In this report, we present an economical and high-performance uniaxial cell stretching device. This paper reports the detailed operation concept of the device, experimental design, and characterization. The device was tested with MDA-MB-231 breast cancer cells. The experimental results agree well with previously documented morphological changes resulting from stretching forces on cancer cells. Remarkably, our new device demonstrates comparable cellular changes within 30 min compared with the previous 2 h stretching duration. This third-generation device significantly improved the stretching capabilities compared with its previous counterparts, resulting in a remarkable reduction in stretching time and a substantial increase in overall efficiency. Moreover, the device design incorporates an open-source software interface, facilitating convenient parameter adjustments such as strain, stretching speed, frequency, and duration. Its versatility enables seamless integration with various optical microscopes, thereby yielding novel insights into the realm of mechanobiology. Full article

One of the advantages of human stem cell-derived cell-based preclinical screening is the reduction of the false negative/positive misjudgment of lead compounds for predicting their effectiveness and risks during the early stage of development. However, as the community effect of cells was neglected in the conventional single cell-based in vitro screening, the potential difference in results caused by the cell number and their spatial arrangement differences has not yet been sufficiently evaluated. Here, we have investigated the effect of the community size and spatial arrangement difference for cardiomyocyte network response against the proarrhythmic compounds from the viewpoint of in vitro cardiotoxicity. Using three different typical types of cell networks of cardiomyocytes, small cluster, large square sheet, and large closed-loop sheet were formed in shaped agarose microchambers fabricated on a multielectrode array chip simultaneously, and their responses were compared against the proarrhythmic compound, E-4031. The interspike intervals (ISIs) in large square sheets and closed-loop sheets were durable and maintained stable against E-4031 even at a high dose of 100 nM. In contrast, those in the small cluster, which fluctuated even without E-4031, acquired stable beating reflecting the antiarrhythmic efficacy of E-4031 from a 10 nM medium dose administration. The repolarization index, field potential duration (FPD), was prolonged in closed-loop sheets with 10 nM E-4031, even though small clusters and large sheets remained normal at this concentration. Moreover, FPDs of large sheets were the most durable against E-4031 among the three geometries of cardiomyocyte networks. The results showed the apparent spatial arrangement dependence on the stability of their interspike intervals, and FPD prolongation, indicating the importance of the geometry control of cell networks for representing the appropriate response of cardiomyocytes against the adequate amount of compounds for in vitro ion channel measurement. Full article

Light-based bioprinter manufacturing technology is still prohibitively expensive for organizations that rely on accessing three-dimensional biological constructs for research and tissue engineering endeavors. Currently, most of the bioprinting systems are based on commercial-grade-based systems or modified DIY (do it yourself) extrusion apparatuses. However, to date, few examples of the adoption of low-cost equipment have been found for light-based bioprinters. The requirement of large volumes of bioinks, their associated cost, and the lack of information regarding the parameter selection have undermined the adoption of this technology. This paper showcases the retrofitting and assessing of a low-cost Light-Based 3D printing system for tissue engineering. To evaluate the potential of a proposed design, a manufacturability test for different features, machine parameters, and Gelatin Methacryloyl (GelMA) concentrations for 7.5% and 10% was performed. Furthermore, a case study of a previously seeded hydrogel with C2C12 cells was successfully implemented as a proof of concept. On the manufacturability test, deviational errors were found between 0.7% to 13.3% for layer exposure times of 15 and 20 s. Live/Dead and Actin-Dapi fluorescence assays after 5 days of culture showed promising results in the cell viability, elongation, and alignment of 3D bioprinted structures. The retrofitting of low-cost equipment has the potential to enable researchers to create high-resolution structures and three-dimensional in vitro models. Full article

To simulate the ADME process such as absorption, distribution, metabolism, and excretion in the human body after drug administration and to confirm the applicability of the mass production process, a microfluidic chip injection molded with polycarbonate (injection-molded chip (I-M chip)) was fabricated. Polycarbonate materials were selected to minimize drug absorption. As a first step to evaluate the I-M chip, RPTEC (Human Renal Proximal Tubule Epithelial Cells) and HUVEC (Human Umbilical Vein Endothelial Cells) were co-cultured, and live and dead staining, TEER (trans-epithelial electrical resistance), glucose reabsorption, and permeability were compared using different membrane pore sizes of 0.4 μm and 3 μm. Drug excretion was confirmed through a pharmacokinetic test with metformin and cimetidine, and the gene expression of drug transporters was confirmed. As a result, it was confirmed that the cell viability was higher in the 3 μm pore size than in the 0.4 μm, the cell culture performed better, and the drug secretion was enhanced when the pore size was large. The injection-molded polycarbonate microfluidic chip is anticipated to be commercially viable for drug screening devices, particularly ADME tests. Full article

Fabrication of three-dimensional tissues using living cells is a promised approach for drug screening experiment and in vitro disease modeling. To study a physiological neuronal function, three-dimensional cell patterning and construction of neuronal cell network were required. In this study, we proposed a three-dimensional cell drawing methodology in hydrogel to construct the three-dimensional neuronal cell network. PC-12 cells, which were used as neuronal cell differentiation model, were dispensed into a collagen hydrogel using a micro injector with a three-dimensional position control. To maintain the three-dimensional position of cells, atelocollagen was kept at sol-gel transition state during cell dispensing. As the results, PC-12 cells were patterned in the atelocollagen gel to form square pattern with different depth. In the patterned cellular lines, PC-12 cells elongated neurites and form a continuous cellular network in the atelocollagen gel. It was suggested that our three-dimensional cell drawing technology has potentials to reconstruct three-dimensional neuronal networks for an investigation of physiological neuronal functions. Full article

3D bioprinting has emerged as a tool for developing in vitro tissue models for studying disease progression and drug development. The objective of the current study was to evaluate the influence of flow driven shear stress on the viability of cultured cells inside the luminal wall of a serpentine network. Fluid–structure interaction was modeled using COMSOL Multiphysics for representing the elasticity of the serpentine wall. Experimental analysis of the serpentine model was performed on the basis of a desirable inlet flow boundary condition for which the most homogeneously distributed wall shear stress had been obtained from numerical study. A blend of Gelatin-methacryloyl (GelMA) and PEGDA200 PhotoInk was used as a bioink for printing the serpentine network, while facilitating cell growth within the pores of the gelatin substrate. Human umbilical vein endothelial cells were seeded into the channels of the network to simulate the blood vessels. A Live-Dead assay was performed over a period of 14 days to observe the cellular viability in the printed vascular channels. It was observed that cell viability increases when the seeded cells were exposed to the evenly distributed shear stresses at an input flow rate of 4.62 mm/min of the culture media, similar to that predicted in the numerical model with the same inlet boundary condition. It leads to recruitment of a large number of focal adhesion point nodes on cellular membrane, emphasizing the influence of such phenomena on promoting cellular morphologies. Full article

Bioactuators have been developed in many studies in the recent decade for actuators of micro-biorobots. However, bioactuators have not shown the same power as animal muscles. Centrifugal force was used in this study to increase the cell density of cultured muscle cells that make up the bioactuator. The effect of the centrifugal force on cells in the matrix gel before curing was investigated, and the optimal centrifugal force was identified to be around 450× g. The compressed modular bioactuator (C-MBA) fabricated in this study exhibited 1.71 times higher cell density than the conventional method. In addition, the contractile force per unit cross-sectional area was 1.88 times higher. The proposed method will contribute to new bioactuators with the same power as living muscles in animals. Full article

Microfluidic spun gelation mechacrylate (GelMA) microfiber has been widely utilized as a promising bioink for 3D bioprinting. However, its weak and easily tuned mechanical properties are still difficult to precisely evaluate, due to the lack of an effective stretching method. In this paper, we propose a force-control-based cyclic loading method for rapidly evaluating the elastic modulus: the E of the microfibers with different GelMA concentrations. A two-tube manipulation system is used to stretch microfiber with a non-destructive process. Based on the model reference adaptive control strategy, the stress response can be fitted into a sinusoidal wave when a small sinusoidal strain is automatically applied onto the microfiber. Afterwards, the maximum tensile stress and tensile stain is obtained to determine the E. Moreover, different stress amplitudes and frequencies are applied to form different stress-strain loops with almost same E. Compared with a frequently-used constant force loading method, the proposed method shows an obvious advantage in measurement accuracy, especially for low-concentration GelMA microfiber. Furthermore, the reasonableness of the measured E for different GelMA concentrations is confirmed by 3D cell culture experiments, and the results show the proposed method has great application potential to investigate the interaction between cell and fibrous bioink substrate. Full article