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Organ-on-a-chip (OOC) is an emerging technology that simulates an artificial organ within a microfluidic cell culture chip. Current cell biology research focuses on in vitro cell cultures due to various limitations of in vivo testing. Unfortunately, in-vitro cell culturing fails to provide an accurate microenvironment, and in vivo cell culturing is expensive and has historically been a source of ethical controversy. OOC aims to overcome these shortcomings and provide the best of both in vivo and in vitro cell culture research. The critical component of the OOC design is utilizing microfluidics to ensure a stable concentration gradient, dynamic mechanical stress modeling, and accurate reconstruction of a cellular microenvironment. OOC also has the advantage of complete observation and control of the system, which is impossible to recreate in in-vivo research. Multiple throughputs, channels, membranes, and chambers are constructed in a polydimethylsiloxane (PDMS) array to simulate various organs on a chip. Various experiments can be performed utilizing OOC technology, including drug delivery research and toxicology. Current technological expansions involve multiple organ microenvironments on a single chip, allowing for studying inter-tissue interactions. Other developments in the OOC technology include finding a more suitable material as a replacement for PDMS and minimizing artefactual error and non-translatable differences.

Organ-like cell clusters, so-called organoids, which exhibit self-organized and similar organ functionality as the tissue of origin, have provided a whole new level of bioinspiration for ex vivo systems. Microfluidic organoid or organs-on-a-chip platforms are a new group of micro-engineered promising models that recapitulate 3D tissue structure and physiology and combines several advantages of current in vivo and in vitro models. Microfluidics technology is used in numerous applications since it allows us to control and manipulate fluid flows with a high degree of accuracy. This system is an emerging tool for understanding disease development and progression, especially for personalized therapeutic strategies for cancer treatment, which provide well-grounded, cost-effective, powerful, fast, and reproducible results. In this review, we highlight how the organoid-on-a-chip models have improved the potential of efficiency and reproducibility of organoid cultures. More widely, we discuss current challenges and development on organoid culture systems together with microfluidic approaches and their limitations. Finally, we describe the recent progress and potential utilization in the organs-on-a-chip practice.

Recent developments of organoids engineering and organ-on-a-chip microfluidic technologies have enabled the recapitulation of the major functions and architectures of microscale human tissue, including tumor pathophysiology. Nevertheless, there remain challenges in recapitulating the complexity and heterogeneity of tumor microenvironment. The integration of these engineering technologies suggests a potential strategy to overcome the limitations in reconstituting the perfusable microvascular system of large-scale tumors conserving their key functional features. Here, we review the recent progress of in vitro tumor-on-a-chip microfluidic technologies, focusing on the reconstruction of microvascularized organoid models to suggest a better platform for personalized cancer medicine.

Various systemic metabolic diseases arise from prolonged crosstalk across multiple organs, triggering serious impairments in various physiological systems. These diseases are intricate systemic pathologies characterized by complex mechanisms and an unclear etiology, making the treatment challenging. Efforts have been made to develop in vitro models to understand these diseases and devise new treatments. However, there are limitations in reconstructing the causal relationships between diseases and interorgan crosstalk, including the tissue‐specific microenvironment. Alternatively, multi‐organ microphysiological systems (MOMPS) present new possibilities for capturing the complexity of systemic metabolic diseases by replicating human microphysiology and simulating diverse interorgan crosstalk. Controlled interactions and scalable representations of biological complexity in MOMPS offer a more accurate portrayal of organ interactions, enabling the identification of novel relationships between organ crosstalk, metabolism, and immunity. This, in turn, can yield valuable insights into disease mechanisms and drug development research and enhance the efficiency of preclinical studies. In this review, the examples and technical capabilities of MOMPS pathological modeling for various diseases are discussed, leveraging state‐of‐the‐art biofabrication technology of MOMPS. It evaluates the current opportunities and challenges in this field. Multi‐organ microphysiological systems (MOMPS) replicate human microphysiology and interorgan crosstalk. The precise fabrication of MOMPS requires various elements, including biomaterials, cell sources, accurate organ crosstalk, biofabrication techniques, and humanized design. The MOMPS enhances the understanding of systemic metabolic disease mechanisms, improves drug development, and increases the efficiency of preclinical studies by capturing the complexity of organ interactions and tissue‐specific microenvironments..

Organ-on-a-chip (OoC), also known as micro physiological systems or “tissue chips” have attracted substantial interest in recent years due to their numerous applications, especially in precision medicine, drug development and screening. Organ-on-a-chip devices can replicate key aspects of human physiology, providing insights into the studied organ function and disease pathophysiology. Moreover, these can accurately be used in drug discovery for personalized medicine. These devices present useful substitutes to traditional preclinical cell culture methods and can reduce the use of in vivo animal studies. In the last few years OoC design technology has seen dramatic advances, leading to a wide range of biomedical applications. These advances have also revealed not only new challenges but also new opportunities. There is a need for multidisciplinary knowledge from the biomedical and engineering fields to understand and realize OoCs. The present review provides a snapshot of this fast-evolving technology, discusses current applications and highlights advantages and disadvantages for biomedical approaches.

Rapid screening of personalized drugs based on patients’ primary cell samples can provide precise and timely treatment guidance for clinical oncology patients. However, this goal faces great challenges due to the scarce clinical samples and large sample consumption, and long experimental time required by current drug screening methods. Here, a rapid, high‐throughput microfluidic drug sensitivity testing system capable of accomplishing single and combination drug screening of multiple antitumor drugs in 5 days is established with minimal amounts of clinical primary tumor samples, avoiding the need for cell pre‐expansion and preserving the tumor heterogeneity. An airflow‐impacting approach is developed to fabricate nanoliter‐scale microcavity arrays with ultra‐smooth microcavity surfaces, with which rapid formation and 3D culture of tumor cell spheroids from small numbers of cell samples, as well as the subsequent high‐throughput drug sensitivity testing can be achieved within 5 days. This applies the system in rapid drug sensitivity testing on primary samples from 21 clinical breast cancer patients to quantify the responses of patient‐derived cells to chemotherapy and endocrine drugs under both the mono‐drug and combinational‐drug treatment modes. This study develops the air‐punched fabrication approach for nanoliter‐scale microcavity arrays with ultra‐smooth microcavity surfaces, with which rapid formation and 3D culture of tumor cell spheroids from small numbers of cell samples, as well as high‐throughput drug sensitivity testing can be achieved within 5 days. The system is applied in rapid, high‐throughput drug sensitivity testing on primary cell samples from 21 clinical breast cancer patients to quantify the responses to chemotherapy drugs and endocrine drugs.

The endometrium is the inner lining of the uterus. Following specific cyclic hormonal stimulation, endometrial stromal fibroblasts (stroma) and vascular endothelial cells exhibit morphological and biochemical changes to support embryo implantation and regulate vascular function, respectively. Herein, we integrated a resin-based porous membrane in a dual chamber microfluidic device in polydimethylsiloxane that allows long term in vitro co-culture of human endometrial stromal and endothelial cells. This transparent, 2-μm porous membrane separates the two chambers, allows for the diffusion of small molecules and enables high resolution bright field and fluorescent imaging. Within our primary human co-culture model of stromal and endothelial cells, we simulated the temporal hormone changes occurring during an idealized 28-day menstrual cycle. We observed the successful differentiation of stroma into functional decidual cells, determined by morphology as well as biochemically as measured by increased production of prolactin. By controlling the microfluidic properties of the device, we additionally found that shear stress forces promoted cytoskeleton alignment and tight junction formation in the endothelial layer. Finally, we demonstrated that the endometrial perivascular stroma model was sustainable for up to 4 weeks, remained sensitive to steroids and is suitable for quantitative biochemical analysis. Future utilization of this device will allow the direct evaluation of paracrine and endocrine crosstalk between these two cell types as well as studies of immunological events associated with normal vs. disease-related endometrial microenvironments.

This review mainly studies the development status, limitations, and future directions of modular microfluidic systems. Microfluidic technology is an important tool platform for scientific research and plays an important role in various fields. With the continuous development of microfluidic applications, conventional monolithic microfluidic chips show more and more limitations. A modular microfluidic system is a system composed of interconnected, independent modular microfluidic chips, which are easy to use, highly customizable, and on-site deployable. In this paper, the current forms of modular microfluidic systems are classified and studied. The popular fabrication techniques for modular blocks, the major application scenarios of modular microfluidics, and the limitations of modular techniques are also discussed. Lastly, this review provides prospects for the future direction of modular microfluidic technologies.

A novel placenta–fetal lung organ-on-a-chip platform enables direct analysis of how maternal treatments influence fetal lung development.The system replicates placental drug transfer and fetal lung surfactant production, offering mechanistic insight into how antenatal corticosteroid therapy promotes fetal lung maturation.Using this platform, we identified that steroid concentrations above 5 mM compromise placental cell viability without further increasing surfactant output, revealing a threshold for safe, effective dosing.These findings inform optimization of antenatal steroid therapy to maximize preterm infant lung maturation benefits while minimizing placental and fetal side effects. Antenatal corticosteroids are recommended for preterm births to enhance lung maturity; however, the guidelines are based on limited studies. Here, we present a placenta–fetal lung microphysiological analysis platform (MAP) to study how corticosteroids promote fetal lung maturation and determine their optimal concentration with minimal side effects. We create trophoblast–capillary–pneumocyte MAP on chips to analyze the transport of corticosteroids from mother to fetus through the placenta. We assessed surfactant production from the pneumocyte after exposure to different concentrations, types, and durations of corticosteroids in the trophoblast layer. We found the concentrations of corticosteroids over 5 mM reduced trophoblast viability and did not increase the surfactant production from pneumocytes. Our research on placenta–fetal lung MAP provides insight into how corticosteroids improve the production of surfactant from immature pneumocytes as they transition from the placenta and suggests that determining the appropriate dosage of corticosteroids to maximize effectiveness while preventing damage to trophoblasts is crucial. [Display omitted] The placenta–fetal lung microphysiological analysis platform (MAP) is at a proof-of-concept stage, meaning its feasibility has been demonstrated in a lab setting. This integrated trophoblast–capillary–fetal lung system models maternal corticosteroid transfer across a placental barrier and the resultant induction of fetal lung surfactant production. However, as a nascent technology, its implementation faces key challenges. The current platform relies on immortalized cell lines for placental and fetal lung tissues, which lack full phenotypic fidelity of primary cells (e.g., limited surfactant production or barrier function). Drug administration in the device is also simplified (directly spiking the microfluidic channels) rather than mimicking physiological delivery routes via maternal circulation and metabolism. These limitations underscore the need for further refinement before advancing beyond laboratory validation. Moving this MAP toward higher readiness will require several improvements. Incorporating primary human cells or iPSC-derived trophoblast and alveolar cells would better recapitulate native placental and fetal lung functions. Integrating 3D organoid structures (placental villi or fetal lung organoids) and simulating multi-route drug delivery (e.g., maternal intravenous dosing with metabolic processing) could more faithfully recreate in vivo conditions. Such enhancements are expected to boost the platform’s predictive power for drug transport and efficacy. With these refinements, the placenta–fetal lung MAP holds significant translational potential. It could reduce reliance on animal studies by providing human-specific data on maternal–fetal drug transfer and fetal outcomes, informing evidence-based antenatal corticosteroid dosing guidelines and fulfilling regulatory needs for safety testing in pregnant populations. Notably, this approach aligns with emerging regulatory initiatives encouraging human-relevant in vitro models in drug development, positioning the platform as a valuable tool for future clinical and regulatory applications. We developed a placenta–fetal lung microphysiological platform to evaluate antenatal corticosteroid transport and fetal lung maturation. Our results indicate corticosteroid concentrations above 5 mM reduce placental cell viability without enhancing lung surfactant production, highlighting the importance of identifying optimal corticosteroid dosages to maximize therapeutic efficacy while minimizing adverse effects.

Augmenting adaptive immunity is a critical goal for developing next-generation cancer therapies. T and B cells infiltrating the tumor dramatically influence cancer progression through complex interactions with the local microenvironment. Cancer cells evade and limit these immune responses by hijacking normal immunologic pathways. Current experimental models using conventional primary cells, cell lines, or animals have limitations for studying cancer-immune interactions directly relevant to human biology and clinical translation. Therefore, engineering methods to emulate such interplay at local and systemic levels are crucial to expedite the development of better therapies and diagnostic tools. In this review, we discuss the challenges, recent advances, and future directions toward engineering the tumor-immune microenvironment (TME), including key elements of adaptive immunity. We first offer an overview of the recent research that has advanced our understanding of the role of the adaptive immune system in the tumor microenvironment. Next, we discuss recent developments in 3D in-vitro models and engineering approaches that have been used to study the interaction of cancer and stromal cells with B and T lymphocytes. We summarize recent advancement in 3D bioengineering and discuss the need for 3D tumor models that better incorporate elements of the complex interplay of adaptive immunity and the tumor microenvironment. Finally, we provide a perspective on current challenges and future directions for modeling cancer-immune interactions aimed at identifying new biological targets for diagnostics and therapeutics.