Organs-on-chips are microphysiological systems that allow to replicate the key functions of human organs and accelerate the innovation in life sciences including disease modeling, drug development, and precision medicine. However, due to the lack of standards in their definition, structural design, cell source, model construction, and functional validation, a wide range of translational application of organs-on-chips remains a challenging. \"Organs-on-chips: Intestine\" is the first group standard on human intestine-on-a-chip in China, jointly agreed and released by the experts from the Chinese Society of Biotechnology on 29th April 2024. This standard specifies the scope, terminology, definitions, technical requirements, detection methods, and quality control in building the human intestinal model on a chip. The publication of this group standard will guide the institutional establishment, acceptance and execution of proper practical protocols and accelerate the international standardization of intestine-on-a-chip for translational applications.

Spheroids and organoids have attracted significant attention as innovative models for disease modeling and drug screening. By employing diverse types of spheroids or organoids, it is feasible to establish microphysiological systems that enhance the precision of disease modeling and offer more dependable and comprehensive drug screening. High-throughput microphysiological systems that support optional, parallel testing of multiple drugs have promising applications in personalized medical treatment and drug research. However, establishing such a system is highly challenging and requires a multidisciplinary approach. This study introduces a dynamic Microphysiological System Chip Platform (MSCP) with multiple functional microstructures that encompass the mentioned advantages. We developed a high-throughput lung cancer spheroids model and an intestine-liver-heart-lung cancer microphysiological system for conducting parallel testing on four anti-lung cancer drugs, demonstrating the feasibility of the MSCP. This microphysiological system combines microscale and macroscale biomimetics to enable a comprehensive assessment of drug efficacy and side effects. Moreover, the microphysiological system enables evaluation of the real pharmacological effect of drug molecules reaching the target lesion after absorption by normal organs through fluid-based physiological communication. The MSCP could serves as a valuable platform for microphysiological system research, making significant contributions to disease modeling, drug development, and personalized medical treatment.

Neural tissues react to injuries through the orchestration of cellular reprogramming, generating specialized cells and activating gene expression that helps with tissue remodeling and homeostasis. Simplified biomimetic models are encouraged to amplify the physiological and morphological changes during neural regeneration at cellular and molecular levels. Recent years have witnessed growing interest in lab-on-a-chip technologies for the fabrication of neural interfaces. Neural system-on-a-chip devices are promisingin vitromicrophysiological platforms that replicate the key structural and functional characteristics of neural tissues. Microfluidics and microelectrode arrays are two fundamental techniques that are leveraged to address the need for microfabricated neural devices. In this review, we explore the innovative fabrication, mechano-physiological parameters, spatiotemporal control of neural cell cultures and chip-based neurogenesis. Although the high variability in different constructs, and the restriction in experimental and analytical access limit the real-life applications of microphysiological models, neural system-on-a-chip devices have gained considerable translatability for modeling neuropathies, drug screening and personalized therapy.

During the last decade, organs-on-chips or organoids microphysiological analysis platforms (MAP) have garnered attention in the practical applications of disease models, drug discovery, and developmental biology. Research on pregnant women has firm limitations due to ethical issues; thus, remodelling human pregnancy in vitro is highly beneficial for treatment modality development via disease remodelling or drug monitoring. This review highlights current efforts in bioengineering devices to reproduce human pregnancy and emphasises the significant convergence of biology, engineering, and maternal-foetal medicine. First, we review recent achievements in culturing cells from tissues involved in pregnancy; specifically, trophoblasts from the placenta. Second, we highlight developments in the reconstitution of pregnancy-related female reproductive organs across several structural and functional interpretations. Last, we examine research on the fundamental comprehension of pregnancy-associated diseases to find bioengineering solutions. Recreating human pregnancy through an engineered model is naturally complex; nevertheless, challenges are inevitable to progress precision medicine.

Atmospheric pollutants, including particulate matters, nanoparticles, bioaerosols, and some chemicals, have posed serious threats to the environment and the human\'s health. The lungs are the responsible organs for providing the interface betweenthecirculatory system and the external environment, where pollutant particles can deposit or penetrate into bloodstream circulation. Conventional studies to decipher the mechanismunderlying air pollution and human health are quite limited, due to the lack of reliable models that can reproduce in vivo features of lung tissues after pollutants exposure. In the past decade, advanced near-to-native lung chips, combining cell biology with bioengineered technology, present a new strategy for atmospheric pollutants assessment and narrow the gap between 2D cell culture and in vivo animal models. In this review, the key features of artificial lung chips and the cutting-edge technologies of the lung chip manufacture are introduced. The recent progresses of lung chip technologies for atmospheric pollutants exposure assessment are summarized and highlighted. We further discuss the current challenges and the future opportunities of the development of advanced lung chips and their potential utilities in atmospheric pollutants associated toxicity testing and drug screening.

Disorders of the synovial joint, such as osteoarthritis (OA) and rheumatoid arthritis (RA), afflict a substantial proportion of the global population. However, current clinical management has not been focused on fully restoring the native function of joints. Organ-on-chip (OoC), also called a microphysiological system, which typically accommodates multiple human cell-derived tissues/organs under physiological culture conditions, is an emerging platform that potentially overcomes the limitations of current models in developing therapeutics. Herein, we review major steps in the generation of OoCs for studying arthritis, discuss the challenges faced when these novel platforms enter the next phase of development and application, and present the potential for OoC technology to investigate the pathogenesis of joint diseases and the development of efficacious therapies.

Organ-on-a-chip (OOC, organ chip) technology can closely simulate the human microenvironment, synthesize organ-like functional units on a fluidic chip substrate, and simulate the physiology of tissues and organs. It will become an increasingly important platform for in vitro drug development and screening. Most importantly, organ-on-a-chip technology, incorporating 3D cell cultures, overcomes the traditional drawbacks of 2D (flat) cell-culture technology in vitro and in vivo animal trials, neither of which generate completely reliable results when it comes to the actual human subject. It is expected that organ chips will allow huge reductions in the incidence of failure in late-stage human trials, thus slashing the cost of drug development and speeding up the introduction of drugs that are effective. There have been three key enabling technologies that have made organ chip technology possible: 3D bioprinting, fluidic chips, and 3D cell culture, of which the last has allowed cells to be cultivated under more physiologically realistic growth conditions than 2D culture. The fusion of these advanced technologies and the addition of new research methods and algorithms has enabled the construction of chip types with different structures and different uses, providing a wide range of controllable microenvironments, both for research at the cellular level and for more reliable analysis of the action of drugs on the human body. This paper summarizes some research progress of organ-on-a-chip in recent years, outlines the key technologies used and the achievements in drug screening, and makes some suggestions concerning the current challenges and future development of organ-on-a-chip technology.

Aortic aneurysm is a common cardiovascular disease characterised by continuous dilation of the aorta, and this disease places a heavy burden on healthcare worldwide. Few drugs have been suggested to be effective in controlling the progression of aortic aneurysms. Preclinical drug responses from traditional cell culture and animals are usually controversial. An effective in vitro model is of great demand for successful drug screening. In this study, we induced an in vitro microphysiological system to test metformin, which is a potential drug for the treatment of aortic aneurysms. Human pluripotent stem cell-derived aortic smooth muscle cells (hPSC-HASMCs) were cultured on an in vitro microphysiological system, which could replicate the cyclic stretch of the human native aortic wall. By using this system, we found that HASMCs were more likely to present a physiologically contractile phenotype compared to static cell cultures. Moreover, we used hPSC-HASMCs in our microphysiological system to perform metformin drug screening. The results showed that hPSC-HASMCs presented a more contractile phenotype via NOTCH 1 signalling while being treated with metformin. This result indicated that metformin could be utilised to rescue hPSC-HASMCs from phenotype switching during aortic aneurysm progression. This study helps to elucidate potential drug targets for the treatment of aortic aneurysms.

Three-dimensional in vitro tumor models provide more physiologically relevant responses to drugs than 2D models, but the lack of proper evaluation indices and the laborious quantitation of tumor behavior in 3D have limited the use of 3D tumor models in large-scale preclinical drug screening. Here we propose two indices of 3D tumor invasiveness-the excess perimeter index (EPI) and the multiscale entropy index (MSEI)-and combine these indices with a new convolutional neural network-based algorithm for tumor spheroid boundary detection. This new algorithm for 3D tumor boundary detection and invasiveness analysis is more accurate than any other existing algorithms. We apply this spheroid monitoring and AI-based recognition technique (\"SMART\") to evaluating the invasiveness of tumor spheroids grown from tumor cell lines and from primary tumor cells in 3D culture.

Musculoskeletal injuries and associated conditions are the leading cause of physical disability worldwide. The concept of tissue engineering has opened up novel approaches to repair musculoskeletal defects in a fast and/or efficient manner. Biomaterials, cells, and signaling molecules constitute the tissue engineering triad. In the past 40 years, significant progress has been made in developing and optimizing all three components, but only a very limited number of technologies have been successfully translated into clinical applications. A major limiting factor of this barrier to translation is the insufficiency of two-dimensional cell cultures and traditional animal models in informing the safety and efficacy of in-human applications. In recent years, microphysiological systems, often referred to as organ or tissue chips, generated according to tissue engineering principles, have been proposed as the next-generation drug testing models. This chapter aims to first review the current tissue engineering-based approaches that are being applied to fabricate and develop the individual critical elements involved in musculoskeletal organ/tissue chips. We next highlight the general strategy of generating musculoskeletal tissue chips and their potential in future regenerative medicine research. Exemplary microphysiological systems mimicking musculoskeletal tissues are described. With sufficient physiological accuracy and relevance, the human cell-derived, three-dimensional, multi-tissue systems have been used to model a number of orthopedic disorders and to test new treatments. We anticipate that the novel emerging tissue chip technology will continually reshape and improve our understanding of human musculoskeletal pathophysiology, ultimately accelerating the development of advanced pharmaceutics and regenerative therapies.