The microvasculature plays a critical role in human physiology and is closely associated to various human diseases. By combining advanced microfluidic-based techniques, the engineered 3D microvascular network model provides a precise and reproducible platform to study the microvasculature in vitro, which is an essential and primary component to engineer organ-on-chips and achieve greater biological relevance. In this review, we discuss current strategies to engineer microvessels in vitro, which can be broadly classified into endothelial cell lining-based methods, vasculogenesis and angiogenesis-based methods, and hybrid methods. By closely simulating relevant factors found in vivo such as biomechanical, biochemical, and biological microenvironment, it is possible to create more accurate organ-specific models, including both healthy and pathological vascularized microtissue with their respective vascular barrier properties. We further discuss the integration of tumor cells/spheroids into the engineered microvascular to model the vascularized microtumor tissue, and their potential application in the study of cancer metastasis and anti-cancer drug screening. Finally, we conclude with our commentaries on current progress and future perspective of on-chip vascularization techniques for fundamental and clinical/translational research.

Autonomous and self-powered micropumps are in critical demand for versatile cell- and tissue-based applications as well as for low-cost point-of-care testing (POCT) in microfluidics fields. The hydrostatic pressure-driven passive micropumps are simple and widely used, but they cannot maintain steady and continuous flow for long periods of time. Here, we propose a hydrostatic pressure-driven passive micropump enhanced with siphon-based autofill function, which can realize the autonomous and continuous perfusion with well-controlled steady flow over an extended time without electric power consumption. The characterization results reveal that both the cycle number in one refilling loop and the siphon diameter will affect the refilling time. Furthermore, this micropump also enables multiplexed medium delivery under either the same or different flow conditions with high flexibility. The system was validated using an in vitro vasculogenesis model over the course of several days. Most importantly, the device can consistently provide steady medium perfusion for up to 5 days at a predefined hydrostatic pressure drop without the need for supplemental medium changes. We believe that this hydrostatic pressure-driven passive micropump will become a critical module for a broad range of sophisticated microfluidic operations and applications.

A closed-loop and self-adaptive cardiac optogenetics is realized by a negative stretching-resistive strain sensor.

Reconstruction of 3D vascularized microtissues within microfabricated devices has rapidly developed in biomedical engineering, which can better mimic the tissue microphysiological function and accurately model human diseases in vitro. However, the traditional PDMS-based microfluidic devices suffer from the microfabrication with complex processes and usage limitations of either material properties or microstructure design, which drive the demand for easy processing and more accessible devices with a user-friendly interface. Here, we present an open microfluidic device through a rapid prototyping method by laser cutting in a cost-effective manner with high flexibility and compatibility. This device allows highly efficient and robust hydrogel patterning under a liquid guiding rail by spontaneous capillary action without the need for surface treatment. Different vascularization mechanisms including vasculogenesis and angiogenesis were performed to construct a 3D perfusable microvasculature inside a tissue chamber with various shapes under different microenvironment factors. Furthermore, as a proof-of-concept we have created a vascularized spheroid by placing a monoculture spheroid into the central through-hole of this device, which formed angiogenesis between the spheroid and microvascular network. This open microfluidic device has great potential for mass customization without the need for complex microfabrication equipment in the cleanroom, which can facilitate studies requiring high-throughput and high-content screening.

The limitations of conventional animal tests and two-dimensional cell culture hinder their advancement in fundamental research and clinical/translational applications. As an emerging alternative technology, organ-on-a-chip serves as a platform that faithfully simulates the key phenotypical, physiological, and functional features of human tissues/organs through the accurate regulation of the parameters such as physical and biochemical microenvironment, as well as cellular patterns. In this review, we mainly introduce the recent progress in the organ-on-a-chip field, including lung, gut, heart, liver, vasculature and multiorgan studies. Furthermore, we highlight the potential applications in drug screening and personalized medicine. Finally, we conclude the review by addressing the current challenges and future perspective in the technology and commercialization of organ-on-chips. We anticipate that the development of organ-on-a-chip technology will revolutionize the studies on biology and medicine by providing new understanding of mechanisms of diseases and insights into clinical therapeutics.

Acetaminophen (APAP) overdose is one of the most common causes of acute liver failure in many countries. The aim of the study was to describe the profiling of phosphatidylcholine (PC) and phosphatidylethanolamine (PE) in the plasma and liver of Acetaminophen -induced liver injured mice. A time course study was carried out using C57BL/6 mice after intraperitoneal administration of 300 mg/kg Acetaminophen 1 h, 3 h, 6 h, 12 h and 24 h. A high-throughput liquid chromatography mass spectrometry (LC-MS) lipidomic method was utilized to detect phosphatidylcholine and phosphatidylethanolamine species in the plasma and liver. The expressions of phosphatidylcholine and phosphatidylethanolamine metabolism related genes in liver were detected by quantitative Reverse transcription polymerase chain reaction (qRT-PCR) and Western-blot. Following Acetaminophen treatment, the content of many PC and PE species in plasma increased from 1 h time point, peaked at 3 h or 6 h, and tended to return to baseline at 24 h time point. The relative contents of almost all PC species in liver decreased from 1 h, appeared to be lowest at 6 h, and then return to normality at 24 h, which might be partly explained by the suppression of phospholipases mRNA expressions and the induction of choline kinase (Chka) expression. Inconsistent with PC profile, the relative contents of many PE species in liver increased upon Acetaminophen treatment, which might be caused by the down-regulation of phosphatidylethanolamine N-methyltransferase (Pemt). Acetaminophen overdose induced dramatic change of many PC and PE species in plasma and liver, which might be caused by damaging hepatocytes and interfering the phospholipid metabolism in Acetaminophen -injured liver.