Functional Blood-Brain Barrier Model with Tight Connected Minitissue by Liquid Substrates Culture.

The functional blood-brain barrier (BBB) model can provide a reliable tool for better understanding BBB transport mechanisms and in vitro preclinical experimentation. However, recapitulating microenvironmental complexities and physiological functions in an accessible approach remains a major challenge. Here, a new BBB model with a high-cell spatial density and tightly connected biomimetic minitissue is presented. The minitissue, pivotal functional structure of the BBB model, is fabricated by a novel and easy-to-use liquid substrate culture (LSC) method, which allows cells to self-assemble and self-heal into macrosized, tightly connected membranous minitissue. The minitissue with uniform thickness can be easily harvested in their entirety with extracellular matrix. Attributed to the tightly connected minitissue formed by LSC, the fabricated BBB biomimetic model has 1 to 2 orders of magnitude higher transendothelial electric resistance than the commonly reported BBB model. It also better prevents the transmission of large molecular substances, recapitulating the functional features of BBB. Furthermore, the BBB biomimetic model provides feedback regarding BBB-destructive drugs, exhibits selective transmission, and shows efflux pump activity. Overall, this model can serve as an accessible tool for life science or clinical medical researchers to enhance the understanding of human BBB and expedite the development of new brain-permeable drugs.

Perfusable Vessel-on-a-Chip for Antiangiogenic Drug Screening with Coaxial Bioprinting.

Vessel-on-a-chips, which can be used to study microscale fluid dynamics, tissue-level biological molecules delivery and intercellular communication under favorable three-dimensional (3D) extracellular matrix microenvironment, are increasingly gaining traction. However, not many of them can allow for long-term perfusion and easy observation of angiogenesis process. Since angiogenesis is necessary for the expansion of tumor, antiangiogenic drugs play a significant role in cancer treatment. In this study, we established an innovative and reliable antiangiogenic drug screening chip that was highly modularly integrated for long-term perfusion (up to 10 days depending on the hydrogel formula) and real-time monitoring. To maintain an unobstructed flow of cell-laden tubes for subsequent perfusion culture on the premise of excellent bioactivities, a polycaprolactone stent inspired by coronary artery stents was introduced to hold up the tubular lumen from the inside, while the perfusion chip was also elaborately designed to allow for convenient observation. After 3 days of perfusion screening, distinct differences in human umbilical vein endothelial cell sprouting were observed for a gradient of concentrations of bevacizumab, which pointed to the effectiveness and reliability of the drug screening perfusion system. Overall, a perfusion system for antiangiogenic drug screening was developed, which can not only conduct drug evaluation, but also be potentially useful in other vessel-mimicking scenarios in the area of tissue engineering, drug screening, pharmacokinetics, and regenerative medicine.

Development of 3D bioprinting: From printing methods to biomedical applications.

Biomanufacturing of tissues/organs in vitro is our big dream, driven by two needs: organ transplantation and accurate tissue models. Over the last decades, 3D bioprinting has been widely applied in the construction of many tissues/organs such as skins, vessels, hearts, etc., which can not only lay a foundation for the grand goal of organ replacement, but also be served as in vitro models committed to pharmacokinetics, drug screening and so on. As organs are so complicated, many bioprinting methods are exploited to figure out the challenges of different applications. So the question is how to choose the suitable bioprinting method? Herein, we systematically review the evolution, process and classification of 3D bioprinting with an emphasis on the fundamental printing principles and commercialized bioprinters. We summarize and classify extrusion-based, droplet-based, and photocuring-based bioprinting methods and give some advices for applications. Among them, coaxial and multi-material bioprinting are highlighted and basic principles of designing bioinks are also discussed.