A vascularized multilayer chip reveals shear stress-induced angiogenesis in diverse fluid conditions

A research article published by the Shanghai University presented a novel microfluidic chip design with a 3-layer configuration that utilizes a polycarbonate (PC) porous membrane to separate the culture fluid channels from the tissue chambers, featuring flexibly designable multitissue chambers. PC porous membranes act as the capillary in the vertical direction, enabling precise hydrogel patterning and successfully constructing a microfluidic environment suitable for microvascular tissue growth.

The new research paper, published on Feb. 28, 2025 in the journal Cyborg and Bionic Systems, presented a flexible and scalable chip that is highly suitable for culturing multiple vascularized organ tissues on a single microfluidic chip, as well as for studying the effects of different fluid factors on microvascular growth.

Recent advances in microfluidic technologies have enabled significant progress in constructing in vitro vascularized tissue models. However, replicating complex fluid environments and long-term stable microvascular networks within a single chip remains challenging, often requiring laborious trial-and-error adjustments. "By vertically integrating a porous membrane to decouple fluid channels and tissue chambers, we achieved precise control over interstitial flow and shear stress distribution, enabling diverse vascular morphogenesis in a single platform," explained corresponding author Na Liu, a professor at Shanghai University. The proposed three-layer microfluidic chip incorporates (a) a polycarbonate (PC) porous membrane for hydrogel confinement, (b) customizable tissue chamber geometries (triangle, rectangle, inverted triangle), and (c) COMSOL-based fluid dynamics simulations to guide design optimization. "This architecture eliminates hydrogel leakage and allows systematic exploration of fluidic effects on angiogenesis," added co-author Tao Yue.

The chip was fabricated using soft lithography with PDMS layers and laser-cut PC membranes, ensuring a 100-μm-thick tissue chamber for 3D cell culture. COMSOL simulations revealed shear stress gradients ranging from 0.3 to 9 mPa across chambers, correlating with microvascular density. Experimental results demonstrated sustained microvascular growth for over 12 days, with rectangle chambers exhibiting the highest network density (17–20% vessel area) due to uniform low shear stress. Fluorescent dextran perfusion confirmed functional lumen integrity, while velocity (0.2–1.6 mm/s) and shear stress (0.15–3.7 dyn/cm²) profiles mirrored physiological capillary conditions.

"Fluid directionality directly guided endothelial cell migration, forming networks aligned with simulated streamlines—a breakthrough for studying mechanobiological cues in angiogenesis," noted Yue. Despite its success, challenges persist in standardizing fluid parameters and scaling for multi-organ integration. "Future work will focus on optimizing chamber geometries for disease-specific models and integrating immune cells to mimic dynamic vascular niches," the team concluded. This platform not only advances drug screening and regenerative medicine but also reduces reliance on animal models through physics-driven, high-fidelity in vitro systems.

Authors of the paper include Tao Yue, Huiying Yang, Yue Wang, Ning Jiang, Hongze Yin, Xiaoqi Lu, Na Liu, Yichun Xu.

This work was supported by grants from the National Natural Science Foundation of China (Nos. 62373235, 62303290, and 62073208) and the Shanghai Science and Technology Committee Natural Science Foundation (No. 23ZR1423700). The authors also acknowledge the fund from the Shanghai Municipal Education Innovation Project (2021-09-E00113).

The paper, “A Vascularized Multilayer Chip Reveals Shear Stress-Induced Angiogenesis in Diverse Fluid Conditions” was published in the journal Cyborg and Bionic Systems on Feb 28 2025, at DOI: 10.34133/cbsystems.0207.

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