Vascular systems are responsible for various physiological and pathological processes related to all organs in vivo, and the survival of engineered tissues for enough nutrient supply in vitro. Thus, biomimetic vascularization is highly needed for constructing both a biomimetic organ model and a reliable engineered tissue. However, many challenges remain in constructing vascularized tissues, requiring the combination of suitable biomaterials and engineering techniques. In this review, the advantages of hydrogels on building engineered vascularized tissues are discussed and recent engineering techniques for building perfusable microchannels in hydrogels are summarized, including micromolding, 3D printing, and microfluidic spinning. Furthermore, the applications of these perfusable hydrogels in manufacturing organ‐on‐a‐chip devices and transplantable engineered tissues are highlighted. Finally, current challenges in recapitulating the complexity of native vascular systems are discussed and future development of vascularized tissues is prospected.

Fabrication of artificial biomimetic materials has attracted abundant attention. As one of the subcategories of biomimetic materials, artificial cells are highly significant for multiple disciplines and their synthesis has been intensively pursued. In order to manufacture robust “alive” artificial cells with high throughput, easy operation, and precise control, flexible microfluidic techniques are widely utilized. Herein, recent advances in microfluidic‐based methods for the synthesis of droplets, vesicles, and artificial cells are summarized. First, the advances of droplet fabrication and manipulation on the T‐junction, flow‐focusing, and coflowing microfluidic devices are discussed. Then, the formation of unicompartmental and multicompartmental vesicles based on microfluidics are summarized. Furthermore, the engineering of droplet‐based and vesicle‐based artificial cells by microfluidics is also reviewed. Moreover, the artificial cells applied for imitating cell behavior and acting as bioreactors for synthetic biology are highlighted. Finally, the current challenges and future trends in microfluidic‐based artificial cells are discussed. This review should be helpful for researchers in the fields of microfluidics, biomaterial fabrication, and synthetic biology.

Materials with microchannels have attracted increasing attention due to their promising perfusability and biomimetic geometry. However, the fabrication of microfibers with more geometrically complex channels in the micro- or nanoscale remains a big challenge. Here, a novel method for generating scalable microfibers with consecutive embedded helical channels is presented using an easily made coaxial microfluidic device. The characteristics of the helical channel can be accurately controlled by simply adjusting the flow rate ratio of the fluids. The mechanism of the helix formation process is theorized with newly proposed heterogenerated rope-coil effect, which enhances the tunability of helical patterns and promotes the comprehension of this abnormal phenomenon. Based on this effect, microfibers with embedded Janus channels and even double helical channels are generated in situ by changing the design of the device. The uniqueness and potential applications of these tubular microfibers are also demonstrated by biomimetic supercoiling structures as well as the perfusable and permeable spiral vessel.

Fiber materials with different structural features, which in many cases endow the fibers extraordinary functions, are drawing considerable attention from biomedical and material researchers. Here, perfusable necklace-like knotted microfibers are presented for the first time. Additionally, a novel microfluidic spinning method facilitates the production of variable knots and channels. Not only spindle-, but also hemisphere- and petal-knotted microfibers can be controllably fabricated. Generation and perfusion of both Janus channels and helical channel in the knotted microfibers are also shown. With no need of oil and surfactant, the spinning process is highly cytocompatible. The potential bioengineering and biomedical application of the knotted hollow microfiber is demonstrated by its cell-encapsulation feasibility and the unique liver acinus-like diffusion gradient in the knot. The merits of perfusability, cytocompatibility, and structural diversity of the microfibers may open more avenues for further material and biomedical investigation.

Microengineered biomimetic systems for organ-on-a-chip or tissue engineering purposes often fail as a result of an inability to recapitulate the in vivo environment, specifically the presence of a well-defined vascular system. To address this limitation, we developed an alternative method to cultivate three-dimensional (3D) tissues by incorporating a microfabricated scaffold, termed AngioChip, with a built-in perfusable vascular network. Here, we provide a detailed protocol for fabricating the AngioChip scaffold, populating it with endothelial cells and parenchymal tissues, and applying it in organ-on-a-chip drug testing in vitro and surgical vascular anastomosis in vivo. The fabrication of the AngioChip scaffold is achieved by a 3D stamping technique, in which an intricate microchannel network can be embedded within a 3D scaffold. To develop a vascularized tissue, endothelial cells are cultured in the lumen of the AngioChip network, and parenchymal cells are encapsulated in hydrogels that are amenable to remodeling around the vascular network to form functional tissues. Together, these steps yield a functional, vascularized network in vitro over a 14-d period. Finally, we demonstrate the functionality of AngioChip-vascularized hepatic and cardiac tissues, and describe direct surgical anastomosis of the AngioChip vascular network on the hind limb of a Lewis rat model.

Kidney-on-a-chip devices may revolutionize the discovery of new therapies. However, fabricating a 3D glomerulus remains a challenge, due to a requirement for a microscale soft material with complex topography to support cell culture in a native configuration. Here, we describe the use of microfluidic spinning to recapitulate complex concave and convex topographies over multiple length scales, required for biofabrication of a biomimetic 3D glomerulus. We produced a microfluidic extruded topographic hollow fiber (h-FIBER), consisting of a vessel-like perfusable tubular channel for endothelial cell cultivation, and a glomerulus-like knot with microconvex topography on its surface for podocyte cultivation. Meter long h-FIBERs were produced in microfluidics within minutes, followed by chemically induced inflation for generation of topographical cues on the 3D scaffold surface. The h-FIBERs were assembled into a hot-embossed plastic 96-well plate. Long-term perfusion, podocyte barrier formation, endothelialization, and permeability tests were easily performed by a standard pipetting technique on the platform. Following long-term culture (1 month), a functional filtration barrier, measured by the transfer of albumin from the blood vessel side to the ultrafiltrate side, suggested the establishment of an engineered glomerulus.

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