In this study, 3D hydrogel-based vascular structures with multilevel fluidic channels (macro-channel for mechanical stimulation and microchannel for nutrient delivery and chemical stimulation) were fabricated by extrusion-based three-dimensional (3D) bioprinting, which could be integrated into organ-on-chip devices that would better simulate the microenvironment of blood vessels. In this approach, partially cross-linked hollow alginate filaments loading fibroblasts and smooth muscle cells were extruded through a coaxial nozzle and then printed along a rotated rod template, and endothelial cells were seeded into the inner wall. Because of the fusion of adjacent hollow filaments, two-level fluidic channels, including a macro-channel in the middle formed from the cylindrical template and a microchannel around the wall resulted from the hollow filaments were formed. By this method, different shapes of vessellike structures of millimeter diameter were printed. The structures printed using 4% alginate exhibited ultimate strength of 0.184 MPa, and L929 mouse fibroblasts encapsulated in the structures showed over 90% survival within 1 week. As a proof of concept, an envisioned load system of both mechanical and chemical stimulation was demonstrated. In addition, a vascular circulation flow system, a cerebral artery surgery simulator, and a cell coculture model were fabricated to demonstrate potential tissue engineering applications of these printed structures.

Three-dimensional (3D) bioprinting of soft large-scale tissues in vitro is still a big challenge due to two limitations, (i) the lack of an effective way to print fine nutrient delivery channels (NDCs) inside the cell-laden structures above the millimetre level; (ii) the need for a feasible strategy to vascularize NDCs. Here, a novel 3D bioprinting method is reported to directly print cell-laden structures with effectively vascularized NDCs. Bioinks with desired tissue cells and endothelial cells (ECs) are separately and simultaneously printed from the outside (mixed with GelMA) and inside (mixed with gelatin) of a coaxial nozzle. As a result, the printed large-scale tissue consists of sheath-core fibers. At the same time, when the core fibers are dissolved to generate channels, the ECs deposit and adhere to the channels automatically. With this method, 3D cell-laden, vascularized tissue constructs (⩾1 cm) with a long-term culture (⩾20 d) are firstly reported. Specifically, vascularized cancer tissue constructs and osteogenic tissue constructs were generated. Considering the above advantages, this advanced bioprinting strategy has significant potential for building large-scale vascularized tissue constructs for applications in tissue engineering, and possibly even in regenerative medicine and organ repair.

Hydrogel structures equipped with internal microchannels offer more in vivo‐relevant models for construction of tissues and organs in vitro. However, currently used microfabrication methods of constructing microfluidic devices are not suitable for the handling of hydrogel. This study presents a novel method of fabricating hydrogel‐based microfluidic chips by combining the casting and bonding processes. A twice cross‐linking strategy is designed to obtain a bonding interface that has the same strength with the hydrogel bulk, which can be applied to arbitrary combinations of hydrogels. It is convenient to achieve the construction of hydrogel structures with channels in branched, spiral, serpentine, and multilayer forms. The experimental results show that the combination of gelatin and gelatin methacrylate (GelMA) owns the best biocompatibility and can promote cell functionalization. Based on these, a vessel‐on‐a‐chip system with vascular function in both physiological and pathological situations is established, providing a promising model for further investigations such as vascularization, vascular inflammation, tissue engineering, and drug development. Taken together, a facile and cytocompatible approach is developed for engineering a user‐defined hydrogel‐based chip that can be potentially useful in developing vascularized tissue or organ models.

Aim: Mesenchymal stem cells (MSC) are a promising candidate for cardiac replacement therapies. However, the majority of transplanted MSC are readily lost after transplantation because of poor blood supply, ischemia-reperfusion, and inflammatory factors. We aimed to study the effects of hypoxia preconditioning (HPC) on hypoxia/reoxygenation-induced apoptosis of MSC. Methods: