Cancer-on-chip (CoC) models, based on microfluidic chips harboring chambers for 3D tumor-cell culture, enable us to create a controlled tumor microenvironment (TME). CoC models are therefore increasingly used to systematically study effects of the TME on the various steps in cancer metastasis. Moreover, CoC models have great potential for developing novel cancer therapies and for predicting patient-specific response to cancer treatments. We review recent developments in CoC models, focusing on three main TME components: (i) the anisotropic extracellular matrix (ECM) architectures, (ii) the vasculature, and (iii) the immune system. We aim to provide guidance to biologists to choose the best CoC approach for addressing questions about the role of the TME in metastasis, and to inspire engineers to develop novel CoC technologies.

This study investigates the impact of channel geometry and applied flow on the orientation and morphology of endothelial cells (ECs) within vessel‐on‐chip (VoC) models. Traditional organ‐on‐chip models often utilize rectangular cross‐section channels, resulting in flat walls, sharp corners, and non‐uniform wall shear stress profiles, which do not accurately mimic physiological conditions. Tubular channels with circular cross‐sections provide a more in vivo‐like geometry and result in a physiological uniform wall shear stress. Here, tubular channels fabricated using sugar 3D‐printing are compared with rectangular channels made via stereolithography 3Dprinting. The results show that ECs from both blood and lymph vessels exhibit more uniform coverage and circumferential alignment in tubular channels than in rectangular channels. Unidirectional or bidirectional flow conditions align ECs parallel to the flow, overruling the circumferential alignment induced by curvature in tubular channels. Pulsatile flow enhances circumferential orientation in tubular channels, while alignment along the flow is maintained in rectangular channels. Additionally, EC orientation induced by flow impacts monocyte rolling velocities, crucial for understanding immune cell motility. This study underlines the importance of the combined effect of channel geometry and flow conditions in VoC models, and advocates for the continued development of advanced organ‐on‐chip systems that better replicate human physiology.

Diffuse large B-cell lymphoma (DLBCL) is the most common aggressive B-cell non-Hodgkin lymphoma, often developing resistance to current treatments. Development and testing of new therapies is hampered by lack of good in vivo and in vitro models mimicking human disease. Here, we developed a lymphoma-on-chip model to investigate the tumor-supportive roles of lymph node stromal cells (LNSCs) – fibroblastic reticular cells (FRCs) and lymphatic endothelial cells (LECs) – in the DLBCL microenvironment. The model includes a tubular vessel lined with LECs surrounded by a hydrogel with DLBCL cells and FRCs. Our findings reveal that FRCs promote DLBCL survival and facilitate tumor cell migration towards lymphatic vessels. Moreover, we demonstrate that DLBCL cells increase permeability of lymphatic vessels, which is further enhanced in presence of FRCs. This lymphoma-on-chip model reveals the important role of LNSCs in DLBCL progression, and offers an innovative tool to study the DLBCL microenvironment and test potential therapeutic targets to improve patient outcomes.

Organ-on-Chip (OoC) models often include microchannel-based vessels and ducts with rectangular cross-sections, and therefore these lack the geometry and morphology found in tubular structures in vivo. Channels with round cross-sections can better mimic the physiology and cellular behavior of tubular structures, such as (micro)vessels and breast ducts, by providing a more in vivo-like geometry. Here, we utilize femtosecond laser machining to integrate tubular channels in an Organ-on-Chip device; our "Lumina-Chip" contains two tubular channels, both connected to a central channel along their entire length. This versatile fabrication technique, combined with replica molding, enables us to obtain a medium-throughput version of the device, including nine Lumina-Chips. In this study, we showcase the Lumina-Chip's capability by modeling breast cancer invasion, migration, and intravasation, all within a single device as a representative application. We use the device to observe the progression of breast cancer cells from a breast duct (formed in the first lumen, lined with normal epithelial cells), through an extracellular matrix (comprised of collagen I in the central channel), and ultimately into a vessel (formed in the second lumen, lined with endothelial cells). A permeability analysis confirms that the vessel wall maintains strong barrier functionality in the absence of cancer cells. Two types of breast cancer tumoroids (invasive and non-invasive) introduced into the breast duct exhibit distinctly different invasive behaviors.

Biofabrication is a multidisciplinary field that integrates diverse technologies to create three-dimensional structures composed of living cells, biomaterials, and other biological components. One of its main goals is the realization of functional tissue constructs with hierarchical architectures, as observed in native biological tissues, for applications in tissue engineering and regenerative medicine, as well as for in vitro modelling. Given its multidisciplinary nature, continued collaboration among experts from various scientific and technological disciplines remains essential to address the challenges ahead and to achieve the ambitious objectives of this rapidly advancing field. Reflecting on the progress made since the first bioprinting attempts, one can only envision the achievements that biofabrication may accomplish in the coming decades. Symposia such as the Alpine winter school for Biofabrication, bring together leading experts and early-stage researchers who collectively shape the future of the discipline through innovation and discussion. During the 2025 edition of the winter school, participants exchanged knowledge on current advances, challenges, and future perspectives in biofabrication. Guided by experts in this field, early-stage researchers discussed and summarized their views on five key topics: (i) the future of devices and technology in biofabrication, (ii) current trends and opportunities in material development, (iii) impact on society, ethics, and communication, (iv) applications and clinical translation, and (v) education and skillsets required for successful research. Their perspectives summarized here, address critical questions about future methodology, material development, and technological improvements that will continue to shape the evolution of biofabrication. Furthermore, aspects such as the impact on society, as well as the required skillset and education for future scientists working in the field are discussed.

This study investigates the impact of channel geometry and applied flow on the morphology and function of endothelial cells (ECs) within vessel-on-chip (VoC) models. Traditional organ-on-chip models often utilize rectangular cross-section channels, resulting in flat walls, sharp corners, and non-uniform wall shear stress profiles, which do not accurately mimic physiological conditions. Tubular channels with a circular cross-section provide a more in vivo-like geometry and result in a physiological uniform wall shear stress. Here, sugar 3D-printing is used for fabricating tubular channels, and stereolithography 3D-printing is applied for making rectangular channels. Using these models, the effects of both channel geometry and various flow conditions on the orientation and morphology of ECs, from both blood and lymph vessels, is explored. The research demonstrates that ECs in tubular channels exhibit a more uniform coverage and circumferential alignment/migration compared to rectangular channels. Unidirectional and bidirectional flow conditions induce alignments parallel to flow, overruling the circumferential alignment induced by curvature in tubular channels. The combination of tubular geometry and pulsatile flow induces enhanced circumferential orientation, different from rectangular channels in which cells remain primarily aligned along the flow direction under pulsatile flow. In summary, our systematic study shows that the channel curvature determines the cell orientation in static conditions, and that adding flow results in a competing effect between geometry and flow for which the resulting cell alignment depends on the flow conditions. Additionally, the study examines the initial adhesive interactions between monocytes and ECs, revealing that EC orientation induced by different flow regimes impacts monocyte rolling velocities. This finding is important for understanding immune cell motility and adhesion in healthy and diseased states. This study underlines the importance of the combined effect of channel geometry and flow conditions in VoC models, and it provides a strong motivation for the continued development of advanced OoC systems with ever more representative geometrical designs and flow control, to maximize the potential of OoC to revolutionize biomedical research and personalized medicine by providing more accurate and functional models of human physiology.