Application of Microfluidics in Tissue Engineering

#microfluidics Research Researchers report a digital microfluidic (DMF) platform that integrates on-chip 3D-printed microstructured scaffolds to enable true 3D spheroid culture with precise droplet control. Using projection stereolithography, they fabricate in a single step the dielectric layer, fence structures, and 3D microstructure arrays directly on an electrode substrate, eliminating cleanroom, multi-mask lithography, and complex alignment. The EWOD-based DMF chip supports robust droplet transport, splitting, and dispensing over these microstructures, while MCF-7 cells loaded in droplets rapidly transition from initial 2D adhesion to stable 3D spheroids with high viability over 72 hours. Systematic characterization of voltage, microstructure height, and electrode spacing shows reliable actuation and good biocompatibility of the printed resin. Link to original study: https://lnkd.in/eqeASBXg

𝗔 𝗺𝗶𝗰𝗿𝗼𝗳𝗹𝘂𝗶𝗱𝗶𝗰 𝗽𝗹𝗮𝘁𝗳𝗼𝗿𝗺 𝗳𝗼𝗿 𝘁𝗵𝗲 𝗰𝗼-𝗰𝘂𝗹𝘁𝘂𝗿𝗶𝗻𝗴 𝗼𝗳 𝗺𝗶𝗰𝗿𝗼𝘁𝗶𝘀𝘀𝘂𝗲𝘀 𝘄𝗶𝘁𝗵 𝗰𝗼𝗻𝘁𝗶𝗻𝘂𝗼𝘂𝘀𝗹𝘆 𝗿𝗲𝗰𝗶𝗿𝗰𝘂𝗹𝗮𝘁𝗶𝗻𝗴 𝘀𝘂𝘀𝗽𝗲𝗻𝘀𝗶𝗼𝗻 𝗰𝗲𝗹𝗹𝘀. In vitro evaluation of novel therapeutic approaches often fails to reliably predict efficacy and toxicity, especially when recapitulating conditions involving recirculating cells. Current testing strategies are often based on static co-culturing of cells in suspension and 3D tissue models, where cell sedimentation on the target tissue can occur. The observed effects may then mostly be a consequence of sedimentation and of the corresponding forced cell-tissue interactions. The realization of continuous medium flow helps to better recapitulate physiological conditions and cell-tissue interactions. To tackle current limitations of perfused organ-on-chip approaches, the authors developed a microfluidic chip and operation concept, which prevents undesired sedimentation and accumulation of suspended cells during multiple days by relying on gravity-driven perfusion. The present platform, which the authors termed “human immune flow (hiFlow) chip,” enables the co-culture of cells in suspension with up to 7 preformed microtissue models. Here, the authors present the design principle and operation of the platform, and the authors validate its performance by culturing cells and microtissues of a variety of different origins. Cells and tissues could be monitored on-chip via high-resolution microscopy, while cell suspensions and microtissues could be easily retrieved for off-chip analysis. The present results demonstrate that primary immune cells and a range of different spheroid models of healthy and diseased tissues can be maintained for over 6 days on chip. As proof-of-concept cell-tissue interaction assay, the authors used an antibody treatment against diffuse midline glioma, a highly aggressive pediatric tumor. The authors are confident that our platform will help to increase the prediction power of in vitro preclinical testing of novel therapeutics that rely on the interaction of circulating cells with organ tissues. https://lnkd.in/gz4hEXh7

A patient-specific lung cancer assembloid model with heterogeneous tumor microenvironments Cancer models play critical roles in basic cancer research and precision medicine. However, current in vitro cancer models are limited by their inability to mimic the three-dimensional architecture and heterogeneous tumor microenvironments (TME) of in vivo tumors. Here, we develop an innovative patient-specific lung cancer assembloid (LCA) model by using droplet microfluidic technology based on a microinjection strategy. This method enables precise manipulation of clinical microsamples and rapid generation of LCAs with good intra-batch consistency in size and cell composition by evenly encapsulating patient tumor-derived TME cells and lung cancer organoids inside microgels. LCAs recapitulate the inter- and intratumoral heterogeneity, TME cellular diversity, and genomic and transcriptomic landscape of their parental tumors. LCA model could reconstruct the functional heterogeneity of cancer-associated fibroblasts and reflect the influence of TME on drug responses compared to cancer organoids. Notably, LCAs accurately replicate the clinical outcomes of patients, suggesting the potential of the LCA model to predict personalized treatments. Collectively, our studies provide a valuable method for precisely fabricating cancer assembloids and a promising LCA model for cancer research and personalized medicine. https://lnkd.in/ezS_NNHj

Researchers developed a microfluidic bioprinting system to fabricate 3D scaffolds with precisely controlled internal porosity. They integrated two microfluidic chips into an extrusion bioprinter: one to generate a liquid foam with tunable bubble size, and a second to gel and extrude the bubble-filled hydrogel fibers in real time. By adjusting flow rates during printing, they dynamically controlled pore size, porosity, and spatial gradients. Using a composite hydrogel ink (alginate, gelatin, and nanoclay), they embedded cells directly into the foamed fibers and showed that internal microporosity influenced cell proliferation and distribution within the constructs. To make the system more physiologically relevant, researchers could explore using CollPlant's recombinant human type I collagen. Read the full publication here: https://lnkd.in/gm3sJ95j #bioprinting #microfluidics #tissueengineering #biomaterials #regenerativemedicine

Excited to share our newest paper published in #ScienceAdvances on "3D bioprinting of collagen-based high-resolution internally perfusable scaffolds for engineering fully biologic tissue systems." Microfluidics and microphysiologic systems can now be constructed entirely out of cells and ECM, no more PDMS or plastic needed! This work was lead by an amazing team including co-first-authors Daniel Shiwarski and Andrew Hudson, Ph.D. together with Joshua Tashman, Ezgi Bakirci, Samuel Moss and Brian Coffin, PhD. The article is open access and free for everyone to read. https://lnkd.in/eQr27gcu The journal cover shows one of our #FRESH #3Dbioprinted collagen CHIPS in the specially designed VAPOR bioreactor for extended in vitro perfusion.

Excited to share our latest publication in Biomaterials! We developed a 3D, vascularized liver tumor model that more closely replicates the complex tumor microenvironment—helping researchers better understand how chemotherapy and immunotherapies (like CAR-T cells) perform in solid tumors. By integrating hypoxia, extracellular matrix, and perfusable vessels in one system, we can more accurately predict therapeutic responses and move closer to personalized treatments. Take a look at how this microphysiological model bridges the gap between standard lab tests and patient outcomes, and why it could serve as a powerful tool to accelerate drug discovery while reducing animal testing. Read the full article here: https://lnkd.in/gQvicmEh Huge thanks to my incredible co-authors and collaborators who made this research possible! Jyothsna Vasudevan, Ph.D., Ragavi Vijayakumar, Jose Antonio Reales Calderon, Maxine Lam, Jin Rong Ow, Joey Aw, Zhi Ming Damien Tan, Anthony Tanoto TAN, Antonio Bertoletti, Giulia Adriani #cancerresearch, #drugdiscovery, #organonchip #ImmunoOncology, #Microfluidics, #Bioengineering, #3DCellCulture #NTULKC