Bead bed microfluidic device for testing mechanical embolization of shear-thinning hydrogels

Hepatocellular carcinoma (HCC) remains one of the leading causes of cancer-related deaths worldwide, despite advancements in therapeutic strategies such as chemotherapeutics, immunotherapy, and transarterial chemoembolization (TACE). The development of embolic agents with enhanced delivery precision and therapeutic efficacy, particularly shear-thinning biomaterials (STBs), has opened new avenues for localized, sustained, and combination cancer therapies. However, current in vitro and ex vivo models for embolic agent testing are limited in their ability to recapitulate the intricate architecture and dynamic microenvironment of human capillary networks. Here, we present a proof-of-concept bead bed microfluidic device designed to emulate physiologically relevant vascular complexity for evaluating mechanical embolic agent performance. This system utilizes photocrosslinkable gelatin methacryloyl (GelMA) microbeads as modular structural elements, where interstitial voids between packed beads mimic capillary-scale networks, and annealed GelMA layers form interconnected pathways representing larger vessels. This platform allows assessment of embolization efficiency, flow behavior, and cell-targeting efficacy of shear-thinning hydrogels and other embolic materials under biologically relevant conditions. By integrating cellular encapsulation within GelMA microbeads, the device enables simultaneous evaluation of embolization and cytotoxic responses, bridging the gap between conventional mechanical flow models and biologically functional assays. This bead bed microfluidic approach provides a versatile and scalable in vitro testing tool aligned with the FDA's initiative toward non-animal testing methodologies, offering a promising route for preclinical screening and optimization of next-generation embolic agents. STATEMENT OF SIGNIFICANCE: This work introduces the first bead-bed microfluidic platform capable of simultaneously evaluating embolization mechanics, drug diffusion, and biological response within a capillary-mimetic 3D matrix. Existing in vitro embolization models rely on simplified bulk gels or rigid channels that fail to reproduce the microscale vascular complexity and dynamic transport conditions governing embolic agent performance. Our system overcomes these limitations by integrating tunable GelMA (gelatin methacryloyl) microbeads, physiologically relevant pore networks, multi-scale channels, and embedded tumor cells to capture both mechanical occlusion and therapeutic delivery behavior. This platform advances non-animal testing approaches and provides a quantitative, biologically functional method for screening next-generation shear-thinning embolic materials.