Constriction-Minimizing Microfluidic Devices Enabling Co-Culture in Engineered Hydrogels

Technology

The device comprises open-top inlet chambers, outlet chambers, cell culture chambers, and connecting channels, all connected in a microfluidic network. Cells are introduced into the chambers within an engineered hydrogel scaffolding substance. The dimensions of the cell culture chambers, propagation channels, and inlet and outlet channels are designed with increased height to support the swelling of the hydrogel scaffold while avoiding additional strain on the substance and minimizing cell compression. In this way, the device supports the formation of complex 3D cell co-cultures, and the interconnected chambers further enable perfusion, cell-cell communication, and cell migration across tissue regions. The configuration of the microfluidic network can be modulated for the biological question being addressed, such as modeling multiple interconnected tissue regions or signaling circuit interactions.

Problem Addressed

Microfluidic 3D cell culture devices support physiologically relevant tissue-like architecture, making them valuable tools for disease modeling and therapeutic discovery. Simultaneously, new engineered biomaterials such as synthetic hydrogels offer improved capabilities in replicating human tissue-like microenvironments and features of pathogenesis. However, there has been limited success in combining these engineered materials with microfluidic device platforms due to their characteristic swelling properties. In conventional microfluidic devices, hydrogel swelling in confined channels creates pressure-induced strain that compresses embedded cells, disrupting tissue formation and often resulting in cell injury or cell death. This invention is a constriction-minimizing microfluidic 3D cell culture device designed to support the swelling of scaffolding material without causing damage to the cultured cells.

Advantages

• Accommodates hydrogel swelling while minimizing cell compression and disruption of tissue formation
• Enables continuous perfusion throughout the device
• Open-top design provides easy access to cells, scaffold, and culture fluid, allowing the delivery of agents such as drugs, cells, and dyes into specific chambers
• Supports complex 3D co-cultures that require accommodation for hydrogel swelling
• Enables compatibility with engineered hydrogels for 3D cell culture, supporting potential applications including vascular network formation, vessel perfusion, and directional cell migration
• Configuration of the microfluidic network can be designed to address specific biological questions