Highly Porous Gas-Blown Hydrogels for Direct Cell Encapsulation with High Cell Viability

Cell transplant therapies show potential as treatments for a large number of diseases. The encapsulation of cells within hydrogels is often used to mimic the extracellular matrix and protect cells from the body's immune response. However, cell encapsulation can be limited in terms of both scaffold size and cell viability due to poor nutrient and waste transport throughout the bulk of larger volume hydrogels. Strategies to address this issue include creating prevascularized or porous structured materials. For example, cell-laden hydrogels can be formed by porogen leaching or three-dimensional printing, but these techniques involve the use of multiple materials, long preparation times, and/or specialized equipment. Postfabrication cell seeding in porous scaffolds can result in inconsistent cell density throughout scaffold volumes and typically requires a bioreactor to ensure even cell distribution. In this study, we developed a highly cytocompatible direct cell encapsulation method during the rapid fabrication of porous hydrogels. Using sodium bicarbonate and citric acid as blowing agents, we employed photocurable polymers to produce highly porous materials within a matter of minutes. Cells were directly encapsulated within methacrylated poly(vinyl alcohol), poly(ethylene glycol), and gelatin hydrogels at viabilities as high as 93% by controlling solution variables, such as citric acid content, viscosity, pH, and curing time. Cell viability within the resulting porous constructs was high (>80%) over 14 days of analysis with multiple cell types. This work provides a simple, versatile, and tunable method for cell encapsulation within highly porous constructs that can be built upon in future work for the delivery of cell-based therapies. Impact Statement This simple method to obtain cell-laden hydrogel foams allows direct cell encapsulation within biomaterials without the need for porogens or microcarriers, while maintaining high cell viability. The successful encapsulation of multiple cell types into gas-blown hydrogels with varied chemistries shows the versatility of this method. While this work focuses on photocrosslinkable polymers, any quick gelling material could be used for foam fabrication in expansion of this work. The potential future impact of this work on the treatment of diseases and injuries that utilize cell therapies is wide-ranging.