Leveraging ultra-low interfacial tension and liquid-liquid phase separation in embedded 3D bioprinting

Many recently developed 3D bioprinting strategies operate by extruding aqueous biopolymer solutions directly into a variety of different support materials constituted from swollen, solvated, aqueous, polymer assemblies. In developing these 3D printing methods and materials, great care is often taken to tune the rheological behaviors of both inks and 3D support media. By contrast, much less attention has been given to the physics of the interfaces created when structuring one polymer phase into another in embedded 3D printing applications. For example, it is currently unclear whether a dynamic interfacial tension between miscible phases stabilizes embedded 3D bioprinted structures as they are shaped while in a liquid state. Interest in the physics of interfaces between complex fluids has grown dramatically since the discovery of liquid-liquid phase separation (LLPS) in living cells. We believe that many new insights coming from this burst of investigation into LLPS within biological contexts can be leveraged to develop new materials and methods for improved 3D bioprinting that leverage LLPS in mixtures of biopolymers, biocompatible synthetic polymers, and proteins. Thus, in this review article, we highlight work at the interface between recent LLPS research and embedded 3D bioprinting methods and materials, and we introduce a 3D bioprinting method that leverages LLPS to stabilize printed biopolymer inks embedded in a bioprinting support material.