Exploring the potential of all-aqueous immiscible systems for preparing complex biomaterials and cellular constructs

Abstract

All-aqueous immiscible systems derived from liquid-liquid phase separation of incompatible hydrophilic agents such as polymers and salts have found increasing interest in the biomedical and tissue engineering fields for the last years. The unique characteristics of aqueous interfaces, namely their low interfacial tension and elevated permeability, as well as the non-toxic environment and high-water content of the immiscible phases, confer to these systems optimal qualities for the development of biomaterials such as hydrogels and soft membranes, as well as for the preparation of in vitro tissues derived from cellular assembly. Here, we overview the main properties of these systems, and present a critical review of recent strategies that have been used for the development of biomaterials with increased levels of complexity using all-aqueous immiscible phases and interfaces, and its potential as cell-confining environments for micropatterning approaches and the bioengineering of cell-rich structures. Importantly, due to the relatively recent emergence in these areas, several key design considerations are presented, in order to guide researchers in the field. Finally, the main present challenges, future directions, and adaptability to develop advanced materials with increased biomimicry and new potential applications are briefly evaluated.