Rapid Self-Assembly of Macroscale Tissue Constructs at Biphasic Aqueous Interfaces

An entirely new approach to tissue engineering is presented that uses the interfacial forces between aqueous solutions of phase-separating polymers to confine cells and promote their assembly into interconnected, macroscopic tissue constructs. This simple and inexpensive general procedure creates free-standing, centimeter-scale constructs from cell suspensions at the interface between poly(ethylene glycol) and dextran aqueous two-phase systems in as little as 2 h. Using this method, skin constructs are produced that integrate with decellularized dermal matrices, on which they differentiate and stratify into skin equivalents. It is demonstrated that the constructs produced by this method have appropriate integrity and mechanical properties for use as in vitro tissue models. Macroscopic tissue constructs composed entirely of cells are formed using the interfacial properties of aqueous two-phase systems. The constructs form rapidly in as little as 2 h using a variety of cell types, offering a new methodology for fabricating tissue-engineered in vitro models and cell-based materials for regenerative therapies.