Deformable and Robust Core–Shell Protein Microcapsules Templated by Liquid–Liquid Phase-Separated Microdroplets

Microcapsules are a key class of microscale materials with applications in areas ranging from personal care to biomedicine, and with increasing potential to act as extracellular matrix (ECM) models of hollow organs, tissues, or biomolecular condensates. Such capsules are conventionally generated from non-ECM materials including synthetic polymers. Here, robust microcapsules with controllable shell thickness from physically- and enzymatically-crosslinked gelatin were fabricated, and a core-shell architecture was achieved by exploiting a liquid-liquid phase-separated aqueous system in a one-step microfluidic process. Microfluidic mechanical testing revealed that the mechanical robustness of thicker-shell capsules could be controlled through modulation of the shell thickness. Furthermore, the microcapsules demonstrated environmentally-responsive deformation, including buckling driven by osmosis and external mechanical forces. A sequential release of cargo species was obtained through the degradation of the capsules. Stability measurements showed the capsules were stable at 37 ◦C for more than two weeks. Finally, through gel-sol transition, microgels functioned as precursors for the formation of all-aqueous liquid-liquid phase-separated systems that were two-phase or multiphase. These smart capsules that can undergo phase transition are promising models of hollow biostructures, microscale drug carriers, and building blocks or compartments for active soft materials and robots.Cambridge Trust (Y.X.; B.L.), the Jardine Foundation (Y.X.), Trinity College Cambridge (Y.X.), Peterhouse College Cambridge (T.C.T.M.), the Swiss National Science Foundation (T.C.T.M.), the Engineering and Physical Sciences Research Council (K.L.S.), the Schmidt Science Fellowship program in partnership with the Rhodes Trust (K.L.S.), St John’s College Cambridge (K.L.S.), China Scholarship Council (H.Z.; B.L.), EPSRC Cambridge NanoDTC (EP/037221/1; A.P.M.G.), the Newman Foundation (T.P.J.K.), the Wellcome Trust (T.P.J.K.), and the European Research Council under the European Union’s Seventh Framework Programme (FP7/2007-2013) through the ERC grant PhysProt (agreement n◦ 337969; T.P.J.K.)