Spontaneous Phase Separation Enables Rapid, Polymerization-Free Fabrication of Dissolvable Hydrogels

ABSTRACT Hydrogels are cross-linked polymeric networks with wide applications in drug delivery, tissue engineering, biosensing, and environmental remediation. These hydrogels additionally host living cells, small molecules and biological propagules, which further expand the applications of these materials. However, most if not all fabrication methods require covalent modifications. In this work, for the first time, we demonstrate that polymer mixtures can access an additional material state beyond the conventionally described homogeneous and two-phase regimes. By deliberately selecting polymers with a known propensity to phase separate and formulating compositions far from the binodal boundary, the system transitions directly into a mechanically stable hydrogel. We demonstrate this technique using a model system of poly (ethylene glycol) (PEG) and dextran (DEX). We have systematically characterized the hydrogels through FTIR, MALDI-TOF to discern the molecular compositions of the hydrogels. We also modulate the optical transparency of these hydrogels by varying the molecular weight of the polymers. These experimental findings are supplemented with coarse grained (CG) simulation insights to investigate the mechanistic origins of phase separation propensity with varying molecular weights of dextran. We utilized coexisting densities in the two phases using CG simulations to predict the role of dextran molecular weight on the partitioning of PEG and DEX in the two phases. Finally, we exploit the fabricated hydrogel’s ability to encapsulate live cells, antibiotics and plant seeds. We anticipate that this ATPS-based fabrication technique will provides a scalable, crosslinker-free route to multifunctional hydrogels enabling advanced applications in drug delivery and responsive materials.