Steering phase-separated droplets to control fibrillar network evolution of supramolecular peptide hydrogels

Controlling the non-covalent cross-linking network morphology of supramolecular hydrogels is of primary importance in tuning their mechanical properties for practical biomaterial applications. In this work, we study the fibrillar network evolution that controls the mechanical properties of hydrogels by modulating the solute-rich metastable droplets formed via liquid-liquid phase separation (LLPS). The size and amount of the droplets, the structural evolution of droplets into pre-fibrils, and fibril network development can be finely tuned by varying the thermal history. There is an optimal initial incubation temperature leading to the hydrogel with the optimized mechanical strength and recovery performance. The mechanism of the temperature dependence of mechanical properties is due to the different non-covalent cross-linked gel network morphology through distinct self-assembly pathways. The findings elucidate the key role of phase-separated droplets in the evolution of self-assembling networks during gelation and provide a deeper understanding of engineering supramolecular hydrogels with flexibly tunable mechanical properties.