Freezing, Salting‐Out and Mineralization — A Simple, Universal and Modular Strategy for Constructing Mineralized Hydrogels

Abstract Mineralized hydrogels have attracted significant attention in the field of bone repair. Herein, an innovative strategy of “freezing, salting‐out and mineralizing” (FSM) is proposed for the construction of mineralized hydrogels. Based on this strategy, a collagen/hydroxyapatite (HA) mineralized hydrogel is synthesized as the template of mineralized hydrogels, and the critical roles of freezing and salting‐out in the formation of hydrogels are demonstrated. Comparative analyses with collagen/HA mineralized hydrogels synthesized through two other traditional methods reveal that the hydrogel constructed by FSM exhibits satisfactory operation simplicity, mineralization degree, uniformity distribution, mechanical property, degradation stability, cytocompatibility, and osteogenic property, indicating that it can serve as an ideal mineralized hydrogel scaffold for bone repair. Furthermore, 16 other kinds of mineralized hydrogels with different systems are constructed by modularly expanding the raw materials used in the FSM process to nine common biomedical polymers, four metal cations and three anions, confirming the universality of the proposed FSM strategy for most mineralized hydrogel. Overall, the three‐step FSM strategy, which integrates the salting‐out effect with mineralization, represents a groundbreaking approach for the fabrication of mineralized hydrogels, offering a simple, universal and modular method for their construction.