Extracellular matrix-mimicking cryogels in tissue engineering and cancer therapy: from structural design to...

Cryogels are a class of macroporous hydrogels fabricated through a cryogelation process at sub-zero temperatures, resulting in a highly interconnected pore structure. This review focuses on cryogels that mimic the natural extracellular matrix (ECM) in composition and molecular architecture. These cryogels not only exhibit the high mechanical strength and elasticity characteristic of traditional cryogels but also possess unique structural features and excellent biocompatibility, providing a supportive microenvironment for cellular vitality and metabolic activity. The interconnected pores of cryogels facilitate the establishment of controllable mass transport and oxygen gradients, making them particularly advantageous for applications such as hypoxic tumor modeling where precise microenvironment control is essential. They also show great promise in vaccine development, drug delivery and screening, and combination chemotherapies. These features position cryogels as an ideal platform for cancer research. This review summarizes the principles, processes, and preparation methods of cryogelation for developing ECM-mimicking cryogels. Furthermore, it discusses the effects of polymer composition, crosslinking agents, freezing conditions, and other factors on the physical, chemical, and biological properties of cryogels. Finally, the biomedical applications of ECM-mimicking cryogels are explored, illustrating their potential roles in tissue engineering, cancer research, and therapeutic interventions.