Dual-Cross-Linked Self-Healing Hydrogels for 3D Cell Applications

host-guest (βCD/adamantane) cross-linked hydrogels have received increasing attention in recent years for cell culture applications. A major challenge of these systems remains the lack of stability and mechanical integrity, which has led to the development of dual cross-linked gels mainly by combining the host-guest (βCD/adamantane) interaction with other physical cross-links based on ionic interactions or H-bonding. In this research, 11 dual-cross-linked hydrogels were produced on the basis of defined βCD/adamantane interactions in addition to covalent cross-linking with PEGDA₃₅₀₀ of thiol-functionalized copolymers. The dual-cross-linked hydrogels exhibit high mechanical strength and improved stability compared with βCD/Ada control hydrogels. The ability to self-heal depends on the initial strength of the gels. Encapsulation of B16F1 cells in these gels showed their uniform distribution and good cytocompatibility. It is particularly noteworthy that a higher number of living B16F1 cells were found in RGD-modified gels compared with Matrigel as a control.