Self-Assembled Supramolecular Hybrid Hydrogels Based on Host-Guest Interaction: Formation and Application in 3D Cell Culture

In recent decades, in vitro three-dimensional (3D) cell culture has been rapidly developed and widely used in many biomedical fields. Based on this background, a kind of self-assembled supramolecular hybrid hydrogel materials based on host-guest interaction of beta-cyclodextrin (beta CD) and adamantane (Ad) is designed for 3D cell culture. First, beta CD is grafted to poly(methyl vinyl ether-alt-maleic acid) (PMM) to obtain the host polymers of beta CD-grafted-PMM (PMM-beta CD). Second, the guest polymers of poly(acrylamide-co-N-adamantyl acrylamide) (PAAm-Ad) are synthesized through free-radical copolymerization of acrylamide and N-adamantyl acrylamide. Finally, the self-assembled supramolecular hybrid hydrogels of PMM-beta CD/PAAm-Ad are formed by simply mixing the aqueous solution of host and guest polymers with a total concentration of 3.3% (w/v) and a beta CD/Ad molar ratio of 1:1. The main cross-linking interactions come from the host-guest interaction of beta CD/Ad as well as hydrogen-bonding interaction of carboxyl/amide groups. The prepared hydrogels with good cytocompatibility have been successfully used as 3D cell culture scaffold for SKOV3, HUVEC, and L929 cells culture. Thus, this work provides a way and biomaterial for the preparation of a functionalized 3D cell culture scaffold, which lays an experimental and theoretical basis for cell follow-up research.