Self-Assembled Supramolecular Hybrid Hydrogels Based on Host–Guest Interaction: Formation and Application in 3D Cell Culture
Pengfei Ren, Faming Wang, Katrien V. Bernaerts, Yifu Fu, Wanjun Hu, Naizhen Zhou, Jidong Dai, Min Liang, Tianzhu Zhang
Abstract
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 β-cyclodextrin (βCD) and adamantane (Ad) is designed for 3D cell culture. First, βCD is grafted to poly(methyl vinyl ether-alt-maleic acid) (PMM) to obtain the host polymers of βCD-grafted-PMM (PMM-βCD). 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-βCD/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 βCD/Ad molar ratio of 1:1. The main cross-linking interactions come from the host–guest interaction of βCD/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.