Shrinkable Hydrogels through Host–Guest Interactions: A Robust Approach to Obtain Tubular Cell‐Laden Scaffolds with Small Diameters

Abstract The availability of realistic in vitro models is crucial for tissue engineering, disease modeling, and drug screening assays. However, reproducing the complex shapes and intricate structures of naturally occurring tissues or organs in the presence of functional cells remains a challenge. For example, it is still not trivial to obtain cell‐laden tubular structures on a micrometer scale present in the nephrons of the human kidney. Here, a unique hydrogel‐based shrinking approach making use of host–guest interactions to decrease the diameters of the preformed hydrogel tubules seeded with cells is proposed as a tool to overcome the abovementioned challenge. The hydrogels are composed of covalently crosslinked methacrylated hyaluronic acid and methacrylated dextran modified with either cyclodextrin or adamantane groups that can form dynamic bonds. The hydrogels are initially formed in the presence of small‐molecule competitors that block any interpolymer host–guest interactions, and the shrinking process is triggered by the release of these competitor molecules. The high shrinking efficiency with a shrinking factor up to eight times in volume and robust cytocompatibility make the host‐guest‐based shrinking approach an appealing tool to obtain hydrogel tubular in vitro models with the desired dimensions on demand.