Guest-host interlinked PEG-MAL granular hydrogels as an engineered cellular microenvironment.

We report the development of a polyethylene glycol (PEG) hydrogel scaffold that provides the advantages of conventional bulk PEG hydrogels for engineering cellular microenvironments and allows for rapid cell migration. PEG microgels were used to assemble a densely packed granular system with an intrinsic interstitium-like negative space. In this material, guest-host molecular interactions provide reversible non-covalent linkages between discrete PEG microgel particles to form a cohesive bulk material. In guest-host chemistry, different guest molecules reversibly and non-covalently interact with their cyclic host molecules. Two species of PEG microgels were made, each with one functional group at the end of the four arm PEG-MAL functionalized using thiol click chemistry. The first was functionalized with the host molecule β-cyclodextrin, a cyclic oligosaccharide of repeating d-glucose units, and the other functionalized with the guest molecule adamantane. These two species provide a reversible guest-host interaction between microgel particles when mixed, generating an interlinked network with a percolated interstitium. We showed that this granular configuration, unlike conventional bulk PEG hydrogels, enabled the rapid migration of THP-1 monocyte cells. The guest-host microgels also exhibited shear-thinning behavior, providing a unique advantage over current bulk PEG hydrogels.