Microgels-on-macrogel: A simple cytophilic surface makeover of soft agarose substrates

Abstract

Microgel-mediated surface modification has shown great promises for a variety of metallic and non-metallic substrates. Yet, despite its compelling merits, this approach is less implemented on soft hydrogel substrates. Here, using the well-known bioinert agarose hydrogel as an example, we highlight a microgels-on-macrogel strategy that readily confers cytophilicity to the agarose surface toward anchorage-dependent cells. Specifically, we selected glycerol diglycidyl ether to tailor design polyetheramine-bisepoxide-based cationic microgels with more prominent ether alcohol features for enhanced chemical compatibility with agarose. Through a simple drop casting method, concurrent modifications of chemical, morphological and mechanical properties of the surface of agarose gel were then achieved with these microgels bound to the surface in a non-covalent yet robust manner. With the mere introduction of the cationic microgels, not only was the non-adhesive agarose surface effectively transformed to be cytophilic shown by the favorable responses from the in vitro culture of MC3T3-E1 cells, but also was hydrophobic reservoir function integrated conveniently. The demonstration of its feasibility and versatility warrants continued research of this straightforward microgels-on-macrogel strategy, which could be of value particularly for the development of novel biointerfaces. • Non-vinylic cationic microgels with prominent ether alcohol features readily prepared in water. • Facile yet robust surface modification of agarose achieved by sessile drop casting of the microgels. • Concurrent changes in agarose surface chemistry, morphology and stiffness mediated by the microgels. • Adhesion and growth of anchorage-dependent cells enabled via surface-bound microgels. • Hydrophobic depot function readily integrated into the surface of a hydrophilic gel substrate.