Robust Biopolymeric Supramolecular “Host−Guest Macromer” Hydrogels Reinforced by in Situ Formed Multivalent Nanoclusters for Cartilage Regeneration

Abstract

Biopolymer-based supramolecular hydrogels cross-linked by host–guest interactions are usually mechanically weak as shown in “inverted vials” instead of freestanding 3D constructs. Herein, we describe a novel host–guest macromer (HGM) approach for preparation of biopolymer-based freestanding supramolecular hydrogels. Host–guest macromers are formed by molecular self-assembly between adamantane-functionalized hyaluronic acid (ADxHA) guest polymers and monoacrylated β-cyclodextrins (mono-Ac-βCD) host monomers. Supramolecular hydrogels are readily prepared by UV-induced polymerization of the preassembled host–guest macromers. Such hydrogels are soely cross-linked by in situ formed multivalent host–guest nanoclusters and show significantly reinforced mechanical properties yet still retain desirable supramolecular features. They can self-heal and be remolded into freestanding 3D constructs which afford effective protection on the encapsulated stem cells during the compression remolding, making them promising ca...