Architecture-Driven Supramolecular Assembly in Bottlebrush Hydrogels

Abstract Supramolecular materials are traditionally designed by strengthening noncovalent interactions or increasing the number of binding motifs. Here, we demonstrate a fundamentally different strategy: using macromolecular architecture to amplify weak molecular interactions into robust material functions. Bottlebrush poly(ethylene glycol) (PEG) polymers, consisting of a linear backbone densely grafted with short side chains, transform tetrazine π–π interactions that are insufficient to gel linear polymers into stable supramolecular hydrogels without covalent crosslinking. The resulting networks remain stable up to ∼65 °C, undergo shear-reversible solid–liquid transitions, and disassemble upon tetrazine deactivation. Density functional theory calculations reveal unusually strong antiparallel tetrazine–tetrazine interactions (∼17 kBT at room temperature), supporting the hypothesis that the bottlebrush architecture promotes molecular alignment and cooperative association. By varying polymer concentration and tetrazine grafting ratio, we uncover a universal scaling relationship between hydrogel stiffness and the distance from the percolation threshold, with two distinct regimes that deviate from classical percolation theory. The hydrogels are cytocompatible and, unlike linear PEG hydrogels, exhibit minimal fibrotic encapsulation following implantation in immunocompetent mice. These findings establish molecular architecture as a design principle for supramolecular assembly, demonstrating that robust material function can emerge from the architectural amplification of weak interactions and enabling a class of injectable antifibrotic biomaterials.