Bioorthogonal Suzuki–Miyaura Cross-linking: Transforming Responsive Hydrogels into Permanent Polymer Networks

In this study, we present a novel approach to convert reversible polymer networks into stable, nonresponsive networks using bio-orthogonal Suzuki-Miyaura coupling (SMC). By leveraging boronic acids, which form reversible boronate esters with cis-diols for shear-thinning injectable gels and serve as SMC substrates to create stable C-C bonds, we achieve switching from responsive to nonresponsive behavior. We demonstrate the concept with a responsive precursor based on sodium alginate modified with phenyl boronic acid, cross-linked with three model iodide-functionalized (macro-)molecules that exhibit irreversible gelation under bio-orthogonal conditions. The resulting networks exhibit robust mechanical stability, minimal pH and temperature responsiveness, high degradation resistance and excellent hemocompatibility. The proposed approach underlines the potency of SMC as a robust synthetic strategy toward the synthesis and transformation of polymer networks for advanced biomedical applications.