Harnessing the Interplay of Triple Cross-Linked Hydrogels toward Multiresponsive Alginate-Based Injectable Gels for 3D Printing Bioapplications

We report on a single chain polymer gelator comprising an alginate backbone double grafted with thermoresponsive P(NIPAM₈₆-co-NtBAM₁₄)-NH₂ polymer grafts and 3-aminophenylboronic acid moieties. The resulting polymer forms robust polymer networks resulting from three cooperative cross-linking mechanisms: (i) the hydrophobic association of the T-responsive polymer grafts above 24 °C, (ii) the formation of boronate esters between the boronic acid and the diols of the alginate backbone at physiological pH, and (iii) the ionic interactions of the residual carboxylate moieties with Ca²⁺ ions. The resulting material showed excellent tunability of the mechanical properties driven by stimuli combinations such as temperature, pH, or the addition of glucose as a network disruptor covering a storage modulus range from ∼260 Pa up to ∼1390 Pa by selective stimuli combinations. Also, the material was found to be nontoxic and could form arbitrary structures via 3D printing that can undergo multi-stimuli-responsive erosion profiles.