Multiresponsive and Self-Healing Hydrogel via Formation of Polymer–Nanogel Interfacial Dynamic Benzoxaborole Esters at Physiological pH

Nanocomposite hydrogels with multiresponsiveness and self-healing property are attracting extensive interest due to their enhanced performance for a wide range of applications. In this work, we have successfully developed novel hydrogels based on interfacial polymer-nanogel benzoxaborolate cross-linking at physiological pH. Temperature-sensitive nanogels (NG-Gal) containing galactose residues on the nanosurface were prepared and subsequently used as macro-cross-linkers to form a hydrogel network through formation of dynamic adducts with benzoxaborole groups of a hydrophilic copolymer poly(DMA-st-MAABO). Benefiting from the low pK_a value of benzoxaborole (∼7.2), hydrogels can be constructed rapidly at physiological pH, which is of great significance for biomedical applications. Changing the molar ratio between benzoxaborole and galactose was found to alter the mechanical properties of hydrogels as confirmed by rheological measurements. The dynamic nature of benzoxaborole esters endowed the hydrogel with moldability and self-healing ability after disruption. Moreover, the hydrogel showed multiresponsiveness toward pH, sugar, adenosine triphosphate (ATP), hydrogen peroxide (H₂O₂), and temperature. Therefore, the novel nanocomposite hydrogel we demonstrated here exhibits great potential for biomedical applications such as tissue engineering and controlled drug delivery.