Molecular Simulation-Elucidated Boronate Ester Gelation in Succinyl Chitosan-Based Hydrogels with Triple-Staged...

A new class of triple-staged, thermosensitive hydrogels has been developed using double cross-linking between succinyl chitosan (SC) and poly(N-isopropylacrylamide-co-5-methacrylamido-1,2-benzoxaborole) and poly(NIPAM-co-MAAmBO) copolymers. Poly(NIPAM-co-MAAmBO) was first synthesized via RAFT polymerization with various monomer ratios and cross-linked by the hydroxyl groups on chitosan with poly(MAAmBO) segments to form the boronate ester bonding. Combining with the thermoresponsive poly(NIPAM) segments, we successfully prepared a dual-cross-linked hydrogel demonstrating a unique triple-staged, temperature-induced, sol-gel-sol transition behavior. This hydrogel exhibits injectability and self-healing capabilities. The mechanical properties of hydrogels can be tuned by adjusting the copolymer structure, hydrogel composition, temperature, and pH conditions. Among the various formulations, the hydrogel with a composition of SC/poly(NIPAM₉₀-co-MAAmBO₁₀) = 5/5 (w/w) exhibited superior mechanical properties, with a storage modulus (G') of approximately 1000 Pa at pH 7.4 and 37 °C. Rheological analysis confirmed the stability, pH responsiveness, and reversible temperature-induced sol-gel-sol transitions of the hydrogel. In summary, we demonstrated that the microstructure and properties of the SC/poly(NIPAM-co-MAAmBO) hydrogels could be tailored through dynamic boronate ester bonds and temperature-responsive hydrogen bonds, showcasing significant potential for biomedical applications.