Intrinsically Thermoresponsive Hydrogels from Molecularly Engineered Chitosan

Thermoresponsive chitosan hydrogels hold significant promise for advancing biomedical technologies, yet their frequent reliance on petroleum-based polymers raises biosafety and environmental concerns. The present study utilized a molecular functionalization strategy to transform chitosan into thermoresponsive alkylated chitosan (ICS). The ICS was subsequently covalently crosslinked to construct a fully degradable, all-chitosan thermoresponsive hydrogel (TR-ICS_gel), showcasing the effective integration of structural design and functionality. By adjusting the ICS concentration, TR-ICS_gels with varying volume phase transition temperatures (VPTTs) were obtained. Above the VPTT, strengthened alkyl chain hydrophobic interactions triggered hydrogel dehydration and pronounced, reversible shrinkage–swelling. The hydrogel maintained a stable swelling response over 20 consecutive temperature-stimulus cycles. Further investigation was conducted on the effects of ionic strength and small-molecule solvents on the thermoresponsive behavior of TR-ICS_gel. Soil burial and buffer solution tests demonstrated that the hydrogel underwent almost complete degradation within 27 and 15 days, respectively, and the degradation rate could be regulated by the ICS concentration. The TR-ICS_gel’s all-chitosan framework ensured excellent biocompatibility, with cell viability maintained above 95%. This study presents a strategy for developing fully bio-based, degradable smart hydrogels, enhancing biosafety and environmental friendliness. Moreover, these results provide crucial performance data and theoretical support for their practical application.