Injectable Glycol Chitosan Thermogels with Programmable Hydrolytic Degradation for Biomedical Applications

Injectable thermogels are promising biomaterials that can be minimally invasively administered and rapidly form a gel depot under physiological conditions. Their retention time is governed by degradation behavior, making precise degradation control essential for therapeutic efficacy. Glycol chitosan (GC) based thermogels offer excellent biocompatibility and injectability; however, their degradation relies primarily on enzymatic cleavage. Because enzyme expression varies across tissues and conditions, predictable control remains challenging.
To address this, we designed a GC thermogel system, whose degradation is predominantly governed by hydrolysis rather than enzymatic activity. Hydrophobic hexyl moieties were introduced to induce temperature-responsive gelation, while hydrolytically cleavable ester linkages were incorporated into the polymer backbone to regulate the degradation. This design enables independent modulation of gel formation and degradation, allowing reproducible control of material lifetime post-injection.
The thermogels were characterized by ¹H NMR and ATR-FTIR spectroscopy. Thermoresponsive behavior was confirmed via tube inverting method and rheological measurements, demonstrating sol-gel transition near physiological temperature. Degradation studies showed that hydrogel lifetime could be systematically tuned by varying polymer concentrations and degree of substitutions, confirming effective kinetic control by the hydrolyzable linker. The thermogels maintained structural integrity while exhibiting predictable degradation independent of enzymatic environments.
This hydrolyzable GC thermogel system offers a practical strategy for overcoming the limited controllability of conventional thermogel systems. Combining programmable hydrolytic degradation with injectable thermogelling behavior, this platform holds broad potential for biomedical applications including tissue engineering and regenerative drug requiring controlled material retention time.