Injectable and self-healing dual-crosslinked thermogel based on octanoyl glycol chitosan and oxidized hyaluronic acid...

The development of thermo-sensitive hydrogels with dynamic properties, including shear-thinning, self-healing, and high mechanical strength, is crucial for biomedical applications, particularly in tissue engineering and localized injectable therapies. Despite significant progress, achieving both rapid thermal gelation and robust structural integrity remains a major challenge. This study presents a novel dual crosslinked injectable thermogel system prepared by simple blending of thermogelling octanoyl glycol chitosan (OGC) with oxidized hyaluronic acid (OHA), forming an OGC/OHA thermogel with enhanced mechanical properties, tunable degradation, and excellent biocompatibility. The gelation process was efficiently initiated through the thermosensitive nature of OGC, while the addition of OHA enables dynamic Schiff base crosslinking, further strengthening the hydrogel network. The resulting OGC/OHA thermogels exhibit rapid and controlled gelation times, ranging from 1.56 ± 0.04 to 3.34 ± 0.01 min, and mechanical strengths between 17.42 ± 4.04 kPa and 40.65 ± 2.12 kPa, depending on the OHA content. Additionally, the degradation profile can be precisely tuned by adjusting the hydrogel composition, allowing for controlled stability tailored for specific biomedical environments. In vitro cytocompatibility and hemocompatibility studies demonstrated that OGC/OHA thermogels supported cell proliferation without cytotoxic effects and minimal hemolytic potential, indicating their suitability for biomedical applications. Given their injectable nature, structural resilience, and biofunctionality, these thermogels show great potential for applications in injectable delivery, regenerative therapy, and tissue engineering. In conclusion, this work highlights the versatility of OGC/OHA thermogel as a promising next-generation biomaterial for advanced therapeutic applications.