Synthesis and Characterization Of N-Octanoyl Glycol Chitosan as a Novel Temperature and Ph-Sensitive Injectable Hydrogel for Biomedical Applications

Abstract

Multi-responsive hydrogel formulations have received significant attention in biomedical applications as promising injectable depots and platforms for tissue regeneration. In this study, a new pH- and temperature-sensitive polymer, octanoyl glycol chitosan (OGC), synthesized by controlled N-octanoylation of glycol chitosan and evaluated as a reversible hydrogel system capable of undergoing sol-gel transition in response to changes in pH and temperature. The OGC hydrogels, with varying degrees of octanoylation (DO), were characterized by 1H NMR and ATR-FTIR analyses, and their physicochemical properties were evaluated in terms of injectability, thermo- and pH-sensitivity, biodegradability, self-healing, cytotoxicity, 3D cell culture support, and in vivo biocompatibility. The OGC exhibited controlled thermosensitive sol-gel transition behavior, with transition temperature ranging from 23°C to 58°C, which could be tuned by adjusting the DO and polymer concentration. The effect of pH on gelation was also observed within the pH range of 5 to 7.4. OGC demonstrated excellent injectability and self-healing properties. In scaffold-free 3D cell culture systems, the OGC supported spheroid formation and maintained stability for up to 7 days. In vivo studies in ICR mice revealed no significant inflammatory response upon implantation. These results suggest that the OGC could be a promising injectable biomaterial for various biomedical applications.

Keywords: N-octanoyl glycol chitosan, pH-sensitive hydrogel, thermosensitive hydrogel, dual-sensitive hydrogel, spheroid culture