Thermo-irreversible glycol chitosan/hyaluronic acid blend hydrogel for injectable tissue engineering

•A blend thermogel (AcHA/HGC) was successfully prepared by mixing of HGC and AcHA.•The AcHA/HGC hydrogel underwent a unique thermo-irreversible sol-gel transition.•The AcHA/HGC exhibited the time-dependent improvement in mechanical strength.•The AcHA/HGC showed good biocompatibility and more effective cartilage formation. Thermogels that undergo temperature-dependent sol-gel transition have recently attracted attention as a promising biomaterial for injectable tissue engineering. However, conventional thermogels usually suffer from poor physical properties and low cell binding affinity, limiting their practical applications. Here, a simple approach for developing a new thermogel with enhanced physical properties and cell binding affinity is proposed. This thermogel (AcHA/HGC) was obtained by simple blending of a new class of polysaccharide-based thermogel, N-hexanoyl glycol chitosan (HGC), with a polysaccharide possessing good cell binding affinity, acetylated hyaluronic acid (AcHA). Gelation of AcHA/HGC was initially triggered by the thermosensitive response of HGC and gradually intensified by additional physical crosslinking mechanisms between HGC and AcHA, resulting in thermo-irreversible gelation. Compared to the thermos-reversible HGC hydrogel, the thermo-irreversible AcHA/HGC hydrogel exhibited enhanced physical stability, mechanical properties, cell binding affinity, and tissue compatibility. These results suggest that our thermo-irreversible hydrogel is a promising biomaterial for injectable tissue engineering.