In situ forming injectable and self-healing gelatin/oxidized hyaluronic acid hydrogels with enhanced mechanical properties for biomedical applications

In situ forming injectable and self-healing hydrogels hold considerable attention in biomedical applications due to their ease of administration with minimal invasiveness and ability to recover functionality after mechanical damage. However, achieving a balance between dynamic properties and mechanical strength remains challenging, and the preparation processes are often complex and require external crosslinkers. In this study, we developed a facile and efficient strategy to fabricate an in situ forming hydrogel based on gelatin and oxidized hyaluronic acid (OHA) without using external crosslinker. OHA with varying oxidation degree was synthesized to introduce tunable aldehyde groups, which reacted with amine functionalities of gelatin via dynamic Schiff base covalent bonding. The Gel/OHA hydrogels exhibited tunable gelation kinetics, enhanced compressive strength, and excellent self-healing, while maintaining a stable three-dimensional structure under physiological conditions. Furthermore, the degradation rate of the hydrogels could be modulated via the oxidation degree of OHA. In vitro biocompatibility test confirmed high cell viability and proliferation of NIH3T3 fibroblasts. These findings highlight the potential of Gel/OHA hydrogels as a versatile and tunable platform for various biomedical applications, including tissue engineering and wound healing. • In-situ forming Gel/OHA hydrogels were formed via Schiff base reaction without external agents. • Gel/OHA hydrogels exhibited tunable gelation time and improved mechanical strength. • The compressive strength of Gel/OHA hydrogels could be modulated by different oxidation degree of OHA. • Gel/OHA hydrogels exhibited shear-thinning and temperature-responsive self-healing. • Gel/OHA hydrogels showed excellent biodegradability and cytocompatibility under physiological conditions.