Preparation of an antibacterial, injectable, thermosensitive, and physically cross-linked hemostatic hydrogel based on quaternized linetype poly(<i>N</i>-isopropylacrylamide)

Bleeding and wound infection are two significant potential risks to life and health. While antibacterial hemostatic hydrogels can meet the requirements for hemostasis and the prevention of wound infections, the inclusion of antibacterial agents inevitably complicates the regulation of interactions between components, making it difficult to synergistically control the mechanical and antibacterial properties of the hydrogels, which limits the overall hydrogel performance. In this study, we propose the use of linear poly(<i>N</i>-isopropylacrylamide) (L-P-(C₆H₁₅N⁺)) with an antibacterial quaternary ammonium end-group for preparing hydrogels, rather than conventionally adding antibacterial agents. An injectable, highly antibacterial and wet-adhesive double-network hemostatic hydrogel was constructed using L-P-(C₆H₁₅N⁺), gelatin (G), and hyaluronic acid (HA). The comprehensive properties of the hydrogel could be adjusted through changing the molecular weight of the L-P-(C₆H₁₅N⁺) and the end-group effects. The G/HA/L-P-(C₆H₁₅N⁺) hydrogel demonstrated a gel time of 12.2-14 s, an adhesion strength of 26.9 ± 2.0 kPa and a burst pressure of 264 ± 20 mmHg. It also exhibited strong antibacterial activity against <i>E. coli</i> (93 ± 2.7%) and <i>S. aureus</i> (97 ± 3.2%), with satisfactory biocompatibility. Additionally, the hydrogel demonstrated good blood clotting ability <i>in vitro</i> and achieved rapid hemostasis (<15 s) <i>in vivo</i>. This work offers a simple and efficient strategy to fabricate high-performance smart antibacterial hemostatic hydrogels.