Carboxymethyl chitosan/dialdehyde quaternized pullulan self-healing hydrogel loaded with tranexamic acid for rapid hemostasis

Abstract

In this study, we designed novel self-healing hydrogels (CMC/DAQP-HGs) using carboxymethyl chitosan (CMC) and dialdehyde quaternized pullulan (DAQP), aimed at loading tranexamic acid (TA) for rapid hemostasis. Meanwhile, CMC/dialdehyde pullulan (DAP) hydrogels (CMC/DAP-HGs) were prepared for comparison with CMC/DAQP-HGs. Experimental results showed that (1) DAQP, DAP, CMC/DAQP-HGs, and CMC/DAP-HGs were successfully prepared; (2) both types of hydrogels demonstrated excellent swelling (swelling ratio of 12.66–22.18 g/g), water retention (> 24 h), self-healing, and injectable properties, biocompatibility (hemolysis ratio < 2 %, relative cell viability of L929 and HSF > 80 %), and degradability; (3) CMC/DAQP-HGs had superior adhesive, antibacterial, and hemostatic properties compared to CMC/DAP-HGs, with CMC/DAQP-HG1 showing the best performance, including a tissue adhesion strength of 6.54 kPa, ~100 % of inhibition against E. coli and S. aureus, and hemostasis time in the three animal models <312 s; (4) the novel hydrogels effectively encapsulated tranexamic acid (TA) and controlled TA release; and (5) the addition of TA significantly enhanced the hydrogels' hemostatic efficacy, with the hemostasis time values in the TA-loaded CMC/DAQP-HG1 (TA/CMC/DAQP-HG1) group being reduced by >56 % compared to those in the gelatin sponge group, indicating that TA/CMC/DAQP-HG1 had the potential to be an ideal hemostatic dressing.