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

Carbohydr Polym. 2025 Jan 15;348(Pt A):122817. doi: 10.1016/j.carbpol.2024.122817. Epub 2024 Oct 8.

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.

Keywords: Carboxymethyl chitosan; Cationic antimicrobial polysaccharide; Drug delivery; Hemostasis; Self-healing hydrogel.

MeSH terms

  • Animals
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology
  • Biocompatible Materials / chemistry
  • Biocompatible Materials / pharmacology
  • Cell Survival / drug effects
  • Chitosan* / analogs & derivatives
  • Chitosan* / chemistry
  • Chitosan* / pharmacology
  • Escherichia coli / drug effects
  • Glucans* / chemistry
  • Glucans* / pharmacology
  • Hemostasis* / drug effects
  • Hemostatics* / chemistry
  • Hemostatics* / pharmacology
  • Hydrogels* / chemistry
  • Hydrogels* / pharmacology
  • Male
  • Mice
  • Rabbits
  • Staphylococcus aureus / drug effects
  • Tranexamic Acid* / administration & dosage
  • Tranexamic Acid* / chemistry
  • Tranexamic Acid* / pharmacology

Substances

  • Chitosan
  • Tranexamic Acid
  • Hydrogels
  • pullulan
  • Glucans
  • carboxymethyl-chitosan
  • Hemostatics
  • Anti-Bacterial Agents
  • Biocompatible Materials