Multifunctional chitosan-based hydrogel wound dressing loaded with Acanthopanax senticosus and Osmundastrum cinnamomeum: Preparation, characterization and coagulation mechanism

Abstract

Considerable potential exists for the development of natural polymer hydrogels that possess notable antibacterial and anti-inflammatory properties, along with excellent biocompatibility and mechanical attributes, to expedite the healing of skin wounds. Recent endeavors have focused on formulating an optimal hydrogel dressing for wound hemostasis and repair. In this pursuit, we have crafted a composite hydrogel using carboxymethyl chitosan and alginic acid, cross-linked with EDC/NHS, and enriched with extracts from Acanthopanax senticosus and Osmundastrum cinnamomeum. This synthesized hydrogel showcases commendable features, including significant swelling capacity (135 ± 3.6%), proficient water retention (94.421 ± 0.154%), and effective water vapor permeability (5845.011 ± 467.799 g/m2/d). Moreover, our drug-loaded hydrogels (CMCS/SA/AS/OC) have demonstrated remarkable efficacy in accelerating wound healing in both in vivo and in vitro models. On the 7th day, the wound healing rate reached 94.905% ± 0.498%, and by the 14th day, the wound was nearly fully healed (98.08% ± 0.323%) with the emergence of hair coverage. Furthermore, these hydrogels exhibited remarkable hemostatic properties, the platelet activity was 89.37% ± 1.29% and the platelet adhesion rate was 66.36% ± 1.42%. In order to elucidate the coagulation mechanism of the Acanthopanax senticosus and Osmundastrum cinnamomeum extracts, a network pharmacology approach was carried out. 41 active compounds and 107 potential therapeutic targets associated with these extracts were identified, revealing a total of 132 coagulation pathways. Platelet activation and complement and coagulation cascades pathways showed the highest levels of enrichment by KEGG analysis, serving as potential mechanisms through which the active components in AS/OC may facilitate coagulation by targeting relevant factors. In summary, our study has successfully developed an innovative drug-loaded hydrogel that not only enhances wound hemostasis and healing but also provides insights into the underlying mechanisms through network pharmacology. This work establishes a robust theoretical foundation for the medical application of our hydrogel.