Efficient, biosafe and tissue adhesive hemostatic cotton gauze with controlled balance of hydrophilicity and hydrophobicity

Massive bleeding from traumatic wounds is a significant cause of death and disability. While cotton gauze is a widely used hemostat, its high hydrophilicity leads to excessive blood absorption and increased blood loss. Existing attempts to improve hemostatic efficacy, such as QuikClot Combat Gauze (QCG) and various composite gauzes, still suffer from drawbacks including kaolin particle loss, distal thrombus risks, and insufficient control of blood permeation. This research aimed to develop a hemostatic cotton gauze addressing these limitations by combining tissue adhesion (inspired by mussel foot proteins), hydrophobicity, and the absorbency of cotton fibers. The hypothesis was that a catechol compound grafted onto the gauze surface would improve tissue adhesion, while a long hydrophobic alkyl chain would help control blood movement.

The paper reviews existing hemostatic materials, focusing on cotton gauze and its limitations. It discusses commercially available options like QCG, highlighting their advantages and disadvantages. The literature review explores previous attempts to enhance hemostatic gauze, such as incorporating inorganic particles (kaolin, zeolites) or creating Janus gauzes with varying hydrophilicity/hydrophobicity. These previous approaches are noted for their successes and shortcomings, setting the stage for the innovative approach presented in the current research.

The researchers synthesized a catechol compound, 1,2-benzenediol-3-(7,9,13-pentadecatrienyl) (USO), and grafted it onto the surface of cotton gauze using a plasma treatment to create free radicals. The chemical composition and surface structure of the modified gauze (USO-g-gauze) were characterized using solid-state ¹³C NMR, FTIR, and XPS. Scanning electron microscopy (SEM) was used to examine the surface morphology. The wettability of the gauze was evaluated using simulated body fluid (SBF) and fresh rat blood. Water vapor permeation rate and water absorption were also measured. The interaction of erythrocytes and platelets with the gauze was explored using SEM. The hemostatic efficacy of the USO-g-gauze was assessed using rat femoral artery and liver laceration models, and pig femoral artery and skin laceration models. These models allowed for evaluation under both compressible and non-compressible conditions. The hemostatic time, blood loss, and re-bleeding were measured. The biocompatibility of USO-g-gauze was evaluated using in vitro cytocompatibility assays (live/dead assay) and in vivo inflammatory assays (subcutaneous implantation in rats). Density functional theory (DFT) calculations were used to investigate the adsorption interaction of amino acids with the catechol group of USO. Peeling force measurements were conducted to quantify tissue adhesion. The effects of modifying the catechol group (chelation with Fe³⁺ or oxidation to quinone) on hemostatic efficacy were investigated.

The USO-g-gauze demonstrated significantly superior hemostatic performance compared to cotton gauze, QCG, and other modified gauzes in all animal models. In the rat femoral artery model, USO-g-gauze reduced blood loss by approximately 71% compared to QCG, and the hemostatic time was reduced by 77%. Similarly, in the rat liver laceration model, USO-g-gauze reduced blood loss by 77% and hemostatic time by 67% compared to QCG. In the pig femoral artery model, USO-g-gauze reduced blood loss to 15.6% and 20.4% of that observed with cotton gauze and QCG, respectively. In pig skin laceration models, blood loss was dramatically reduced compared to other gauzes. Notably, USO-g-gauze exhibited no re-bleeding in any of the models. The superior performance was attributed to a combination of tissue adhesion by the catechol group, hydrophobicity of the alkyl chain controlling blood spreading, and the moderate hydrophilicity of the cotton fibers allowing for efficient blood wicking and erythrocyte aggregation. DFT calculations showed strong interactions between amino acids and the catechol group, confirming the strong tissue adhesion. In vitro and in vivo biocompatibility studies showed that the USO modification did not compromise the biocompatibility of cotton gauze. The modification was also successfully applied to chitosan nonwoven fabric with similar improvements in hemostatic efficacy.

The findings demonstrate the successful development of a highly efficient, biosafe, and tissue-adhesive hemostatic cotton gauze. The controlled balance of hydrophilicity and hydrophobicity, coupled with the strong tissue adhesion provided by the catechol group, resulted in a unique hemostatic mechanism. The gauze effectively restricts blood movement, promoting rapid clot formation with minimal blood loss and eliminating re-bleeding. The results significantly advance the field of hemostatic materials, offering a potential solution for controlling traumatic bleeding in various settings. The findings highlight the potential for rational design of hemostatic materials by manipulating surface chemistry to control blood-material interactions. The success in applying this modification to chitosan nonwoven suggests broader applicability of this strategy.

This study successfully developed a novel hemostatic cotton gauze through surface modification with a catechol compound (USO). The superior hemostatic performance was attributed to a synergistic effect of tissue adhesion, controlled hydrophobicity, and blood wicking properties. The gauze showed significantly improved hemostatic efficacy compared to existing products and exhibited excellent biocompatibility. This approach holds promise for improving trauma care and reducing mortality associated with severe bleeding. Future research could explore modifications to further optimize the balance of hydrophilicity and hydrophobicity or explore different catechol compounds.

The study was primarily conducted using animal models. Further research is needed to confirm the efficacy and safety of USO-g-gauze in humans. The long-term effects of the modified gauze on wound healing and tissue regeneration warrant further investigation. While biocompatibility studies were performed, larger-scale clinical trials are necessary before widespread clinical adoption.