Fabricating the multibranch carboxyl-modified cellulose for hemorrhage control

Abstract

Excessive bleeding is associated with a high mortality risk. In this study, citric acid and ascorbic acid were sequentially modified on the surface of microcrystalline cellulose (MCAA) to increase its carboxyl content, and their potential as hemostatic materials was investigated. The MCAA exhibited a carboxylic group content of 9.52 %, higher than that of citric acid grafted microcrystalline cellulose (MCA) at 4.6 %. Carboxyl functionalization of microcrystalline cellulose surfaces not only plays a fundamental role in the structure of composite materials but also aids in the absorption of plasma and stimulation of platelets. Fourier -transform infrared (FT-IR), thermogravimetric analysis (TGA) and X-ray photoelectron spectroscopy (XPS) spectra confirmed that carboxyl groups were successfully introduced onto the cellulose surface. Physical properties tests indicated that the MCAA possessed higher thermal stability (Tmax = 472.2 °C) compared to microcrystalline cellulose (MCC). Additionally, in vitro hemocompatibility, cytotoxicity and hemostatic property results demonstrated that MCAA displayed good biocompatibility (hemolysis ratio <1 %), optimal cell compatibility (cell viability exceeded 100 % after 72 h incubation), and impressive hemostatic effect (BCIMCAA = 31.3 %). Based on these findings, the hemostatic effect of covering a wound with MCAA was assessed, revealing enhanced hemostatic properties using MCAA in tail-amputation and liver-injury hemorrhage models. Furthermore, exploration into hemostatic mechanisms revealed that MCAA can significantly accelerate coagulation through rapid platelet aggregation and activation of the clotting cascade. Notably, MCAA showed remarkable biocompatibility and induced minimal skin irritation. In conclusion, the results affirmed that MCAA is a safe and potentially effective hemostatic agent for hemorrhage control.