Zeolite-Mimetic Hemostatic Gauze Based on Calcium-Chelated Cellulose Nanofibers for Efficient and Safe Hemostasis

Commercial inorganic hemostatic agents such as QuikClot Combat Gauze (QCG) and WoundStat demonstrate strong hemostatic efficacy, yet their clinical utility is limited by issues such as exothermic reaction and foreign body response. To address these limitations, a cellulose nanofiber-based hemostat was developed to replicate the coagulation mechanism of zeolite. This was achieved by first covalently grafting carboxymethylated cellulose nanofibers (CMCNFs) onto medical gauze to form a stable, negatively charged nanofibrous network. Subsequently, calcium ion (Ca²⁺) was incorporated into this network via ion exchange, yielding the final Ca²⁺-chelated, citrate-crosslinked CMCNF gauze (CC/Ca-gauze). The negatively charged surface and chelated Ca²⁺ promoted local adsorption of coagulation-associated proteins and supported thrombin generation and fibrin clot formation. In vitro assays confirmed good hemocompatibility/cytocompatibility and potent procoagulant activity of CC/Ca-gauze. In vivo evaluations further demonstrated its superior hemostatic performance, achieving faster hemorrhage control and significantly reduced blood loss compared to QCG. These results support CC/Ca-gauze as a promising cellulose-based hemostatic platform for rapid hemorrhage control.