Superwettable calcium ion exchanged carboxymethyl cellulose powder with self-gelation, tissue adhesion and bioabsorption for effective hemorrhage control

Abstract

Water-soluble polymers can be used to develop self-gelling hemostatic powders, and powder wettability potentially plays the key role in determining their hemostatic efficacy. Herein, a superwettable calcium ion exchanged carboxymethyl cellulose (Ca-ex-CMC) powder is reported for effective hemorrhage control. Despite being water-soluble, Ca-ex-CMC powder can form a physically crosslinked hydrogel upon contact with water (self-gelation), and the rate of water permeating the hydrogel to achieve dissolution is extremely slow. With increased calcium content, Ca-ex-CMC powder shows not only improved procoagulant activity, but enhanced wettability which can facilitate the fusion of the powders with water, resulting in promoted water uptake and in-situ formation of strong hydrogel barriers with enhanced tissue adhesion. Applying Ca-ex-CMC powder to non-compressible (liver and tail) and massive (artery) hemorrhage wounds in rat and rabbit models can stanch bleeding instantly, because of complete sealing of the bleeding sites by enhanced in-situ self-gelation. Moreover, owing to water-solubility, Ca-ex-CMC powder shows outstanding bioabsorbability and histocompatibility after implantation into rabbit liver and gluteus. These findings not only support Ca-ex-CMC powder as a promising hemostatic agent for extensive application but identify the critical role of wettability in promoting hemostasis for self-gelling powders.