Engineering a Naturally-Derived Dual-Network Expandable Sponge for Rapid Control of Noncompressible Hemorrhage

Developing biocompatible expandable hemostatic sponges that integrate rapid and high-capacity fluid uptake, mechanical resilience, and strong procoagulant activity remains highly desirable for the management of noncompressible hemorrhage in trauma care. Herein, a naturally derived injectable self-expanding γ-poly(glutamic acid)/carboxymethyl cellulose (γPGA/CMC) sponge was developed for noncompressible hemorrhage management. The sponge was fabricated through stirring-assisted foaming and further reinforced by a physical-chemical dual-network structure comprising covalent crosslinking of methacrylate-functionalized γPGA and Ca2+-mediated ionic interactions with carboxyl groups. Through systematic optimization of the formulation, the resulting γPGA/CMC sponge exhibited a highly interconnected porous structure with higher porosity, enhanced fluid absorption capacity, and improved procoagulant activity compared with commercial gelatin sponge and XSTAT. In addition, the sponge exhibited favorable biocompatibility and degradability. In rat liver perforation and femoral artery transection models, the γPGA/CMC sponge demonstrated significantly improved hemostatic efficacy compared with gelatin sponge and XSTAT. Furthermore, it effectively controlled severe bleeding in porcine liver and femoral artery injury models. Together, these results highlight the potential of the γPGA/CMC sponge for noncompressible hemorrhage management.