Bubble Evolution‐Guided Interconnected Hierarchical Macroporous Sponges for Non‐Compressible Hemostasis in Preclinical Models

ABSTRACT Treatment of uncontrolled non‐compressible hemorrhage remains challenging due to complex anatomical constraints and limitations of existing expandable hemostatic materials, which often lack sufficient porosity, mechanical robustness, biocompatibility, and capacity to support tissue regeneration. To address these issues, an injectable self‐expanding hemostatic sponge was developed using a vacuum‐assisted foaming strategy that harnesses bubble evolution to enlarge pores and enhance interconnectivity, with mechanical stability reinforced by a physically‐chemically integrated double‐network matrix. The optimized formulation (IHMS) exhibited hierarchically interconnected macroporous networks with excellent fatigue resistance, retaining 94.2% of peak stress and 92.7% of strain after 100 compression cycles at 80% strain. It outperformed commercial hemostatic sponges in fluid absorption, blood retention, clot formation, and tamponade sealing. Systematic evaluations demonstrated its intrinsic antibacterial activity, favorable biocompatibility, and ability to promote tissue repair. In rat liver perforation and femoral artery transection models, IHMS achieved superior hemostatic efficacy compared with cotton and commercial sponges. In lethal porcine hemorrhage models under normal and anticoagulated conditions, IHMS provided rapid and durable tamponade, outperforming the FDA‐approved XSTAT, and could be easily removed after hemostasis. Its efficacy was further validated in junctional gunshot wound models. These findings advance the design of high‐performance expandable hemostats for life‐threatening non‐compressible hemorrhage.