Coagulation-Independent Hemostasis Through Architecturally Programmed Chitosan Aerogels with Dual-Crosslinked Networks.

Abstract

Hemorrhage control remains a central unmet need in emergency medicine and surgery, as uncontrolled bleeding causes preventable mortality and is exacerbated by anticoagulation or coagulopathy, where many hemostats that depend on the coagulation cascade lose efficacy. Hierarchically structured, dual-crosslinked ultra-highly deacetylated chitosan (DC-UDCS) aerogels enable rapid, coagulation-independent hemostasis via a dual-crosslinked hierarchical capillary-elastic memory (DC-HCEM) mechanism. Directionally ice-templated pore architectures provide fast capillary infiltration that unlocks reversible hydrogen-bonded fixation, while covalent crosslinks store elastic energy to drive blood-triggered, ultrafast self-expansion and stable mechanical tamponade, physically occluding bleeding tracts and vessels. Concurrently, the cationic chitosan network promotes electrostatic erythrocyte aggregation and cellular adhesion, supporting sealing without requiring fibrin formation. In vitro and in vivo evaluations demonstrate rapid pressure generation and effective bleeding control in both normal and anticoagulated hemorrhage models, outperforming conventional gauze-type controls, while maintaining intrinsic antibacterial activity and favorable hemocompatibility/biocompatibility. This architecture-chemistry integrated aerogel platform provides a transferrable strategy for lifesaving hemostasis when coagulation is compromised.