A thermal cross-linking approach to developing a reinforced elastic chitosan cryogel for hemostatic management of heavy bleeding.

Uncontrolled hemorrhage stands as the primary cause of potentially preventable deaths following traumatic injuries in both civilian and military populations. Addressing this critical medical need requires the development of a hemostatic material with rapid hemostatic performance and biosafety. This work describes the engineering of a chitosan-based cryogel construct using thermo-assisted cross-linking with α-ketoglutaric acid after freeze-drying. The resulting cryogel exhibited a highly interconnected macro-porous structure with low thermal conductivity, exceptional mechanical properties, and great fluid absorption capacity. Notably, assessments using rabbit whole blood in vitro, as well as rat liver volume defect and femoral artery injury models simulating severe bleeding, showed the remarkable hemostatic performance of the chitosan cryogel. Among the cryogel variants with different chitosan molecular weights, the 150 kDa one demonstrated superior hemostatic efficacy, reducing blood loss and hemostasis time by approximately 73 % and 63 % in the hepatic model, and by around 60 % and 68 %, in the femoral artery model. Additionally, comprehensive in vitro and in vivo evaluations underscored the good biocompatibility of the chitosan cryogel. Taken together, these results strongly indicate that the designed chitosan cryogel configuration holds significant potential as a safe and rapid hemostatic material for managing severe hemorrhage.

Thermo-assisted fabrication of a novel shape-memory hyaluronic acid sponge for non-compressible hemorrhage control.

Hyaluronic acid (HA), a major component of skin extracellular matrix, provides an excellent framework for hemostatic design; however, there still lacks HA materials tailored with superior mechanical properties to address non-compressible hemorrhages. Here, we present a solvent-free thermal approach for constructing a shape-memory HA sponge for this application. Following facile thermal incubation around 130 °C, HA underwent cross-linking via esterification with poly(acrylic acid) within the sponge pre-shaped through a prior freeze-drying process. The resulting sponge system exhibited extensively interconnected macropores with a high fluid absorption capacity, excellent shape-memory property, and robust mechanical elasticity. When introduced to whole blood in vitro, the HA sponges demonstrated remarkable hemostatic properties, yielding a shorter coagulation time and lower blood clotting index compared to the commercial gelatin sponge (GS). Furthermore, in vivo hemostatic studies involving two non-compressible hemorrhage models (rat liver volume defect injury or femoral artery injury) achieved a significant reduction of approximately 64% (or 56%) and 73% (or 70%) in bleeding time and blood loss, respectively, which also outperformed GS. Additionally, comprehensive in vitro and in vivo evaluations suggested the good biocompatibility and biodegradability of HA sponges. This study highlights the substantial potential for utilizing the designed HA sponges in massive bleeding management.