Ethanol-mediated freeze-drying enables robust bacterial cellulose aerogels for enhanced drug loading and hemostasis...

This work reports an ethanol-mediated freeze-drying (EMFD) strategy that enables the scalable production of high-performance bacterial cellulose aerogels (BCAs), effectively addressing key limitations of conventional methods such as supercritical drying and standard freeze-drying, including fragility, low mechanical strength, and high cost. Specifically, by replacing water in bacterial cellulose hydrogels (BCHs) with ethanol-water solution (EWs) prior to freeze-drying, the process limits ice crystal formation and reduces capillary forces and adhesion, thereby preserving structural integrity and enhancing mechanical properties. The effects of EWs concentration on BCA morphology, volume shrinkage, mechanical strength, and pore structure were systematically investigated. The BCA derived from 10 % EWs exhibits optimal performance, with improved tensile strength (0.75 MPa) and specific surface area (228.7 m²/g), exceeding that of conventionally freeze-dried aerogel (0.05 MPa; 98.1 m²/g). Our method enables retaining a robust 3D nanofiber network, ultra-low density (7.44 mg/cm³), and very high porosity (~99 %). When applied as drug carriers and hemostatic materials, these BCAs demonstrate rapid drug loading (2 min), a 4.4-fold increase in loading capacity, and sustained release, along with superior hemostatic performance in both in vitro and in vivo models. Overall, this EMFD approach offers a simple, cost-effective, and scalable method for fabricating high-performance BCAs for biomedical applications.