Altangerel Amarjargal, Bartlomiej Kalaska, Karol Depczynski, Dorota Kolbuk, Viraj P. Nirwan, Rebecca Hengsbach, Amir Fahmi
• A facile method for deprotonated carboxylate-assisted direct electrospinning of 3D sponge was reported for the first time. • Deprotonated carboxylate simultaneously imparts 3D, superhydrophilicity, and negatively charged surfaces to fibrous matrices. • Hybrid fiber could facilitate the adherence and aggregation of abundant blood cells, forming an impermeable barrier. • 3D hybrid fiber sponge shows superior hemostasis performance than traditional alternatives. Effective management of non-compressible hemorrhage remains a significant challenge in the field of biomaterials development. Although fluffy fiber sponges with strong hemostatic properties and excellent biocompatibility have been a promising solution, their fabrication has been rather complicated. This study presents a facile in situ deprotonation-induced direct electrospinning approach that enables the fabrication of three-dimensional Gelatin/Eudragit S100 (3D Gel/ES)-based fiber sponges. These sponges are equipped with multiple hemostatic-enhancing moieties to address non-compressible bleeding. The generated 3D sponges exhibit a fluffy texture composed of continuous and interconnected fibers. Results demonstrate a remarkable compressibility, exceptional porosity (>90 %), excellent water absorption capabilities (>2000 %), very low hemolytic rate (<0.1 %), and non-cytotoxic characteristics (cell viability > 85 %). Furthermore, their hemostatic response has been improved, especially by the incorporation of CaCO 3. Consequently, activating the intrinsic pathway of the coagulation cascade, along with the adhesion, enrichment, and activation properties of erythrocytes and platelets. In vivo analyses of hybrid fiber sponges confirm their superior hemostatic capabilities compared to traditional gauze and commercial sponge materials. This fabrication strategy is anticipated to open a new avenue for the development of next-generation advanced hemostatic 3D fiber sponge, specifically targeting rapid and effective hemostasis in mild-to-moderate bleeding.