A chitosan based multimodal “soft” hydrogel for rapid hemostasis of non-compressible hemorrhages and its mode of action

Abstract

Uncontrolled hemorrhages during accidents or surgery require non-compressible dressings to halt bleeding and avoid damage to soft tissue and organs. Here, we report the synthesis of a sodium tripolyphosphate crosslinked chitosan-based hemostatic hydrogel dressing incorporating hemostasis agonists like aluminum chloride, an aggregation enhancer and silica nanoparticles, a contact activator, as confirmed by FTIR analyses. Rheology studies displayed G” > G’ values confirming typical soft gel-like behavior that was maintained upto shear rate 10/s. Further, composite had excellent water absorption capacity (737 ± 50%) and showed 6-fold enhanced in vitro hemostasis as compared to bare hydrogel. Platelet aggregation was enhanced with composite as compared to SFLLRN peptide (a thrombin mimic) and adenosine diphosphate (calcium release activator) while it was absent with heparin (thrombin inhibitor). Enhanced activation and release of calcium were observed by composite with a specific fluorescent calcium dye in A549 cell model. The composite was biocompatible and in vivo evaluation of hemostatic efficiency in rat liver injury revealed enhanced blood clotting (16 ± 2.1 s) of hydrogel composite as compared to commercial HemoStat Clear gel (55 ± 5 s). Thus, developed soft hydrogel composite has potential for application as a safe, easy-to-apply, rapid, non-compressible hemostatic agent.