A multifunctional injectable hemostatic hydrogel for sustained tranexamic acid delivery and ROS attenuation in intracerebral hemorrhage.

Intracerebral hemorrhage (ICH) demands immediate and localized hemostatic intervention to curtail hematoma expansion and mitigate secondary brain injury. However, achieving sustained local antifibrinolytic delivery within the cranial microenvironment remains a significant challenge. In this study, we developed a multifunctional, injectable alginate-gelatin hydrogel engineered for the localized delivery of tranexamic Acid (TXA). To optimize mechanical compliance and injectability, we implemented a binary-salt crosslinking strategy using CaCl2 and Ca(Gluconate)2, overcoming the rapid, non-uniform gelation typical of single-salt systems. Among the screened formulations, the A4G4-TXA system stood out as the optimal candidate, exhibiting brain-tissue-compatible rheological properties suitable for the delicate cranial microenvironment, achieving rapid in situ gel formation after mixing, and sustaining TXA release governed by the Hopfenberg model. Crucially, the matrix significantly reduces intracellular ROS levels, suggesting a protective role against oxidative stress. The platform demonstrated potent pro-coagulant activity, achieving a rapid clotting time of 33.67 ± 3.51 s in rat models. Furthermore, comprehensive in vitro and in vivo evaluations confirmed that the hydrogel is non-toxic and integrates seamlessly with brain tissue, with no evidence of persistent or widespread neuroinflammatory damage during the 7-day observation period. Collectively, this mechanically tailored, binary-ion system offers a synergistic approach to localized hemorrhage control and therapeutic modulation in neurosurgical applications.