Abstract
Uncontrolled bleeding in trauma and surgical settings requires rapid, minimally invasive materials that can effectively stop bleeding and provide durable wound sealing. Here, we introduce an injectable, pH-responsive amphiphilic hydrogel designed for quick hemostasis, strong wet-tissue adhesion, and controlled therapeutic release. The hydrogel is prepared via a mild nucleophilic substitution reaction between tertiary amines of Poly(2-(dimethylamino)ethyl methacrylate (PDMA) and gallic acidfunctionalized branched polyethyleneimine PEI(GA), using chloride-terminated Pluronic F-127 (Cl-Plu-Cl) as a crosslinker. The shear-thinning, uniform prepolymer allows for consistent laparoscopic delivery and rapidly gels in situ (∼54 seconds) across a physiological pH range (5.07.4). In vitro and in vivo tests, including a mouse liver hemorrhage model, showed a 61% reduction in blood loss, comparable to Truseal (∼63%), while providing better injectability, biocompatibility, flexibility, and adjustable degradation and gelation properties. The (Cl-Plu-Cl/PDMA/PEI(GA)) hydrogel demonstrates strong adhesion strength (∼47 kPa) and withstands burst pressures up to 220 mmHg, exceeding typical arterial blood pressure. Sustained, pH-responsive release of amoxicillin (∼60% at pH 7.4 and ∼98% at pH 5.0 over 80 hours) displayed antibacterial activity against Staphylococcus aureus and MRSA. Alamar Blue and Live/Dead assays confirmed over 90% cell viability, and the gradual in vitro degradation over three weeks indicates safe resorption and potential for clinical use.