Injectable Stimuli-Responsive Amphiphilic Hydrogel for Rapid Hemostasis, Robust Tissue Adhesion, and Controlled Drug Delivery in Trauma and Surgical Care

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.