Programming hemostasis and healing via charge-density modulation in a thermo-responsive hydrogel

Uncontrolled bleeding and impaired healing are two interlinked challenges in wound management. Here, we introduce charge-density modulation of polymers as a universal design strategy to program biointerfaces that actively promote both hemostasis and healing. By tuning the cationic density of ε-polylysine, we develop an intermediate variant (EPL-C2) that preferentially interacts with fibrinogen over abundant plasma-protein competitors, as supported by protein-adsorption assays, LC-MS/MS analysis, and isothermal titration calorimetry. Incorporating EPL-C2 into a thermo-responsive hydrogel (FN-C2) creates a hemostatic interface that enhances fibrinogen adsorption and platelet adhesion while avoiding broad or excessive activation of the plasma coagulation cascade, leading to superior hemostatic performance in vitro and in a severe arterial injury model. A key advantage of this charge-optimized FN-C2 platform is its ability to serve as a matrix for integrated therapeutic delivery without compromising its hemostatic interface. By loading insulin, the obtained FN-C2-I formulation facilitates sustained release and significantly accelerates skin and intestinal wound healing through enhanced granulation tissue formation, collagen deposition, and a pro-healing immune response. This work presents a synergistic structure-function strategy for next-generation wound dressings, in which tailored control of charge density creates a fibrinogen-selective hemostatic interface inherently compatible with integrated therapeutic delivery.