Thermo-aided citrate cross-linking of a pullulan sponge incorporating tissue factor and collagen for potent bleeding wound care

Abstract

Most existing wound dressings provide only passive hemostasis and protection, and lack robust bio-interactions, active coagulation capabilities, or pro-healing functions, often leading to prolonged bleeding, delayed repair or recurrent bleeding. This paper describes a multifunctional spongy dressing fabricated via thermo-aided citrate cross-linking of pullulan, incorporating tissue factor (TF, a potent physiological coagulation initiator) and collagen. The composite sponge featured an interconnected hierarchical porous structure (porosity >80%) for high blood absorption, along with favorable mechanical strength and shape-recovery property. Functional analysis demonstrated that TF encapsulation accelerated in vitro whole blood coagulation and reduced bleeding time and blood loss by ∼73.9% and ∼77.7% in a rat liver injury model, while collagen encapsulation promoted full-thickness skin wound healing. These effects stem from three synergistic mechanisms: pullulan’s porous structure and large surface area enabling ample interactions with blood or the wound bed, TF amplifying extrinsic coagulation, and collagen inducing clot formation and tissue repair. Additionally, the sponge comprising multiple bio-derived components exhibited good biocompatibility. These findings establish the TF-incorporated cross-linked pullulan/collagen sponge as a highly promising platform for addressing heavy bleeding and orchestrating subsequent wound healing.