Injectable Protocatechualdehyde-FeNanocomposite HydrogelLoaded with Au/Se Nanoparticles for Rapid Hemostasis and Wound Healing

Abstract Effective wound healing remains a clinical challenge due to complications such as hemorrhage, oxidative stress, and the growing threat of antibiotic resistance. To overcome these obstacles, we have developed an injectable, dynamic hydrogel system constructed through a protocatechualdehyde-Fe3+ coordination network and adipic dihydrazide (ADH)-grafted gelatin cross-linking, further integrated with gold/selenium nanoparticles (Au/Se NPs). The dynamic catechol-Fe3+ interactions endow the hydrogel with self-healing properties and enable controlled release of embedded nanoparticles. This multifunctional hydrogel demonstrates potent antibacterial efficacy, achieving bactericidal rates exceeding 98% against E. coli and S. aureus under NIR. It also exhibits remarkable antioxidant capacity, with over 97% DPPH radical scavenging activity, alongside robust mechanical strength (withstanding 80% compressive strain at 1.09 MPa) and strong tissue adhesion (26.43 kPa). The incorporated Au/Se NPs exhibit cascade enzyme-mimetic activities, including catalase- and peroxidase-like functions, enabling continuous regulation of reactive oxygen species and oxygen generation within the wound microenvironment. This cascade catalytic behavior synergistically enhances antibacterial efficacy and mitigates oxidative stress during the early stages of wound healing. Notably, the hydrogel achieves rapid hemostasis within 50 s in a rat liver hemorrhage model. In a murine full-thickness skin wound model, the Au/Se NP-doped hydrogel promotes granulation tissue formation and collagen remodeling, significantly accelerating wound healing compared with the control group. The composite hydrogel exerts its therapeutic effects through two synergistic mechanisms: acting as a physical barrier and delivering active nanoparticles. These results highlight the potential of this hydrogel as a promising platform for rapid hemostasis and enhanced tissue regeneration in clinical wound care applications.