A Multifunctional Nanocomposite Hydrogel Platform with a Sequentially Coordinated Strategy for Infected Wound Healing

Effective healing of infected wounds is hindered by the inability of single-function materials to dynamically address the distinct biological phases of infection control and tissue regeneration. Herein, we present a versatile drug-loaded nanocomposite hydrogel platform (ML-OCP) that employs a sequentially coordinated strategy for efficient infected wound repair. The ML-OCP hydrogel was fabricated by incorporating l-arginine-loaded mesoporous polydopamine nanoparticles (MPDA@l-Arg NPs) into a dual-network matrix, which was formed through the Schiff base linkage between oxidized hyaluronic acid (OHA) and carboxymethyl chitosan (CMCS), along with hydrogen bonding from polyvinylpyrrolidone (PVP). ML-OCP hydrogel exhibits excellent tissue adhesiveness, self-healing ability, and mechanical properties, enabling its adaptation to the dynamic wound environment and rapid hemostasis. Building upon this stable foundation, the hydrogel implements a sequentially coordinated therapeutic strategy: the MPDA@l-Arg NPs provide immediate antibacterial (via photothermal therapy, PTT) and antioxidant actions to control early infection, while the sustained release of l-arginine ensures continuous bioactive support for the subsequent proliferation and remodeling. In a rat model of infected full-thickness skin defect, ML-OCP hydrogel demonstrated significant antibacterial activity, promoted angiogenesis, and reduced inflammation. Collectively, this work provides a versatile hydrogel platform based on a sequentially coordinated strategy, offering a new therapeutic approach for infected wounds.