An effective drug-free hydrogel for accelerating the whole healing process of bacteria-infected wounds†

Abstract

Wound healing is a dynamic and complex process involving hemostasis, inflammation, fibroblast proliferation, and tissue remodeling. This process is highly susceptible to bacterial infection, which often leads to impaired and delayed wound repair. While antibiotic therapy remains the primary clinical approach for treating bacteria-infected wounds, its widespread use poses a significant risk of developing bacterial resistance. Here, a novel drug-free hydrogel was fabricated using polysaccharides and humic acid (HU) to facilitate the healing of bacteria-infected wounds. Specifically, hyaluronic acid (HA) was modified via oxidation with sodium periodate, introducing aldehyde groups along its main chains. Pectin (PT) was grafted with amino groups on its side chains through an amidation reaction with ethylenediamine. HU, a natural organic compound with hemostatic, antioxidant, antibacterial, anti-inflammatory, and photothermal properties, was reduced using sodium borohydride to generate an increased number of phenolic hydroxyl and catechol groups. The resulting hydrogel, called HA-PT/HUOH, was prepared by integrating these three chemically modified biomaterials through dynamic Schiff base cross-linking and hydrogen bonding. The HA-PT/HUOH hydrogel showed excellent injectability, strong bioadhesiveness, rapid self-healing capabilities, and potent photothermal performance. Both in vitro and in vivo studies demonstrated that HA-PT/HUOH significantly accelerated the healing of bacteria-infected wounds by modulating the entire wound-healing process. This included enhancing hemostasis, bacteriostasis, antioxidation, anti-inflammatory responses, fibroblast proliferation, and tissue remodeling. In summary, this multifunctional drug-free hydrogel presents a highly promising solution as a wound dressing for clinical application.