A dual-responsive self-healing injectable hydrogel loaded with Isatis root-derived carbon dots toward efficient infected wound therapy.

Abstract

Bacteria-infected wounds are very difficult to treat, largely because the pathological microenvironment involved is dynamic. The requirements for infected wound repair are multifaceted, and conventional hydrogel dressings cannot adequately meet them due to their limited functionality. In this study, we report the construction of a multifunctional, pH/ROS dual-responsive hydrogel based on dynamic Schiff base and borate ester linkages. Oxidized pullulan (OPu) was used to fabricate the hydrogel, and the bioactive polyphenol chlorogenic acid (CA) acted as the crosslinking agent. Next, we synthesized the carbon dots derived from Isatis root (IR-CDs) using the hydrothermal method and subsequently incorporated them into the hydrogel. The hydrogel exhibited excellent injectability and self-healing capability, enabling application at irregular wound sites. Under the acidic and oxidative conditions of infected wounds, the hydrogel gradually dissociated, releasing IR-CDs and CA in a controlled manner. IR-CDs exhibited potent antibacterial activity, while CA and IR-CDs in combination efficiently scavenged excessive reactive oxygen and nitrogen species, therefore promoting tissue regeneration and reducing inflammation. Both in vitro and in vivo evaluations confirmed that the hydrogel was highly biocompatible and provided anti-infective, anti-oxidative, and anti-inflammatory effects during the early stages of healing, followed by an increase in angiogenesis and acceleration of the wound healing process. The hydrogel developed in this study is versatile and can serve as a promising and effective biomaterial platform for managing bacteria-infected wounds.