A Dynamic Polysaccharide Hydrogel With Reactive Oxygen Species-Scavenging, Antibacterial Activity, and Angiogenesis for Pressure Injury and Diabetic Wound Healing.

Abstract

Chronic wound healing is often delayed due to the inability of conventional dressings to provide a suitable extracellular matrix (ECM) microenvironment that supports the survival and function of endogenous cells. This deficiency leads to persistent inflammation, impaired angiogenesis, and excessive reactive oxygen species (ROS) production, forming a vicious cycle to exacerbate tissue damage. Herein, we propose a dual-crosslinked injectable dynamic polysaccharide hydrogel. Leveraging anti-inflammatory oxidized xyloglucan, and carboxymethyl chitosan to construct a first dynamic network based on Schiff-base chemistry, this biomimetic extracellular matrix mimics dynamic changes to promote cell proliferation and resolve inflammation. Furthermore, strontium ions with pro-angiogenic activity and protocatechualdehyde with antioxidant activity serve as crosslinking points for the second dynamic network. This design ensures spatiotemporal alignment between material mechanics and therapeutic action, effectively disrupting the vicious cycle of persistent inflammation, oxidative stress, and impaired angiogenesis in chronic wounds. Additionally, this hydrogel possesses commendable self-healing, tissue-adhesive and antibacterial properties. RNA sequencing analysis revealed that the hydrogel interrupts the inflammatory cascade, modulates immune processes, and accelerates collagen deposition and angiogenesis, promoting chronic wound healing. Collectively, these findings establish a foundation for designing straightforward and multifunctional hydrogel dressings capable of accelerating chronic wound repair by establishing a regenerative microenvironment.