Development of an Asymmetric Alginate Hydrogel Loaded with S-Nitrosoglutathione and Its Application in Chronic Wound Healing.

Nitric oxide (NO) is an endogenous signaling molecule that plays a critical role in wound healing. However, the gaseous nature, short half-life, and low stability of NO present challenges for its clinical application. To address these issues, this study introduces an innovative S-nitrosoglutathione (GSNO)-loaded asymmetric alginate (SA) hydrogel (GSNO-SA) as a novel solution for treating infected chronic wounds. The hydrogel is designed with a layer-by-layer melting-permeation crosslinking approach, forming a dense upper layer and a sparse lower layer structure, effectively promoting exudate management while delaying NO release. The results demonstrate that the GSNO-SA hydrogel extends NO release for up to 48 h, exhibits rapid exudate absorption (72.3 ± 1.5% equilibrium swelling after 5 min), significant antibacterial activity (over 90% antibacterial rate against E. coli and S. aureus), and anti-inflammatory effects (marked reduction in TNF-α expression), and promotes angiogenesis (90.00 ± 5.92% migration rate at 48 h). Additionally, animal studies show that the GSNO-SA hydrogel accelerates wound healing, achieving a 99.2 ± 0.1% closure rate at 14 days. Histological and immunohistochemical evaluations further confirm its ability to regulate inflammation (13.34-fold upregulation of CD163) and promote angiogenesis (3.02-fold upregulation of α-SMA). Theoretically, this asymmetric design provides a novel strategy for developing exudate-managing dressings by integrating controlled NO release with hierarchical pore structures.